Objective:To determine the protective effect of co-enzyme Q10(CoQ10)on testicular tissue and sperm parameters in male rats treated with SunsetYellow FCF.Methods:Sixty male Sprague-Dawley rats were randomly divided int...Objective:To determine the protective effect of co-enzyme Q10(CoQ10)on testicular tissue and sperm parameters in male rats treated with SunsetYellow FCF.Methods:Sixty male Sprague-Dawley rats were randomly divided into 6 groups of the control,CoQ10(10 mg/kg/day),low dose of Sunset Yellow(2.5 mg/kg),high dose of Sunset Yellow(70 mg/kg),low dose of Sunset Yellow(2.5 mg/kg)plus CoQ10,and high dose of Sunset Yellow(70 mg/kg)plus CoQ10.The drugs were administered via daily oral gavages for 6 weeks.At the end of the experiment,sperm analysis,stereological and histological assessments of the testis were carried out.Results:The normal morphology(by 41.1%)and progressive spermatozoa(by 74.8%),testicle volume(by 33.4%),lumen volume(by 38.3%),interstitial tissue volume(by 44.7%),seminiferous tubule volume(by 40.7%),and number of spermatogonia(by 53.9%)and Leydig cells(by 70.7%)reduced in the rats that received high doses of Sunset Yellow in comparison to the control group.Nonetheless,all these alterations were recovered by CoQ10 treatment in the CoQ10 plus high dose of Sunset Yellow group.Furthermore,low doses of Sunset Yellow did not affect different parameters of the testis and sperm.Conclusions:CoQ10 could,to some extent,prevent structural changes of the testis induced by the high dose of SunsetYellow.展开更多
Objective:To evaluate the protective effects of probiotic microorganisms on the reproductive and nervous systems of male rats treated with acrylamide.Methods:Thirty-two rats were randomly divided into 4 groups and rec...Objective:To evaluate the protective effects of probiotic microorganisms on the reproductive and nervous systems of male rats treated with acrylamide.Methods:Thirty-two rats were randomly divided into 4 groups and received normal saline through gavage(control),acrylamide 20 mg/kg body weight,acrylamide plus probiotic microorganisms(Lactobacillus acidophilus,Lactobacillus casei,Lactobacillus bulgaricus,Lactobacillus rhamnosus,Bifidobacterium breve,Bifidobacterium infantis,Streptococcus thermophilus and fructooligosaccharides,all mixed in sachets)20 or 200 mg/kg body weight,respectively.After 30 days,the testis,prostate,seminal vesicle and cerebellum were removed,fixed and stained with hematoxylin-eosin(H&E).The Johnsen score was used to classify spermatogenesis.Cavalieri's principle method was used to evaluate the total volume(in mm3)of the testes.The number of each intratubular cell type as well as intertubular Leydig cells in whole samples was measured using the physical dissector counting techniques.Stereological analysis and the grids were used to determine the volume of cerebellar layers as well as the Purkinje cell number.Results:The testis weight decreased significantly in the acrylamide-treated group compared to the other groups(P<0.001).The number of spermatogonia,spermatocytes,spermatids and Leydig cells in the acrylamide-treated group were significantly less compared to the control group(P<0.05),while they were increased significantly in the acrylamide+200 mg/kg probiotic group(P<0.05;P<0.01).The mean Johnsen score in the acrylamide-treated group was lower than in the control group(P<0.001).Acrylamide-induced changes including congestion,vacuolization in the secretory epithelial cells,and epithelial rupture were observed in the prostate and seminal vesicle.The volumes of cerebellar layers were decreased in the acrylamide group compared to the control group while recovered in both probiotic treated groups.Conclusions:Probiotic microorganisms alleviate acrylamide-induced toxicities against the reproductive and cerebellar tissues in rats.展开更多
Objective:To examine light and heat effects on the morphological,histological,and micrometric structure of the prostate of rats.Methods:Thirty adult male rats were divided into three groups.The control group was kept ...Objective:To examine light and heat effects on the morphological,histological,and micrometric structure of the prostate of rats.Methods:Thirty adult male rats were divided into three groups.The control group was kept under 20℃-22℃ and an artificial 12 h/12 h day/night cycle;the temperature group was under normal light and at(42±1)℃ heat for 4 to 5 h daily,and the light group was exposed to 8 h/16 h day/night cycle with 20℃-22℃.Rats were weighed five times(at the beginning of the study and every seven days).Five milliliters(mL)of their peripheral blood were taken.The tissue staining was performed using the hematoxylin-eosin(H&E)stain and periodic acid-Schiff(PAS).In the following,tissue and cellular reactions to the PAS were examined.Results:Folds were located entirely on the surface of the anterior lobe and periphery of the other lobes.The secretory units in the anterior lobe were more than the lateral lobe.A strong reaction of the secretory cells to the PAS was observed.Testosterone serum levels of the light group also significantly increased compared to the control group(P<0.05).The most histometric changes of the lobes were established in the lateral lobes.Heat stress resulted in a significant decrease in testosterone levels and transformed prostate tissue.The epithelium and parenchyma to scaffold ratio in the temperature group decreased.Conclusions:Maximum and minimum changes in the ventral lobe happened under the ascent of temperature and light,respectively.The ventral lobe in the study of prostatic hyperplasia should be more considered.展开更多
Aim: The harmful effects of pesticides have been largely documented in recent times. But effective therapeutic solutions to pesticide related male infertility are yet to be established. This study investigated the cur...Aim: The harmful effects of pesticides have been largely documented in recent times. But effective therapeutic solutions to pesticide related male infertility are yet to be established. This study investigated the curative effects of Lannea acida on imidacloprid (IMI)-induced hypofertility in male Wistar rats. Methods: Rats of 150 – 200 g were administered IMI (22.5 mg/kg) for two weeks and partitioned into control (distilled water, vitamin E, clomiphene citrate) or test (aqueous (340 mg/kg), methanol (170 mg/kg) extract) groups for eight weeks treatment. Animals were sacrificed at the end of the treatment and samples were collected for sperm, antioxidant and hormonal analysis. Fertility tests were performed from treatment day 47 for fertility indices estimation. Results were expressed as mean ± SEM and one way ANOVA was applied using STATISTICA Software. Results: Exposition to IMI resulted in a significant decrease in sperm count, motility, viability and normality, testosterone and LH, coupled to an increase in oxidative stress markers. Moreover, IMI impaired male fertility evidenced by a significant drop in fertility index and litter size. Similar to clomiphene citrate and vitamin E, plant extracts significantly improved the sperm parameters, sexual hormones and decreased the oxidative stress markers. More importantly, the fertility index and litter size were restored, especially with the aqueous extract. Conclusion: Present results indicate that L. acida possesses curative potentials against IMI-induced hypofertility through its androgenic and antioxidant properties. However, the effects the extract on spermatozoa DNA structure and the fertility of offsprings from exposed parents are yet to be studied to conclude on total recovery from IMI toxicity.展开更多
