Prevelance of Bovine Cysticercosis in Egypt and the Cysticidal Effect of Two Extracts Obtained from Balanites aegyptiaca and Moringa oleifera on Mice Model Affected with T. saginata Cysticerci

The aim of the present study was to determine the prevalence of bovine cysticercosis in both cattle and buffloas, in Egypt and to assess the cysticidal efficacy of Balanites aegyptiaca fruits (B. aegyptiaca) and Moringa oleifera seeds (M. oleifera) extracts in experimentally infected mice. The study detected the level of tumor necrosis factor (TNF-α) to monitor the immune and inflammatory responses of experimentally infected mice. Through meat inspection, a total number of 2125 male bovine, 2 to 5 years old, (1125 cattle and 1000 buffloes) were examined under the authority of Albsatine and Alwaraq official abattoirs in Cairo Governorate, Egypt covering the period extended from March 2022 to April 2023. The overall prevalence of the disease among bovine was 7.8% (6.31% of cattle and 9.5% of buffloes). Besides, B. aegyptiaca and M. oleifera extracts showed cysticidal activity in experimentally infected mice. A decrease in the numbers of cysticerci was found in all treated mice groups, and up to 88% reduction was achieved in the B. aegyptiaca-treated group;higher than that was recorded in both M. oleifera (72.23%) and albendazole-treated ones (80.56%). Postmortem findings proved that M. oleifera and B. aegyptiaca reduced cysticerci numbers comparable to a commercial anthelmintic. The study showed a significant decrease (P 0.001) in TNF-α levels after treatment with Balanites and Moringa extracts, compared with the untreated control and the albendazole-treated groups.

Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model

AIM:To investigate the role of autophagy inhibitor 3-methyladenine(3-MA)on a diabetic mice model(DM)and the potential mechanism.METHODS:Male C57BL/6J mice were randomly divided into a normal control group(NC group)and an DM group.DM were induced by multiple low-dose intraperitoneal injection of streptozotocin(STZ)60 mg/kgd for 5 consecutive days.DM mice were randomly subdivided into untreated group(DM group),3-MA(10 mg/kgd by gavage)treated group(DM+3-MA group)and chloroquine(CQ;50 mg/kg by intraperitoneal injection)treated group(DM+CQ group).The fasting blood glucose(FBG)levels were recorded every week.At the end of experiment,retinal samples were collected.The expression levels of pro-apoptotic proteins cleaved caspase-3,cleaved poly ADP-ribose polymerase 1(PARP1)and Bax,anti-apoptotic protein Bcl-2,fibrosisassociated proteins Fibronectin and type 1 collagenα1 chain(COL1A1),vascular endothelial growth factor(VEGF),inflammatory factors interleukin(IL)-1βand tumor necrosis factor(TNF)-α,as well as autophagy related proteins LC3,Beclin-1 and P62 were determined by Western blotting.The oxidative stress indicators 8-hydroxydeoxyguanosine(8-OHdG)and malondialdehyde(MDA)were detected by commercial kits.RESULTS:Both 3-MA and CQ had shor t-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1βand TNF-αin DM mice.3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA,decreased the expression of fibrosisrelated proteins Fibronectin and COL1A1,pro-apoptotic proteins cleaved caspase-3,cleaved PARP1,as well as the ratio of Bax/Bcl-2.CQ had no significant impact on the oxidative stress indicators,fibrosis,and apoptosis related proteins.The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment,and the expression of P62 was further increased by CQ treatment.CONCLUSION:3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice,and can attenuate retinal oxidative stress,VEGF expression and the production of inflammatory factors in the retina of DM mice.The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.

