Growth hormone-releasing hormone(GHRH)is a hypothalamic releasing hormone that plays a crucial physiological role in regulating the synthesis and release of anterior pituitary hormones.In recent years,studies have fou...Growth hormone-releasing hormone(GHRH)is a hypothalamic releasing hormone that plays a crucial physiological role in regulating the synthesis and release of anterior pituitary hormones.In recent years,studies have found that GHRH possesses functions like antiinflammation,promoting cell proliferation,and facilitating cell migration.It participates in regulating the development of uveitis and diabetic retinopathy.Additionally,it also has an impact on the development of retinal ganglion cells by modulating the inflammatory response and mediating the immune response.Given the important roles of GHRH in ophthalmic diseases,elucidating the molecular regulation of the GHRH-GHRH receptor(GHRHR)signal and the innovative development of intervention pathways that directly or indirectly target GHRH serve as strong evidence of how basic research guides innovation and translation.In this review,research reports on GHRH in ophthalmic diseases including retinal diseases and uveitis were summarized and analyzed.展开更多
BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)...BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)and GH deficiency(GHD).Irrespective of the presence of GHD,NS is a Food and Drug Administration-approved indication for recombinant-GH therapy.Few case reports of combined anterior pituitary hormone deficiency(CPHD)in NS have been reported.AIM To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.METHODS An ambispective case-control study was conducted to compare the clinicohormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.RESULTS Five children with NS and CPHD were compared to 6 patients with NS but without CPHD.The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia(n=3,60%),followed by hypogonadotropic hypogonadism and secondary hypothyroidism(n=1 each).Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD.Patients with NS and CPHD had lower standard deviation scores of height(-4.18 vs-2.52,P=0.009),bodyweight,and body mass index but a slightly better first year response to recombinant GH(9.2 vs 5.5,P=0.06).There were no differences in dysmorphisms and other anomalies between the two groups.Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS.One patient with NS and CPHD developed hypocortisolism after GH initiation.CONCLUSION Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.展开更多
Background Ectopic adrenocorticotrophic hormone(ACTH)syndrome(EAS)is a rare but severe condition characterized by intense hypercortisolism,which can occur independently of the underlying tumor.Surgical resection of th...Background Ectopic adrenocorticotrophic hormone(ACTH)syndrome(EAS)is a rare but severe condition characterized by intense hypercortisolism,which can occur independently of the underlying tumor.Surgical resection of the primary lesion is curative in approximately 40%of patients with EAS,and up to 80%of these cases result in complete remission.Therefore,localizing the source of EAS is crucial.Methods We report an unusual case of a patient presenting with both EAS and syndrome of inappropriate antidiuretic hormone secretion,characterized by hypokalemia and hyponatremia,in the absence of classic manifestations of Cushing’s syndrome.Results Following the resection of an ACTH-negative staining tumor located in the right sellar nodule,the patient achieved complete remission.Conclusion The study findings indicate that physicians should pay more attention to electrolyte disturbances,as they are crucial for diagnosing occult EAS.展开更多
BACKGROUND Acute pancreatitis(AP)is a severe inflammatory condition of the pancreas that leads to significant morbidity and metabolic disturbances.Hypercalcemia,or elevated serum calcium levels,is a concerning complic...BACKGROUND Acute pancreatitis(AP)is a severe inflammatory condition of the pancreas that leads to significant morbidity and metabolic disturbances.Hypercalcemia,or elevated serum calcium levels,is a concerning complication that may contribute to kidney stone formation and exacerbate renal issues.Calcium homeostasis is regulated by hormones,such as parathyroid hormone(PTH),calcitonin,and vitamin D,which can be altered in AP.Understanding the interplay among hypercalcemia,kidney stones,and hormonal changes is crucial for improving management strategies and clinical outcomes in patients with AP.AIM To investigate the relationship between hypercalcemia and kidney stone formation in patients with AP,along with changes in calcium-regulating hormone levels.METHODS This study was conducted in 200 patients diagnosed with AP at Ningbo Urology and Nephrology Hospital.The participants underwent regular monitoring of serum calcium levels and kidney stone formation using imaging.Additionally,blood samples were analyzed to measure the levels of calcium-regulating hormones,including PTH,calcitonin,and vitamin D,at baseline and during the course of the disease.RESULTS Of the 185 patients who completed the study,31(16.8%)developed kidney stones during the 7-day follow-up period.Hypercalcemia occurred in 53 patients(28.6%),with a peak incidence on day 3.Among hypercalcemic patients,41.5%developed kidney stones compared to 6.8%in normocalcemic patients(odds ratio=9.67,95%confidence interval:4.12-22.68,P<0.001).A significant positive correlation was found between hypercalcemia and kidney stone formation(P<0.001).Elevated PTH levels were noted in 60%of the patients with hypercalcemia,indicating a strong association between increased PTH levels,hypercalcemia,and kidney stone formation.CONCLUSION This study highlights the complex interplay between AP,calcium metabolism,and renal complications,providing insights that may guide future therapeutic strategies.展开更多
BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyro...BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyroxine(T4),free T3(FT3),free T4(FT4),thyroid stimulating hormone(TSH)and schizophrenia.METHODS In this study,100 schizophrenia patients were selected from our hospital between April 2022 and April 2024.Their clinical data were analyzed retrospectively.Based on the Positive and Negative Syndrome Scale(PANSS)score,patients were divided into mild(1-3 points,n=39),moderate(4 points,n=45),and severe groups(5-7 points,n=16).Additionally,55 healthy individuals served as a control group.Venous blood samples were collected to measure T3,T4,FT3,FT4,TSH,and cortisol concentrations,analyzing their relationship with PANSS scores.RESULTS The serum levels of T3,FT3,FT4,TSH and cortisol in the schizophrenia group were lower than those in the control group(P<0.05).With the increase of the severity of the disease,the concentrations of T3 and T4 decreased,while the con-centrations of TSH and cortisol increased(P<0.05).The concentrations of TSH and cortisol were positively correlated with the PANSS score,while T3 and T4 were negatively correlated with the PANSS score(P<0.05).The receiver ope-rating characteristic curve results showed that T3,T4,TSH,and cortisol had good efficacy in the diagnosis of schizophrenia.Logistic results showed that decreased T3 level,decreased T4 level,decreased TSH level and increased cortisol level may be independent risk factors for schizophrenia.CONCLUSION Thyroid hormone levels are associated with the severity of schizophrenia symptoms,which can provide new solutions for the diagnosis and treatment of schizophrenia.展开更多
Growth hormone-secreting pituitary adenomas(GHPAs)cause acromegaly,a condition characterized by persistent excess of growth hormone(GH)and its target hormone,insulin-like growth factor 1(IGF-1).This hormonal imbalance...Growth hormone-secreting pituitary adenomas(GHPAs)cause acromegaly,a condition characterized by persistent excess of growth hormone(GH)and its target hormone,insulin-like growth factor 1(IGF-1).This hormonal imbalance gives rise to diverse comorbidities,ultimately resulting in a shortened lifespan compared to the general population(Piccard et al.,2012).Extensive research has demonstrated that tumors exert a pivotal promoting effects on inflammation,and conversely,inflammatory responses exert reciprocal influence on various biological processes of tumors(Fridlender et al.,2009;Piccard et al.,2012).The microbiome profoundly impacts brain function,behavior,and neuroendocrine responses to stress.Through the hypothalamic-pituitary-adrenal(HPA)axis,the neuroendocrine system modulates the composition and permeability of the gastrointestinal tract,indicating a bidirectional network between gut microbiome and neuroendocrine system(Farzi et al.,2018).In the present study,we explored the microbiome profile in patients with GH adenomas and its potential role in inflammation,utilizing Mendelian randomization(MR)to reveal the casual relationship between microbiome and inflammation markers.展开更多
Bud dormancy represents a critical adaptation mechanism in perennial fruit plants,enabling survival during unfavorable environmental conditions.While this adaptive strategy is essential for plant survival and reproduc...Bud dormancy represents a critical adaptation mechanism in perennial fruit plants,enabling survival during unfavorable environmental conditions.While this adaptive strategy is essential for plant survival and reproduction,its molecular mechanisms remain incompletely understood.This study investigated two grape transcription factors:EARLY BUD BREAK(VvEBB)and SHORT VEGETATIVE PHASE 4(VvSVP4).Through heterologous transformation in poplar,the research demonstrated that VvSVP4 functions as a negative regulator of bud break,while VvEBB serves as a positive regulator.Transcriptome analysis revealed significant enrichment of plant hormone signaling pathways particularly ABA,IAA,and CK in plants overexpressing VvSVP4(VvSVP4-OE)and VvEBB(VvEBB-OE)compared to controls.Endogenous hormone level changes correlated positively with transcriptome data.During endodormancy,VvSVP4 directly and positively regulated the ABA receptor gene Vv PYL9 expression,maintaining bud dormancy.Conversely,during ecodormancy,rapid upregulation of VvEBB negatively regulated the expression of sucrose nonfermenting 1-related protein kinase 2 gene(Vv SAPK2),facilitating dormancy release.This study provides comprehensive insights into how VvSVP4 and VvEBB genes regulate dormancy and bud break through cell cycle regulation and multiple hormone signaling pathways.展开更多
Background: Diabetes is a set of metabolic abnormalities typified by hyperglycemia believed to be associated with aberrant insulin secretion, insulin action, or both. Erectile dysfunction and infertility are globally ...Background: Diabetes is a set of metabolic abnormalities typified by hyperglycemia believed to be associated with aberrant insulin secretion, insulin action, or both. Erectile dysfunction and infertility are globally prevalent complications among male diabetic patients. There is a need to understand the role of a male reproductive hormone in the etiology of infertility in diabetic patients. Objective: This study aims to determine the effect of diabetes mellitus on the Male reproductive hormone (testosterone) on diabetic patients attending the Urology unit of Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria and the effect of industrial sugar consumption in rats model. Materials and Methods: 30 samples (including repeats, n = 3) were collected from known diabetic patients and 30 (including repeats, n = 3) control-non diabetic healthy individuals. Five millilitres (5 ml) of blood was collected from the antecubital vein of each participant and placed into a plain container for serum testosterone measurement using the enzyme-linked immunoassay technique. Blood was also collected from the same subjects in a fluoride oxalate container for plasma enzymatic glucose estimation using a Randox Glucose oxidase kit. For in vivo rat model, the albino rats were grouped into 2 of five (5) rats. The control group (1) was only given normal rat food and water while the test group (2) was treated with 0.4 g of industrial sugar/mL/body weight in addition to rat food and water via oral intubation for 21 days. Blood samples were collected via ocular puncture into plain tubes for testosterone measurement as described above. Results: There is a significant (p Conclusion: In conclusion, data available from this study suggests that increased plasma glucose levels and excessive industrial sugar consumption are associated with decreased testosterone levels in both human and animal models respectively. The mechanism is yet unclear but it could be that DM alters conventional sperm parameters, spermatogenesis, and biosynthesis of testosterone and induces degenerative changes in the testis and epididymis and ejaculatory dysfunction. These mechanisms need to be investigated.展开更多
