The leptin( LP) receptor gene heterozygous mice were mated in four ways. Genomic DNA was extracted from offspring tails and analyzed by PCR. The result showed that the ratios of the offspring genotypes fit the Mende...The leptin( LP) receptor gene heterozygous mice were mated in four ways. Genomic DNA was extracted from offspring tails and analyzed by PCR. The result showed that the ratios of the offspring genotypes fit the Mendel's laws. The male and female LP^(-/-)mice( DB / DB mice) were infertile. LP^(-/-)mice could be effectively bred by mating of male and female LP^(+/-)mice. PCR methods could identify LP^(-/-)mice precisely.展开更多
To investigate the expression of mRNA of leptin long-form receptor (OB-Rb) in luteinized granulosa ceils of obese women with polycystic ovary syndrome (PCOS), and to determine the role of leptin in the physiopatho...To investigate the expression of mRNA of leptin long-form receptor (OB-Rb) in luteinized granulosa ceils of obese women with polycystic ovary syndrome (PCOS), and to determine the role of leptin in the physiopathology of PCOS, luteinized granulosa cells were collected from the follicle fluid of 10 obese women who met the diagnostic criteria for PCOS and their BMI was equal to or greater than 25 kg/m^2, and at the same time, granulosa cells were collected from 10 normal women undergoing IVF-ET who served as the control group. Some luteinized granulosa cells were taken from normal women for in-vitro culture, into which human leptin of different concentrations was added (0, 10, 100 and 1000 ng/mL). After stimulation with leptin for 48 h, RT-PCR was employed for the detection of the expression of OB-RLInRNA in the luteinized granulosa cells. Our results showed that the level of OB-RLmRNA in luteinized granulosa cells of obese PCOS women was higher than those in the control (P〈0.05). In luteinized granulosa cells cultured in vitro and stimulated by human leptin for 48 h, the level of OB-RLmRNA was higher than those without leptin stimulation (P〈0.01), and when leptin concentration was at 100 ng/mL, and the level of OB-RLmRNA reached a peak, It is concluded that in obese PCOS women, the level of serum leptin is increased, which promotes the expression of OB-RL in luteinized granulosa cells and increases the sensitivity of the granulosa cells to leptin. Leptin may contribute to anovulation in obese women with PCOS.展开更多
Aim: To evaluate the expression of leptin and leptin receptor in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), and to investigate whether they are associated with the development and progression o...Aim: To evaluate the expression of leptin and leptin receptor in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), and to investigate whether they are associated with the development and progression of PCa. Methods: hnmunohistochemical staining was performed to examine the expression of leptin and leptin receptor in BPH and PCa. PCa was divided into three groups: localized PCa, locally advanced PCa and metastatic PCa. The positive staining was identified and the percentage of the positive staining was graded. We also assessed the relationship between both the Gleason score and body mass index (BMI) and PCa. Results: The percentage of the leptin expression in PCa was significantly higher than that in BPH (P 〈 0.01). For the PCa group, the expressed levels of leptin showed a considerable correlation with localized PCa and metastatic PCa (P 〈 0.05). Leptin receptor, however, did not reveal a definite difference between BPH and PCa. The expression of leptin indicated a significant difference between well-differentiated PCa (Gleason score ≤6) and poorly differentiated PCa (Gleason score 8-10) (P 〈 0.05). The relation between the leptin expression level in PCa and the BMI was not remarkable (P = 0.447). Conclusion: Our results suggest that leptin might have a promoting effect on the carcinogenesis and progression of PCa.展开更多
In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobili...In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobilization stress were significantly decreased compared with the control group. Dual-labeling immunofluorescence revealed that the expression of leptin receptor and the co-localization coeffient in these leptic receptor neurons in the arcuate nucleus of the hypothalamus were both upregulated, while the number of neuropeptide Y neurons was decreased. Chronic immobilization stress induced high expression of leptin receptor in the arcuate nucleus and suppressed the synthesis and secretion of neuropeptide Y, thereby disrupting the pathways in the arcuate nucleus that regulate feeding behavior, resulting in diminished food intake and reduced body weight.展开更多
The effects of metformin treatment on soluble leptin receptor (sOB-R) levels in women with polycystic ovary syndrome (PCOS) were investigated.This prospective and open-label study was conducted by the Department of Ob...The effects of metformin treatment on soluble leptin receptor (sOB-R) levels in women with polycystic ovary syndrome (PCOS) were investigated.This prospective and open-label study was conducted by the Department of Obstetrics & Gynecology at Union Hospital,Tongji Medical College of Huazhong University of Science and Technology,China.Fifty-five women with PCOS and insulin resistance (IR) were treated with metformin for 6 months.According to body mass index (BMI),the patients were divided into two groups:lean PCOS group (BMI <23 kg/m^2,n=34) and overweight or obese PCOS group (BMI >23 kg/m^2,n=21).Before and after treatment,serum luteinizing hormone (LH),follicle stimulating hormone (FSH),testosterone (T),androstenedione (A),dehydroepiandrosterone sulfate (DHEAS),insulin and sOB-R levels were determined.Thirty-one BMI-matched ovulatory women served as controls.The results showed:(1) The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR),androgen levels and hirsutism scores were higher,and sOB-R levels were lower in PCOS groups than in control group.A subgroup analysis of lean and overweight or obese PCOS patients revealed there was significant difference in sOB-R level between lean PCOS group and overweight or obese PCOS group.There were no significant differences in anthropometric parameters between lean PCOS patients and BMI-matched controls.However,sOB-R level was significantly lower in lean PCOS women than in controls.