Genetic algorithm-optimized backpropagation neural network establishes a diagnostic prediction model for diabetic nephropathy:Combined machine learning and experimental validation in mice

Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of DN to reduce the prevalence and delay the development of DN.Kidney biopsy is the gold standard for diagnosing DN;however,its invasive character is its primary limitation.The machine learning approach provides a non-invasive and specific criterion for diagnosing DN,although traditional machine learning algorithms need to be improved to enhance diagnostic performance.Methods:We applied high-throughput RNA sequencing to obtain the genes related to DN tubular tissues and normal tubular tissues of mice.Then machine learning algorithms,random forest,LASSO logistic regression,and principal component analysis were used to identify key genes(CES1G,CYP4A14,NDUFA4,ABCC4,ACE).Then,the genetic algorithm-optimized backpropagation neural network(GA-BPNN)was used to improve the DN diagnostic model.Results:The AUC value of the GA-BPNN model in the training dataset was 0.83,and the AUC value of the model in the validation dataset was 0.81,while the AUC values of the SVM model in the training dataset and external validation dataset were 0.756 and 0.650,respectively.Thus,this GA-BPNN gave better values than the traditional SVM model.This diagnosis model may aim for personalized diagnosis and treatment of patients with DN.Immunohistochemical staining further confirmed that the tissue and cell expression of NADH dehydrogenase(ubiquinone)1 alpha subcomplex,4-like 2(NDUFA4L2)in tubular tissue in DN mice were decreased.Conclusion:The GA-BPNN model has better accuracy than the traditional SVM model and may provide an effective tool for diagnosing DN.

Assessment of immune responses and intestinal flora in BALB/c mice model of wheat food allergy via different sensitization methods

Increasing incidences showed that food allergies have attracted more and more attention from researchers.BALB/c mice were sensitized with wheat gluten combined with aluminum hydroxide adjuvant via intraperitoneal injection,transdermal sensitization,and oral gavage sensitization route.Results showed that all the three sensitization methods could induce allergic symptoms;increase the serum antibody(total immunoglobulin E(IgE),specific IgE,IgG,IgA)and histamine content;promote the secretion of Th2 cytokines(interleukin(IL)-4,IL-5,IL-13)and inflammatory factors(IL-6,IL-17 A,IL-10);and inhibit the production of Th1 cytokines(IFN-γ,IL-2).However,the allergic symptoms of mice sensitized by intraperitoneal injection were the most obvious among the three models.The level of serum antibodies in intraperitoneal injection group was significantly higher than control.Subsequently,16 S rRNA sequencing technology was used to analyze the intestinal flora of mice.The results showed that the abundance of Firmicutes in the wheat protein sensitized group was lower than that in the normal group,while the abundance of Bacteroidetes was higher,and Lactobacillus was the difference marker in normal group.Bacterial species diversity analysis showed that the species richness and diversity of intestinal flora in mice were decreased,the difference between mice induced by intraperitoneal injection and normal control group mice was the most significant.Taken together,these results show that among three sensitization methods used to build a mouse model with aluminum hydroxide as adjuvant,intraperitoneal injection is the comparably best way to build a mouse sensitization mode.

Immortalized hippocampal astrocytes from 3xTg-AD mice,a new model to study disease-related astrocytic dysfunction:a comparative review

Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific pathology.Astrocytes,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including AD.Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways.Tumor-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in AD.Surprisingly,no stable cell lines were available from genetic mouse AD models.Recently,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary cultures.Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier models.Here we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived astrocytes.We conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.

Effect of Human Umbilical Cord Mesenchymal Stem Cells on GRP78/ATF4 Pathway in Alzheimer s Disease Model Mice

[Objectives]To study the effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)on GRP78/ATF4 pathway in APP/PS1 mice.[Methods]Twelve 6-month-old female APP/PS1 mice were randomly divided into model group(MOD,n=6)and human umbilical cord mesenchymal stem cell treatment group(MSC,n=6);six 6-month-old C57BL/6N mice were used as control group(CON,n=6).The mice in each group were treated with the fourth generation of human umbilical cord mesenchymal stem cells through tail vein.Four weeks later,the mice in each group were killed.The expression of GFP78 and ATF4 in the cortex of mice in each group was detected by Western blotting and real-time fluorescence quantitative PCR.[Results]The results of immunoblotting and real-time fluorescence quantitative PCR showed that the expression of GRP78 in MOD group was lower than that in CON group and the expression of ATF4 increased.The expression of GRP78 protein in MSC group was higher than that in MOD group,but the expression of ATF4 protein was lower.The results of real-time fluorescence quantitative PCR showed that the mRNA level of GRP78 decreased and the mRNA level of ATF4 increased in MOD group compared with CON group.The mRNA level of GRP78 in MSC group was higher than that in MOD group,while the mRNA level of ATF4 in MSC group was lower than that in MOD group.[Conclusions]Human umbilical cord mesenchymal stem cells can regulate the expression of GRP78/ATF4 pathway in APP/PSI mice,which may be related to the stress level of endoplasmic reticulum in the brain of APP/PS1 mice mediated by human umbilical cord mesenchymal stem cells.