Dear Editor,Sleep and memory are highly linked across species.Sleep gates and stabilizes memory,critical for memory processing.Insufficient sleep impairs cognition acutely/chronically,in vertebrates and invertebrates[...Dear Editor,Sleep and memory are highly linked across species.Sleep gates and stabilizes memory,critical for memory processing.Insufficient sleep impairs cognition acutely/chronically,in vertebrates and invertebrates[1,2].While key elements are characterized[3,4],how a single molecule integrates sleep and memory remains unknown.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and H...BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and HCC,although this relationship remains contentious.Complements and immunoglobulin(Ig),which serve as surrogates of cirrhosis-associated immune dysfunc-tion,are associated with the severity and outcomes of liver cirrhosis(LC).To date,there is a lack of evidence supporting the recommendation of TH,Ig,and com-plement tests in patients at high risk of HCC.AIM To assess the predictive value of TH,Ig,and complements for HCC development.METHODS Data from 142 patients,comprising 72 patients with CC and 70 patients with DC,were analysed as a training set.Among them,100 patients who underwent complement and Ig tests were considered for internal validation.Logistic regression was employed to identify independent risk factors for HCC development.RESULTS The median follow-up duration was 32(24-37 months)months.The incidence of HCC was significantly higher in the DC group(16/70,22.9%)compared to the CC group(3/72,4.2%)(χ^(2)=10.698,P<0.01).Patients with DC exhibited lower total tetraiodothyronine(TT4),total triiodothyronine(TT3),free triiodothyronine,complement C3,and C4(all P<0.01),and higher IgA and IgG(both P<0.01).In both CC and DC patients,TT3 and TT4 positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),and gamma-glutamyl transpeptidase(GGT).IgG positively correlated with IgM,IgA,ALT,and AST,while it negatively correlated with C3 and C4.Multivariable analysis indicated that age,DC status,and GGT were independent risk factors for HCC development.CONCLUSION The predictive value of TH,Ig,and complements for HCC development is suboptimal.Age,DC,and GGT emerge as more significant factors during HCC surveillance in hepatitis B virus-related LC.展开更多
To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testic...To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testicular volumes(TVs)who underwent microdissection testicular sperm extraction(micro-TESE).A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital(formerly Shenzhen Zhongshan Urology Hospital,Shenzhen,China)were retrospectively reviewed.The subjects were divided into four groups based on average TV quartiles.Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups.Overall sperm retrieval rate was 57.6%.FSH levels(median[interquartile range])were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was<5 ml(first quartile[Q1:TV<3 ml]:43.32[17.92]IU l^(−1) vs 32.95[18.56]IU l−1,P=0.048;second quartile[Q2:3 ml≤TV<5 ml]:31.31[15.37]IU l^(−1) vs 25.59[18.40]IU l^(−1),P=0.042).Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were<5 ml(adjusted odds ratio[OR]:1.06 per unit increase;95%confidence interval[CI]:1.01–1.11;P=0.011).In men with TVs≥5 ml,larger TVs were associated with lower odds of sperm retrieval(adjusted OR:0.84 per 1 ml increase;95%CI:0.71–0.98;P=0.029).In conclusion,elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs<5 ml.In men with TV≥5 ml,increases in average TVs were associated with lower odds of sperm retrieval.展开更多
Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The d...Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers.展开更多
Feeding behavior is regulated by a complex network of endogenous neuropeptides.In chordates,this role is suggested to be under the control of diverse factors including thyrotropin-releasing hormone(TRH).However,whethe...Feeding behavior is regulated by a complex network of endogenous neuropeptides.In chordates,this role is suggested to be under the control of diverse factors including thyrotropin-releasing hormone(TRH).However,whether this regulatory activity of TRH is functionally conserved in non-chordate metazoans,and to what extent this process is underpinned by interactions of TRH with other neuropeptides such as cholecystokinin(CCK,known as a satiety signal),remain unclear.This study investigated the TRH signaling system in the echinoderm Apostichopus japonicus.Bioinformatic analyses and ligand-binding assays identified a functional TRH receptor(AjTRHR)that activated signaling via the MAPK/ERK1/2pathways.Experimental administration of TRH significantly reduced feeding activity,while up-regulating CCK expression.RNA interference(RNAi)experiments confirmed that both CCK and TRH are essential components of satiety signaling,working synergistically to mediate feeding inhibition.Evolutionary analysis of TRHtype peptides revealed greater conservation of the short isoform of TRH compared to the long isoform,probably driven by strong selection acting on the functional redundancy.These findings provide compelling evidence of a TRH-mediated signaling system in non-chordate deuterostomes,expandingourunderstandingof neuropeptide-regulated feeding mechanisms in marine invertebrates.展开更多
