17α-Ethynylestradiol（EE2） in natural waters may cause adverse effects on organisms due to its high estrogenic potency. Laboratory studies were performed to study the effects of a local humic acid（LHA）, fulvic aci...17α-Ethynylestradiol（EE2） in natural waters may cause adverse effects on organisms due to its high estrogenic potency. Laboratory studies were performed to study the effects of a local humic acid（LHA）, fulvic acid（LFA） and Aldrich humic acid（AHA） on the photochemical behavior and estrogenic potency of EE2. Here photolytic experiments demonstrated that pure aqueous EE2 could undergo direct and self-sensitized photodegradation at a global rate of 0.0068 hr^-1.Photodegradation rate of EE2 in 5.0 mg/L dissolved humic substances（DHS） was determined to be 0.0274, 0.0296 and 0.0254 hr^-1 for LHA, LFA and AHA, respectively. Reactive oxygen species（ROS） and triplet dissolved humic substances（^3DHS＊） scavenging experiments indicated that the promotion effect of DHS on EE2 photodegradation was mainly aroused by the reactions of HOU（35%–50%）,~1O2（〈10%） andDHS＊（22%–34%）. However, the photodegradation of EE2 could also be inhibited when DHS exceeded the threshold of 10 mg/L. Three hydroxylation products of EE2 were identified using GC–MS and their formation pathways were also proposed. In vitro estrogenicity tests showed that EE2 was transformed into chemicals without estrogenic potency. These findings could extend our knowledge on the photochemical behaviors of steroid estrogens in sunlit natural waters.展开更多
Permanganate was used as an oxidant to control estrone in the present study. Kinetics was determined at pH 2.5-9.4 and temperature 15–40°C for the reaction of estrone with potassium permanganate. It was found th...Permanganate was used as an oxidant to control estrone in the present study. Kinetics was determined at pH 2.5-9.4 and temperature 15–40°C for the reaction of estrone with potassium permanganate. It was found that the reaction is second-order overall and first-order with respect to both estrone and permanganate. The second-order rate constant for the reaction at pH 5.8 and 25°C is 44.45 L mol-1 s-1. The reaction rate first decreased with the increase of pH in the range of 2.5-6.6 and then increased greatly with the increase of pH in the range of 6.6-9.4. In addition, the rate constant exponentially increased with the increase of reaction temperature. Removal of estrogenicity was also investigated during the degradation of estrone using yeast estrogen screen (YES). Results show that the estrogenicity increased in the initial 15 min of reaction and then decreased fast, with a removal rate of 73.8% within the 30 min of reaction. Results also demonstrate that the reaction rate between estrone and permanganate is faster in natural water background than in the ultra-pure water system. Permanganate oxidation is therefore a feasible option for removal of estrone in drinking water treatment processes. However, the contact time must be enough in order to remove estrone without causing the increase of estrogenicity.展开更多
The uterotrophic assay has been commonly used to test environmental estrogens in vivo, however, it is often not sensitive enough sometimes. An alternative way is to evaluate estrogenicity through biomarker genes. Micr...The uterotrophic assay has been commonly used to test environmental estrogens in vivo, however, it is often not sensitive enough sometimes. An alternative way is to evaluate estrogenicity through biomarker genes. MicroRNA （miRNA） is a class of regulatory gene, which has been shown to be a good biomarker for many diseases and toxicological effects in recent years, and some evidences showed that estrogen induced response was partially mediated by miRNAs. In this study, two types of microarrays were used to test the 17[3-estradiol （E2） induced miRNA expression profile at different time points in the immature mouse uterus. Statistical analysis showed the aldehyde slide based array had less variation than the amino slide based array, and 11 dysregulated miRNAs were screened out for significant fold change. Real-time PCR was performed to further confirm that 4 out of 7 selected miRNAs, namely miR-451, miR-155, miR-335- 5p, and miR-365, are E2 regulated miRNAs in the uterus. The function of the predicted targets of these miRNAs is involved in cell grow control, which is consistent with the main E2 function in the uterus. MiR-451 had similar strong responses to E2 in the uterus of both immature and overiectomized mice, and could be a potential biomarker for estrogenicity in the uterus.展开更多
Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be f...Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis.To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments.We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages(BMMs)at various concentrations.TRAc P experiments were conducted to examine BQTL's impact on osteoclast differentiation.RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation.Finally,in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings.This study revealed that BQTL suppressed receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity.The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity,primarily through attenuation of the MAPK,NF-κB,and Calcineurin signaling pathways.BQTL's inhibitory capacity was further examined in vivo using an ovariectomized(OVX)rat model,demonstrating a strong protective effect against bone loss.BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.展开更多
Objective Selective estrogen receptor modulators(SERMs)have demonstrated efficacy in the treatment of hypogonadism in males and male factor infertility.Two SERMs,clomiphene citrate and tamoxifen,are now prescribed for...Objective Selective estrogen receptor modulators(SERMs)have demonstrated efficacy in the treatment of hypogonadism in males and male factor infertility.Two SERMs,clomiphene citrate and tamoxifen,are now prescribed for off-label use to treat both conditions in males.However,existing literature compares mixed protocols with active management.We aimed to conduct a meta-analysis to evaluate the effect of clomiphene and tamoxifen versus placebo on natural pregnancy rates.Methods We conducted a comprehensive systematic review of electronic databases:MEDLINE,PubMed/PMC,EMBASE,CINAHL,Cochrane Central Register of Controlled Trials(CENTRAL),Scopus,Google Scholar,and Web of Science.Articles satisfying all selection criteria were analyzed.The primary outcome was the incidence of pregnancy after receiving the treatment.Secondary outcomes included serum follicle-stimulating hormone,luteinizing hormone,and testosterone levels,and sperm count and motility.We calculated the pooled odds ratio,risk ratio,and risk difference to ascertain possible alterations in the direction of the pooled effect size.Results Ten randomized controlled trials were ultimately included and underwent data extraction.Clomiphene citrate and placebo groups had similar pregnancy rates(10.4%and 7.1%,respectively;odds ratio 1.30[95%confidence interval 0.27–6.17];p=0.74).No meta-analysis could be calculated for pregnancy rates in tamoxifen versus placebo groups.Heterogeneity among the studies of both SERMs ranged from low to high.Conclusion Although clomiphene citrate and tamoxifen are often used off-label for the treatment of male infertility secondary to hypogonadism,studies of SERMs in the treatment of idiopathic male factor infertility are limited and heterogenous,preventing this meta-analysis from investigating the efficacy of SERMs on male infertility.The effect of clomiphene citrate or tamoxifen on the pregnancy rate remains uncertain.展开更多
In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epice...In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.展开更多
