Quantification of Steroid Receptors Gene Expression in Breast Cancer Patients: Possible Correlation with Serum Level of Adipocytokines

Background: While the role of adipocyte-derived hormones in breast cancer pathogenesis well studied, it is speculated that there is a crosstalk between adipocytokines and Esterogen receptor(ER) signaling. To test this hypothesis we evaluate the possible correlation between serum levels of adipocytokins with steroid hormone receptors gene expression in breast cancer patients. Methods: In this case-control study, 70 women with breast cancer participated with different grades of obesity (36 none obese, BMI 0.05). In case of leptin, we observed a positive correlation between leptin and ERα and PR mRNA. (r = 0.553, n = 64, p < 0.001, r = 0.359, n = 64, p = 0.002 and a reverse significant correlation between leptin and ERβ (r= –0.506, n = 64 and p < 0.001). We also observed a significant correlation between TNFα and IL6 with steroid receptors gene expression in samples (P < 0.05). Conclusion: As the presence of steroid receptors are used as the most common prognostic markers in breast cancer patients, so targeting adipocytokines as potential regulators of steroid receptorsgene expression can be a new approach in treatment of obese breast cancer subjects.

Liver expression of steroid hormones and Apolipoprotein D receptors in hepatocellular carcinoma

AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. METHODS: We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specif ic antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitive score based on their intensity, and the percentage of immunostained cells was measured. RESULTS: A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. CONCLUSION: Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.

CORRELATION OF STEROID HORMONE RECEPTORS AND CLINICAL PATHOLOGICAL FEATURES WITH PROGNOSIS OF HUMAN BREAST CANCER

Clinical, pathological features and steroid hormone receptors (SR) including receptors of estrogen (ER), progesterone (PR) and androgen (AR) were observed in 58 cases of breast carcinoma, and related to patient 5- year survival rate through stratification and multivariatc analysis. The results showed that histologic tumor type and grading, lymphnode status, ER value and patient age took more important role in patient survival, and SR, especially, conferred survival advantage in advanced cases with tumor size larger than 2 cm, node involved, or TNM Stage Ⅱ-Ⅲ.

Breast cancer stem cells: The role of sex steroid receptors

Breast cancer(BC)is the most common cancer among women,and current available therapies often have high success rates.Nevertheless,BC might acquire drug resistance and sometimes relapse.Current knowledge about the most aggressive forms of BC points to the role of specific cells with stem properties located within BC,the so-called“BC stem cells”(BCSCs).The role of BCSCs in cancer formation,growth,invasiveness,therapy resistance and tumor recurrence is becoming increasingly clear.The growth and metastatic properties of BCSCs are regulated by different pathways,which are only partially known.Sex steroid receptors(SSRs),which are involved in BC etiology and progression,promote BCSC proliferation,dedifferentiation and migration.However,in the literature,there is incomplete information about their roles.Particularly,there are contrasting conclusions about the expression and role of the classical BC hormonal biomarkers,such as estrogen receptor alpha(ERα),together with scant,albeit promising information concerning ER beta(ERβ)and androgen receptor(AR)properties that control different transduction pathways in BCSCs.In this review,we will discuss the role that SRs expressed in BCSCs play to BC progression and recurrence and how these findings have opened new therapeutic possibilities.

Olfactory receptors in neural regeneration in the central nervous system

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

Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

The striking gender disparity observed in the incidence of hepatocellutar carcinoma （HCC） suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor （ER） and androgen receptor （AR） in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro, in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC.

Chromatin remodeling regulated by steroid and nuclearreceptors

Coactivators and corepressors regulate transcriptionby controlling interactions between sequence-specific transcription factors, the basal transcriptional machinery andthe chromatin environment. This review consider the access of nuclear and steroid receptors to chromatin, theiruse of corepressors and coactivators to modify chromatinstructure and the implications for transcriptional control.The assembly of specific nucleoprotein architectures andtargeted histone modification emerge as central controlling elements for gene expression.

Evaluation of Steroid Receptors mRNA Fingerprints in Two Groups of Normozoospermic Patients: Men from Unexplained Infertility Couples vs. Men from Couples with Tubal Factor Infertility

The study of sperm cellular components at molecular level is crucial for the diagnosis of male unexplained infertility. The aim of the study was to compare the molecular profile of steroid receptors and aromatase in spermatozoa obtained from two normozoospermic groups of patients issued from couples treated for infertility. We investigated 46 male patients from unexplained infertility couples and from men, 38 where female partners presented with tubal infertility. Sperm ERs (estrogen receptors: alpha and beta), GPER (G protein-coupled estrogen receptor), AR (androgen receptor) and aromatase mRNA expression levels by TaqMan qPCR were analyzed. AR transcript level was significantly lower in sperm of men from unexplained infertility couples vs. men from couples with tubal factor infertility (P = 0.04). Although the AR mRNA expression level did not had any effect on embryo development and its implantation, a significant correlation between AR mRNA levels and clinical pregnancy in unexplained infertility patients was observed. Taken together, AR transcript presence in ejaculated spermatozoa could be a potential marker for unexplained infertility.