(2) There was no correlation between sOB-R level and BMI,waist and hip circumference,total testosterone,androstendione,DHEAS,LH or hirsutism scores in PCOS patients,but there was a significant negative correlation between sOB-R and HOMA-IR.(3) After treatment with metformin for 6 months,serum insulin levels decreased,and sOB-R levels increased significantly (P<0.01).It was suggested that considering low sOB-R levels supposedly compensate diminished leptin action,PCOS per se might cause leptin resistance.It is likely that reduction of hyperinsulinemia produced by metformin effectively improves the sOB-R levels in PCOS.展开更多
OBJECTIVE: The aim of this study was to investigate the messenger ribonucleic acid expression of leptin (L-mRNA) and the leptin receptor (OB-RmRNA) in subcutaneous fat tissue and to determine their relationship with l...OBJECTIVE: The aim of this study was to investigate the messenger ribonucleic acid expression of leptin (L-mRNA) and the leptin receptor (OB-RmRNA) in subcutaneous fat tissue and to determine their relationship with leptin and testosterone and steroid serum levels over the course of the menstrual cycle (MC), in obese (OBW) and non-obese women (NOW). DESIGN: Observational study investigating mRNA transcript expression of leptin and the leptin receptor from human subcutaneous fat specimens, as well as leptin serum levels, both in relation to the testosterone and sex hormones during the MC in obese and non-obese women. METHODS: Nineteen women, thirteen with a body mass index (BMI) > 25 Kg/m2 and 6 with BMI 2 were included. RT-PCR was used to detect L-mRNA transcripts of leptin and its receptor in samples from 28 fat biopsies taken from seven volunteers (20 from OW and 8 from NOW). The serum concentrations of leptin and steroid hormones were measured throughout the MC using radioinmuno analysis. RESULTS: The percentages of women expressing leptin L-mRNA during the phases of the MC were: early follicular (EF), 14.3%;late follicular (LF), 28.6%;early luteal (EL), 14.3%;and late luteal (LL), 42.9%. The percentages of OB-RmRNA were: EF, 71.4%;LF, 14.3%;EL, 28.6%;and LL, 71.4%. Leptin serum levels were directly related to BMI (p < 0.001), and testosterone (p < 0.001) and indirectly to SHBG (p < 0.001). CONCLUSION: The L-mRNA expression and its receptor in subcutaneous human tissue are regulated throughout the MC in a periodic manner. The physiological role of testosterone in regulation of expression L-mRNA and OB-RmRNA during the secretory phase of the MC in obese women requires further investigation.展开更多
[ Objective] To study the expression of long form leptin receptor (Ob.Rb) mRNA in pituitary of pigs around puberty and explore the rela- tionship between Ob-Rb mRNA and porcine development around pituitary. [Method]...[ Objective] To study the expression of long form leptin receptor (Ob.Rb) mRNA in pituitary of pigs around puberty and explore the rela- tionship between Ob-Rb mRNA and porcine development around pituitary. [Method] Three Sujiang pigs were randomly selected at the age of 120 d, puberty and 180 d, respectively. A pair of primers was designed according to the Ob-Rb sequence published in the GenBank. Total RNAs were extracted from pituitary. The expression of Ob-Rb mRNA was detected by the real-time quantitative RT-PCR. [ Result] The Ob-Rb mRNA was de- tected in pituitaries of pigs at the age of 120 d, puberty and 180 d, respectively. The expression level of Ob-Rb mRNA was lowest at puberty. It was significantly different from that in the 120-day-old pigs and not significantly different from that in the 180-day-old pigs. [ Conclusion] The low expres- sion level of Ob-Rb mRNA is conductive to the arrival of puberty.展开更多
AIM: To determine the role of leptin system in non-al- coholic fatty liver disease (NAFLD) development by deli- neating the changes in serum levels of leptin and soluble leptin receptor (sOB-R). METHODS: Blood samples...AIM: To determine the role of leptin system in non-al- coholic fatty liver disease (NAFLD) development by deli- neating the changes in serum levels of leptin and soluble leptin receptor (sOB-R). METHODS: Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis (stationary phase) as controls. Serum leptin levels were determined by radio- immunoassay and concentration of sOB-R was measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected. RESULTS: Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the con- trols (both P < 0.001), but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group (all P < 0.001). The- re was a significant negative correlation between serum leptin and sOB-R levels (r = -0.725, P < 0.001). Multiva- riate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance (HOMA IR) were independently rela- ted to serum leptin levels. CONCLUSION: Elevated serum leptin seems to be afeature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R con- centration, which suggests higher resistance of periphe- ral tissues towards the action of leptin.展开更多