4-Nonylphenol(NP)is a kind of estrogen belonging to the endocrine disrupter,widely used in various agricultural and industrial goods.However,extensive use of NP with direct release to environment poses high risks to b...4-Nonylphenol(NP)is a kind of estrogen belonging to the endocrine disrupter,widely used in various agricultural and industrial goods.However,extensive use of NP with direct release to environment poses high risks to both human health and ecosystems.Herein,for the first time,we developed near-infrared(NIR)responsive upconversion luminescence nanosensor for NP detection.The Förster resonance energy transfer based upconversion nanoparticles(UCNPs)-graphene oxide sensor offers highly selective and sensitive detection of NP in linear ranges of 5−200 ng/mL and 200−1000 ng/mL under 980 nm and 808 nm excitation,respectively,with LOD at 4.2 ng/mL.The sensors were successfully tested for NP detection in real liquid milk samples with excellent recovery results.The rare-earth fluoride based upconversion luminescence nanosensor with NIR excitation wavelength,holds promise for sensing food,environmental,and biological samples due to their high sensitivity,specific recognition,low LOD,negligible autofluorescence,along with the deep penetration of NIR excitation sources.展开更多
Estrogens are a group of steroid hormones produced by ovary,placenta,and other organs.They have historically been associated with female reproduction,but according to current evidence estrogens regulate also male repr...Estrogens are a group of steroid hormones produced by ovary,placenta,and other organs.They have historically been associated with female reproduction,but according to current evidence estrogens regulate also male reproductive and nonreproductive organs.Estrogens play a crucial role in female reproductive development and maintenance either directly by increasing glycogen levels,epithelial thickness and mucus secretion or indirectly,by decreasing vaginal pH through the maintenance of lactobacilli dominance and lactic acid production.Several studies demonstrated that dysbiosis and/or specific bacteria could have impact on the development of sex-hormone driven cancers such as endometrial,cervical,ovarian,breast and prostate cancers,through mechanisms involving modulation of estrogen metabolism.This modulation is realized through secretion ofβ-glucuronidase which deconjugates estrogens into their active forms.When gut dysbiosis occurs,microbial diversity decreases and so the deconjugation diminishes leading to a decrease of circulating estrogens.Low levels of circulating estrogen may adversely affect a wide range of physiological factors,with clinical implications especially for gut health.In this review,we discuss the different aspects of the critical interplay between gut microbiome and estrogens in sexhormone driven cancers and the potential outcomes on their clinical management.展开更多
Menopause is characterized by the cessation of menstruation and a decline in reproductive function,which is an intrinsic component of the aging process.However,it has been a frequently overlooked field of women’s hea...Menopause is characterized by the cessation of menstruation and a decline in reproductive function,which is an intrinsic component of the aging process.However,it has been a frequently overlooked field of women’s health.The oral and gut microbiota,constituting the largest ecosystem within the human body,are important for maintaining human health and notably contribute to the healthy aging of menopausal women.Therefore,a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance.This paper presents the current understanding of the microbiome during menopause,with a particular focus on alterations in the oral and gut microbiota.Our study elucidates the complex interplay between the microbiome and sex hormone levels,explores microbial crosstalk dynamics,and investigates the associations between the microbiome and diseases linked to menopause.Additionally,this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases.Given that menopause can last for approximately 30 years,gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions,which may result in symptomatic relief from menopause and an increase in quality of life in women.展开更多
Objective This study aims to explore the correlation between traditional Chinese medicine(TCM)syndromes and the expression status of estrogen receptor(ER)and progesterone receptor(PR)in breast cancer patients before a...Objective This study aims to explore the correlation between traditional Chinese medicine(TCM)syndromes and the expression status of estrogen receptor(ER)and progesterone receptor(PR)in breast cancer patients before and after adjuvant chemotherapy.Methods A total of 222 breast cancer patients with consistent ER and PR expression scheduled to undergo adjuvant chemotherapy were classified according to TCM syndrome differentiation before and after chemotherapy.The data were analyzed using chi-square tests and binary logistic regression with SPSS 26.0 software,and compared with ER/PR expression results.Results(i)In the ER-positive/PR-positive group,compared with prechemotherapy,syndromes of spleen qi deficiency,spleen deficiency with dampness-phlegm,and spleen–kidney deficiency significantly increased during mid-chemotherapy and after chemotherapy.Compared with mid-chemotherapy,spleen yang deficiency syndrome significantly increased after chemotherapy,with statistical significance(p<0.05).(ii)In the ER-negative/PR-negative group,compared with prechemotherapy,syndromes of spleen qi deficiency and spleen deficiency with dampness-phlegm significantly increased during mid-chemotherapy,while spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased after chemotherapy.Compared with mid-chemotherapy,spleen–kidney deficiency and spleen yang deficiency syndromes significantly increased after chemotherapy,with statistical significance(p<0.05).(iii)The distribution of spleen qi deficiency syndrome during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group,with statistical significance(p<0.05).(iv)ER and PR were not independent influencing factors for the various syndrome types before and after adjuvant chemotherapy(p>0.05).Conclusion After chemotherapy initiation,syndromes of spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased in both ER-positive/PR-positive and ER-negative/PR-negative groups.The distribution of spleen qi deficiency during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group.ER and PR were not independent influencing factors for the syndrome types before and after adjuvant chemotherapy.展开更多
Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network pharmacology to evaluate the therapeutic target...Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R.Highperformance liquid chromatography-mass spectrometry(HPLC-MS)identified 86 compounds in TXD.Network pharmacological analysis predicted potential target genes and their modes of action.Cardiac function,ischaemic ST changes,lactate dehydrogenase(LDH),malondialdehyde(MDA),superoxide dismutase(SOD)activity,myocardial fiber,and infarct size were assessed using in vivo and in vitro I/R injury models.Estrogen receptor alpha(ERα)protein expression and estradiol(E2)levels were measured to confirm TXD's impact on estrogen levels and ERαexpression.To examine if TXD reduces I/R injury through ERα,an AZD group(300 nmol·L^(-1)AZD9496 and 15%TXD serum)was compared to a TXD group(15%TXD serum).The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway.I/R injury-induced ferroptosis was identified using a Fer-1 group(1.0μmol·L^(-1)Fer-1 and 15%TXD serum)to elucidate the potential association between ferroptosis and ERαproteins.A DCFH-DA probe detected reactive oxygen species(ROS)and Fe^(2+),while Western blotting assessed target protein expression.Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels,improving cardiac injury biomarkers(LDH,MDA,and SOD),alleviating pathological features,and preventing I/R-induced loss of cell viability in vitro.The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells.The TXD group showed significantly decreased ROS and Fe^(2+)levels,while the AZ group(treated with AZD9496)exhibited increased levels.The TXD group demonstrated enhanced expression of ERαand glutathione peroxidase 4(GPX4),with reduced levels of P53 protein and ferritinheavy polypeptide 1(FTH1).The AZ group exhibited contrasting effects on these expression levels.The literature indicated a novel connection between ERαand ferroptosis.TXD activates the ERαsignaling pathway,promoting protection against I/R-induced myocardial cell ferroptosis.This study provides evidence supporting TXD use for myocardial ischemia treatment,particularly in older female patients who may benefit from its therapeutic outcomes.展开更多