Dear Editor,Varicocele(VC)is a vascular condition characterized by abnormal tortuosity and dilation of the pampiniform plexus veins within the spermatic cord.VC is commonly observed in young adults,predominantly on th...Dear Editor,Varicocele(VC)is a vascular condition characterized by abnormal tortuosity and dilation of the pampiniform plexus veins within the spermatic cord.VC is commonly observed in young adults,predominantly on the left side;it is a frequent cause of male infertility and can lead to testicular hypofunction,pain,and discomfort.Microsurgical varicocelectomy is the gold standard for treating infertility caused by VC.VC repair is strongly recommended for couple infertility,oligoasthenoteratozoospermia(OAT),Grade 2 or 3 clinical VC,partner age<37 years,patient age<40 years,or testicular hypotrophy in children and adolescents.展开更多
Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction d...Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.展开更多
Recombinant human growth hormone(rhGH)has been widely used for the treatment of disorders associated with GH deficiency and multiple clinical indications[1].Accurate determination of biological activity is essential i...Recombinant human growth hormone(rhGH)has been widely used for the treatment of disorders associated with GH deficiency and multiple clinical indications[1].Accurate determination of biological activity is essential in the development,registration,and quality control of rhGH pharmaceutical products[2].However,the existing in vivo bioassay procedure based on somatropin-induced weight gain in rats is complicated,and the use of a rat cell line-based approach(Nb2-11 bioassay),which measures the production of adenosine triphosphate(ATP)as a direct indicator of cell growth,has a low mechanism of action(MOA)relevance.Therefore,novel rhGH bioassays are still needed.To this end,we developed a reporter gene assay(RGA)based on the GH/insulin-like growth factor-1(IGF-1)axis.展开更多
Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis.Granulosa cells(GCs)mediate these processes by secreting estradiol(E_(2...Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis.Granulosa cells(GCs)mediate these processes by secreting estradiol(E_(2))and progesterone(P_(4)),which are essential for follicular maturation and ovulatory competence.While circular RNAs(circRNAs)have been implicated in steroid hormone synthesis,their involvement in the regulation of gilt estrous remains unclear.In this study,circRNA sequencing was performed on ovarian tissues of estrus(ES)and non-estrus(NES)gilts,resulting in the identification of a novel circRNA,termed circular SHOC2 leucine rich repeat scaffold protein(circSHOC2),which exhibited marked up-regulation in ES ovaries.Functional assays demonstrated that circSHOC2 overexpression enhanced E_(2)and P_(4)synthesis and increased the protein levels of key steroidogenic enzymes.Mechanistic investigation revealed that circSHOC2 sponges miR-130b-5p.Silencing miR-130b-5p significantly enhanced E_(2)and P_(4)production,along with the up-regulation of steroidogenic proteins.Additionally,miR-130b-5p targeted ASH1-like histone lysine methyltransferase(ASH1L),while its overexpression significantly inhibited ASH1L.Cotransfection experiments revealed that ASH1L mitigated the inhibitory effects of miR-130b-5p on E_(2)and P_(4)synthesis in GCs.These findings establish a regulatory axis in which circSHOC2 modulates steroidogenic capacity in porcine GCs via the miR-130b-5p/ASH1L pathway,offering mechanistic insight into the molecular basis of gilt estrus and providing potential targets to enhance reproductive efficiency.展开更多
Prostate cancer is the most prevalent malignant tumor among men,ranking first in incidence and second in mortality globally.Novel hormone therapies(NHT)targeting the androgen receptor(AR)pathway have become the standa...Prostate cancer is the most prevalent malignant tumor among men,ranking first in incidence and second in mortality globally.Novel hormone therapies(NHT)targeting the androgen receptor(AR)pathway have become the standard of care for metastatic prostate cancer.This review offers a comprehensive overview of NHT,including abiraterone,enzalutamide,apalutamide,darolutamide,and rezvilutamide,which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life.Nevertheless,resistance to NHT remains a critical challenge.The mechanisms underlying resistance are complex,involving AR gene amplification,mutations,splice variants,increased intratumoral androgens,and AR-independent pathways such as the glucocorticoid receptor,neuroendocrine differentiation,DNA repair defects,autophagy,immune evasion,and activation of alternative signaling pathways.This review discusses these resistance mechanisms and examines strategies to counteract them,including sequential treatment with novel AR-targeted drugs,chemotherapy,poly ADP-ribose polymerase inhibitors,radionuclide therapy,bipolar androgen therapy,and approaches targeting specific resistance pathways.Future research should prioritize elucidating the molecular basis of NHT resistance,optimizing existing therapeutic strategies,and developing more effective combination regimens.Additionally,advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies.These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.展开更多
BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have...BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.展开更多
Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regula...Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regulate gene transcription via nuclear receptors TRα/β,modulating proliferation,apoptosis,and AR signaling,while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K-Akt signaling,driving metabolic reprogramming,migration,and angiogenesis.Local DIO enzymes fine-tune T3/T4 levels,with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion.Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk,whereas experimental models show inconsistent effects,reflecting regulation by hormone levels,receptor distribution,and tumor molecular features.Bibliometric analyses reveal a shift from epidemiological studies to molecular,immune,and metabolic mechanistic research,though clinical translation remains limited.This review synthesizes current knowledge on THs in PCa,highlighting mechanistic insights,evidence gaps,and future directions,aiming to inform early detection,stratification,and therapeutic strategies.展开更多
基金Supported by Central Government Guidance Funds for Local Science and Technology Development 2024(No.STKJ2024074).