The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is ...The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.展开更多
Introduction: Inappropriate and excess vitamin supplementation, particularly for vitamin A, is increasingly recognized as a public health problem in developed countries. On the other hand, blind supplementation of vit...Introduction: Inappropriate and excess vitamin supplementation, particularly for vitamin A, is increasingly recognized as a public health problem in developed countries. On the other hand, blind supplementation of vitamin A, for children in developing countries is a subject of controversy in the literature. The crucial role of vitamin A in the process of spermatogenesis in adult rodents is well established, but only a few publications are consecrated to the long-term effect of vitamin A intake at a young age on testicular development and differentiation. Objectives: Our study aimed to evaluate the long-term effects of acute supplementation at an early age, in the post-natal period, on spermatogenesis and testicular trophicity at adult age. Material and Methods: Young Wistar Albinos rats of 22 days received an acute high dose of supplementation of vitamin A (retinyl palmitate). The control group, group 1, received only extra virgin olive oil, Group 2 a dose of 7000 IU/kg of retinyl palmitate, group 3, 14,000 IU/kg, and Group 4 a dose of 28,000 IU/kg. At 10 weeks of age, the testes’ testosterone levels were measured by ELISA. For histological assessment, sections were stained with Hematoxylin eosin, and the Johnsen score was used to evaluate spermatogenesis in the seminiferous tubules. Results: The average testicular weights of rats were significantly lower in group 4 (p < 0.05), and so was the testosterone level in the testis compared to the control group (p .01). Most of the seminiferous tubules were concerned by an arrest of spermatogenesis and the Johnsen score was decreased with a mean score of 5.96 ± 1.60 (p .001) in that Group. In Group 3, Johnsen’s score was significantly better than the one obtained with the control. Conclusion: We observed a negative effect in the long term with a high acute dose of supplementation of retinyl palmitate at a young age, on testicular development and differentiation. Despite a return to normal diet after that supplementation, during childhood, impaired spermatogenesis was identified at the adult age with an arrest of spermatogenesis. The reversibility of that lack of differentiation by a return to a normal diet is questionable and would need more investigation.展开更多
BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combinat...BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.展开更多
BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing results.Current surgical techniques can achieve satisfactory outcomes for treatment of C...BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing results.Current surgical techniques can achieve satisfactory outcomes for treatment of CCs.Consequently,recent studies have focused more on clinical issues rather than basic research.Therefore,we need appropriate animal models to further basic research.AIM To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs.METHODS Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group,sham surgical group,or control group.A rat model of CC was established by partial ligation of the bile duct.The reliability of the model was confirmed by measurements of serum biochemical indices,morpho-logy of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues.RESULTS Dilation classified as mild(diameter,≥1 mm to<3 mm),moderate(≥3 mm to<10 mm),and severe(≥10 mm)was observed in 17,17,and 2 rats in the surgical group,respectively,while no dilation was observed in the control and sham surgical groups.Serum levels of alanine aminotransferase,aspartate aminotrans-ferase,total bilirubin,direct bilirubin,and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery,while direct bilirubin,total bilirubin,and gamma-glutamyltransferase were further increased 14 d after surgery.Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery.The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues.CONCLUSION The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC,which may contribute to investigating the pathogenesis of CC.展开更多
●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in spe...●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-related diseases for further studies.展开更多
Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treati...Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.展开更多
BACKGROUND Despite much work having been conducted on magnetic compression anastomo-sis(MCA)in the digestive tract,there are no reports on the influence of magnetic force on the anastomosis.AIM To investigate the effe...BACKGROUND Despite much work having been conducted on magnetic compression anastomo-sis(MCA)in the digestive tract,there are no reports on the influence of magnetic force on the anastomosis.AIM To investigate the effect of different magnetic force magnets on the MCA of the digestive tract.METHODS Two groups of magnets of the same sizes but different magnetic forces were designed and produced.A total of 24 Sprague-Dawley rats were randomly assigned into two groups(powerful magnet group and common magnet group),with 12 rats in each group.Two types of magnets were used to complete the colonic side-to-side anastomosis of the rats.The operation time and magnet discharge time were recorded.The anastomotic specimens were obtained 4 wk after the operation and then the burst pressure and diameter of the anastomosis were measured,and the anastomosis was observed via the naked eye and subjected to histological examination.RESULTS The magnetic forces of the powerful and common magnet groups at zero distance were 8.26 N and 4.10 N,respectively.The colonic side-to-side anastomosis was completed in all 24 rats,and the operation success rate and postoperative survival rate were 100%.No significant difference was noted in the operation time between the two groups.The magnet discharge time of the powerful magnet group was slightly longer than that of the common magnet group,but the difference was not statistically significant(P=0.513).Furthermore,there was no statistical difference in the burst pressure(P=0.266)or diameter of magnetic anastomosis(P=0.095)between the two groups.The gross specimens of the two groups showed good anastomotic healing,and histological observation indicated good mucosal continuity without differences on healing.CONCLUSION In the rat colonic side-to-side MCA model,both the powerful magnet with 8.26 N and the common magnet with 4.10 N showed no significant impact on the anastomosis establishment process or its effect.展开更多
AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl trans...AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.展开更多