AIM: To investigate the expression of leptin and leptin receptor (ob-R) in intestinal-type gastric cancer and precancerous lesions, and to explore the possible mechanism and role of the leptin system in developing int...AIM: To investigate the expression of leptin and leptin receptor (ob-R) in intestinal-type gastric cancer and precancerous lesions, and to explore the possible mechanism and role of the leptin system in developing intestinal-type gastric adenocarcinoma.METHODS: Immunohistochemistry was performed to examine the expression of leptin and leptin receptor in archival samples of gastric adenocarcinoma and preneoplastic lesions, including intestinal metaplasia and mild to severe gastric epithelial dysplasia. Positive staining was identified and percentage of positive staining was graded.RESULTS: Dual expression of leptin and leptin receptor were detected in 80% (16/20) intestinal metaplasia,86.3% (25/30) mild gastric epithelial dysplasia, 86.7%(26/30) moderate gastric epithelial dysplasia, 93.3%(28/30) severe gastric epithelial dysplasia, 91.3% (55/60)intestinal-type gastric adenocarcinoma and 30.0% (9/30)difffuse-type gastric carcinoma. The percentage of dual expression of leptin and leptin receptor in intestinal-type gastric adenocarcinoma was significantly higher than that in diffuse-type gastric adenocarcinoma (x2 = 37.022,P<0.01).CONCLUSION: Our results indicate the presence of an autocrine loop of leptin system in the development of intestinal-type gastric adenocarcinoma.展开更多
Background: In mammals, leptin is an attractive candidate for mediating the metabolic signal and the reproductive function via the specific receptor in hypothalamus. However, till now, the role of leptin on reproduct...Background: In mammals, leptin is an attractive candidate for mediating the metabolic signal and the reproductive function via the specific receptor in hypothalamus. However, till now, the role of leptin on reproduction in birds is less well established. This experiment was conducted to elucidate the role of leptin on the onset of reproduction in bird, as a first step, to detect the changes of peripheral leptin and leptin receptor mRNA expression in hypothalamus between mature and immature hens at the same age. 120 ISA brown pullets at D60 were allocated randomly into two groups, long light (LL) group being raised under artificial light regimes with incrementally increased light phase (from 8 L:]6D to 14 L:]2D) and short light (SL) group raised on consistent light (8 L:16D) for 12 wk. Results: The results showed that pullets in LL group reached sexual maturation 15 d earlier than those in SL group. Serum E2 showed a significant increase with age, but no difference was observed between two groups. Serum leptin concentration decreased significantly from D112 to D136 in LL, and was markedly higher in LL group than that in SL at D112, while there was no significant difference between two groups at D136. Leptin receptor and GnRH-I mRNA expression in hypothalamus were significantly increased with age, yet there was no significant difference between SL and LL chickens at the same age. The expression of FSH-13 and LH-13 mRNA in pituitary was increased with age but did not show significant difference between LL and gland, and decreased from D112 to D136 in LL but not groups at the same age. SL group. GnfiH-I mRNA expression was very rich in pinea n SL group, and there was no difference between two Conclusions: These results indicate that the earlier sexual maturation in hens induced by long-light regime is not accompanied with an increase in serum leptin or leptin receptor gene expression in hypothalamus, or genes expression in HPG axis.展开更多
AIM: To examine the expression of leptin and its receptor, OB-R, in normal gastric mucosa and neoplasia. METHODS: By immunohistochemical staining using specifi c antibodies, we evaluated the expression of leptin and O...AIM: To examine the expression of leptin and its receptor, OB-R, in normal gastric mucosa and neoplasia. METHODS: By immunohistochemical staining using specifi c antibodies, we evaluated the expression of leptin and OB-R in 207 gastric carcinomas (100 early and 107 advanced carcinomas) and analyzed their relationship with clinicopathological features. RESULTS: Both normal gastric epithelium and carci- noma cells expressed a significant level of leptin. In cases with OB-R staining, carcinoma cells showed OB-R- positive expression, but the intensity was weaker than that in normal mucosa. The expression of OB-R showed a signifi cant correlation with the level of leptin expres- sion. The expression levels of both leptin and OB-R tend- ed to increase as the depth of tumor invasion or TMN stage increased (P < 0.01). Lymph node metastasis was detected in 49.5% (47/95) of leptin-strong cases and in 50.5% (48/95) of OB-R-positive cases, and the rate was 33% (37/112) in leptin-weak cases and 17% (19/112) in OB-R-negative cases. Both venous and lymphatic inva- sion also tended to be observed frequently in positive tumors as compared with negative tumors. Interestingly, in the 96 leptin- or OB-R-positive tumors, hematogenous metastasis was detected preoperatively in 3 (3.1%) pa- tients. In contrast, none of the carcinomas that lacked expression of leptin and OB-R showed hematogenous metastasis. CONCLUSION: Overexpression of leptin and expres- sion of OB-R may play a positive role in the process of progression in gastric cancer. Functional upregulation of leptin/OB-R may have a positive role in the development and initial phase of progression in gastric cancer.展开更多
Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated tau.Targeting amyloid-beta plaques has b...Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated tau.Targeting amyloid-beta plaques has been a primary direction for developing Alzheimer’s disease treatments in the last decades.However,existing drugs targeting amyloid-beta plaques have not fully yielded the expected results in the clinic,necessitating the exploration of alternative therapeutic strategies.Increasing evidence unravels that astrocyte morphology and function alter in the brain of Alzheimer’s disease patients,with dysregulated astrocytic purinergic receptors,particularly the P2Y1 receptor,all of which constitute the pathophysiology of Alzheimer’s disease.These receptors are not only crucial for maintaining normal astrocyte function but are also highly implicated in neuroinflammation in Alzheimer’s disease.This review delves into recent insights into the association between P2Y1 receptor and Alzheimer’s disease to underscore the potential neuroprotective role of P2Y1 receptor in Alzheimer’s disease by mitigating neuroinflammation,thus offering promising avenues for developing drugs for Alzheimer’s disease and potentially contributing to the development of more effective treatments.展开更多
BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to asce...BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic activity.METHODS Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and MC5R.Colonic sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal mucosa.CONCLUSION MC3R and MC5R are expressed in the colon of IBD patients.Furthermore,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.展开更多
Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. Leptin receptor (LEPR) gene has been intensively evaluated in the search of variants that could be relate...Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. Leptin receptor (LEPR) gene has been intensively evaluated in the search of variants that could be related to obesity. The results of most of these studies have been controversial. We investigated the effects of leptin receptor gene 3’-untranslated region (3’-UTR) polymorphism on phenotype, metabolic parameters and anthropometric measurements of obese Saudi females. 122 healthy women aged 19 to 36 years. The subjects were divided into 3 groups according to their body mass index BMI;lean (BMI 18 - 24), overweight (BMI 25 - 29) and obese (BMI ≥ 30). There were 13 homozygotes and 34 heterozygotes for the 3’-UTR insertion allele amongst all 122 women. The results of this study show that the allele frequency of the insertion allele (I) of 3’UTR was significantly higher in overweight (35.3) and obese females (32.2) compared to the frequency in lean females (15.6). The insertion allele was associated with increased BMI in obese groups. The results obtained from this study indicated that in the obese subjects most variable values increased in I/I homozygote but the significant high value recorded among BMI (40.9 ± 7.11 kg/m2, P = 0.042). Our findings indicated that, the obesity in Saudi females is influenced by alteration in the leptin receptor gene 3’-UTR polymorphism.展开更多
BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diar...BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.展开更多
Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibi...Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investigation in ongoing clinical trials. Investigation has also been demonstrating that combinatorial therapies of growth inhibitors with other therapies, such as growth factors or stem-cell therapies, produce stronger results and their potential application in the clinics opens new venues in spinal cord injury treatment.展开更多
Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2...Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.展开更多
More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but s...More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.展开更多
To study the diagnosis and therapy for radiation intestinal fistula (RIF).Methods From 1998~2004,a total of 28 patients,with RIF were retrospectively analyzed.Results The reviewed diagnosis were 26 cervical cancer af...To study the diagnosis and therapy for radiation intestinal fistula (RIF).Methods From 1998~2004,a total of 28 patients,with RIF were retrospectively analyzed.Results The reviewed diagnosis were 26 cervical cancer after radiotherapy,1 rectal cancer and 1 bladder cancer every after operation.RIF often occurred in 0.5 to 2 years.Radiation enteritis occurred before intestinal fistula in different degree.The reviewed diagnosis were 24 cases of rectovaginal fistulas including 2 complex rectovaginal fistulas accepted colostomy frontward altering the fecal.2 ileovesical fistulas cases and 1 colon sigmiodeumva injury and 1 perforation of intestine accepted resection of ileum fistulas and re-anastomosis of the ileum.Conclusion RIF is one of the long-term severe complications by radiation injury and related to the irradiation absorbed dose of normal tissues,individual difference and et al.Radiation enteritis is the early symptoms of RIF.Colostomy frontward altering the fecal or resection of ileum fistulas and re-anastomosis of the ileum are the main methods of treatment.8 refs,1 tab.展开更多
To determine the expression of leptin and leptin receptor in gastric carcinoma and investigate their role in carciagenesis and development of gastric carcinoma.Methods The expression of leptin and leptin receptor prot...To determine the expression of leptin and leptin receptor in gastric carcinoma and investigate their role in carciagenesis and development of gastric carcinoma.Methods The expression of leptin and leptin receptor protein was detected in 54 cases of gastric carcinoma tissues by immunohistochemistry.The correlatin between their expression and clinicallpathological parameters was also analysized.Results The expression rate of leptin and leptin receptor in gastric carcinoma was 72.22%(39/54) and 74.07%(40/54) respectively.The expression rate of leptin in intestinal-type gastric cancer was significantly higher than in diffuse-type gastric cancer.The expression rate of leptin was associated with differentiation,tumor size,metastasis,and TNM stage.Conclusion Leptin and leptin receptor were dually expressed in gastric carcinoma.They participate in the early stage of malignant transformation and have certain role in the advanced stage.3 refs,1 tab.展开更多
文摘The leptin( LP) receptor gene heterozygous mice were mated in four ways. Genomic DNA was extracted from offspring tails and analyzed by PCR. The result showed that the ratios of the offspring genotypes fit the Mendel's laws. The male and female LP^(-/-)mice( DB / DB mice) were infertile. LP^(-/-)mice could be effectively bred by mating of male and female LP^(+/-)mice. PCR methods could identify LP^(-/-)mice precisely.
