Olfactory receptors in neural regeneration in the central nervous system

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.

Immunomodulation of Proton-activated G Protein-coupled Receptors in Inflammation

Proton-activated G protein-coupled receptors(GPCRs),initially discovered by Ludwig in 2003,are widely distributed in various tissues.These receptors have been found to modulate the immune system in several inflammatory diseases,including inflammatory bowel disease,atopic dermatitis,and asthma.Proton-activated GPCRs belong to the G protein-coupled receptor family and can detect alternations in extracellular pH.This detection triggers downstream signaling pathways within the cells,ultimately influencing the function of immune cells.In this review,we specifically focused on investigating the immune response of proton-activated GPCRs under inflammatory conditions.

Metabotropic glutamate receptors(mGluRs)in epileptogenesis:an update on abnormal mGluRs signaling and its therapeutic implications

Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

Characterization of Domeless receptors and the role of Bd Domeless3 in anti-symbiont-like virus defense in Bactrocera dorsalis

The Janus kinase/signal transducers and activators of transcription(JAK/STAT)signaling pathway play a pivotal role in innate immunity.Among invertebrates,Domeless receptors serve as the key upstream regulators of this pathway.In our study on Bactrocera dorsalis,we identified three cytokine receptors:BdDomeless1,BdDomeless2,and BdDomeless3.Each receptor encompasses five fibronectin-type-III-like(FN III)extracellular domains and a transmembrane domain.Furthermore,these receptors exhibit the increased responsiveness to diverse pathogenic challenges.Notably,only BdDomeless3 is upregulated during symbiont-like viral infections.Moreover,silencing BdDomeless3 enhanced the infectivity of Bactrocera dorsalis cripavirus(BdCV)and B.dorsalis picorna-like virus(BdPLV),underscoring BdDomeless3’s crucial role in antiviral defense of B.dorsalis.Following the suppression of Domeless3 expression,six antimicrobial peptide genes displayed decreased expression,potentially correlating with the rise in viral infectivity.To our knowledge,this is the first study identifying cytokine receptors associated with the JAK/STAT pathway in tephritid flies,shedding light on the immune mechanisms of B.dorsalis.

The Role of Toll-Like Receptors and Nuclear Factor κB p65 Protein in the Pathogenesis of Otitis Media

The role of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) proteins in the pathogenesis of otitis media is explored. In recent years, the incidence of otitis media has been rising globally, becoming a significant threat to human health. More and more studies have found that Toll-like receptor 4 (TLR4), as a member of the Toll-like receptor family, can promote the generation of inflammatory factors and is closely related to the body’s immune response and inflammatory response. Nuclear factor-κB p65 (NF-κB p65) is a nuclear transcription factor that can interact with various cytokines, growth factors, and apoptotic factors, participating in processes such as oxidative stress, apoptosis, and inflammation in the body [1]. This article elaborates on the structure, function, and signaling pathways of TLR4 and NF-κB p65 proteins in the pathogenesis of otitis media, aiming to provide more precise targets and better therapeutic efficacy for the diagnosis and treatment of otitis media. The role of inflammation in disease.

Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population

Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling adaptive immunity.The role of TLR2 in the progression of psoriasis is not well understood.Methods:A case-control study was conducted on a northern Chinese Han population,consisting of psoriasis patients and healthy control subjects.Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction(ARMS-PCR),and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.Results:Four TLR2 SNPs(rs11938228,rs4696480,rs3804099,rs5743699)were genotyped and found to be in linkage disequilibrium.The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model.The haplotypes ATTC and ATCC were found to be protective against psoriasis.Conclusion:Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

Role of bitter contributors and bitter taste receptors:a comprehensive review of their sources,functions and future development

Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.