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient like metastatic model of human HCC in nude mice (LCI-D20)and a Iow metastatic model of human HCC in nude mice LCI-D35 ) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding.Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including antiangiogenesis, antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.

Can outbred mice be used as a mouse model of mild cognitive impairment?

Deficits in spatial learning and memory are some of the earliest symptoms in mild cognitive impairment （MCI）. However, there are few valid MCI animal models available to evaluate putative therapeutic strategies. The aim of this study was to obtain a natural animal model of MCI. Outbred Kunming （aged 5 and 12.5 months） and ICR （7 and 12 months） mice were utilized in the present study. Morris water maze and radial six-arm water maze （RAWM） were simultaneously used to evaluate impaired spatial learning and memory in middle-aged mice （approximately 12 months of age）. Compared with younger mice in the respective groups, the middle-aged mice suffered visible impairment of spatial memory in the Morris water maze and RAWM, and mild spatial learning deficiency occurred in the RAWM study alone. Thus outbred Kunming and ICR mice could be utilized as a natural animal model for MCI, in particular for memory impairment studies.

Establishment of Xenotransplantation Model of Human CN-AML with FLT3-ITD^(mut)/NPM1 in NOD/SCID Mice

Summary： Patients with FLT3-ITD^mmutt/NPM1- cytogenetically normal acute myeloid leukemia （CN-AML）, as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD^mut/NPM1- CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD^mut/NPM1- CN-AML primary cells. The FLT3-ITD^mut/NPM1- CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary genera- tion models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully estab- lished xenotransplantation model of human FLT3-ITD^mut/NPM1- CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.

Study of Candida Albicans Vaginitis Model in Kunming Mice

The model of vaginal candidiasis in Kunming mice was constructed in order to search for the optima construction conditions and provide an economic animal model of Candida albicans (C. albicans) vaginitis. Estrogen benzoate (E2) was given to mice at different concentrations ranging from 0.0 to 0.05 mg/mouse (4 levels) beginning 72 h prior to vaginal inoculation, then mice were in- oculated intravaginally with various concentrations of stationary-phase C. albicans blastoconidia (ATCC90028) (5 levels) in 20 μL of phosphate-buffered saline (PBS) in each E2 level. General state, scores of genital pathology, the hyphae and vaginal fungal burden (CFU) in vaginal lavage fluid, the hydrops rate of uterus and vaginal tissues for pathological section in mice were observed and ob- tained at day 2, 4, 7, 14 and 21 after inoculation. The results showed the infection rate in mice was related to the dosage of E2 and concentration of C. albicans blastoconidia. Additionally there was better cross-effect between the two treated factors. The infection rate was about 80% on the day 4, and could reach 100% on the day 7 until the end of experiment after inoculated intravaginally in groups of E2I3, E2 0.025 mg/mouse injected hypodermically and inoculated intravaginally with 5×104 C. albicans blastoconidia, and large amount of hyphae and blastoconidia could be observe in superfi- cial layer tissue and canal of vaginal by PAS. From the results in our experiment it was concluded that E2I3 was the optima construction condition in kunming mice.

Dynamics of Advantageous Mutant Spread in Spatial Death-Birth and Birth-Death Moran Models

The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized that in real-world applications, the population usually has an explicit spatial structure which can significantly influence the dynamics. In the context of cancer initiation in epithelial tissue, several recent works have analyzed the dynamics of advantageous mutant spread on integer lattices, using the biased voter model from particle systems theory. In this spatial version of the Moran model, individuals first reproduce according to their fitness and then replace a neighboring individual. From a biological standpoint, the opposite dynamics, where individuals first die and are then replaced by a neighboring individual according to its fitness, are equally relevant. Here, we investigate this death-birth analogue of the biased voter model. We construct the process mathematically, derive the associated dual process, establish bounds on the survival probability of a single mutant, and prove that the process has an asymptotic shape. We also briefly discuss alternative birth-death and death-birth dynamics, depending on how the mutant fitness advantage affects the dynamics. We show that birth-death and death-birth formulations of the biased voter model are equivalent when fitness affects the former event of each update of the model, whereas the birth-death model is fundamentally different from the death-birth model when fitness affects the latter event.