文摘To investigate the expression of mRNA of leptin long-form receptor (OB-Rb) in luteinized granulosa ceils of obese women with polycystic ovary syndrome (PCOS), and to determine the role of leptin in the physiopathology of PCOS, luteinized granulosa cells were collected from the follicle fluid of 10 obese women who met the diagnostic criteria for PCOS and their BMI was equal to or greater than 25 kg/m^2, and at the same time, granulosa cells were collected from 10 normal women undergoing IVF-ET who served as the control group. Some luteinized granulosa cells were taken from normal women for in-vitro culture, into which human leptin of different concentrations was added (0, 10, 100 and 1000 ng/mL). After stimulation with leptin for 48 h, RT-PCR was employed for the detection of the expression of OB-RLInRNA in the luteinized granulosa cells. Our results showed that the level of OB-RLmRNA in luteinized granulosa cells of obese PCOS women was higher than those in the control (P〈0.05). In luteinized granulosa cells cultured in vitro and stimulated by human leptin for 48 h, the level of OB-RLmRNA was higher than those without leptin stimulation (P〈0.01), and when leptin concentration was at 100 ng/mL, and the level of OB-RLmRNA reached a peak, It is concluded that in obese PCOS women, the level of serum leptin is increased, which promotes the expression of OB-RL in luteinized granulosa cells and increases the sensitivity of the granulosa cells to leptin. Leptin may contribute to anovulation in obese women with PCOS.
文摘Aim: To evaluate the expression of leptin and leptin receptor in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), and to investigate whether they are associated with the development and progression of PCa. Methods: hnmunohistochemical staining was performed to examine the expression of leptin and leptin receptor in BPH and PCa. PCa was divided into three groups: localized PCa, locally advanced PCa and metastatic PCa. The positive staining was identified and the percentage of the positive staining was graded. We also assessed the relationship between both the Gleason score and body mass index (BMI) and PCa. Results: The percentage of the leptin expression in PCa was significantly higher than that in BPH (P 〈 0.01). For the PCa group, the expressed levels of leptin showed a considerable correlation with localized PCa and metastatic PCa (P 〈 0.05). Leptin receptor, however, did not reveal a definite difference between BPH and PCa. The expression of leptin indicated a significant difference between well-differentiated PCa (Gleason score ≤6) and poorly differentiated PCa (Gleason score 8-10) (P 〈 0.05). The relation between the leptin expression level in PCa and the BMI was not remarkable (P = 0.447). Conclusion: Our results suggest that leptin might have a promoting effect on the carcinogenesis and progression of PCa.
基金supported by the National Natural Science Foundation of China,No.30672578,81072756and81202644China National Funds for Distinguished Young Scientists,No.30825046+2 种基金Program for Innovative Research Team in Beijing University of Chinese Medicine,No.2011CXTD-07Program for University Key Teacher of Hebei Medical UniversitySpecialized Research Fund for the Doctoral Program of Higher Education,No.20121323120016
文摘In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobilization stress were significantly decreased compared with the control group. Dual-labeling immunofluorescence revealed that the expression of leptin receptor and the co-localization coeffient in these leptic receptor neurons in the arcuate nucleus of the hypothalamus were both upregulated, while the number of neuropeptide Y neurons was decreased. Chronic immobilization stress induced high expression of leptin receptor in the arcuate nucleus and suppressed the synthesis and secretion of neuropeptide Y, thereby disrupting the pathways in the arcuate nucleus that regulate feeding behavior, resulting in diminished food intake and reduced body weight.