Sex hormones,including androgens and estrogens,are known to have widespread physiological actions beyond the reproductive system via binding to their cognitive receptors,members of the nuclear receptor superfamily tha...Sex hormones,including androgens and estrogens,are known to have widespread physiological actions beyond the reproductive system via binding to their cognitive receptors,members of the nuclear receptor superfamily that function as ligand-inducible transcription factors.Meanwhile,a growing body of evidence has indicated the involvement of androgen receptor,as well as estrogen receptors such as estrogen receptor-αand estrogen receptor-β,in the pathogenesis and growth of various types of malignancies,including urothelial cancer.Additionally,in bladder cancer,the activity of sex hormone receptors has been implicated in modulating sensitivity to conventional non-surgical therapy.These may clearly explain sex-related differences in the incidence and prognosis of bladder cancer.This article focuses on summarizing the recent progress on understanding the role of sex hormones and their receptors in urothelial tumorigenesis,urothelial cancer progression,and resistance to non-surgical therapy for bladder cancer.Specifically,potential downstream effectors of sex hormone receptors have been newly identified.Thus,most of previous and subsequent data have indicated that activation of the androgen receptor or estrogen receptor-βpathway is favorable for urothelial cancer,while conflicting data exist especially on estrogen receptor-αfunctions.展开更多
Background:Globally,breast cancer constitutes the predominant malignancy in women.Abnormal regulation of epigenetic factors plays a key role in the development of tumors.Anti-apoptosis is a characteristic of tumor cel...Background:Globally,breast cancer constitutes the predominant malignancy in women.Abnormal regulation of epigenetic factors plays a key role in the development of tumors.Anti-apoptosis is a characteristic of tumor cells.Therefore,exploring and identifying relevant epigenetic factors that regulate the apoptosis of tumor cells is the foundation for clarifying the pathogenesis of tumors and achieving precision antitumor therapy.Method:This study focused on exploring the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive(ER^(+))breast cancer.We used overexpressing FLAG-FOXK1 MCF-7 cells to perform silver staining mass spectrometry analysis and conducted Co-IP experiments to verify the interactions.ChIP-seq was conducted on MCF-7 cells to examine FOXK1's binding across the genome and its transcriptional target sites.To validate the ChIP-seq results,qChIP,western blotting,and quantitative polymerase chain reaction(qPCR)were performed.Through TUNEL assay,cell counting assay,colony formation assay,and the mouse xenograft models,the effect of FOXK1 on breast cancer progression was detected.Finally,by analyzing online databases,the correlation between FOXK1 and the survival of breast cancer patients was examined.Results:FOXK1 interacts with the REST/CoREST transcriptional corepression complex to transcriptionally inhibit target genes representing the apoptotic pathway.Abnormally high expression of FOXK1 prevents the apoptosis of ER+breast cancer cells in vitro and promotes ER+breast tumor progression in vivo.Furthermore,the expression of FOXK1 is negatively correlated with the survival of ER+breast cancer patients.Conclusion:FOXK1 promotes ER+breast carcinogenesis through anti-apoptosis and acts as a potential target for ER+breast cancer treatment.展开更多
The natural estrogens,including estrone(E_(1)),17β-estradiol(E_(2)),and estriol(E_(3)),are frequently detected in aquatic environment at relatively high levels.The most commonly used biomarkers for estrogens are main...The natural estrogens,including estrone(E_(1)),17β-estradiol(E_(2)),and estriol(E_(3)),are frequently detected in aquatic environment at relatively high levels.The most commonly used biomarkers for estrogens are mainly expressed in the liver of fish.Analyses of the global gene profiling in fish liver cells under estrogens treatment will provide precise toxicogenomic information of the natural estrogens which is still not well known.In this study,we developed methods for isolation and culture of primary hepatocytes from liver tissue of male Chinese medaka(Oryzias sinensis),and analyzed the global gene expression profiling in the primary hepatocytes treated with E_(1)(1,10,and 100 nmol/L),E_(2)(0.01,0.1,1,10,and 100 nmol/L),and E_(3)(1,10,and 100 nmol/L)using RNA-seq.It was found that 175,248,and 218 genes were differentially expressed in the E_(1),E_(2),and E_(3) groups,respectively.These differentially expressed genes(DEGs)were mainly enriched in Gene Ontology(GO)terms of“response to estradiol”,“response to estrogen”,and“lipid transport”.Of the DEGs,vitellogenin genes,including vtg1,vtg2,and vtg3,were the mostly up-regulated and followed by zona pellucida genes which include zp2.3,zp2l1 and zp3a.2.In addition,genes of slc41a1,zp2.1,esr1,pkd1l1,fam^(2)0ca,best3,etc.were also obviously up-regulated by the estrogens in concentration-dependent patterns.RT-qPCR was used to validate the results of RNA-seq and found that vtg2 should be the best biomarker gene for estrogen study,which could well response to natural estrogens and weak estrogenic chemical,propyl 4-hydroxybenzoate.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infect...BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infection with the hepatitis C virus(HCV).Clinical observations have established sex-based differences in HCV infection with the disease progressing more severely and more rapidly in males and postmenopausal females compared to premenopausal females,suggesting that estrogens and their receptors may play an important role in hepatic defenses and development of HCV-mediated HCC.However,the precise mechanism of estrogen protection and their effects on inflammation is poorly understood.AIM To determine whether estrogen receptor(ER)expression is correlated with the expression of tumor necrosis factor-alpha(TNF-α)in males and females with HCV-associated diseases.METHODS The role of ERs in modulating innate immune responses was investigated using human liver tissues with HCV/cirrhosis and HCV/HCC.Messenger RNA(mRNA)and protein(nuclear and cytoplasmic)expression were measured for all markers of interest and compared to normal human liver tissue samples.RESULTS ERβwas reported for the first time to have a greater mRNA expression than ERαin normal liver(P≤0.001).In addition,ERβmRNA expression was found to be decreased in diseased livers(P≤0.05),while TNF-αexpression was increased(P≤0.0001).Upon stratifying by sex within each disease group,ESR1 was found to be negatively correlated with ESR2 in females with HCV/cirrhosis(r=-0.84,P≤0.001),whereas males with HCV/cirrhosis were found to have a significant positive correlation(r=0.57,P≤0.05).ESR2 mRNA expression had a significant positive correlation with TNF-αin both HCV/cirrhosis(r=0.61,P≤0.001)and HCV/HCC patients(r=0.45,P≤0.05).CONCLUSION All together,these findings indicate that changes in ERβand TNF-αexpression are associated with worsening disease,and may be part of the sex-dependent factors in HCC pathogenesis.展开更多