Prevention and Treatment of Chinese Herbal Preparation Yinqiaotiangan against Pathologic Model of Streptococcus suis Serotype II in Kunming Mice

[ Objectlve] This study aimed to investigate the antimicrobial effect of Chinese herbal preparation Yinqiaotiangan against Streptococcus suis serotype II in vivo. [ Method ] The prevention and treatment tests were conducted with Kunming mice weighing about 18 -22 g. In the prevention test, Kunming mice were inocu- lated with Streptococcus suis serotype II and simultaneously taken orally 0.5, 1.0 and 2.0 g/ml Chinese herbal preparation Yinqiaotiangan respectively for continu- ous 3 d, once a day; the incidence rate, mortality rate and protective rate were detected after 7 d. In the treatment test, Kunming mice were inoculated with Strepto- coccus suis serotype II to establish the Streptococcus suis serotype II pathogenic model, and then taken orally 0.5, 1.0 and 2.0 g/ml Chinese herbal preparation Yin- qiaotiangan respectively for continuous 3 d, twice a day; the mortality rate, cure rate and effective rate were detected after 7 d. [ Result ] Results of the prevention test showed that the protective rate in experimental groups was extremely significantly higher than that in control group （P 〈0.01 ）, while the incidence rate and mortality rate were extremely significantly lower than that in control group （P 〈0.01 ）. Results of the treatment test showed that the incidence rate in experimental groups was extremely significantly lower than that in control group （P 〈0.01 ）, the cure rate in 0.5 g/ml group was extremely significantly higher than that in 1.0 g/ml group and 2.0 g/ml group （P 〈 0.01 ）, the effective rate in 0.5 g/ml group was significantly higher than that in 1.0 g/ml group and 2.0 g/ml group （ P 〈 0.05 ）, with no significant difference from the positive group （P 〉 0.05 ）. [ Conclusion ] The pathologic model of Streptococcus su/s serotype II could be effec- tively prevented and treated by oral intake of low dose of Chinese herbal preparation Yinqiaotiangan in Kunming mice.

A Model of Spontaneous Chronic Otitis Media with Effusion in Mice with ENU Induced Mutations

Background Chronic otitis media(COM) is a significant clinical problem.Understanding the mechanisms of COM is critical for its control and treatment.However,little is known of the processes leading to COM as a result of lack of animal models of N-ethyl-N-nitrosourea(ENU) induced mutations in otitis media with effusion(OME).Methods Otoscopy and auditory brain response(ABR) evaluation were carried out under sedation in Nmf391nmf/nmf mice of 2,4,6 and 8 months of age.The mice were killed for study of middle and inner ear pathology.Results Tympanic membrane visualization and ABR thresholds in 1-to 8-month-old Nmf391nmf/nmf mice showed spontaneous OME and inner ear diseases in approximately 100% of the animals.The significant elevation of ABR thresholds suggested a sensorineural component in hearing loss in addition to the conductive loss.Middle and inner ear histology showed various degrees of outer hair cells loss and middle ear inflammation in all the mice,but no inflammation cells in the inner ear.The ABR threshold at 32 kHz was significantly elevated.Conclusions This study shows histopathologic changes in the Nmf391nmf/nmf mouse model of COM with effusion that have not been reported in human COM.This ENU induced mutation model of COM will be valuable for the characterization of middle ear inflammation and inner ear disease processes that are induced by middle ear infections.We propose that COM with effusion in this ENU induced mutation model is the cause of the cochlea hair cells damage.

A murine model of dengue virus infection in suckling C57BL/6 and BALB/c mice

Dengue is a significant public health concern across tropical and subtropical regions worldwide,principally causing disease in children.Very young children are at increased risk of severe manifestations of dengue infection.The mechanism of dengue disease in this population is not fully understood.In this study,we present a murine model of dengue virus primary infection in suckling C57BL/6 and BALB/c mice in order to investigate disease pathogenesis.Three-day-old C57BL/6 mice intraperitoneally infected with DENV-2 NGC were more susceptible to infection than BALB/c mice,showing increased liver enzymes,extended viremia,dissemination to organs and histological alterations in liver and small intestine.Furthermore,the immune response in DENV-infected C57BL/6 mice exhibited a marked Th1 bias compared to BALB/c mice.These findings highlight the possibility of establishing an immunocompetent mouse model of DENV-2 infection in suckling mice that reproduces certain signs of disease observed in humans and that could be used to further study agerelated mechanisms of dengue pathogenesis.