文摘The effects of metformin treatment on soluble leptin receptor (sOB-R) levels in women with polycystic ovary syndrome (PCOS) were investigated.This prospective and open-label study was conducted by the Department of Obstetrics & Gynecology at Union Hospital,Tongji Medical College of Huazhong University of Science and Technology,China.Fifty-five women with PCOS and insulin resistance (IR) were treated with metformin for 6 months.According to body mass index (BMI),the patients were divided into two groups:lean PCOS group (BMI <23 kg/m^2,n=34) and overweight or obese PCOS group (BMI >23 kg/m^2,n=21).Before and after treatment,serum luteinizing hormone (LH),follicle stimulating hormone (FSH),testosterone (T),androstenedione (A),dehydroepiandrosterone sulfate (DHEAS),insulin and sOB-R levels were determined.Thirty-one BMI-matched ovulatory women served as controls.The results showed:(1) The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR),androgen levels and hirsutism scores were higher,and sOB-R levels were lower in PCOS groups than in control group.A subgroup analysis of lean and overweight or obese PCOS patients revealed there was significant difference in sOB-R level between lean PCOS group and overweight or obese PCOS group.There were no significant differences in anthropometric parameters between lean PCOS patients and BMI-matched controls.However,sOB-R level was significantly lower in lean PCOS women than in controls.(2) There was no correlation between sOB-R level and BMI,waist and hip circumference,total testosterone,androstendione,DHEAS,LH or hirsutism scores in PCOS patients,but there was a significant negative correlation between sOB-R and HOMA-IR.(3) After treatment with metformin for 6 months,serum insulin levels decreased,and sOB-R levels increased significantly (P<0.01).It was suggested that considering low sOB-R levels supposedly compensate diminished leptin action,PCOS per se might cause leptin resistance.It is likely that reduction of hyperinsulinemia produced by metformin effectively improves the sOB-R levels in PCOS.
文摘OBJECTIVE: The aim of this study was to investigate the messenger ribonucleic acid expression of leptin (L-mRNA) and the leptin receptor (OB-RmRNA) in subcutaneous fat tissue and to determine their relationship with leptin and testosterone and steroid serum levels over the course of the menstrual cycle (MC), in obese (OBW) and non-obese women (NOW). DESIGN: Observational study investigating mRNA transcript expression of leptin and the leptin receptor from human subcutaneous fat specimens, as well as leptin serum levels, both in relation to the testosterone and sex hormones during the MC in obese and non-obese women. METHODS: Nineteen women, thirteen with a body mass index (BMI) > 25 Kg/m2 and 6 with BMI 2 were included. RT-PCR was used to detect L-mRNA transcripts of leptin and its receptor in samples from 28 fat biopsies taken from seven volunteers (20 from OW and 8 from NOW). The serum concentrations of leptin and steroid hormones were measured throughout the MC using radioinmuno analysis. RESULTS: The percentages of women expressing leptin L-mRNA during the phases of the MC were: early follicular (EF), 14.3%;late follicular (LF), 28.6%;early luteal (EL), 14.3%;and late luteal (LL), 42.9%. The percentages of OB-RmRNA were: EF, 71.4%;LF, 14.3%;EL, 28.6%;and LL, 71.4%. Leptin serum levels were directly related to BMI (p < 0.001), and testosterone (p < 0.001) and indirectly to SHBG (p < 0.001). CONCLUSION: The L-mRNA expression and its receptor in subcutaneous human tissue are regulated throughout the MC in a periodic manner. The physiological role of testosterone in regulation of expression L-mRNA and OB-RmRNA during the secretory phase of the MC in obese women requires further investigation.
文摘[ Objective] To study the expression of long form leptin receptor (Ob.Rb) mRNA in pituitary of pigs around puberty and explore the rela- tionship between Ob-Rb mRNA and porcine development around pituitary. [Method] Three Sujiang pigs were randomly selected at the age of 120 d, puberty and 180 d, respectively. A pair of primers was designed according to the Ob-Rb sequence published in the GenBank. Total RNAs were extracted from pituitary. The expression of Ob-Rb mRNA was detected by the real-time quantitative RT-PCR. [ Result] The Ob-Rb mRNA was de- tected in pituitaries of pigs at the age of 120 d, puberty and 180 d, respectively. The expression level of Ob-Rb mRNA was lowest at puberty. It was significantly different from that in the 120-day-old pigs and not significantly different from that in the 180-day-old pigs. [ Conclusion] The low expres- sion level of Ob-Rb mRNA is conductive to the arrival of puberty.
文摘AIM: To determine the role of leptin system in non-al- coholic fatty liver disease (NAFLD) development by deli- neating the changes in serum levels of leptin and soluble leptin receptor (sOB-R). METHODS: Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis (stationary phase) as controls. Serum leptin levels were determined by radio- immunoassay and concentration of sOB-R was measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected. RESULTS: Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the con- trols (both P < 0.001), but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group (all P < 0.001). The- re was a significant negative correlation between serum leptin and sOB-R levels (r = -0.725, P < 0.001). Multiva- riate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance (HOMA IR) were independently rela- ted to serum leptin levels. CONCLUSION: Elevated serum leptin seems to be afeature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R con- centration, which suggests higher resistance of periphe- ral tissues towards the action of leptin.