Gut microbiota affects the estrus return of sows by regulating the metabolism of sex steroid hormones

Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.Results In this study,we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows.Using metagenomic sequencing data from 85 fecal samples,we identified 37 bacterial species that were significantly associated with estrus return.Normally returning sows were characterized by increased abundances of L.reuteri and P.copri and decreased abundances of B.fragilis,S.suis,and B.pseudolongum.The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome.The results were confirmed in a validation cohort.Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis.An integrated analysis of differential bacterial species,metagenome,and fecal metabolome provided evidence that normal return-associated bacterial species L.reuteri and Prevotella spp.participated in the degradation of pregnenolone,progesterone,and testosterone,thereby promoting estrogen biosynthesis.Furthermore,the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.Conclusions An integrated analysis of differentially abundant bacterial species,metagenome,and fecal metabolome revealed the involvement of L.reuteri and Prevotella spp.in sow estrus return.These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones,suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.

Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment

Background: Sudden sensorineural hearing loss(SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy(IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy(SST).Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors.Methods: Totally, 74 patients who were aged 22–81 years with SSNHL were enrolled and allocated to either the control group(n = 25) or the treatment group(n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2–6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST.Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies(250-8000 Hz) compared with the control group(P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment(P = 0.002), whereas age, duration of SST, and time of IST were not(P > 0.05).Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

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

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

Predictors of stricture after endoscopic submucosal dissection of the esophagus and steroids application

BACKGROUND Endoscopic submucosal dissection(ESD)is a reliable method to resect early esophageal cancer.Esophageal stricture is one of the major complications after ESD of the esophagus.Steroid prophylaxis for esophageal strictures,particularly local injection of triamcinolone acetonide(TA),is a relatively effective method to prevent esophageal strictures.However,even with steroid prophylaxis,stenosis still occurs in up to 45%of patients.Predicting the risk of stenosis formation after local TA injection would enable additional interventions in risky patients.AIM To identify the predictors of esophageal strictures after steroids application.METHODS Patients who underwent esophageal ESD and steroid prophylaxis and who were comprehensively assessed for lesion-and ESD-related factors at Southeast University Affiliated Zhongda Hospital between February 2018 and March 2023 were included in the study.The univariate and multivariate regression analyses were conducted to identify the predictors of stricture among patients undergoing steroid prophylaxis.RESULTS A total of 120 patients were included in the analysis.In the oral prednisone and oral prednisone combined with local tretinoin injection groups,the stenosis rates were 44/53(83.0%)and 56/67(83.6%),respectively.Among them,univariate analysis showed that the lesion circumference(P=0.01)and submucosal injection solution(P=0.04)showed significant correlation with the risk of stenosis formation.Logistic regression analyses were then performed using predictors that were significant in the univariate analyses and combined with known predictors from previous reports,such as additional chemoradiotherapy and tumor location.We identified a lesion circumference<5/6(OR=0.19;P=0.02)and submucosal injection of sodium hyaluronate(OR=0.15;P=0.03)as independent predictors of on esophageal stricture formation.CONCLUSION Steroid prophylaxis effectively prevents stenosis.Moreover,the lesion circumference and submucosal injection of sodium hyaluronate were independent predictors of esophageal strictures.Additional interventions should be considered in high-risk patients.

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

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

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

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

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

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

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

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

Catheter-Assisted Interlaminar Approach for Cervical Epidural Steroid Injection in Patient with Cervical Stenosis Caused by Ossification of Posterior Longitudinal Ligament: A Case Report

We present the case of a 64-year-old man with cervical ossification of the posterior longitudinal ligament (OPLL) experiencing chronic neck pain and radiculopathy for 6 months. A catheter-assisted interlaminar Cervical Epidural Steroid Injection (CESI) was performed under fluoroscopic guidance, targeting the affected C2-C6 levels. Significant improvement was observed after this procedure, with decreased pain scores (visual analogue scale (VAS) 8 to 2) and improved mobility. This technique not only enhances the effectiveness of CESI but also reduces the likelihood of complications such as stroke or epidural hematoma and thus provides an alternative treatment option for patients with multiple stenotic levels who are unsuitable for surgery or are unresponsive to conservative therapy such as medication or physical therapy.

Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

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

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