血清Leptin、Apelin水平与增生型糖尿病性视网膜病变患者玻璃体切割术后视力残疾的关系

目的探讨血清瘦素(Leptin)、爱帕琳肽(Apelin)水平与增生型糖尿病性视网膜病变(PDR)患者玻璃体切割术(PPV)后视力残疾的关系。方法选取接受PPV治疗的PDR患者198例(198眼),术后随访1年,根据是否发生视力残疾将患者分为视力残疾组48例、视力良好组150例。收集两组临床资料,术前用酶联免疫吸附试验检测血清Leptin、Apelin,多因素Logistic回归分析血清Leptin、Apelin水平对PDR患者PPV后视力残疾的影响,受试者工作特征(ROC)曲线分析血清Leptin、Apelin水平对PDR患者PPV后视力残疾的预测价值。结果与视力良好组比较,视力残疾组年龄大,PDR程度、术前虹膜新生血管比例、糖化血红蛋白水平及血清Leptin、Apelin水平高(P均<0.05)。多因素Logistic回归分析结果显示,重度PDR、术前虹膜新生血管、Leptin升高、Apelin升高为PDR患者PPV后视力残疾的独立危险因素(P均<0.05)。ROC曲线分析显示,血清Leptin、Apelin联合预测PDR患者PPV后视力残疾的曲线下面积为0.921,大于二者单独预测的曲线下面积(P均<0.05)。结论血清Leptin、Apelin水平升高是PDR患者PPV后视力残疾的危险因素,二者联合检测对PDR患者PPV后视力残疾的预测价值较高。

Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity?

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.

Intricate roles of estrogen and estrogen receptors in digestive system cancers:a systematic review

Gender disparities are evident across different types of digestive system cancers,which are typically characterized by a lower incidence and mortality rate in females compared to males.This finding suggests a potential protective role of female steroid hormones,particularly estrogen,in the development of these cancers.Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors(ERs),including the classic(ERαand ERβ)and non-traditional ERs[G protein-coupled estrogen receptor(GPER)].Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers.In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers,including hepatocellular,pancreatic,esophageal,gastric,and colorectal carcinoma.Furthermore,we discuss the potential molecular mechanisms underlying ERα,ERβ,and GPER effects,and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs.The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved.Additionally,deciphering the intricate roles of estrogen,ERs,and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers,eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.

血清FGFR2、Leptin对特发性矮小症患儿的诊断价值及其水平与骨代谢指标的相关性

目的探讨血清成纤维生长因子受体2(FGFR2)、瘦素(Leptin)水平与特发性矮小症患儿骨代谢指标的相关性及其对疾病的诊断价值。方法选取2021年9月至2023年9月于该院就诊的138例特发性矮小症患儿为观察组,另选取同期于该院进行健康体检的141例健康儿童为对照组。采用酶联免疫吸附试验检测血清FGFR2、Leptin水平;采用全自动生化分析仪检测25-羟基维生素D[25-(OH)D]、Ⅰ型前胶原氨基酸前肽(PⅠNP)、骨钙素(OC)、骨特异性碱性磷酸酶(BAP)等骨代谢指标水平;采用Pearson相关分析特发性矮小症患儿血清FGFR2、Leptin水平与骨代谢指标水平的相关性;采用多因素Logistic回归分析影响特发性矮小症发病的因素;绘制受试者工作特征(ROC)曲线分析血清FGFR2、Leptin单独及联合检测对特发性矮小症的诊断价值。结果观察组体质量、身高及25-(OH)D、PⅠNP、OC、BAP、FGFR2、Leptin水平显著低于对照组,性发育状态Ⅱ~Ⅴ期患儿比例显著高于对照组,差异均有统计学意义(P<0.05)。Pearson相关性分析结果显示,特发性矮小症患儿血清FGFR2、Leptin水平与25-(OH)D、PⅠNP、OC、BAP水平均呈正相关(P<0.05)。多因素Logistic回归分析结果显示,FGFR2、Leptin水平升高是特发性矮小症发病的保护因素(P<0.05)。ROC曲线结果显示,血清FGFR2、Leptin单独及联合诊断特发性矮小症的曲线下面积分别为0.834、0.851、0.914。结论特发性矮小症患儿血清FGFR2、Leptin水平均较低,且二者均与骨代谢指标显著相关,推测其在诊断特发性矮小症中具有一定价值。