Pharmacokinetic-Pharmacodynamic modeling of the analgesic effect of bupredermTM, in mice

Purpose: BupredermTM-Buprenorphine transdermal delivery system (BTDS) was developed for the treatment of post-operative and chronic pains. This study examined the relationship between the plasma concentration of buprenorphine and its analgesic effect (tail flick test) in order to assess the usefulness of pharmacokinetic-pharmacodynamic (PK-PD) modeling in describing this relationship. Methods: After patch application, plasma concentrations of bu- prenorphine in mice were measured for 72 hours with a validated LC/MS/MS system, and the analgesic effects were assessed by tail flick test for the period of 24 hours. A modified two- compartment open model was used to explain the PK properties of BTDS, and the PD model was characterized by slow receptor binding. Results: The peak buprenorphine level in plasma was achieved at 1-24 h and the effective therapeutic drug concentration was maintained for 72 hours. BupredermTM induced prolongation of tail-flick latency in a dose and time dependent manner. Maximum analgesic effect was attained at 3-6 h and was maintained for 24 h after patch application. Counter-clockwise hysteresis between the plasma concentration and the analgesic efficacy of BTDS was observed after BupredermTM application, indicating there was a delay between plasma concentrations and the effect observed. From the developed PK-PD model, Kd values (0.69-0.82 nM) that were derived from the pharmacodynamic parameters (Kon and Koff) are similar to the reported values (Kd = 0.76 ± 0.14 nM). Good agreement between the predicted and observed values was noted for the rate of change in analgesic effect data (R2 = 0.822, 0.852 and 0.774 for 0.24, 0.8 and 2.4 mg/patch, respectively). Conclusions: The established PK- PD model successfully described the relationship between plasma concentration of buprenorphine and its analgesic efficacy measured by the tail flick test. Our model might be useful in estimation and prediction of onset, magnitude and time course of concentration and pharmacological effects of BTDS and will be useful to simulate PK-PD profiles with clinical regimens.

Type Ⅰ interferon receptor knockout mice as models for infection of highly pathogenic viruses with outbreak potential

Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.

Characterization of Amino Acid Based Molecular Micelles with Molecular Modeling

The enantiomers of chiral drugs often have different potencies, toxicities, and biochemical properties. Therefore, the FDA and other worldwide regulatory agencies require manufactures to test and prove the enantiomeric purity of chiral drugs. Amino acid based molecular micelles (AABMM) have been used in chiral CE separations since the 1990’s because of their low environmental impact and because their properties can easily be tuned by changing the amino acids in the chiral surfactant head groups. Using molecular dynamics simulations to investigate the structures and properties of AABMM is part of an ongoing study focusing on investigating and elucidating the factors responsible for chiral recognition with AABMM. The results will be useful for the proper design and selection of more efficient chiral selectors. The micelles investigated contained approximately twenty covalently linked surfactant monomers. Each monomer was in turn composed of an undecyl hydrocarbon chain bound to a dipeptide headgroup containing of all combinations of L-Alanine, L-Valine, and L-Leucine. These materials are of interest because they are effective chiral selectors in capillary electrophoresis separations. Molecular dynamics simulation analyses were used to investigate how the sizes and positions of the headgroup amino acid R-groups affected the solvent accessible surface areas of each AABMM chiral center. In addition, headgroup dihedral angle analyses were used to investigate how amino acid R-group size and position affected the overall headgroup conformations. Finally, distance measurements were used to study the structural and conformational flexibilities of each AABMM headgroup. All analyses were performed in the context of a broader study focused on developing structure-based predictive tools to identify the factors responsible for a) self-assembly, b) function, c) higher ordered structure and d) molecular recognition of these amino acid based molecular micelles.