This review examines the mechanisms of anxiety and depression in menopausal syndrome from an integrated physiological to psychological perspective.Fluctuations in estrogen and progesterone levels during menopause affe...This review examines the mechanisms of anxiety and depression in menopausal syndrome from an integrated physiological to psychological perspective.Fluctuations in estrogen and progesterone levels during menopause affect neurotransmitter systems(including serotonin,norepinephrine,and dopamine),hypothalamic-pituitary-adrenal axis function,inflammatory processes,and neurotrophic factor expression,collectively diminishing the resilience of emotional regulation neural circuits.Simultaneously,vasomotor symptoms(such as hot flashes and night sweats),sleep disruption,genetic susceptibility,and epigenetic modifications interact with mood disorders,while psychosocial factors(such as midlife stressors and role transitions)and cognitive factors(including negative schemas about aging,attentional bias toward threats,and difficulties in emotional regulation)further shape women’s experiences of menopausal changes.Clinical practice should adopt a biopsychosocial model,employing personalized multimodal approaches through hormone therapy,antidepressants,psychotherapy,and lifestyle adjustments,while future research should focus on developing biomarkers,utilizing advanced technologies,and developing targeted interventions to support women’s psychological wellbeing during menopause.展开更多
Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and pro...Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and prognosis in patients with estrogen receptor-positive(ER+)breast cancer.Methods:This prospective study enrolled nine female patients with breast cancer(mean age 45.5±11.5 years).Eight patients were confirmed to have ER+disease.All participant underwent both[^(68)Ga]Ga-RM2 PET/CT and[^(18)F]FDG PET/CT scans within a one-week interval.The maximum standardized uptake values(SUV_(max))was measured for primary tumors,lymph nodes,and metastatic lesions.The physiological distribution of[^(68)Ga]GaRM2 was also evaluated.Results:No adverse events were observed.Metastatic were identified in lymph nodes(n=29 lesions),bone(n=19),liver(n=7),brain(n=3),and multiple other sites.[^(68)Ga]Ga-RM2 demonstrated a significantly higher median SUV_(max)than[^(18)F]FDG across all lesions[7.5(interquartile range,IQR,3.4-14.0)vs.4.0(IQR,2.3-6.1);P<0.001].Similarly,the tumor-to-background ratio(TBR)was significantly superior with[^(68)Ga]Ga-RM2 for all type of lesions:primary tumors[12.3(IQR,10.4-18.3)vs.7.0(IQR,6.0-10.0);P<0.001],lymph node metastases[17.8(IQR,4.4-39.0)vs.4.7(IQR,2.7-10.2);P<0.001],hepatic metastases[5.4(IQR,3.7-8.3)vs.1.0(IQR,0.9-1.5);P<0.001],and osseous metastases[13.9(IQR,7.3-18.0)vs.4.3(IQR,1.6-5.9);P<0.001].Physiological uptake of[^(68)Ga]Ga-RM2 was the highest in the pancreas(SUV_(max),77.82±22.64),with moderate uptake in the kidneys(2.82±0.62),heart(1.83±0.29),and liver(1.33±0.41).Conclusions:[^(68)Ga]Ga-RM2 PET/CT demonstrates superior uptake metrics for the detection of metastatic lesions,particularly in the brain and breast,suggesting its potential as a valuable complementary imaging modality to[^(18)F]FDG PET/CT.These promising foundings warrant further validation in larger cohorts to confirm their clinical impact and to standardize imaging protocols.展开更多
Except in cases of hypogonadotropic hypogonadism,the use of medical therapy before microsurgical testicular sperm extraction(micro-TESE)is controversial.In some studies,hormone therapy has been shown to improve the po...Except in cases of hypogonadotropic hypogonadism,the use of medical therapy before microsurgical testicular sperm extraction(micro-TESE)is controversial.In some studies,hormone therapy has been shown to improve the possibility of sperm retrieval during micro-TESE and even lead to the presence of sperm in the ejaculate in some cases,thereby obviating the need for micro-TESE.However,their routine use before micro-TESE in cases of nonobstructive azoospermia(NOA)being associated with hypergonadotropic hypogonadism and eugonadism(normogonadotropic condition)has not been supported with robust evidence.In this review,we discuss different types of medical therapy used before micro-TESE for NOA,their risks and benefits,and the available evidence surrounding their use in this setting.展开更多
Membrane-initiated estrogen receptorα(mERα)signaling has been shown to affect bone mass in murine models.However,it remains unknown which cell types mediate the mERα-dependent effects on bone.In this study,we gener...Membrane-initiated estrogen receptorα(mERα)signaling has been shown to affect bone mass in murine models.However,it remains unknown which cell types mediate the mERα-dependent effects on bone.In this study,we generated a novel mouse model with a conditional C451A mutation in Esr1,which enables selective knockout of the palmitoylation site essential for the membrane localization of ERα(C451A^(f/f)).First,we used Runx2-Cre mice to generate Runx2-C451A^(f/f)mice with conditional inactivation of mERαsignaling in Runx2-expressing osteoblast lineage cells.No significant changes were observed in body weight,weights of estrogen-responsive organs,or serum concentrations of estradiol between female Runx2-C451A^(f/f)and homozygous C451A^(f/f)littermate controls.High-resolution microcomputed tomography analysis showed a consistent decrease in cortical bone mass in the tibia,femur,and vertebra L5 of Runx2-C451A^(f/f)mice and three-point bending analysis of humerus revealed an impaired mechanical bone strength in Runx2-C451A^(f/f)female mice compared to controls.Additionally,primary osteoblast cultures from mice lacking mERαsignaling showed impaired differentiation compared to controls.展开更多
Premature ovarian insufficiency(POI)is characterized by irreversible loss of ovarian function before 40 years of age and affects 3.7%of women worldwide(Golezar et al.,2019;Huang et al.,2021).Raised serum follicle-stim...Premature ovarian insufficiency(POI)is characterized by irreversible loss of ovarian function before 40 years of age and affects 3.7%of women worldwide(Golezar et al.,2019;Huang et al.,2021).Raised serum follicle-stimulating hormone(FSH)levels,menstrual disturbance,and estrogen deficiency are the main symptoms of POl(European Society for Human Reproduction et al.,2016).Besides infertility,patients have an increased risk of long-term complications due to the early deficiency of ovarian steroids,such as osteoporosis,cardiovascular disease,and metabolic disorders(lshizuka,2021).Due to the lack of biomarkers for prediction or early diagnosis,most patients are not diagnosed until the failure stage(serum levels of FSH above 25 IU/L and amenorrhea),missing opportunities for intervention.Therefore,developing sensitive biomarkers for diminished ovarian reserves is paramount for timely treatment to improve reproductive outcomes and prevent long-term complications.展开更多
基金sponsored by the National Natural Science Foundation of China(No.41401558)the Application Fundamental Key Basic Research Foundation of Yunnan Province,China(No.2013FA011)+1 种基金the Education Department Science Research Foundation of Yunnan Province,China(No.2014J022)the China Postdoctoral Science Foundation(No.2014T70887)
文摘17α-Ethynylestradiol（EE2） in natural waters may cause adverse effects on organisms due to its high estrogenic potency. Laboratory studies were performed to study the effects of a local humic acid（LHA）, fulvic acid（LFA） and Aldrich humic acid（AHA） on the photochemical behavior and estrogenic potency of EE2. Here photolytic experiments demonstrated that pure aqueous EE2 could undergo direct and self-sensitized photodegradation at a global rate of 0.0068 hr^-1.Photodegradation rate of EE2 in 5.0 mg/L dissolved humic substances（DHS） was determined to be 0.0274, 0.0296 and 0.0254 hr^-1 for LHA, LFA and AHA, respectively. Reactive oxygen species（ROS） and triplet dissolved humic substances（^3DHS＊） scavenging experiments indicated that the promotion effect of DHS on EE2 photodegradation was mainly aroused by the reactions of HOU（35%–50%）,~1O2（〈10%） andDHS＊（22%–34%）. However, the photodegradation of EE2 could also be inhibited when DHS exceeded the threshold of 10 mg/L. Three hydroxylation products of EE2 were identified using GC–MS and their formation pathways were also proposed. In vitro estrogenicity tests showed that EE2 was transformed into chemicals without estrogenic potency. These findings could extend our knowledge on the photochemical behaviors of steroid estrogens in sunlit natural waters.