Exploring the vital role of microglial membrane receptors in Alzheimer’s disease pathogenesis: a comprehensive review

Neurodegenerative diseases constitute a broad category of diseases caused by the degeneration of the neurons.They are mainly manifested by the gradual loss of neuron structure and function and eventually can cause death or loss of neurons.As the global population ages rapidly,increased people are being diagnosed with neurodegenerative diseases.It has been established that the onset of Alzheimer’s disease(AD)is closely linked with increasing age and its major pathological features include amyloid-beta plaques(Aβ),Tau hyperphosphorylation,Neurofibrillary tangles(NFTs),neuronal death as well as synaptic loss.The involvement of microglia is crucial in the pathogenesis and progression of AD and exhibits a dual role.For instance,in the early stage of AD,microglia surface membrane proteins or receptors can participate in immunophagocytosis,and anti-inflammatory functions and act as a physical barrier after recognizing various ligands such as Aβand NFTs.However,in the later stage of the disease,membrane receptors on the surface of microglia can cause its activation to release a substantial quantity of pro-inflammatory factors.Which can amplify the neuroinflammatory response.The rapid decline of normal immune phagocytosis can result in the continuous accumulation of abnormal proteins,leading to neuronal dysfunction and destruction of the formed physical barrier as well as the neurovascular microenvironment.It can also increase the transformation of microglia from anti-inflammatory phenotype M2 to pro-inflammatory phenotype M1,induce severe neuronal injury or apoptosis,and aggravate the progression of AD.Due to few articles have focused on the AD-related membrane protein receptors on microglia,thus in this paper,we have reviewed several representative microglial membrane proteins or receptors about their specific roles and functions implicated in AD,and expect that there will be more in-depth research and scientific research results in the treatment of AD by targeted regulation of microglia membrane protein receptors in the future.

HE4、CEA和leptin表达对肺癌的诊断价值及其与病理分期、分化程度的关系

目的分析人附睾蛋白4(Human epididymis protein 4,HE4)、癌胚抗原(Carcinoembryonic antigen,CEA)和瘦素(leptin)表达水平对肺癌患者的诊断价值及其与患者病理分期、分化程度的关系。方法本研究纳入2022年1月~2023年12月在本院就诊的肺癌患者为研究组,共计120例,选取同期在本院体检的健康体检者为对照组以及经检查后为肺部良性疾病者为肺部良性疾病组,各60例。对比三组患者血清中HE4、CEA和leptin水平;对比不同分期以及不同细胞分化程度患者血清中HE4、CEA和leptin水平;分析血清中HE4、CEA和leptin水平与肺癌分期以及分化程度的相关性;采用受试者工作特征(Receiver operating characteristic,ROC)曲线分析血清中HE4、CEA、leptin单独或联合检测对肺癌的诊断价值。结果肺癌患者血清中HE4、leptin及CEA水平均显著高于肺部良性组和对照组(P<0.05);Ⅰ~Ⅱ期组患者血清中HE4、leptin及CEA水平均显著低于Ⅲ~Ⅳ期组(P<0.05);高分化组血清中HE4、leptin及CEA水平均显著高于中分化组以及低分化组(P<0.05);Spearman相关性分析表明血清中HE4、leptin和CEA水平与肺癌分期以及分化程度呈显著正相关(P<0.05);ROC曲线表明,HE4、CEA、leptin单独及联合检测诊断肺癌的曲线下面积分别为0.870、0.849、0.879以及0.958。结论肺癌患者的血清HE4、CEA和leptin水平均显著升高,且与肺癌的临床分期和细胞分化程度有一定的相关性,联合检测HE4、CEA和leptin指标对肺癌的诊断具有较高的价值,可以作为肺癌的筛查和早期诊断工具。

N-acetylcysteine and zinc sulphate abate di-2-ethylhexyl phthalate-mediated reproductive dysfunction in rats:Focus on oxidative and sex hormone receptors mechanisms