文摘Growth hormone-releasing hormone(GHRH)is a hypothalamic releasing hormone that plays a crucial physiological role in regulating the synthesis and release of anterior pituitary hormones.In recent years,studies have found that GHRH possesses functions like antiinflammation,promoting cell proliferation,and facilitating cell migration.It participates in regulating the development of uveitis and diabetic retinopathy.Additionally,it also has an impact on the development of retinal ganglion cells by modulating the inflammatory response and mediating the immune response.Given the important roles of GHRH in ophthalmic diseases,elucidating the molecular regulation of the GHRH-GHRH receptor(GHRHR)signal and the innovative development of intervention pathways that directly or indirectly target GHRH serve as strong evidence of how basic research guides innovation and translation.In this review,research reports on GHRH in ophthalmic diseases including retinal diseases and uveitis were summarized and analyzed.
文摘BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)and GH deficiency(GHD).Irrespective of the presence of GHD,NS is a Food and Drug Administration-approved indication for recombinant-GH therapy.Few case reports of combined anterior pituitary hormone deficiency(CPHD)in NS have been reported.AIM To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.METHODS An ambispective case-control study was conducted to compare the clinicohormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.RESULTS Five children with NS and CPHD were compared to 6 patients with NS but without CPHD.The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia(n=3,60%),followed by hypogonadotropic hypogonadism and secondary hypothyroidism(n=1 each).Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD.Patients with NS and CPHD had lower standard deviation scores of height(-4.18 vs-2.52,P=0.009),bodyweight,and body mass index but a slightly better first year response to recombinant GH(9.2 vs 5.5,P=0.06).There were no differences in dysmorphisms and other anomalies between the two groups.Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS.One patient with NS and CPHD developed hypocortisolism after GH initiation.CONCLUSION Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.
文摘Background Ectopic adrenocorticotrophic hormone(ACTH)syndrome(EAS)is a rare but severe condition characterized by intense hypercortisolism,which can occur independently of the underlying tumor.Surgical resection of the primary lesion is curative in approximately 40%of patients with EAS,and up to 80%of these cases result in complete remission.Therefore,localizing the source of EAS is crucial.Methods We report an unusual case of a patient presenting with both EAS and syndrome of inappropriate antidiuretic hormone secretion,characterized by hypokalemia and hyponatremia,in the absence of classic manifestations of Cushing’s syndrome.Results Following the resection of an ACTH-negative staining tumor located in the right sellar nodule,the patient achieved complete remission.Conclusion The study findings indicate that physicians should pay more attention to electrolyte disturbances,as they are crucial for diagnosing occult EAS.
基金Supported by Zhejiang Province Medical and Health Science and Technology Program Project,No.2021KY1067.
文摘BACKGROUND Acute pancreatitis(AP)is a severe inflammatory condition of the pancreas that leads to significant morbidity and metabolic disturbances.Hypercalcemia,or elevated serum calcium levels,is a concerning complication that may contribute to kidney stone formation and exacerbate renal issues.Calcium homeostasis is regulated by hormones,such as parathyroid hormone(PTH),calcitonin,and vitamin D,which can be altered in AP.Understanding the interplay among hypercalcemia,kidney stones,and hormonal changes is crucial for improving management strategies and clinical outcomes in patients with AP.AIM To investigate the relationship between hypercalcemia and kidney stone formation in patients with AP,along with changes in calcium-regulating hormone levels.METHODS This study was conducted in 200 patients diagnosed with AP at Ningbo Urology and Nephrology Hospital.The participants underwent regular monitoring of serum calcium levels and kidney stone formation using imaging.Additionally,blood samples were analyzed to measure the levels of calcium-regulating hormones,including PTH,calcitonin,and vitamin D,at baseline and during the course of the disease.RESULTS Of the 185 patients who completed the study,31(16.8%)developed kidney stones during the 7-day follow-up period.Hypercalcemia occurred in 53 patients(28.6%),with a peak incidence on day 3.Among hypercalcemic patients,41.5%developed kidney stones compared to 6.8%in normocalcemic patients(odds ratio=9.67,95%confidence interval:4.12-22.68,P<0.001).A significant positive correlation was found between hypercalcemia and kidney stone formation(P<0.001).Elevated PTH levels were noted in 60%of the patients with hypercalcemia,indicating a strong association between increased PTH levels,hypercalcemia,and kidney stone formation.CONCLUSION This study highlights the complex interplay between AP,calcium metabolism,and renal complications,providing insights that may guide future therapeutic strategies.
文摘BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyroxine(T4),free T3(FT3),free T4(FT4),thyroid stimulating hormone(TSH)and schizophrenia.METHODS In this study,100 schizophrenia patients were selected from our hospital between April 2022 and April 2024.Their clinical data were analyzed retrospectively.Based on the Positive and Negative Syndrome Scale(PANSS)score,patients were divided into mild(1-3 points,n=39),moderate(4 points,n=45),and severe groups(5-7 points,n=16).Additionally,55 healthy individuals served as a control group.Venous blood samples were collected to measure T3,T4,FT3,FT4,TSH,and cortisol concentrations,analyzing their relationship with PANSS scores.RESULTS The serum levels of T3,FT3,FT4,TSH and cortisol in the schizophrenia group were lower than those in the control group(P<0.05).With the increase of the severity of the disease,the concentrations of T3 and T4 decreased,while the con-centrations of TSH and cortisol increased(P<0.05).The concentrations of TSH and cortisol were positively correlated with the PANSS score,while T3 and T4 were negatively correlated with the PANSS score(P<0.05).The receiver ope-rating characteristic curve results showed that T3,T4,TSH,and cortisol had good efficacy in the diagnosis of schizophrenia.Logistic results showed that decreased T3 level,decreased T4 level,decreased TSH level and increased cortisol level may be independent risk factors for schizophrenia.CONCLUSION Thyroid hormone levels are associated with the severity of schizophrenia symptoms,which can provide new solutions for the diagnosis and treatment of schizophrenia.