Establishment of Experimental Model of Hepatic Schistosoma Japonicum Egg Granulomas in Mice

An experimental model of hepatic Schistosoma japonicum egg granuloma was established in C57BL/6 mice sensitized with soluble egg antigen(SEA) by direct injection of vital egg suspension into the spleen. The mice infected with cercariae of Schistosoma japonicum in abdominal skin were used for comparative studies. The results showed that morbidity of hepatic Schistosoma japonicum egg granulomas in the group sensitized with SEA was 100% and that the morphology, cellular constituents, developing process and the diameter and size of the egg granulomas in the group sensitized with SEA were similar to those of the group infected with cercariae. The authors suggest that this experimental model is a useful and appropriate tool for the study on egg granulomas of Schistosoma japonicum.

BALB/c mice model of cytomegalovirus-induced myocarditis

Objective: A BALB/c mice model of cytomegalovirus-induced myocarditis was established. Methods: Twenty-five inbred female BALB/c mice free of murine cytomegalovirus(MCMV) infection (5 weeks old, 16-18 g),were infected with 1×10~4 PFU MCMV by the intraperitoneal (i.p.) administration. All experimental mice were sacrificed on day 3, 5, 7, 10,and 14 after i. p. administration. The hearts were removed under aseptic conditions, and were transected along the midline. Aliquots of hearts were handled with Bouin's fixative for histological examination. Residual hearts were immediately frozen in liquid nitrogen and stored at -80℃ until MCMV titre was determined by a plaque assay. Seurm cTnI level was assayed by ELISA. Results: MCMV in the heart was at extremely low level on day 3 after i. p. administration, reached to the peak on day 7-10, and then ran down. A mixed cellular infiltrate composed of polymorphonuclear neutrophils and mononuclear lymphocytes was observed on day 3, reaching to the peak on day 7-10 after MCMV infection, and was maintained for at least 3-4 months later. Seurm cTnI levels were elevated on day 3 after i.p. administration, reaching to the peak it day 7-10. Conclusion: The BALB/c mice model for cytomegalovirus-induced myocarditis was successfully established, that might make it possible to screen antiviral drugs for treating viral myocarditis and to investigate and evaluate the pathogenesis and prognosis of this disease.

Dietary Nε-(carboxymethyl)lysine affects cardiac glucose metabolism and myocardial remodeling in mice

BACKGROUND Myocardial remodeling is a key factor in the progression of cardiovascular disease to the end stage.In addition to myocardial infarction or stress overload,dietary factors have recently been considered associated with myocardial remodeling.Nε-(carboxymethyl)lysine(CML)is a representative foodborne toxic product,which can be ingested via daily diet.Therefore,there is a marked need to explore the effects of dietary CML on the myocardium.AIM To explore the effects of dietary CML(dCML)on the heart.METHODS C57 BL/6 mice were divided into a control group and a dCML group.The control group and the dCML group were respectively fed a normal diet or diet supplemented with CML for 20 wk.Body weight and blood glucose were recorded every 4 wk.^(18)F-fluorodeoxyglucose(FDG)was used to trace the glucose uptake in mouse myocardium,followed by visualizing with micro-positron emission tomography(PET).Myocardial remodeling and glucose metabolism were also detected.In vitro,H9C2 cardiomyocytes were added to exogenous CML and cultured for 24 h.The effects of exogenous CML on glucose metabolism,collagen I expression,hypertrophy,and apoptosis of cardiomyocytes were analyzed.RESULTS Our results suggest that the levels of fasting blood glucose,fasting insulin,and serum CML were significantly increased after 20 wk of dCML.Micro-PET showed that ^(18)F-FDG accumulated more in the myocardium of the dCML group than in the control group.Histological staining revealed that dCML could lead to myocardial fibrosis and hypertrophy.The indexes of myocardial fibrosis,apoptosis,and hypertrophy were also increased in the dCML group,whereas the activities of glucose metabolism-related pathways and citrate synthase(CS)were significantly inhibited.In cardiomyocytes,collagen I expression and cellular size were significantly increased after the addition of exogenous CML.CML significantly promoted cellular hypertrophy and apoptosis,while pathways involved in glucose metabolism and level of Cs mRNA were significantly inhibited.CONCLUSION This study reveals that dCML alters myocardial glucose metabolism and promotes myocardial remodeling.