Objective:To investigate the potential of N-acetylcysteine(NAC)and zinc sulphate(ZnSO_(4))in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate(DEHP)in rats and to understand the underlying mechanisms,specifically oxidative stress and sex hormone receptor activity.Methods:Thirty-five male Wistar rats were randomly divided into five equal groups(n=7 per group).Group 1 was administered 0.5 mL of distilled water and served as the control group.Group 2 was given only DEHP(750 mg/kg/day),while group 3,4 and 5 were given DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day),DEHP(750 mg/kg/day)plus ZnSO_(4)(0.5 mg/kg/day),and DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day)as well as ZnSO_(4)(0.5 mg/kg/day),respectively.All treatments lasted for 21 days.Samples were obtained after the rats were sacrificed,and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent assay.The amount of androgen receptors in the testicles was determined by immunohistochemistry,and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking studies.Results:DEHP decreased reproductive hormones,testicular antioxidant enzymes,increased malondialdehyde levels,and negatively impacted histology of the pituitary and testes.NAC or ZnSO_(4) treatment showed a marked improvement in testicular antioxidant status and hormone levels,as well as a positive effect on the histology of the pituitary and testes.The combination of both treatments appeared to be more effective.The affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling,which can further result in dysfunction of hormones related to androgen.However,NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors,as well as gonadotropin-releasing hormone receptors,when compared to DEHP.Conclusions:The possibility that NAC and ZnSO_(4) could downregulate DEHP-induced sex hormone changes is suggested by their potential to reduce toxicity.

Exploring the therapeutic potential of precision T-Cell Receptors (TCRs) in targeting KRAS G12D cancer through in vitro development

Objectives:The Kirsten rat sarcoma virus(KRAS)G12D oncogenic mutation poses a significant challenge in treating solid tumors due to the lack of specific and effective therapeutic interventions.This study aims to explore innovative approaches in T cell receptor(TCR)engineering and characterization to target the KRAS G12D7-16 mutation,providing potential strategies for overcoming this therapeutic challenge.Methods:In this innovative study,we engineered and characterized two T cell receptors(TCRs),KDA11-01 and KDA11-02 with high affinity for the KRAS G12D7-16 mutation.These TCRs were isolated from tumor-infiltrating lymphocytes(TILs)derived from tumor tissues of patients with the KRAS G12D mutation.We assessed their specificity and anti-tumor activity in vitro using various cancer cell lines.Results:KDA11-01 and KDA11-02 demonstrated exceptional specificity for the HLA-A*11:01-restricted KRAS G12D7-16 epitope,significantly inducing IFN-γrelease and eliminating tumor cells without cross-reactivity or alloreactivity.Conclusions:The successful development of KDA11-01 and KDA11-02 introduces a novel and precise TCR-based therapeutic strategy against KRAS G12D mutation,showing potential for significant advancements in cancer immunotherapy.

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Novel Role of Calcium-Sensitive Receptors in Chronic Hypoxia-Induced Proliferation of Pulmonary Vein Smooth Muscle Cells

Objective:Vascular remodeling due to chronic hypoxia(CH)occurs not only in the pulmonary arteries but also in the pulmonary veins.Pulmonary vascular remodeling arises from the proliferation of pulmonary vascular myocytes.However,the mechanism by which CH induces the proliferation of pulmonary vein smooth muscle cells(PVSMCs)is unknown.This study aimed to investigate the mechanism by which CH affects the proliferation of PVSMCs.Methods:PVSMCs were isolated from rat distal pulmonary veins and exposed to CH(4%O2,60h),and the expression of the calcium-sensitive receptor(CaSR)was detected by Western blotting and immunofluorescence.MTT assay was used to detect the proliferation viability of the cells,and the changes in the intracellular calcium concentration were detected by laser confocal scanning technique.Results:CaSR expression was present in rat distal PVSMCs,and CaSR protein expression was upregulated under hypoxia.The positive regulator spermine not only enhanced CH-induced CaSR upregulation but also enhanced CH-induced increase in cell viability and calcium ion concentration.The negative CaSR regulator NPS2143 not only attenuated CH-induced CaSR upregulation but also inhibited CH-induced cell viability and calcium ion concentration.Conclusion:CaSR-mediated hyperproliferation is a novel pathogenic mechanism for the development of proliferation in distal PVSMCs under CH conditions.