[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were ran...[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were randomly divided into AMI-RI model control group and citrus pigment A/B/C groups(n=8).The naringenin A,B,and C groups were administrated 20,40 and 80 mg/(kg•d)for 10 d.The AMI group served as the negative control and was not treated.At the conclusion of the treatment regimen,a sample of intraventricular blood was collected for the purpose of measuring lactate dehydrogenase(LDH),glutathione peroxidase(GLH-PX),nitric oxide(NO),and superoxide dismutase(SOD)levels.Additionally,myocardial tissue was identified within the ischemic region.The content of malondialdehyde(MDA)was determined by inducing nitric oxide synthase(iNOS)and endodermal nitric oxide synthase(eNOS)positive cells in the left anterior descending coronary artery.[Results]Following citrus treatment,the contents of GLH-PX and SOD in ventricular blood of the citrus B group were found to be significantly elevated,while the contents of NO and LDH in myocardial MDA and ventricle were observed to be significantly reduced.The number of eNOS-positive cells was significantly increased,while the number of iNOS-positive cells was significantly decreased.The difference was statistically significant when compared with the AMI-RI group(P<0.05).The changes observed in the above indicators in the citrus C group were more pronounced than those observed in the citrus B group.The difference between the citrus C and the B group was statistically significant(P<0.05),indicating that this effect is concentration dependent.[Conclusions]In addition to its ability to inhibit myocardial lipid peroxidation during AMI-RI by increasing SOD activity,naringenin may also affect the synthesis and release of NO by regulating eNOS and iNOS,thereby achieving protection against AMI-RI.One effect is enhanced as the dose of the drug increases.展开更多
BACKGROUND Lung transplantation is a well-established treatment of end-stage lung disease.A rodent model is an inexpensive way to collect biological data from a living model after lung transplantation.However,masterin...BACKGROUND Lung transplantation is a well-established treatment of end-stage lung disease.A rodent model is an inexpensive way to collect biological data from a living model after lung transplantation.However,mastering the surgical technique takes time owing to the small organ size.AIM To conduct rat lung transplantation using a shunt cannula(SC)or modified cannula(MC)and assess their efficacy.METHODS Rat lung transplantation was performed in 11 animals in the SC group and 12 in the MC group.We devised a method of rat lung transplantation using a coronary SC for coronary artery bypass surgery as an anastomosis of pulmonary arteri-ovenous vessels and bronchioles.The same surgeon performed all surgical proce-dures in the donor and recipient rats without using a magnifying glass.The success rate of lung transplantation,operating time,and PaO2 values were com-pared after 2-h reperfusion after transplantation.RESULTS Ten and 12 lungs were successfully transplanted in the SC and MC groups,respectively.In the SC group,one animal had cardiac arrest within 1 h after reperfusion owing to bleeding during pulmonary vein anastomosis.The opera-ting time for the removal of the heart-lung block from the donor and preparation of the left lung graft was 26.8±2.3 and 25.7±1.3 min in the SC and MC groups,respectively(P=0.21).The time required for left lung transplantation in the recipients was 37.5±2.8 min and 35.9±1.4 min in the SC and MC groups,respectively(P=0.12).PaO2 values at 2 h after reperfusion were 456.2±25.5 and INTRODUCTION Lung transplantation is a well-established treatment of end-stage lung disease.Many immune and non-immune mech-anisms in lung transplantation are highly complex,and post-transplant complications such as infections and primary and chronic lung allograft dysfunction must be reduced to improve survival.Therefore,there is a need for immunological and pathophysiological analyses using animal lung transplantation models.The rat lung transplantation model was first reported in 1971[1],followed by the Mizuta Cuff model[2]in 1989.Since then,various improvements in surgical techniques,cuffs,and instruments have been reported[3-7].The advantage of using a rodent model is that it permits inexpensive collection of biological data from a living model after lung transplantation.Although trained surgeons can perform the transplantation procedure,mastering the surgical technique takes time due to the small size of the organs.The risks associated with this technique include damage to the vulnerable pulmonary artery(PA)and pulmonary vein(PV)vessel walls during anastomosis,as well as stenosis of the anastomotic site.We developed an anastomotic technique using a coronary shunt cannula(SC)for cardiac coronary artery bypass surgery as an alternative to the previously reported cuff method[2-6].This method enables anastomosis by inserting and ligating a cannula into the lumen of the PA,PV,and bronchus(Br),which is simpler and more reliable than conventional methods.This study aimed to determine problems with rat lung transplantation using the SC,develop an improved cannula,and investigate its utility.RESULTS After creating 11 lung transplantation model animals in the SC group and 12 in the MC group,all animals underwent reperfusion.One animal in the SC group had cardiac arrest 1 h after reperfusion due to hemorrhage caused by vessel wall injury during PV anastomosis.Two hours after reperfusion,we visually confirmed the maintenance of recipient hemody-namics and blood flow in the graft pulmonary cannula in 10 animals in the SC group and 12 in the MC group.The operating time for the removal of the heart-lung block from the donor and graft lung creation was 26.8±2.3 min in the SC group and 25.7±1.3 min in the MC group(P=0.21,Table 1).The duration for left lung transplantation into the recipient was 37.5±2.8 min in the SC group and 35.9±1.4 min(P=0.12,Table 1)in the MC group.Although no significant difference was found between the SC and MC groups,animals in the MC group experienced a slightly shorter operating time,smoother surgical technique,and less stressful procedure for the surgeons compared with those in the SC group.The graft lung coloration(Grade 1/2/3)after reperfusion was 0/2/8(SC group)and 0/2/10(MC group),and all grafts were reported to be successful,except in one animal in the SC group that had cardiac arrest(Table 2).The PaO2 values after 2 h of reperfusion were 456.2±25.5 mmHg in the SC group and 461.2±21.5 mmHg in the MC group(P=0.63,Table 3),showing no significant difference between the groups.展开更多
Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT<sub>1</sub> and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including func...Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT<sub>1</sub> and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α<sub>1</sub>-adrenergic receptors (α<sub>1</sub>-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10<sup>−5</sup> M), and in some experiments, 5-Methylurapidil (α<sub>1A</sub>-AR antagonist), AH11110A (α<sub>1B</sub>-AR antagonist), or BMY-7378 (α<sub>1D</sub>-AR antagonist), were used to identify the α<sub>1</sub>-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α<sub>1D</sub>-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α<sub>1</sub>-ARs proteins were evaluated. α<sub>1D</sub>-AR increased at 30 and 60 min post Ang II exposure, the α<sub>1A</sub>-AR diminished from 1 to 4 h, while α<sub>1B</sub>-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α<sub>1D</sub>-AR at short times, and BMY-7378 protected α<sub>1D</sub>-AR from desensitization.展开更多
BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an imp...BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation.Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features.Despite the advances in experimental protocols and techniques,designing a high-quality study is still challenging for the investigators as there is a plethora of different models used.AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats.METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.To identify eligible studies,a comprehensive literature search was performed in the electronic databases PubMed(MEDLINE)and Scopus,covering the period from conception until 18 October 2023.RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis.Methods of assessing anastomotic healing were extracted and were individually appraised.CONCLUSION Anastomotic healing studies have evolved over the last decades,but the findings are yet to be translated into human studies.There is a need for high-quality,well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.展开更多
Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chron...Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.展开更多
BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-...BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress,the inflammatory response,apoptosis and myocardial fibrosis.AIM To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats,further clarified the protective effect of liraglutide on the heart,and provided a new option for the treatment of DCM.METHODS Forty healthy male SD rats aged 6 wk were randomly divided into two groups,a normal control group(n=10)and a model group(n=30),which were fed an ordinary diet and a high-sugar and high-fat diet,respectively.After successful modeling,the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group(further divided into a high-dose group and a low-dose group).The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention.Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles.Intact heart tissue was dissected,and its weight was used to calculate the heart weight index.Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.RESULTS The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group,and those in the intervention group were decreased compared with those in the model group,with a more obvious decrease observed in the high-dose group(P<0.05).In the model group,myocardial fibers were disordered,and inflammatory cells and interstitial fibrosis were observed.The cardiomyopathy of rats in the intervention group was improved to different degrees,the myocardial fibers were arranged neatly,and the myocardial cells were clearly striated;the improvement was more obvious in the high-dose group.Compared with the normal control group,the expression of PARP-1 in myocardial tissue of the model group was increased,and the difference was statistically significant(P<0.05).After liraglutide intervention,compared with the model group,the expression of PARP-1 in myocardial tissue was decreased,and the reduction was more obvious in the high-dose group(P<0.05)but still higher than that in the normal control group.CONCLUSION Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.展开更多
Trinitrotoluene (TNT) increased the formation of adrenochrome from adrenaline and the formation of formaldehyde from methanol in rat liver mitochondria and microsomes in vitro as well as in monkey liver mitrochondria ...Trinitrotoluene (TNT) increased the formation of adrenochrome from adrenaline and the formation of formaldehyde from methanol in rat liver mitochondria and microsomes in vitro as well as in monkey liver mitrochondria and microsomes in vivo. The effects were more prominent at higher TNT concentrations. These findings indicate that TNT enhances the production of superoxide radicals (O_2^-) and hydrogen peroxide (H_2O_2). The production of O_2^- was more prominent in systems containing added TNT than in those containing added benzyl viologen. H_2O_2 production by mitochondria was more pronounced in the liver than in other organs, but its production by microsomes was more pronounced in the brain than in other organs. The results suggest that TNT undergoes cycling reduction which produces oxidative stress. 1989 Academic Press, Inc.展开更多
Objective To investigate the effects of 3,4-dichloroaniline (3,4-DCA) on activities of testicle enzymes as biological markers in rats. Methods Fifty male rats were randomly divided into 5 groups (n=10). One group ...Objective To investigate the effects of 3,4-dichloroaniline (3,4-DCA) on activities of testicle enzymes as biological markers in rats. Methods Fifty male rats were randomly divided into 5 groups (n=10). One group was left untreated and used as a solvent control (administered orally by corn oil), while the other 4 groups were treated with 3, 4-DCA. Corn oil was used as a solvent, and 3,4-DCA was diluted into tested concentrations (39, 81, 170, and 357 mg/kg). All the groups orally administered 3,4-DCA or corn oil, once a day for 4 weeks. The testicle tissue was homogenized in a 0.1 mol/L potassium phosphate buffer (0.1 mol/L, pH 7.2). The crude homogenate was centrifuged at 6000 rpm for 5 min at 4 ~C. The supernatant obtained was used as an enzyme extract for determination of the enzyme activities. Results Compared with the control, the activities of ALP, ACP, and SDH were increased significantly at a lower level of 3,4-DCA, and decreased at a higher level of 3, 4-DCA, whreas the activities of LDH, LDH-X, and G6PDH were inhibited significantly with the increased 3,4-DCA concentration. Organ coefficient "organ weight/total body weight × 100" of testis, liver, and spleen increased significantly with the increased 3,4-DCA concentration. These results suggest that 3,4-DCA toxicity to the male reproductive system was associated with the activities of testicular enzymes which are the sensitive biochemical endpoints reflecting 3,4-DCA toxicity to the male reproductive system. Conclusion 3,4-DCA has toxicity to the reproductive system in male rats.展开更多
文摘Objective:To determine the protective effect of co-enzyme Q10(CoQ10)on testicular tissue and sperm parameters in male rats treated with SunsetYellow FCF.Methods:Sixty male Sprague-Dawley rats were randomly divided into 6 groups of the control,CoQ10(10 mg/kg/day),low dose of Sunset Yellow(2.5 mg/kg),high dose of Sunset Yellow(70 mg/kg),low dose of Sunset Yellow(2.5 mg/kg)plus CoQ10,and high dose of Sunset Yellow(70 mg/kg)plus CoQ10.The drugs were administered via daily oral gavages for 6 weeks.At the end of the experiment,sperm analysis,stereological and histological assessments of the testis were carried out.Results:The normal morphology(by 41.1%)and progressive spermatozoa(by 74.8%),testicle volume(by 33.4%),lumen volume(by 38.3%),interstitial tissue volume(by 44.7%),seminiferous tubule volume(by 40.7%),and number of spermatogonia(by 53.9%)and Leydig cells(by 70.7%)reduced in the rats that received high doses of Sunset Yellow in comparison to the control group.Nonetheless,all these alterations were recovered by CoQ10 treatment in the CoQ10 plus high dose of Sunset Yellow group.Furthermore,low doses of Sunset Yellow did not affect different parameters of the testis and sperm.Conclusions:CoQ10 could,to some extent,prevent structural changes of the testis induced by the high dose of SunsetYellow.
