Endocrinology Research Articles

Generic Drugs: Balancing Efficacy, Safety, and Accessibility

Generic drugs, defined as pharmaceutically equivalent versions of brand-name medications with identical active ingredients, deliver equivalent clinical outcomes at substantially lower cost. In the United States, generics represent around 90 percent of all dispensed prescriptions and offer savings of 50 to 80 percent compared to originator products, thereby expanding access to essential therapies in both high-income and resource-limited settings. This editorial examines the regulatory approval process for generics, which depends on bioequivalence studies demonstrating that pharmacokinetic measures (area under the curve and peak concentration) fall within 80 to 125 percent of the reference drug, thus obviating the need for repeat efficacy trials. We review evidence from randomized controlled trials and large observational studies across cardiovascular, endocrine, and chronic disease treatments that overwhelmingly confirm equivalence in efficacy and safety. Exceptions arise with narrow-therapeutic-index drugs, including certain antiepileptics and immunosuppressants, where careful monitoring during formulation switches is recommended. Economic analyses indicate annual savings in the United States exceed tens of billions of dollars, while global public health programs rely on generics for HIV/AIDS and tuberculosis treatment. Challenges such as manufacturing quality under cost pressures and periodic drug shortages underscore the need for vigilant oversight. We advocate policy measures that align affordability with stringent quality standards and enhanced communication to reinforce confidence in generic therapies.

Gender differences in drug-induced precocious puberty: a real-world analysis of adverse event reports from the FDA FAERS database (2004–2024)

BackgroundPrecocious puberty (PP) is the early onset of secondary sexual characteristics before the typical age of puberty, which can be caused by hormonal imbalances or external factors, such as medications. Drug-induced precocious puberty (DIPP) has become a growing concern, particularly in pediatric populations. However, the impact of gender differences on DIPP risk and the challenges in drug safety assessments have not been fully explored.ObjectiveTo investigate gender-specific differences in the occurrence of drug-induced precocious puberty (DIPP) and identify potential risk signals related to medication use, utilizing data from the U.S. FDA Adverse Event Reporting System (FAERS).MethodsData from the FAERS database (2004–2024) were used to identify adverse event reports related to drug-induced precocious puberty. Disproportionality analysis (DPA) was applied to detect potential signals of DIPP. The analysis considered demographic variables, including drug, age, gender, weight, indications, and reporting country. Only the most recent report for each unique “caseid” was retained.ResultsA total of 529 reports of DIPP were identified, with a significant increase in reports from 2004 to 2024. The number of reports rose from 9 in 2004 to 53 in 2024, with an average of 40 reports per year from 2018 to 2024. The most frequently implicated drugs were testosterone (N = 88), somatropin (N = 52), and methylphenidate (N = 49). Drugs with the highest Reporting Odds Ratios (RORs) included mitotane (ROR = 220.35), mecasermin (ROR = 145.42), and clomifene (ROR = 141.35). Gender differences were observed, with 56.9% of reports from females and 36.3% from males. The majority of reports came from developed countries, with the U.S. contributing 50.47% of cases. The median time to adverse event occurrence was 238 days, with males showing a median induction time of 192.5 days and females at 242 days, though no statistically significant difference in induction time between males and females was found (p > 0.05).ConclusionsDrug-induced precocious puberty presents a significant clinical concern, particularly in pediatric populations. Gender-specific differences in drugs associated with precocious puberty highlight the need for personalized drug safety assessments. Key drugs associated with DIPP, but not listed as risk factors in labeling, underscore the importance of long-term monitoring. Further research is necessary to explore the mechanisms behind gender differences and enhance drug safety strategies, particularly for children and adolescents.

An investigation into male infertility caused by hormonal imbalance and hypertension brought on by SARS-CoV-2