乳腺癌患者血清Leptin水平检测及其临床意义

目的:研究瘦素(Leptin)对乳腺癌诊断的价值,为乳腺癌与乳腺良性病变的鉴别诊断提供实验依据。方法:应用放射免疫分析(RIA)分别检测46例乳腺癌、28例乳腺良性病变患者及41例正常对照组外周血中Leptin含量。结果:乳腺癌组病人血中Leptin含量(21.97±9.13ng/ml)明显高于乳腺良性病变组(16.78±5.13ng/ml)及正常对照组(12.25±2.39ng/ml),差别有显著性(P<0.01)。随着乳腺癌病情的进展,从乳腺癌Ⅰ期至Ⅳ期,Leptin水平逐渐升高,有显著性差异(P<0.01)。乳腺癌淋巴有转移组Leptin水平(26.29±8.83ng/ml),明显高于乳腺癌无淋巴转移组(16.35±6ng/ml),差异有显著性(P<0.01)。结论:Leptin的检测可作为乳腺癌诊断的实验室指标,对乳腺癌的分期和预后的评价有重要价值,对治疗方案的选择有重要的指导意义。

Expression and functional study of cholecystokinin-A receptors on the interstitial Cajal-like cells of the guinea pig common bile duct

BACKGROUND Many studies have shown that interstitial Cajal-like cell(ICLC)abnormalities are closely related to a variety of dynamic gastrointestinal disorders.ICLCs are pacemaker cells for gastrointestinal movement and are involved in the transmission of nerve impulses.AIM To elucidate the expression profile and significance of cholecystokinin-A(CCK-A)receptors in ICLCs in the common bile duct(CBD),as well as the role of CCK in regulating CBD motility through CCK-A receptors on CBD ICLCs.METHODS The levels of tyrosine kinase receptor(c-kit)and CCK-A receptors in CBD tissues and isolated CBD cells were quantified using the double immunofluorescence labeling technique.The CCK-mediated enhancement of the movement of CBD muscle strips through CBD ICLCs was observed by a muscle strip contraction test.RESULTS Immunofluorescence showed co-expression of c-kit and CCK-A receptors in the CBD muscularis layer.Observations of isolated CBD cells showed that c-kit was expressed on the surface of ICLCs,the cell body and synapse were colored and polygonal,and some cells presented protrusions and formed networks adjacent to the CBD while others formed filaments at the synaptic terminals of local cells.CCK-A receptors were also expressed on CBD ICLCs.At concentrations ranging from 10^(-6) mol/L to 10^(-10) mol/L,CCK promoted CBD smooth muscle contractility in a dose-dependent manner.In contrast,after ICLC removal,the contractility mediated by CCK in CBD smooth muscle decreased.CONCLUSION CCK-A receptors are highly expressed on CBD ICLCs,and CCK may regulate CBD motility through the CCK-A receptors on ICLCs.

Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease

Chronic and recurrent inflammatory disorders of the gastrointestinal tract caused by a complex interplay between genetics and intestinal dysbiosis are called inflammatory bowel disease.As a result of the interaction between the liver and the gut microbiota,bile acids are an atypical class of steroids produced in mammals and traditionally known for their function in food absorption.With the development of genomics and metabolomics,more and more data suggest that the pathophysiological mechanisms of inflammatory bowel disease are regulated by bile acids and their receptors.Bile acids operate as signalling molecules by activating a variety of bile acid receptors that impact intestinal flora,epithelial barrier function,and intestinal immunology.Inflammatory bowel disease can be treated in new ways by using these potential molecules.This paper mainly discusses the increasing function of bile acids and their receptors in inflammatory bowel disease and their prospective therapeutic applications.In addition,we explore bile acid metabolism and the interaction of bile acids and the gut microbiota.