基金Shahid Sadoughi University of Medical Sciences,Yazd,Iran(grant number 5689).
文摘Objective:To evaluate the protective effects of probiotic microorganisms on the reproductive and nervous systems of male rats treated with acrylamide.Methods:Thirty-two rats were randomly divided into 4 groups and received normal saline through gavage(control),acrylamide 20 mg/kg body weight,acrylamide plus probiotic microorganisms(Lactobacillus acidophilus,Lactobacillus casei,Lactobacillus bulgaricus,Lactobacillus rhamnosus,Bifidobacterium breve,Bifidobacterium infantis,Streptococcus thermophilus and fructooligosaccharides,all mixed in sachets)20 or 200 mg/kg body weight,respectively.After 30 days,the testis,prostate,seminal vesicle and cerebellum were removed,fixed and stained with hematoxylin-eosin(H&E).The Johnsen score was used to classify spermatogenesis.Cavalieri's principle method was used to evaluate the total volume(in mm3)of the testes.The number of each intratubular cell type as well as intertubular Leydig cells in whole samples was measured using the physical dissector counting techniques.Stereological analysis and the grids were used to determine the volume of cerebellar layers as well as the Purkinje cell number.Results:The testis weight decreased significantly in the acrylamide-treated group compared to the other groups(P<0.001).The number of spermatogonia,spermatocytes,spermatids and Leydig cells in the acrylamide-treated group were significantly less compared to the control group(P<0.05),while they were increased significantly in the acrylamide+200 mg/kg probiotic group(P<0.05;P<0.01).The mean Johnsen score in the acrylamide-treated group was lower than in the control group(P<0.001).Acrylamide-induced changes including congestion,vacuolization in the secretory epithelial cells,and epithelial rupture were observed in the prostate and seminal vesicle.The volumes of cerebellar layers were decreased in the acrylamide group compared to the control group while recovered in both probiotic treated groups.Conclusions:Probiotic microorganisms alleviate acrylamide-induced toxicities against the reproductive and cerebellar tissues in rats.
基金financially supported by Zabol University of Medical Sciences.
文摘Objective:To examine light and heat effects on the morphological,histological,and micrometric structure of the prostate of rats.Methods:Thirty adult male rats were divided into three groups.The control group was kept under 20℃-22℃ and an artificial 12 h/12 h day/night cycle;the temperature group was under normal light and at(42±1)℃ heat for 4 to 5 h daily,and the light group was exposed to 8 h/16 h day/night cycle with 20℃-22℃.Rats were weighed five times(at the beginning of the study and every seven days).Five milliliters(mL)of their peripheral blood were taken.The tissue staining was performed using the hematoxylin-eosin(H&E)stain and periodic acid-Schiff(PAS).In the following,tissue and cellular reactions to the PAS were examined.Results:Folds were located entirely on the surface of the anterior lobe and periphery of the other lobes.The secretory units in the anterior lobe were more than the lateral lobe.A strong reaction of the secretory cells to the PAS was observed.Testosterone serum levels of the light group also significantly increased compared to the control group(P<0.05).The most histometric changes of the lobes were established in the lateral lobes.Heat stress resulted in a significant decrease in testosterone levels and transformed prostate tissue.The epithelium and parenchyma to scaffold ratio in the temperature group decreased.Conclusions:Maximum and minimum changes in the ventral lobe happened under the ascent of temperature and light,respectively.The ventral lobe in the study of prostatic hyperplasia should be more considered.
文摘Aim: The harmful effects of pesticides have been largely documented in recent times. But effective therapeutic solutions to pesticide related male infertility are yet to be established. This study investigated the curative effects of Lannea acida on imidacloprid (IMI)-induced hypofertility in male Wistar rats. Methods: Rats of 150 – 200 g were administered IMI (22.5 mg/kg) for two weeks and partitioned into control (distilled water, vitamin E, clomiphene citrate) or test (aqueous (340 mg/kg), methanol (170 mg/kg) extract) groups for eight weeks treatment. Animals were sacrificed at the end of the treatment and samples were collected for sperm, antioxidant and hormonal analysis. Fertility tests were performed from treatment day 47 for fertility indices estimation. Results were expressed as mean ± SEM and one way ANOVA was applied using STATISTICA Software. Results: Exposition to IMI resulted in a significant decrease in sperm count, motility, viability and normality, testosterone and LH, coupled to an increase in oxidative stress markers. Moreover, IMI impaired male fertility evidenced by a significant drop in fertility index and litter size. Similar to clomiphene citrate and vitamin E, plant extracts significantly improved the sperm parameters, sexual hormones and decreased the oxidative stress markers. More importantly, the fertility index and litter size were restored, especially with the aqueous extract. Conclusion: Present results indicate that L. acida possesses curative potentials against IMI-induced hypofertility through its androgenic and antioxidant properties. However, the effects the extract on spermatozoa DNA structure and the fertility of offsprings from exposed parents are yet to be studied to conclude on total recovery from IMI toxicity.