BackgroundRecent statistics suggest that birth rates are declining worldwide; in parallel, recent studies have also shown that birth rates have decreased since the emergence of SARS-CoV-2. The etiology of the viral infection and its relationship to fertility is currently being investigated.AimAs a result, this study focused on males who recovered from SARS-CoV-2 and had hormonal anomalies associated with high blood pressure, which might lead to male infertility.MethodsThe study population consisted of men aged 20–39 years (N = 150) from the Vellore region who had recovered from SARS-CoV-2 infection within the previous 6 months, as determined through a questionnaire-based survey. Ethical approval was obtained from the relevant institutional review board prior to data collection. Semen samples were collected and analysed according to the World Health Organization (WHO) guidelines (2021) for conventional semen parameters. Standard hormonal and biochemical tests were performed using established protocols. In addition, trace element concentrations in serum and seminal plasma were analysed. Hypo-osmotic swelling test (HOST) was used to assess sperm viability, and acrosome integrity was evaluated with staining techniques.ResultsIncreased blood pressure (BP) was suggested by semen parameters with reduced sperm motility and sperm count in patients infected with SARS-CoV-2 compared to healthy subjects. Despite the reduction in sperm protein, it was associated with a decrease in biochemical nutrients. Furthermore, poorer antioxidant and biochemical markers against ROS were observed, and these differences were statistically significant (P < 0.05). Differences were identified between SARS-CoV-2 recovered men and healthy fertile men in terms of sperm protein fragmentation and loss of sperm membrane integrity, accompanied by structural damage to the acrosome.ConclusionThis study confirmed that SARS-CoV-2 enters the body via angiotensin-converting enzyme 2 (ACE2) in recovered patients, affecting the physiological homeostasis mechanism by triggering blood pressure changes associated with declined male reproductive characteristics (especially testosterone), resulting in a poor semen profile and infertility.

Excess and reduced work absence during COVID-19 in Poland: insights from cause-specific time-series models

BackgroundThe COVID-19 pandemic profoundly disrupted workplace attendance, yet its impact on cause-specific work absence remains largely unexplored.AimTo estimate the cause-specific excess/reduced work absence associated with COVID-19 in Poland.MethodsFollowing the concept of excess mortality, we define excess work absence as the difference between observed and expected absence, where the latter reflects the level anticipated in the absence of the pandemic. Using time-series analysis (Seasonal Autoregressive Integrated Moving Average) on pre-pandemic (2012–2019) quarterly (Q) social insurance data, we forecasted absence rates for disease groups (classified by ICD-10 chapters) and caregiving-related absenteeism. Forecasted absence rates were then compared to observed values during 2020–2024, allowing for the identification of excess or reduced work absence.ResultsWe observed notable deviations in work absence rates during the pandemic period (until the end of Q1-2022). The highest excess absence was identified in caregiving-related absenteeism at the pandemic’s onset, exceeding expected levels by over fivefold. A mental health crisis that began with the pandemic resulted in four consecutive quarters of excess absence, reaching a 54% excess in Q2-2020. We identified a notable excess absence in three ICD-10 chapters that reflect the indirect effects of the pandemic, such as increased diagnostic uncertainty, modified coding practices during early COVID-19 waves, and widespread implementation of public health interventions. Absence rates were lower than expected in neoplasms, endocrine and digestive diseases until the end of the pandemic period, likely reflecting reduced healthcare accessibility. Similarly, absence related to injuries and poisoning was below the expected level until mid-2022, indicating decreased social mobility.ConclusionsCOVID-19 substantially reshaped work absence patterns in Poland, particularly during the early pandemic phase. Pronounced increases and decreases were identified across disease categories. These diverging trends plausibly reflect both the COVID-19’s effects on the development of other conditions and disruptions in healthcare access. These findings highlight the need for disease-specific policy responses to mitigate future health crises and ensure continuity of care during pandemics.

Unraveling the Genetic Link Between Endocrine Hormones and Psychiatric Disorders: An Atlas of Genetic Correlations

Background/Objectives: Endocrine hormones play critical roles in regulating physiological processes, and previous studies have reported their associations with psychiatric disorders. Levels of endocrine hormones and the risk of developing psychiatric disorders are influenced by both genetic and non-genetic factors. However, the shared genetic basis underlying these associations remains largely unexplored. This study aims to dually evaluate the genetic correlations among endocrine hormones, including thyroid and sex hormones, as well as between endocrine hormone metrics and psychiatric disorders to identify potential shared genetic architectures. Methods: We obtained genome-wide association study summary statistics for six thyroid hormone metrics, three sex hormone metrics, and ten psychiatric disorders from predominantly European-ancestry populations. Genetic correlations were computed using linkage disequilibrium score regression after harmonizing variant data to ensure consistency across studies. Results: Significant genetic correlations were observed among thyroid and sex hormone metrics, indicating a strong shared genetic basis. Sex hormones exhibited multiple genetic correlations with psychiatric disorders, including negative correlations between sex hormone-binding globulin and attention-deficit hyperactivity disorder (ADHD) (p = 3.95 × 10−12) and major depressive disorder (p = 4.67 × 10−5), and positive genetic correlations with anorexia nervosa (p = 2.86 × 10−12) and schizophrenia (p = 2.00 × 10−4). Testosterone and estradiol had negative genetic correlations with ADHD and major depressive disorder, while testosterone had positive genetic correlations with anorexia nervosa and schizophrenia. Although thyroid hormone metrics did not exhibit Bonferroni-significant genetic correlations, nominal associations were observed, such as a negative genetic correlation between thyroid-stimulating hormone and major depressive disorder (p = 2.33 × 10−2). Conclusions: These findings suggest a shared genetic basis between endocrine hormones and psychiatric disorders, particularly for sex hormones. Future studies leveraging larger, more diverse populations are warranted to validate and extend the genetic correlations observed in this study.