基金supported by the National Natural Science Foundation of China(82372624 to X.J.)Guangdong Basic and Applied Basic Research Foundation(2024A1515013102 and 2022A1515012430 to X.J.)The funders had no role in study design,data collection and interpretation,or the decision to submit the work for publication.
文摘Growth hormone-secreting pituitary adenomas(GHPAs)cause acromegaly,a condition characterized by persistent excess of growth hormone(GH)and its target hormone,insulin-like growth factor 1(IGF-1).This hormonal imbalance gives rise to diverse comorbidities,ultimately resulting in a shortened lifespan compared to the general population(Piccard et al.,2012).Extensive research has demonstrated that tumors exert a pivotal promoting effects on inflammation,and conversely,inflammatory responses exert reciprocal influence on various biological processes of tumors(Fridlender et al.,2009;Piccard et al.,2012).The microbiome profoundly impacts brain function,behavior,and neuroendocrine responses to stress.Through the hypothalamic-pituitary-adrenal(HPA)axis,the neuroendocrine system modulates the composition and permeability of the gastrointestinal tract,indicating a bidirectional network between gut microbiome and neuroendocrine system(Farzi et al.,2018).In the present study,we explored the microbiome profile in patients with GH adenomas and its potential role in inflammation,utilizing Mendelian randomization(MR)to reveal the casual relationship between microbiome and inflammation markers.
基金supported by the China Agriculture Research System of MOF and MARA(CARS-29)the Xinjiang Uygur Autonomous Region Tianchi Talent Introduction Program,Chinathe Key R&D Technology Commissioner Projects in Hainan Province,China(ZDYF2024KJTPY008)。
文摘Bud dormancy represents a critical adaptation mechanism in perennial fruit plants,enabling survival during unfavorable environmental conditions.While this adaptive strategy is essential for plant survival and reproduction,its molecular mechanisms remain incompletely understood.This study investigated two grape transcription factors:EARLY BUD BREAK(VvEBB)and SHORT VEGETATIVE PHASE 4(VvSVP4).Through heterologous transformation in poplar,the research demonstrated that VvSVP4 functions as a negative regulator of bud break,while VvEBB serves as a positive regulator.Transcriptome analysis revealed significant enrichment of plant hormone signaling pathways particularly ABA,IAA,and CK in plants overexpressing VvSVP4(VvSVP4-OE)and VvEBB(VvEBB-OE)compared to controls.Endogenous hormone level changes correlated positively with transcriptome data.During endodormancy,VvSVP4 directly and positively regulated the ABA receptor gene Vv PYL9 expression,maintaining bud dormancy.Conversely,during ecodormancy,rapid upregulation of VvEBB negatively regulated the expression of sucrose nonfermenting 1-related protein kinase 2 gene(Vv SAPK2),facilitating dormancy release.This study provides comprehensive insights into how VvSVP4 and VvEBB genes regulate dormancy and bud break through cell cycle regulation and multiple hormone signaling pathways.
文摘Background: Diabetes is a set of metabolic abnormalities typified by hyperglycemia believed to be associated with aberrant insulin secretion, insulin action, or both. Erectile dysfunction and infertility are globally prevalent complications among male diabetic patients. There is a need to understand the role of a male reproductive hormone in the etiology of infertility in diabetic patients. Objective: This study aims to determine the effect of diabetes mellitus on the Male reproductive hormone (testosterone) on diabetic patients attending the Urology unit of Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria and the effect of industrial sugar consumption in rats model. Materials and Methods: 30 samples (including repeats, n = 3) were collected from known diabetic patients and 30 (including repeats, n = 3) control-non diabetic healthy individuals. Five millilitres (5 ml) of blood was collected from the antecubital vein of each participant and placed into a plain container for serum testosterone measurement using the enzyme-linked immunoassay technique. Blood was also collected from the same subjects in a fluoride oxalate container for plasma enzymatic glucose estimation using a Randox Glucose oxidase kit. For in vivo rat model, the albino rats were grouped into 2 of five (5) rats. The control group (1) was only given normal rat food and water while the test group (2) was treated with 0.4 g of industrial sugar/mL/body weight in addition to rat food and water via oral intubation for 21 days. Blood samples were collected via ocular puncture into plain tubes for testosterone measurement as described above. Results: There is a significant (p Conclusion: In conclusion, data available from this study suggests that increased plasma glucose levels and excessive industrial sugar consumption are associated with decreased testosterone levels in both human and animal models respectively. The mechanism is yet unclear but it could be that DM alters conventional sperm parameters, spermatogenesis, and biosynthesis of testosterone and induces degenerative changes in the testis and epididymis and ejaculatory dysfunction. These mechanisms need to be investigated.