基金supported by the Ministry of Education of China under the scheme of Key Project of Innovation (Grant No. 705013)the National Natural Science Foundation of China under the Scheme of National Creative Research Groups (Grant No. 50821002)
文摘Permanganate was used as an oxidant to control estrone in the present study. Kinetics was determined at pH 2.5-9.4 and temperature 15–40°C for the reaction of estrone with potassium permanganate. It was found that the reaction is second-order overall and first-order with respect to both estrone and permanganate. The second-order rate constant for the reaction at pH 5.8 and 25°C is 44.45 L mol-1 s-1. The reaction rate first decreased with the increase of pH in the range of 2.5-6.6 and then increased greatly with the increase of pH in the range of 6.6-9.4. In addition, the rate constant exponentially increased with the increase of reaction temperature. Removal of estrogenicity was also investigated during the degradation of estrone using yeast estrogen screen (YES). Results show that the estrogenicity increased in the initial 15 min of reaction and then decreased fast, with a removal rate of 73.8% within the 30 min of reaction. Results also demonstrate that the reaction rate between estrone and permanganate is faster in natural water background than in the ultra-pure water system. Permanganate oxidation is therefore a feasible option for removal of estrone in drinking water treatment processes. However, the contact time must be enough in order to remove estrone without causing the increase of estrogenicity.
文摘The uterotrophic assay has been commonly used to test environmental estrogens in vivo, however, it is often not sensitive enough sometimes. An alternative way is to evaluate estrogenicity through biomarker genes. MicroRNA （miRNA） is a class of regulatory gene, which has been shown to be a good biomarker for many diseases and toxicological effects in recent years, and some evidences showed that estrogen induced response was partially mediated by miRNAs. In this study, two types of microarrays were used to test the 17[3-estradiol （E2） induced miRNA expression profile at different time points in the immature mouse uterus. Statistical analysis showed the aldehyde slide based array had less variation than the amino slide based array, and 11 dysregulated miRNAs were screened out for significant fold change. Real-time PCR was performed to further confirm that 4 out of 7 selected miRNAs, namely miR-451, miR-155, miR-335- 5p, and miR-365, are E2 regulated miRNAs in the uterus. The function of the predicted targets of these miRNAs is involved in cell grow control, which is consistent with the main E2 function in the uterus. MiR-451 had similar strong responses to E2 in the uterus of both immature and overiectomized mice, and could be a potential biomarker for estrogenicity in the uterus.
基金supported by the Natural Science Foundation of Guangdong Province,China(No.2021A1515012168)the Administration of Traditional Chinese Medicine of Guangdong Province,China(Nos.20221146 and 20241091)+5 种基金the Basic and Applied Basic Research Fund Project in Guangdong Province,China(No.2020A1515110948)the Basic and Applied Basic Research in Jointly Funded Projects of City Schools(Institutes)Projects,China(Nos.202201020500 and 202201020295)the Project of Guangzhou Science and Technology Department,China(No.202102021040)the Guangzhou Science and Technology Plan Project,China(No.2023B03J0379)the Chinese Society of Traditional Chinese Medicine Youth Talent Lifting Project(No.2022-QNRC2-B11)the Hospital Young and Middle-aged Key Talent Cultivation Project of The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine(2023-10)。
文摘Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis.To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments.We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages(BMMs)at various concentrations.TRAc P experiments were conducted to examine BQTL's impact on osteoclast differentiation.RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation.Finally,in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings.This study revealed that BQTL suppressed receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity.The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity,primarily through attenuation of the MAPK,NF-κB,and Calcineurin signaling pathways.BQTL's inhibitory capacity was further examined in vivo using an ovariectomized(OVX)rat model,demonstrating a strong protective effect against bone loss.BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
文摘Objective Selective estrogen receptor modulators(SERMs)have demonstrated efficacy in the treatment of hypogonadism in males and male factor infertility.Two SERMs,clomiphene citrate and tamoxifen,are now prescribed for off-label use to treat both conditions in males.However,existing literature compares mixed protocols with active management.We aimed to conduct a meta-analysis to evaluate the effect of clomiphene and tamoxifen versus placebo on natural pregnancy rates.Methods We conducted a comprehensive systematic review of electronic databases:MEDLINE,PubMed/PMC,EMBASE,CINAHL,Cochrane Central Register of Controlled Trials(CENTRAL),Scopus,Google Scholar,and Web of Science.Articles satisfying all selection criteria were analyzed.The primary outcome was the incidence of pregnancy after receiving the treatment.Secondary outcomes included serum follicle-stimulating hormone,luteinizing hormone,and testosterone levels,and sperm count and motility.We calculated the pooled odds ratio,risk ratio,and risk difference to ascertain possible alterations in the direction of the pooled effect size.Results Ten randomized controlled trials were ultimately included and underwent data extraction.Clomiphene citrate and placebo groups had similar pregnancy rates(10.4%and 7.1%,respectively;odds ratio 1.30[95%confidence interval 0.27–6.17];p=0.74).No meta-analysis could be calculated for pregnancy rates in tamoxifen versus placebo groups.Heterogeneity among the studies of both SERMs ranged from low to high.Conclusion Although clomiphene citrate and tamoxifen are often used off-label for the treatment of male infertility secondary to hypogonadism,studies of SERMs in the treatment of idiopathic male factor infertility are limited and heterogenous,preventing this meta-analysis from investigating the efficacy of SERMs on male infertility.The effect of clomiphene citrate or tamoxifen on the pregnancy rate remains uncertain.
基金supported by COBRE(P30GM149367)the Puerto Rico Science&Technology Trust(2022-00125)+1 种基金MBRS-RISE Program(R25 GM061838)SC1GM144032 program(all to JDM)。
文摘In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.