基金supported by the National Natural Science Foundation of China(No.31901635)。
文摘The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.
文摘Introduction: Inappropriate and excess vitamin supplementation, particularly for vitamin A, is increasingly recognized as a public health problem in developed countries. On the other hand, blind supplementation of vitamin A, for children in developing countries is a subject of controversy in the literature. The crucial role of vitamin A in the process of spermatogenesis in adult rodents is well established, but only a few publications are consecrated to the long-term effect of vitamin A intake at a young age on testicular development and differentiation. Objectives: Our study aimed to evaluate the long-term effects of acute supplementation at an early age, in the post-natal period, on spermatogenesis and testicular trophicity at adult age. Material and Methods: Young Wistar Albinos rats of 22 days received an acute high dose of supplementation of vitamin A (retinyl palmitate). The control group, group 1, received only extra virgin olive oil, Group 2 a dose of 7000 IU/kg of retinyl palmitate, group 3, 14,000 IU/kg, and Group 4 a dose of 28,000 IU/kg. At 10 weeks of age, the testes’ testosterone levels were measured by ELISA. For histological assessment, sections were stained with Hematoxylin eosin, and the Johnsen score was used to evaluate spermatogenesis in the seminiferous tubules. Results: The average testicular weights of rats were significantly lower in group 4 (p < 0.05), and so was the testosterone level in the testis compared to the control group (p .01). Most of the seminiferous tubules were concerned by an arrest of spermatogenesis and the Johnsen score was decreased with a mean score of 5.96 ± 1.60 (p .001) in that Group. In Group 3, Johnsen’s score was significantly better than the one obtained with the control. Conclusion: We observed a negative effect in the long term with a high acute dose of supplementation of retinyl palmitate at a young age, on testicular development and differentiation. Despite a return to normal diet after that supplementation, during childhood, impaired spermatogenesis was identified at the adult age with an arrest of spermatogenesis. The reversibility of that lack of differentiation by a return to a normal diet is questionable and would need more investigation.
文摘BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.
基金the Key R&D Program of Zhejiang,No.2023C03029Health Science and Technology Plan of Zhejiang Province,No.2022RC201Zhejiang Provincial Natural Science Foundation Project,No.LY20H030007.
文摘BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing results.Current surgical techniques can achieve satisfactory outcomes for treatment of CCs.Consequently,recent studies have focused more on clinical issues rather than basic research.Therefore,we need appropriate animal models to further basic research.AIM To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs.METHODS Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group,sham surgical group,or control group.A rat model of CC was established by partial ligation of the bile duct.The reliability of the model was confirmed by measurements of serum biochemical indices,morpho-logy of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues.RESULTS Dilation classified as mild(diameter,≥1 mm to<3 mm),moderate(≥3 mm to<10 mm),and severe(≥10 mm)was observed in 17,17,and 2 rats in the surgical group,respectively,while no dilation was observed in the control and sham surgical groups.Serum levels of alanine aminotransferase,aspartate aminotrans-ferase,total bilirubin,direct bilirubin,and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery,while direct bilirubin,total bilirubin,and gamma-glutamyltransferase were further increased 14 d after surgery.Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery.The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues.CONCLUSION The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC,which may contribute to investigating the pathogenesis of CC.
基金Supported by Regional Science Foundation Project of the National Natural Science Foundation of China(No.82060827,No.82260891)The Key Discipline of Universities in the“14th Five-Year Plan”Autonomous Region-Traditional Chinese Medicine at Xinjiang Medical University.
文摘●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-related diseases for further studies.
基金supported by grants The Natural Science Foundation of Inner Mongolia(2019MS08104)The Natural Science Foundation of Inner Mongolia(2022ZD09)The Central Government Guiding Special Funds for Development of Local Science and Technology(2020ZY0020).
文摘Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.
基金Supported by the Key Research and Development Program of Shaanxi,No.2022SF-036the Institutional Foundation of The First Affiliated Hospital of Xi’an Jiaotong University,No.2022MS-07the Fundamental Research Funds for the Central Universities,No.xzy022023068.
文摘BACKGROUND Despite much work having been conducted on magnetic compression anastomo-sis(MCA)in the digestive tract,there are no reports on the influence of magnetic force on the anastomosis.AIM To investigate the effect of different magnetic force magnets on the MCA of the digestive tract.METHODS Two groups of magnets of the same sizes but different magnetic forces were designed and produced.A total of 24 Sprague-Dawley rats were randomly assigned into two groups(powerful magnet group and common magnet group),with 12 rats in each group.Two types of magnets were used to complete the colonic side-to-side anastomosis of the rats.The operation time and magnet discharge time were recorded.The anastomotic specimens were obtained 4 wk after the operation and then the burst pressure and diameter of the anastomosis were measured,and the anastomosis was observed via the naked eye and subjected to histological examination.RESULTS The magnetic forces of the powerful and common magnet groups at zero distance were 8.26 N and 4.10 N,respectively.The colonic side-to-side anastomosis was completed in all 24 rats,and the operation success rate and postoperative survival rate were 100%.No significant difference was noted in the operation time between the two groups.The magnet discharge time of the powerful magnet group was slightly longer than that of the common magnet group,but the difference was not statistically significant(P=0.513).Furthermore,there was no statistical difference in the burst pressure(P=0.266)or diameter of magnetic anastomosis(P=0.095)between the two groups.The gross specimens of the two groups showed good anastomotic healing,and histological observation indicated good mucosal continuity without differences on healing.CONCLUSION In the rat colonic side-to-side MCA model,both the powerful magnet with 8.26 N and the common magnet with 4.10 N showed no significant impact on the anastomosis establishment process or its effect.