基金supported by the National Natural Science Foundation of China(32371063,82341248,and 32071009)Guangdong Basic and Applied Basic Research Foundation(2024A1515011500)the Shenzhen Science and Technology Program(ZDSYS20200811142401005).
文摘Dear Editor,Sleep and memory are highly linked across species.Sleep gates and stabilizes memory,critical for memory processing.Insufficient sleep impairs cognition acutely/chronically,in vertebrates and invertebrates[1,2].While key elements are characterized[3,4],how a single molecule integrates sleep and memory remains unknown.
基金Supported by The Research Foundation of Jiangsu Province Administration of Traditional Chinese Medicine,No.MS2023088The Science and Technology Project of Changzhou,No.CE20225040+1 种基金The Research Foundation of Nanjing Medical University Changzhou Medical Center,No.CMCC202311Leading Talent of Changzhou“The 14th Five-Year Plan”High-Level Health Talents Training Project,No.2022CZLJ021.
文摘BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and HCC,although this relationship remains contentious.Complements and immunoglobulin(Ig),which serve as surrogates of cirrhosis-associated immune dysfunc-tion,are associated with the severity and outcomes of liver cirrhosis(LC).To date,there is a lack of evidence supporting the recommendation of TH,Ig,and com-plement tests in patients at high risk of HCC.AIM To assess the predictive value of TH,Ig,and complements for HCC development.METHODS Data from 142 patients,comprising 72 patients with CC and 70 patients with DC,were analysed as a training set.Among them,100 patients who underwent complement and Ig tests were considered for internal validation.Logistic regression was employed to identify independent risk factors for HCC development.RESULTS The median follow-up duration was 32(24-37 months)months.The incidence of HCC was significantly higher in the DC group(16/70,22.9%)compared to the CC group(3/72,4.2%)(χ^(2)=10.698,P<0.01).Patients with DC exhibited lower total tetraiodothyronine(TT4),total triiodothyronine(TT3),free triiodothyronine,complement C3,and C4(all P<0.01),and higher IgA and IgG(both P<0.01).In both CC and DC patients,TT3 and TT4 positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),and gamma-glutamyl transpeptidase(GGT).IgG positively correlated with IgM,IgA,ALT,and AST,while it negatively correlated with C3 and C4.Multivariable analysis indicated that age,DC status,and GGT were independent risk factors for HCC development.CONCLUSION The predictive value of TH,Ig,and complements for HCC development is suboptimal.Age,DC,and GGT emerge as more significant factors during HCC surveillance in hepatitis B virus-related LC.
基金supported by the Shenzhen Fundamental Research Program(No.JCYJ20210324121807021).
文摘To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testicular volumes(TVs)who underwent microdissection testicular sperm extraction(micro-TESE).A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital(formerly Shenzhen Zhongshan Urology Hospital,Shenzhen,China)were retrospectively reviewed.The subjects were divided into four groups based on average TV quartiles.Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups.Overall sperm retrieval rate was 57.6%.FSH levels(median[interquartile range])were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was<5 ml(first quartile[Q1:TV<3 ml]:43.32[17.92]IU l^(−1) vs 32.95[18.56]IU l−1,P=0.048;second quartile[Q2:3 ml≤TV<5 ml]:31.31[15.37]IU l^(−1) vs 25.59[18.40]IU l^(−1),P=0.042).Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were<5 ml(adjusted odds ratio[OR]:1.06 per unit increase;95%confidence interval[CI]:1.01–1.11;P=0.011).In men with TVs≥5 ml,larger TVs were associated with lower odds of sperm retrieval(adjusted OR:0.84 per 1 ml increase;95%CI:0.71–0.98;P=0.029).In conclusion,elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs<5 ml.In men with TV≥5 ml,increases in average TVs were associated with lower odds of sperm retrieval.
基金supported in part by the National Natural Science Foundation of China(Nos.32270555 and 32072954).
文摘Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers.
基金supported by the National Natural Science Foundation of China (42276103)。
文摘Feeding behavior is regulated by a complex network of endogenous neuropeptides.In chordates,this role is suggested to be under the control of diverse factors including thyrotropin-releasing hormone(TRH).However,whether this regulatory activity of TRH is functionally conserved in non-chordate metazoans,and to what extent this process is underpinned by interactions of TRH with other neuropeptides such as cholecystokinin(CCK,known as a satiety signal),remain unclear.This study investigated the TRH signaling system in the echinoderm Apostichopus japonicus.Bioinformatic analyses and ligand-binding assays identified a functional TRH receptor(AjTRHR)that activated signaling via the MAPK/ERK1/2pathways.Experimental administration of TRH significantly reduced feeding activity,while up-regulating CCK expression.RNA interference(RNAi)experiments confirmed that both CCK and TRH are essential components of satiety signaling,working synergistically to mediate feeding inhibition.Evolutionary analysis of TRHtype peptides revealed greater conservation of the short isoform of TRH compared to the long isoform,probably driven by strong selection acting on the functional redundancy.These findings provide compelling evidence of a TRH-mediated signaling system in non-chordate deuterostomes,expandingourunderstandingof neuropeptide-regulated feeding mechanisms in marine invertebrates.