文摘AIM: To investigate the expression of leptin and leptin receptor (ob-R) in intestinal-type gastric cancer and precancerous lesions, and to explore the possible mechanism and role of the leptin system in developing intestinal-type gastric adenocarcinoma.METHODS: Immunohistochemistry was performed to examine the expression of leptin and leptin receptor in archival samples of gastric adenocarcinoma and preneoplastic lesions, including intestinal metaplasia and mild to severe gastric epithelial dysplasia. Positive staining was identified and percentage of positive staining was graded.RESULTS: Dual expression of leptin and leptin receptor were detected in 80% (16/20) intestinal metaplasia,86.3% (25/30) mild gastric epithelial dysplasia, 86.7%(26/30) moderate gastric epithelial dysplasia, 93.3%(28/30) severe gastric epithelial dysplasia, 91.3% (55/60)intestinal-type gastric adenocarcinoma and 30.0% (9/30)difffuse-type gastric carcinoma. The percentage of dual expression of leptin and leptin receptor in intestinal-type gastric adenocarcinoma was significantly higher than that in diffuse-type gastric adenocarcinoma (x2 = 37.022,P<0.01).CONCLUSION: Our results indicate the presence of an autocrine loop of leptin system in the development of intestinal-type gastric adenocarcinoma.
基金supported by a grant from National Natural Science Foundation of China(Project No.30800809)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Background: In mammals, leptin is an attractive candidate for mediating the metabolic signal and the reproductive function via the specific receptor in hypothalamus. However, till now, the role of leptin on reproduction in birds is less well established. This experiment was conducted to elucidate the role of leptin on the onset of reproduction in bird, as a first step, to detect the changes of peripheral leptin and leptin receptor mRNA expression in hypothalamus between mature and immature hens at the same age. 120 ISA brown pullets at D60 were allocated randomly into two groups, long light (LL) group being raised under artificial light regimes with incrementally increased light phase (from 8 L:]6D to 14 L:]2D) and short light (SL) group raised on consistent light (8 L:16D) for 12 wk. Results: The results showed that pullets in LL group reached sexual maturation 15 d earlier than those in SL group. Serum E2 showed a significant increase with age, but no difference was observed between two groups. Serum leptin concentration decreased significantly from D112 to D136 in LL, and was markedly higher in LL group than that in SL at D112, while there was no significant difference between two groups at D136. Leptin receptor and GnRH-I mRNA expression in hypothalamus were significantly increased with age, yet there was no significant difference between SL and LL chickens at the same age. The expression of FSH-13 and LH-13 mRNA in pituitary was increased with age but did not show significant difference between LL and gland, and decreased from D112 to D136 in LL but not groups at the same age. SL group. GnfiH-I mRNA expression was very rich in pinea n SL group, and there was no difference between two Conclusions: These results indicate that the earlier sexual maturation in hens induced by long-light regime is not accompanied with an increase in serum leptin or leptin receptor gene expression in hypothalamus, or genes expression in HPG axis.
文摘AIM: To examine the expression of leptin and its receptor, OB-R, in normal gastric mucosa and neoplasia. METHODS: By immunohistochemical staining using specifi c antibodies, we evaluated the expression of leptin and OB-R in 207 gastric carcinomas (100 early and 107 advanced carcinomas) and analyzed their relationship with clinicopathological features. RESULTS: Both normal gastric epithelium and carci- noma cells expressed a significant level of leptin. In cases with OB-R staining, carcinoma cells showed OB-R- positive expression, but the intensity was weaker than that in normal mucosa. The expression of OB-R showed a signifi cant correlation with the level of leptin expres- sion. The expression levels of both leptin and OB-R tend- ed to increase as the depth of tumor invasion or TMN stage increased (P < 0.01). Lymph node metastasis was detected in 49.5% (47/95) of leptin-strong cases and in 50.5% (48/95) of OB-R-positive cases, and the rate was 33% (37/112) in leptin-weak cases and 17% (19/112) in OB-R-negative cases. Both venous and lymphatic inva- sion also tended to be observed frequently in positive tumors as compared with negative tumors. Interestingly, in the 96 leptin- or OB-R-positive tumors, hematogenous metastasis was detected preoperatively in 3 (3.1%) pa- tients. In contrast, none of the carcinomas that lacked expression of leptin and OB-R showed hematogenous metastasis. CONCLUSION: Overexpression of leptin and expres- sion of OB-R may play a positive role in the process of progression in gastric cancer. Functional upregulation of leptin/OB-R may have a positive role in the development and initial phase of progression in gastric cancer.