基金Supported by grant from Fundamental Research Grant Scheme by Ministry of Higher Education(MoHE)600-IRMI/FRGS 5/3(101/2019).
文摘AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.
文摘[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were randomly divided into AMI-RI model control group and citrus pigment A/B/C groups(n=8).The naringenin A,B,and C groups were administrated 20,40 and 80 mg/(kg•d)for 10 d.The AMI group served as the negative control and was not treated.At the conclusion of the treatment regimen,a sample of intraventricular blood was collected for the purpose of measuring lactate dehydrogenase(LDH),glutathione peroxidase(GLH-PX),nitric oxide(NO),and superoxide dismutase(SOD)levels.Additionally,myocardial tissue was identified within the ischemic region.The content of malondialdehyde(MDA)was determined by inducing nitric oxide synthase(iNOS)and endodermal nitric oxide synthase(eNOS)positive cells in the left anterior descending coronary artery.[Results]Following citrus treatment,the contents of GLH-PX and SOD in ventricular blood of the citrus B group were found to be significantly elevated,while the contents of NO and LDH in myocardial MDA and ventricle were observed to be significantly reduced.The number of eNOS-positive cells was significantly increased,while the number of iNOS-positive cells was significantly decreased.The difference was statistically significant when compared with the AMI-RI group(P<0.05).The changes observed in the above indicators in the citrus C group were more pronounced than those observed in the citrus B group.The difference between the citrus C and the B group was statistically significant(P<0.05),indicating that this effect is concentration dependent.[Conclusions]In addition to its ability to inhibit myocardial lipid peroxidation during AMI-RI by increasing SOD activity,naringenin may also affect the synthesis and release of NO by regulating eNOS and iNOS,thereby achieving protection against AMI-RI.One effect is enhanced as the dose of the drug increases.
文摘BACKGROUND Lung transplantation is a well-established treatment of end-stage lung disease.A rodent model is an inexpensive way to collect biological data from a living model after lung transplantation.However,mastering the surgical technique takes time owing to the small organ size.AIM To conduct rat lung transplantation using a shunt cannula(SC)or modified cannula(MC)and assess their efficacy.METHODS Rat lung transplantation was performed in 11 animals in the SC group and 12 in the MC group.We devised a method of rat lung transplantation using a coronary SC for coronary artery bypass surgery as an anastomosis of pulmonary arteri-ovenous vessels and bronchioles.The same surgeon performed all surgical proce-dures in the donor and recipient rats without using a magnifying glass.The success rate of lung transplantation,operating time,and PaO2 values were com-pared after 2-h reperfusion after transplantation.RESULTS Ten and 12 lungs were successfully transplanted in the SC and MC groups,respectively.In the SC group,one animal had cardiac arrest within 1 h after reperfusion owing to bleeding during pulmonary vein anastomosis.The opera-ting time for the removal of the heart-lung block from the donor and preparation of the left lung graft was 26.8±2.3 and 25.7±1.3 min in the SC and MC groups,respectively(P=0.21).The time required for left lung transplantation in the recipients was 37.5±2.8 min and 35.9±1.4 min in the SC and MC groups,respectively(P=0.12).PaO2 values at 2 h after reperfusion were 456.2±25.5 and INTRODUCTION Lung transplantation is a well-established treatment of end-stage lung disease.Many immune and non-immune mech-anisms in lung transplantation are highly complex,and post-transplant complications such as infections and primary and chronic lung allograft dysfunction must be reduced to improve survival.Therefore,there is a need for immunological and pathophysiological analyses using animal lung transplantation models.The rat lung transplantation model was first reported in 1971[1],followed by the Mizuta Cuff model[2]in 1989.Since then,various improvements in surgical techniques,cuffs,and instruments have been reported[3-7].The advantage of using a rodent model is that it permits inexpensive collection of biological data from a living model after lung transplantation.Although trained surgeons can perform the transplantation procedure,mastering the surgical technique takes time due to the small size of the organs.The risks associated with this technique include damage to the vulnerable pulmonary artery(PA)and pulmonary vein(PV)vessel walls during anastomosis,as well as stenosis of the anastomotic site.We developed an anastomotic technique using a coronary shunt cannula(SC)for cardiac coronary artery bypass surgery as an alternative to the previously reported cuff method[2-6].This method enables anastomosis by inserting and ligating a cannula into the lumen of the PA,PV,and bronchus(Br),which is simpler and more reliable than conventional methods.This study aimed to determine problems with rat lung transplantation using the SC,develop an improved cannula,and investigate its utility.RESULTS After creating 11 lung transplantation model animals in the SC group and 12 in the MC group,all animals underwent reperfusion.One animal in the SC group had cardiac arrest 1 h after reperfusion due to hemorrhage caused by vessel wall injury during PV anastomosis.Two hours after reperfusion,we visually confirmed the maintenance of recipient hemody-namics and blood flow in the graft pulmonary cannula in 10 animals in the SC group and 12 in the MC group.The operating time for the removal of the heart-lung block from the donor and graft lung creation was 26.8±2.3 min in the SC group and 25.7±1.3 min in the MC group(P=0.21,Table 1).The duration for left lung transplantation into the recipient was 37.5±2.8 min in the SC group and 35.9±1.4 min(P=0.12,Table 1)in the MC group.Although no significant difference was found between the SC and MC groups,animals in the MC group experienced a slightly shorter operating time,smoother surgical technique,and less stressful procedure for the surgeons compared with those in the SC group.The graft lung coloration(Grade 1/2/3)after reperfusion was 0/2/8(SC group)and 0/2/10(MC group),and all grafts were reported to be successful,except in one animal in the SC group that had cardiac arrest(Table 2).The PaO2 values after 2 h of reperfusion were 456.2±25.5 mmHg in the SC group and 461.2±21.5 mmHg in the MC group(P=0.63,Table 3),showing no significant difference between the groups.