文摘4-Nonylphenol(NP)is a kind of estrogen belonging to the endocrine disrupter,widely used in various agricultural and industrial goods.However,extensive use of NP with direct release to environment poses high risks to both human health and ecosystems.Herein,for the first time,we developed near-infrared(NIR)responsive upconversion luminescence nanosensor for NP detection.The Förster resonance energy transfer based upconversion nanoparticles(UCNPs)-graphene oxide sensor offers highly selective and sensitive detection of NP in linear ranges of 5−200 ng/mL and 200−1000 ng/mL under 980 nm and 808 nm excitation,respectively,with LOD at 4.2 ng/mL.The sensors were successfully tested for NP detection in real liquid milk samples with excellent recovery results.The rare-earth fluoride based upconversion luminescence nanosensor with NIR excitation wavelength,holds promise for sensing food,environmental,and biological samples due to their high sensitivity,specific recognition,low LOD,negligible autofluorescence,along with the deep penetration of NIR excitation sources.
文摘Estrogens are a group of steroid hormones produced by ovary,placenta,and other organs.They have historically been associated with female reproduction,but according to current evidence estrogens regulate also male reproductive and nonreproductive organs.Estrogens play a crucial role in female reproductive development and maintenance either directly by increasing glycogen levels,epithelial thickness and mucus secretion or indirectly,by decreasing vaginal pH through the maintenance of lactobacilli dominance and lactic acid production.Several studies demonstrated that dysbiosis and/or specific bacteria could have impact on the development of sex-hormone driven cancers such as endometrial,cervical,ovarian,breast and prostate cancers,through mechanisms involving modulation of estrogen metabolism.This modulation is realized through secretion ofβ-glucuronidase which deconjugates estrogens into their active forms.When gut dysbiosis occurs,microbial diversity decreases and so the deconjugation diminishes leading to a decrease of circulating estrogens.Low levels of circulating estrogen may adversely affect a wide range of physiological factors,with clinical implications especially for gut health.In this review,we discuss the different aspects of the critical interplay between gut microbiome and estrogens in sexhormone driven cancers and the potential outcomes on their clinical management.
基金supported by Science&Technology Fundamental Resources Investigation Program(2022FY100800)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-12M-1-023/2023-12M-C&T-B-005)+1 种基金Funding for Reform and Development of Beijing Municipal Health Commissionthe National High Level Hospital Clinical Research Funding(2022-PUMCH-B-094).
文摘Menopause is characterized by the cessation of menstruation and a decline in reproductive function,which is an intrinsic component of the aging process.However,it has been a frequently overlooked field of women’s health.The oral and gut microbiota,constituting the largest ecosystem within the human body,are important for maintaining human health and notably contribute to the healthy aging of menopausal women.Therefore,a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance.This paper presents the current understanding of the microbiome during menopause,with a particular focus on alterations in the oral and gut microbiota.Our study elucidates the complex interplay between the microbiome and sex hormone levels,explores microbial crosstalk dynamics,and investigates the associations between the microbiome and diseases linked to menopause.Additionally,this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases.Given that menopause can last for approximately 30 years,gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions,which may result in symptomatic relief from menopause and an increase in quality of life in women.
基金supported by the 2022 Traditional Chinese Medicine Scientific Research Special Project of Henan Province,China(2022ZY1048)2023 Traditional Chinese Medicine Scientific Research Special Project of Henan Province,China(2023YZ2043)General Program of Natural Science Foundation of Henan Province,China(232300421183).
文摘Objective This study aims to explore the correlation between traditional Chinese medicine(TCM)syndromes and the expression status of estrogen receptor(ER)and progesterone receptor(PR)in breast cancer patients before and after adjuvant chemotherapy.Methods A total of 222 breast cancer patients with consistent ER and PR expression scheduled to undergo adjuvant chemotherapy were classified according to TCM syndrome differentiation before and after chemotherapy.The data were analyzed using chi-square tests and binary logistic regression with SPSS 26.0 software,and compared with ER/PR expression results.Results(i)In the ER-positive/PR-positive group,compared with prechemotherapy,syndromes of spleen qi deficiency,spleen deficiency with dampness-phlegm,and spleen–kidney deficiency significantly increased during mid-chemotherapy and after chemotherapy.Compared with mid-chemotherapy,spleen yang deficiency syndrome significantly increased after chemotherapy,with statistical significance(p<0.05).(ii)In the ER-negative/PR-negative group,compared with prechemotherapy,syndromes of spleen qi deficiency and spleen deficiency with dampness-phlegm significantly increased during mid-chemotherapy,while spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased after chemotherapy.Compared with mid-chemotherapy,spleen–kidney deficiency and spleen yang deficiency syndromes significantly increased after chemotherapy,with statistical significance(p<0.05).(iii)The distribution of spleen qi deficiency syndrome during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group,with statistical significance(p<0.05).(iv)ER and PR were not independent influencing factors for the various syndrome types before and after adjuvant chemotherapy(p>0.05).Conclusion After chemotherapy initiation,syndromes of spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased in both ER-positive/PR-positive and ER-negative/PR-negative groups.The distribution of spleen qi deficiency during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group.ER and PR were not independent influencing factors for the syndrome types before and after adjuvant chemotherapy.
基金supported by the National Natural Science Foundation of China (No. 8196140154)the Natural Science Foundation of Xinjiang Uygur Autonomous Region (Nos.2023D01C139 and 2023D01C63)the State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund (No. SKL-HIDCA-2020-8)。
文摘Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R.Highperformance liquid chromatography-mass spectrometry(HPLC-MS)identified 86 compounds in TXD.Network pharmacological analysis predicted potential target genes and their modes of action.Cardiac function,ischaemic ST changes,lactate dehydrogenase(LDH),malondialdehyde(MDA),superoxide dismutase(SOD)activity,myocardial fiber,and infarct size were assessed using in vivo and in vitro I/R injury models.Estrogen receptor alpha(ERα)protein expression and estradiol(E2)levels were measured to confirm TXD's impact on estrogen levels and ERαexpression.To examine if TXD reduces I/R injury through ERα,an AZD group(300 nmol·L^(-1)AZD9496 and 15%TXD serum)was compared to a TXD group(15%TXD serum).The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway.I/R injury-induced ferroptosis was identified using a Fer-1 group(1.0μmol·L^(-1)Fer-1 and 15%TXD serum)to elucidate the potential association between ferroptosis and ERαproteins.A DCFH-DA probe detected reactive oxygen species(ROS)and Fe^(2+),while Western blotting assessed target protein expression.Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels,improving cardiac injury biomarkers(LDH,MDA,and SOD),alleviating pathological features,and preventing I/R-induced loss of cell viability in vitro.The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells.The TXD group showed significantly decreased ROS and Fe^(2+)levels,while the AZ group(treated with AZD9496)exhibited increased levels.The TXD group demonstrated enhanced expression of ERαand glutathione peroxidase 4(GPX4),with reduced levels of P53 protein and ferritinheavy polypeptide 1(FTH1).The AZ group exhibited contrasting effects on these expression levels.The literature indicated a novel connection between ERαand ferroptosis.TXD activates the ERαsignaling pathway,promoting protection against I/R-induced myocardial cell ferroptosis.This study provides evidence supporting TXD use for myocardial ischemia treatment,particularly in older female patients who may benefit from its therapeutic outcomes.