文摘Dear Editor,Varicocele(VC)is a vascular condition characterized by abnormal tortuosity and dilation of the pampiniform plexus veins within the spermatic cord.VC is commonly observed in young adults,predominantly on the left side;it is a frequent cause of male infertility and can lead to testicular hypofunction,pain,and discomfort.Microsurgical varicocelectomy is the gold standard for treating infertility caused by VC.VC repair is strongly recommended for couple infertility,oligoasthenoteratozoospermia(OAT),Grade 2 or 3 clinical VC,partner age<37 years,patient age<40 years,or testicular hypotrophy in children and adolescents.
基金supported by the National Natural Science Foundation of China(81673680)the Fundamental Research Funds for the Central Public Welfare Research Institutes(YZX-202306).
文摘Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.
基金supported by the first batch of grants from the State Key Laboratory of Drug Regulatory Science,China(Grant No.:2023SKLDRS0108).
文摘Recombinant human growth hormone(rhGH)has been widely used for the treatment of disorders associated with GH deficiency and multiple clinical indications[1].Accurate determination of biological activity is essential in the development,registration,and quality control of rhGH pharmaceutical products[2].However,the existing in vivo bioassay procedure based on somatropin-induced weight gain in rats is complicated,and the use of a rat cell line-based approach(Nb2-11 bioassay),which measures the production of adenosine triphosphate(ATP)as a direct indicator of cell growth,has a low mechanism of action(MOA)relevance.Therefore,novel rhGH bioassays are still needed.To this end,we developed a reporter gene assay(RGA)based on the GH/insulin-like growth factor-1(IGF-1)axis.
基金supported by the National Key Research and Development Program of China(2022YFD1300303,2021YFF1000602)National Natural Science Foundation of China(32472878)China Agriculture Research System(CARS-35-PIG)。
文摘Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis.Granulosa cells(GCs)mediate these processes by secreting estradiol(E_(2))and progesterone(P_(4)),which are essential for follicular maturation and ovulatory competence.While circular RNAs(circRNAs)have been implicated in steroid hormone synthesis,their involvement in the regulation of gilt estrous remains unclear.In this study,circRNA sequencing was performed on ovarian tissues of estrus(ES)and non-estrus(NES)gilts,resulting in the identification of a novel circRNA,termed circular SHOC2 leucine rich repeat scaffold protein(circSHOC2),which exhibited marked up-regulation in ES ovaries.Functional assays demonstrated that circSHOC2 overexpression enhanced E_(2)and P_(4)synthesis and increased the protein levels of key steroidogenic enzymes.Mechanistic investigation revealed that circSHOC2 sponges miR-130b-5p.Silencing miR-130b-5p significantly enhanced E_(2)and P_(4)production,along with the up-regulation of steroidogenic proteins.Additionally,miR-130b-5p targeted ASH1-like histone lysine methyltransferase(ASH1L),while its overexpression significantly inhibited ASH1L.Cotransfection experiments revealed that ASH1L mitigated the inhibitory effects of miR-130b-5p on E_(2)and P_(4)synthesis in GCs.These findings establish a regulatory axis in which circSHOC2 modulates steroidogenic capacity in porcine GCs via the miR-130b-5p/ASH1L pathway,offering mechanistic insight into the molecular basis of gilt estrus and providing potential targets to enhance reproductive efficiency.
文摘Prostate cancer is the most prevalent malignant tumor among men,ranking first in incidence and second in mortality globally.Novel hormone therapies(NHT)targeting the androgen receptor(AR)pathway have become the standard of care for metastatic prostate cancer.This review offers a comprehensive overview of NHT,including abiraterone,enzalutamide,apalutamide,darolutamide,and rezvilutamide,which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life.Nevertheless,resistance to NHT remains a critical challenge.The mechanisms underlying resistance are complex,involving AR gene amplification,mutations,splice variants,increased intratumoral androgens,and AR-independent pathways such as the glucocorticoid receptor,neuroendocrine differentiation,DNA repair defects,autophagy,immune evasion,and activation of alternative signaling pathways.This review discusses these resistance mechanisms and examines strategies to counteract them,including sequential treatment with novel AR-targeted drugs,chemotherapy,poly ADP-ribose polymerase inhibitors,radionuclide therapy,bipolar androgen therapy,and approaches targeting specific resistance pathways.Future research should prioritize elucidating the molecular basis of NHT resistance,optimizing existing therapeutic strategies,and developing more effective combination regimens.Additionally,advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies.These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.
基金National Natural Science Foundation of China,No.82270881 and No.82200928National High-Level Hospital Clinical Research Funding,No.BJ-2023-124 and No.BJ-2023-130.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.
基金Guangzhou Medical and Health Science and Technology Project(Project No.:20231A011103)General projects of Guangzhou municipal Science and Technology Bureau(Project No.:2023A04J0598)Guangdong Basic and Applied Basic Research Foundation(Project No.:2022A1515111122)。
文摘Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regulate gene transcription via nuclear receptors TRα/β,modulating proliferation,apoptosis,and AR signaling,while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K-Akt signaling,driving metabolic reprogramming,migration,and angiogenesis.Local DIO enzymes fine-tune T3/T4 levels,with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion.Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk,whereas experimental models show inconsistent effects,reflecting regulation by hormone levels,receptor distribution,and tumor molecular features.Bibliometric analyses reveal a shift from epidemiological studies to molecular,immune,and metabolic mechanistic research,though clinical translation remains limited.This review synthesizes current knowledge on THs in PCa,highlighting mechanistic insights,evidence gaps,and future directions,aiming to inform early detection,stratification,and therapeutic strategies.