文摘Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT<sub>1</sub> and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α<sub>1</sub>-adrenergic receptors (α<sub>1</sub>-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10<sup>−5</sup> M), and in some experiments, 5-Methylurapidil (α<sub>1A</sub>-AR antagonist), AH11110A (α<sub>1B</sub>-AR antagonist), or BMY-7378 (α<sub>1D</sub>-AR antagonist), were used to identify the α<sub>1</sub>-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α<sub>1D</sub>-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α<sub>1</sub>-ARs proteins were evaluated. α<sub>1D</sub>-AR increased at 30 and 60 min post Ang II exposure, the α<sub>1A</sub>-AR diminished from 1 to 4 h, while α<sub>1B</sub>-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α<sub>1D</sub>-AR at short times, and BMY-7378 protected α<sub>1D</sub>-AR from desensitization.
文摘BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation.Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features.Despite the advances in experimental protocols and techniques,designing a high-quality study is still challenging for the investigators as there is a plethora of different models used.AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats.METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.To identify eligible studies,a comprehensive literature search was performed in the electronic databases PubMed(MEDLINE)and Scopus,covering the period from conception until 18 October 2023.RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis.Methods of assessing anastomotic healing were extracted and were individually appraised.CONCLUSION Anastomotic healing studies have evolved over the last decades,but the findings are yet to be translated into human studies.There is a need for high-quality,well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.
文摘Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.
基金Supported by Shanxi Provincial Natural Science Foundation,No.201701D121159Shanxi Provincial Health and Family Planning Commission,No.2014016Health Commission of Shanxi Province,No.2019020.
文摘BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress,the inflammatory response,apoptosis and myocardial fibrosis.AIM To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats,further clarified the protective effect of liraglutide on the heart,and provided a new option for the treatment of DCM.METHODS Forty healthy male SD rats aged 6 wk were randomly divided into two groups,a normal control group(n=10)and a model group(n=30),which were fed an ordinary diet and a high-sugar and high-fat diet,respectively.After successful modeling,the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group(further divided into a high-dose group and a low-dose group).The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention.Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles.Intact heart tissue was dissected,and its weight was used to calculate the heart weight index.Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.RESULTS The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group,and those in the intervention group were decreased compared with those in the model group,with a more obvious decrease observed in the high-dose group(P<0.05).In the model group,myocardial fibers were disordered,and inflammatory cells and interstitial fibrosis were observed.The cardiomyopathy of rats in the intervention group was improved to different degrees,the myocardial fibers were arranged neatly,and the myocardial cells were clearly striated;the improvement was more obvious in the high-dose group.Compared with the normal control group,the expression of PARP-1 in myocardial tissue of the model group was increased,and the difference was statistically significant(P<0.05).After liraglutide intervention,compared with the model group,the expression of PARP-1 in myocardial tissue was decreased,and the reduction was more obvious in the high-dose group(P<0.05)but still higher than that in the normal control group.CONCLUSION Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.
基金This study was supported by grants from the Chinese Health Ministry (Funds supplement 75-62-03-29-05).
文摘Trinitrotoluene (TNT) increased the formation of adrenochrome from adrenaline and the formation of formaldehyde from methanol in rat liver mitochondria and microsomes in vitro as well as in monkey liver mitrochondria and microsomes in vivo. The effects were more prominent at higher TNT concentrations. These findings indicate that TNT enhances the production of superoxide radicals (O_2^-) and hydrogen peroxide (H_2O_2). The production of O_2^- was more prominent in systems containing added TNT than in those containing added benzyl viologen. H_2O_2 production by mitochondria was more pronounced in the liver than in other organs, but its production by microsomes was more pronounced in the brain than in other organs. The results suggest that TNT undergoes cycling reduction which produces oxidative stress. 1989 Academic Press, Inc.
基金supported by the Natural Science Foundation of Beijing(No.7063071).
文摘Objective To investigate the effects of 3,4-dichloroaniline (3,4-DCA) on activities of testicle enzymes as biological markers in rats. Methods Fifty male rats were randomly divided into 5 groups (n=10). One group was left untreated and used as a solvent control (administered orally by corn oil), while the other 4 groups were treated with 3, 4-DCA. Corn oil was used as a solvent, and 3,4-DCA was diluted into tested concentrations (39, 81, 170, and 357 mg/kg). All the groups orally administered 3,4-DCA or corn oil, once a day for 4 weeks. The testicle tissue was homogenized in a 0.1 mol/L potassium phosphate buffer (0.1 mol/L, pH 7.2). The crude homogenate was centrifuged at 6000 rpm for 5 min at 4 ~C. The supernatant obtained was used as an enzyme extract for determination of the enzyme activities. Results Compared with the control, the activities of ALP, ACP, and SDH were increased significantly at a lower level of 3,4-DCA, and decreased at a higher level of 3, 4-DCA, whreas the activities of LDH, LDH-X, and G6PDH were inhibited significantly with the increased 3,4-DCA concentration. Organ coefficient "organ weight/total body weight × 100" of testis, liver, and spleen increased significantly with the increased 3,4-DCA concentration. These results suggest that 3,4-DCA toxicity to the male reproductive system was associated with the activities of testicular enzymes which are the sensitive biochemical endpoints reflecting 3,4-DCA toxicity to the male reproductive system. Conclusion 3,4-DCA has toxicity to the reproductive system in male rats.