文摘Sex hormones,including androgens and estrogens,are known to have widespread physiological actions beyond the reproductive system via binding to their cognitive receptors,members of the nuclear receptor superfamily that function as ligand-inducible transcription factors.Meanwhile,a growing body of evidence has indicated the involvement of androgen receptor,as well as estrogen receptors such as estrogen receptor-αand estrogen receptor-β,in the pathogenesis and growth of various types of malignancies,including urothelial cancer.Additionally,in bladder cancer,the activity of sex hormone receptors has been implicated in modulating sensitivity to conventional non-surgical therapy.These may clearly explain sex-related differences in the incidence and prognosis of bladder cancer.This article focuses on summarizing the recent progress on understanding the role of sex hormones and their receptors in urothelial tumorigenesis,urothelial cancer progression,and resistance to non-surgical therapy for bladder cancer.Specifically,potential downstream effectors of sex hormone receptors have been newly identified.Thus,most of previous and subsequent data have indicated that activation of the androgen receptor or estrogen receptor-βpathway is favorable for urothelial cancer,while conflicting data exist especially on estrogen receptor-αfunctions.
基金Beijing High-Level Innovation and Entrepreneurship Talent Support Plan,Grant/Award Number:G04070024National Natural Science Foundation of China,Grant/Award Number:82073122。
文摘Background:Globally,breast cancer constitutes the predominant malignancy in women.Abnormal regulation of epigenetic factors plays a key role in the development of tumors.Anti-apoptosis is a characteristic of tumor cells.Therefore,exploring and identifying relevant epigenetic factors that regulate the apoptosis of tumor cells is the foundation for clarifying the pathogenesis of tumors and achieving precision antitumor therapy.Method:This study focused on exploring the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive(ER^(+))breast cancer.We used overexpressing FLAG-FOXK1 MCF-7 cells to perform silver staining mass spectrometry analysis and conducted Co-IP experiments to verify the interactions.ChIP-seq was conducted on MCF-7 cells to examine FOXK1's binding across the genome and its transcriptional target sites.To validate the ChIP-seq results,qChIP,western blotting,and quantitative polymerase chain reaction(qPCR)were performed.Through TUNEL assay,cell counting assay,colony formation assay,and the mouse xenograft models,the effect of FOXK1 on breast cancer progression was detected.Finally,by analyzing online databases,the correlation between FOXK1 and the survival of breast cancer patients was examined.Results:FOXK1 interacts with the REST/CoREST transcriptional corepression complex to transcriptionally inhibit target genes representing the apoptotic pathway.Abnormally high expression of FOXK1 prevents the apoptosis of ER+breast cancer cells in vitro and promotes ER+breast tumor progression in vivo.Furthermore,the expression of FOXK1 is negatively correlated with the survival of ER+breast cancer patients.Conclusion:FOXK1 promotes ER+breast carcinogenesis through anti-apoptosis and acts as a potential target for ER+breast cancer treatment.
基金supported by the Fisheries Innovation Team of Beijing Agriculture Innovation Consortium(No.BAIC07–2023–02)the National Natural Science Foundation of China(Nos.22176004 and 21777003).
文摘The natural estrogens,including estrone(E_(1)),17β-estradiol(E_(2)),and estriol(E_(3)),are frequently detected in aquatic environment at relatively high levels.The most commonly used biomarkers for estrogens are mainly expressed in the liver of fish.Analyses of the global gene profiling in fish liver cells under estrogens treatment will provide precise toxicogenomic information of the natural estrogens which is still not well known.In this study,we developed methods for isolation and culture of primary hepatocytes from liver tissue of male Chinese medaka(Oryzias sinensis),and analyzed the global gene expression profiling in the primary hepatocytes treated with E_(1)(1,10,and 100 nmol/L),E_(2)(0.01,0.1,1,10,and 100 nmol/L),and E_(3)(1,10,and 100 nmol/L)using RNA-seq.It was found that 175,248,and 218 genes were differentially expressed in the E_(1),E_(2),and E_(3) groups,respectively.These differentially expressed genes(DEGs)were mainly enriched in Gene Ontology(GO)terms of“response to estradiol”,“response to estrogen”,and“lipid transport”.Of the DEGs,vitellogenin genes,including vtg1,vtg2,and vtg3,were the mostly up-regulated and followed by zona pellucida genes which include zp2.3,zp2l1 and zp3a.2.In addition,genes of slc41a1,zp2.1,esr1,pkd1l1,fam^(2)0ca,best3,etc.were also obviously up-regulated by the estrogens in concentration-dependent patterns.RT-qPCR was used to validate the results of RNA-seq and found that vtg2 should be the best biomarker gene for estrogen study,which could well response to natural estrogens and weak estrogenic chemical,propyl 4-hydroxybenzoate.
基金Supported by Cancer Sucks,Bixby,Oklahoma Research Grant.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infection with the hepatitis C virus(HCV).Clinical observations have established sex-based differences in HCV infection with the disease progressing more severely and more rapidly in males and postmenopausal females compared to premenopausal females,suggesting that estrogens and their receptors may play an important role in hepatic defenses and development of HCV-mediated HCC.However,the precise mechanism of estrogen protection and their effects on inflammation is poorly understood.AIM To determine whether estrogen receptor(ER)expression is correlated with the expression of tumor necrosis factor-alpha(TNF-α)in males and females with HCV-associated diseases.METHODS The role of ERs in modulating innate immune responses was investigated using human liver tissues with HCV/cirrhosis and HCV/HCC.Messenger RNA(mRNA)and protein(nuclear and cytoplasmic)expression were measured for all markers of interest and compared to normal human liver tissue samples.RESULTS ERβwas reported for the first time to have a greater mRNA expression than ERαin normal liver(P≤0.001).In addition,ERβmRNA expression was found to be decreased in diseased livers(P≤0.05),while TNF-αexpression was increased(P≤0.0001).Upon stratifying by sex within each disease group,ESR1 was found to be negatively correlated with ESR2 in females with HCV/cirrhosis(r=-0.84,P≤0.001),whereas males with HCV/cirrhosis were found to have a significant positive correlation(r=0.57,P≤0.05).ESR2 mRNA expression had a significant positive correlation with TNF-αin both HCV/cirrhosis(r=0.61,P≤0.001)and HCV/HCC patients(r=0.45,P≤0.05).CONCLUSION All together,these findings indicate that changes in ERβand TNF-αexpression are associated with worsening disease,and may be part of the sex-dependent factors in HCC pathogenesis.