文摘Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated tau.Targeting amyloid-beta plaques has been a primary direction for developing Alzheimer’s disease treatments in the last decades.However,existing drugs targeting amyloid-beta plaques have not fully yielded the expected results in the clinic,necessitating the exploration of alternative therapeutic strategies.Increasing evidence unravels that astrocyte morphology and function alter in the brain of Alzheimer’s disease patients,with dysregulated astrocytic purinergic receptors,particularly the P2Y1 receptor,all of which constitute the pathophysiology of Alzheimer’s disease.These receptors are not only crucial for maintaining normal astrocyte function but are also highly implicated in neuroinflammation in Alzheimer’s disease.This review delves into recent insights into the association between P2Y1 receptor and Alzheimer’s disease to underscore the potential neuroprotective role of P2Y1 receptor in Alzheimer’s disease by mitigating neuroinflammation,thus offering promising avenues for developing drugs for Alzheimer’s disease and potentially contributing to the development of more effective treatments.
基金The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of University of Campania Luigi Vanvitelli(Protocol code 795 on December 23,2019).
文摘BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic activity.METHODS Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and MC5R.Colonic sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal mucosa.CONCLUSION MC3R and MC5R are expressed in the colon of IBD patients.Furthermore,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.
文摘Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. Leptin receptor (LEPR) gene has been intensively evaluated in the search of variants that could be related to obesity. The results of most of these studies have been controversial. We investigated the effects of leptin receptor gene 3’-untranslated region (3’-UTR) polymorphism on phenotype, metabolic parameters and anthropometric measurements of obese Saudi females. 122 healthy women aged 19 to 36 years. The subjects were divided into 3 groups according to their body mass index BMI;lean (BMI 18 - 24), overweight (BMI 25 - 29) and obese (BMI ≥ 30). There were 13 homozygotes and 34 heterozygotes for the 3’-UTR insertion allele amongst all 122 women. The results of this study show that the allele frequency of the insertion allele (I) of 3’UTR was significantly higher in overweight (35.3) and obese females (32.2) compared to the frequency in lean females (15.6). The insertion allele was associated with increased BMI in obese groups. The results obtained from this study indicated that in the obese subjects most variable values increased in I/I homozygote but the significant high value recorded among BMI (40.9 ± 7.11 kg/m2, P = 0.042). Our findings indicated that, the obesity in Saudi females is influenced by alteration in the leptin receptor gene 3’-UTR polymorphism.
基金The Health Commission of Jinshan District,Shanghai,China,No.JSKJ-KTMS-2019-01The Youth Research Foundation of Jinshan Hospital of Fudan University,No.JYQN-JC-202101 and No.JYQN-JC-202216The Reserve Discipline Construction of Jinshan Hospital of Fudan University,No.HBXK-2021-2.
文摘BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.
基金a Ph D fellowship by FCT-Fundacao para a Ciência Tecnologia (SFRH/BD/135868/2018)(to SSC)。
文摘Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investigation in ongoing clinical trials. Investigation has also been demonstrating that combinatorial therapies of growth inhibitors with other therapies, such as growth factors or stem-cell therapies, produce stronger results and their potential application in the clinics opens new venues in spinal cord injury treatment.
文摘Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.
文摘More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.
文摘To study the diagnosis and therapy for radiation intestinal fistula (RIF).Methods From 1998~2004,a total of 28 patients,with RIF were retrospectively analyzed.Results The reviewed diagnosis were 26 cervical cancer after radiotherapy,1 rectal cancer and 1 bladder cancer every after operation.RIF often occurred in 0.5 to 2 years.Radiation enteritis occurred before intestinal fistula in different degree.The reviewed diagnosis were 24 cases of rectovaginal fistulas including 2 complex rectovaginal fistulas accepted colostomy frontward altering the fecal.2 ileovesical fistulas cases and 1 colon sigmiodeumva injury and 1 perforation of intestine accepted resection of ileum fistulas and re-anastomosis of the ileum.Conclusion RIF is one of the long-term severe complications by radiation injury and related to the irradiation absorbed dose of normal tissues,individual difference and et al.Radiation enteritis is the early symptoms of RIF.Colostomy frontward altering the fecal or resection of ileum fistulas and re-anastomosis of the ileum are the main methods of treatment.8 refs,1 tab.
文摘To determine the expression of leptin and leptin receptor in gastric carcinoma and investigate their role in carciagenesis and development of gastric carcinoma.Methods The expression of leptin and leptin receptor protein was detected in 54 cases of gastric carcinoma tissues by immunohistochemistry.The correlatin between their expression and clinicallpathological parameters was also analysized.Results The expression rate of leptin and leptin receptor in gastric carcinoma was 72.22%(39/54) and 74.07%(40/54) respectively.The expression rate of leptin in intestinal-type gastric cancer was significantly higher than in diffuse-type gastric cancer.The expression rate of leptin was associated with differentiation,tumor size,metastasis,and TNM stage.Conclusion Leptin and leptin receptor were dually expressed in gastric carcinoma.They participate in the early stage of malignant transformation and have certain role in the advanced stage.3 refs,1 tab.