基金Supported by Zhejiang Provincial Medical and Health Science and Technology Program,No.2025KY196.
文摘This review examines the mechanisms of anxiety and depression in menopausal syndrome from an integrated physiological to psychological perspective.Fluctuations in estrogen and progesterone levels during menopause affect neurotransmitter systems(including serotonin,norepinephrine,and dopamine),hypothalamic-pituitary-adrenal axis function,inflammatory processes,and neurotrophic factor expression,collectively diminishing the resilience of emotional regulation neural circuits.Simultaneously,vasomotor symptoms(such as hot flashes and night sweats),sleep disruption,genetic susceptibility,and epigenetic modifications interact with mood disorders,while psychosocial factors(such as midlife stressors and role transitions)and cognitive factors(including negative schemas about aging,attentional bias toward threats,and difficulties in emotional regulation)further shape women’s experiences of menopausal changes.Clinical practice should adopt a biopsychosocial model,employing personalized multimodal approaches through hormone therapy,antidepressants,psychotherapy,and lifestyle adjustments,while future research should focus on developing biomarkers,utilizing advanced technologies,and developing targeted interventions to support women’s psychological wellbeing during menopause.
基金supported by the National Natural Science Foundation of China(No.82372001,82171973,82171980)the Youth Talent Support Program(No.A002863)Scientific Research Foundation of Peking University Cancer Hospital(No.BJCH2024CZ02)。
文摘Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and prognosis in patients with estrogen receptor-positive(ER+)breast cancer.Methods:This prospective study enrolled nine female patients with breast cancer(mean age 45.5±11.5 years).Eight patients were confirmed to have ER+disease.All participant underwent both[^(68)Ga]Ga-RM2 PET/CT and[^(18)F]FDG PET/CT scans within a one-week interval.The maximum standardized uptake values(SUV_(max))was measured for primary tumors,lymph nodes,and metastatic lesions.The physiological distribution of[^(68)Ga]GaRM2 was also evaluated.Results:No adverse events were observed.Metastatic were identified in lymph nodes(n=29 lesions),bone(n=19),liver(n=7),brain(n=3),and multiple other sites.[^(68)Ga]Ga-RM2 demonstrated a significantly higher median SUV_(max)than[^(18)F]FDG across all lesions[7.5(interquartile range,IQR,3.4-14.0)vs.4.0(IQR,2.3-6.1);P<0.001].Similarly,the tumor-to-background ratio(TBR)was significantly superior with[^(68)Ga]Ga-RM2 for all type of lesions:primary tumors[12.3(IQR,10.4-18.3)vs.7.0(IQR,6.0-10.0);P<0.001],lymph node metastases[17.8(IQR,4.4-39.0)vs.4.7(IQR,2.7-10.2);P<0.001],hepatic metastases[5.4(IQR,3.7-8.3)vs.1.0(IQR,0.9-1.5);P<0.001],and osseous metastases[13.9(IQR,7.3-18.0)vs.4.3(IQR,1.6-5.9);P<0.001].Physiological uptake of[^(68)Ga]Ga-RM2 was the highest in the pancreas(SUV_(max),77.82±22.64),with moderate uptake in the kidneys(2.82±0.62),heart(1.83±0.29),and liver(1.33±0.41).Conclusions:[^(68)Ga]Ga-RM2 PET/CT demonstrates superior uptake metrics for the detection of metastatic lesions,particularly in the brain and breast,suggesting its potential as a valuable complementary imaging modality to[^(18)F]FDG PET/CT.These promising foundings warrant further validation in larger cohorts to confirm their clinical impact and to standardize imaging protocols.
文摘Except in cases of hypogonadotropic hypogonadism,the use of medical therapy before microsurgical testicular sperm extraction(micro-TESE)is controversial.In some studies,hormone therapy has been shown to improve the possibility of sperm retrieval during micro-TESE and even lead to the presence of sperm in the ejaculate in some cases,thereby obviating the need for micro-TESE.However,their routine use before micro-TESE in cases of nonobstructive azoospermia(NOA)being associated with hypergonadotropic hypogonadism and eugonadism(normogonadotropic condition)has not been supported with robust evidence.In this review,we discuss different types of medical therapy used before micro-TESE for NOA,their risks and benefits,and the available evidence surrounding their use in this setting.
基金supported by the Swedish Research Council(2017-01286,2020-01840)the Swedish state under the agreement between the Swedish government and the county councils(ALF-agreement)(ALFGBG721581)+2 种基金the Gustaf V 80-years fund(FAI-2018-0466)the IngaBritt and Arne Lundberg Foundation(LU2017-0076)the Novo Nordisk Foundation(26844).
文摘Membrane-initiated estrogen receptorα(mERα)signaling has been shown to affect bone mass in murine models.However,it remains unknown which cell types mediate the mERα-dependent effects on bone.In this study,we generated a novel mouse model with a conditional C451A mutation in Esr1,which enables selective knockout of the palmitoylation site essential for the membrane localization of ERα(C451A^(f/f)).First,we used Runx2-Cre mice to generate Runx2-C451A^(f/f)mice with conditional inactivation of mERαsignaling in Runx2-expressing osteoblast lineage cells.No significant changes were observed in body weight,weights of estrogen-responsive organs,or serum concentrations of estradiol between female Runx2-C451A^(f/f)and homozygous C451A^(f/f)littermate controls.High-resolution microcomputed tomography analysis showed a consistent decrease in cortical bone mass in the tibia,femur,and vertebra L5 of Runx2-C451A^(f/f)mice and three-point bending analysis of humerus revealed an impaired mechanical bone strength in Runx2-C451A^(f/f)female mice compared to controls.Additionally,primary osteoblast cultures from mice lacking mERαsignaling showed impaired differentiation compared to controls.
基金supported by the National Key Research&Developmental Program of China(2022YFC2703800,2022YFC2703000)the National Natural Science Foundation of China(82125014,82371646,32070847)+1 种基金Basic Science Center Program of NSFC(31988101)the Natural Science Foundation of Shandong Province(ZR202105250005,ZR2022YQ69,tsqn202211371).
文摘Premature ovarian insufficiency(POI)is characterized by irreversible loss of ovarian function before 40 years of age and affects 3.7%of women worldwide(Golezar et al.,2019;Huang et al.,2021).Raised serum follicle-stimulating hormone(FSH)levels,menstrual disturbance,and estrogen deficiency are the main symptoms of POl(European Society for Human Reproduction et al.,2016).Besides infertility,patients have an increased risk of long-term complications due to the early deficiency of ovarian steroids,such as osteoporosis,cardiovascular disease,and metabolic disorders(lshizuka,2021).Due to the lack of biomarkers for prediction or early diagnosis,most patients are not diagnosed until the failure stage(serum levels of FSH above 25 IU/L and amenorrhea),missing opportunities for intervention.Therefore,developing sensitive biomarkers for diminished ovarian reserves is paramount for timely treatment to improve reproductive outcomes and prevent long-term complications.