Thyroid Dysfunction in Patients with Type 2 Diabetes Mellitus attending Medical Outpatient/Inpatient Departments at a Tertiary Care Hospital

Background &amp; Objectives: Diabetes mellitus and thyroid dysfunction are the two most common endocrine disorders in clinical practice. The unrecognized thyroid dysfunction may adversely affect the metabolic control and add more risk to an already predisposing scenario for cardiovascular diseases. The objective was to find out the spectrum of thyroid dysfunction in patients of type 2 diabetes mellitus. Materials and Methods: Seventy patients (40 female and 30 male) of age more than 30 years with type 2 diabetes mellitus were evaluated for one year visiting Nepal Medical College and Teaching Hospital. All the patients were evaluated for thyroid dysfunction by testing thyroid function test. The correlation of prevalence of thyroid disorder with gender distribution, age distribution, HbA1c, duration of diabetes was evaluated. The observations and interpretations were recorded and results obtained were statistically analyzed. Results: There was a high prevalence (27.1%) of thyroid disorders in patients of type 2 diabetes mellitus. Among all, the most common was subclinical hypothyroidism (20.0%) which was further found to be more in females (30.0%) and elderly patients (37.0%). Duration of diabetes had positive association with the incidence of thyroid disorders (P value 0.003). Conclusion: Findings of this study suggests that thyroid disorders were commonly associated with diabetes mellitus among which subclinical hypothyroidism being the commonest. Moreover, thyroid disorders were more common in females and elderly population.

Regulatory Mechanism of Ghrelin on Testosterone Secretion in Type 1 Diabetic Rats.

Ghrelin, which is a hormone comprised of 28 amino acids that is mainly produced in the stomach, is also secreted by Leydig cells in the testes of rats and humans. The hypothalamus regulates testosterone secretion by releasing gonadotropin-releasing hormone (GnRH), which stimulates the pituitary gland to release luteinizing hormone (LH). LH then prompts the testes to produce testosterone via the activity of steroidogenic acute regulatory protein (StAR). Consequently, ghrelin may play a regulatory role in gonadal function. Male Sprague-Dawley rats were randomly assigned to four groups, including the control, ghrelin-treated, diabetic, and diabetic plus ghrelin treatment groups. After the rats were sacrificed, plasma samples were collected. Leydig cells were isolated and cultured with human chorionic gonadotropin (hCG, which is similar to luteinizing hormone and is used to stimulate Leydig cells to synthesize testosterone), 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP, which is an activator of cyclic adenosine monophosphate-dependent protein kinase), or forskolin (an activator of adenylyl cyclase in a wide variety of cell types). Compared with normal treatment, ghrelin treatment in diabetic rats markedly increased plasma testosterone levels by 3.75-fold (P<0.05), Leydig cell testosterone secretion by 2.8-fold (P<0.05), GnRH-mediated LH release from the anterior pituitary by 2.95-fold (P<0.05), and StAR expression by 1.96-fold (P<0.05) in testicular Leydig cells. These findings indicated that ghrelin enhanced testosterone production in diabetic rats, which was partially achieved by the hypothalamic-pituitary-gonadal axis and StAR. This study emphasized the potential use of ghrelin as a treatment for improving testosterone levels and gonadal function in individuals with diabetes. This study explored how a hormone known as ghrelin (which is mainly produced in the stomach) may help in regulating testosterone levels. Researchers examined male rats in four groups, including diabetic rats treated with ghrelin, and discovered that ghrelin increased testosterone production in diabetic rats by improving the communication between the brain, pituitary gland, and testes. This hormone also helped specific cells in the testes to function more effectively. The diabetic rats treated with ghrelin exhibited notable increases in testosterone levels and improved hormone function. These findings suggest that ghrelin could potentially help to address hormonal imbalances related to diabetes and improve reproductive health. This research highlights the potential benefits of ghrelin in addressing hormonal imbalances.

Impact of Health Education on Knowledge About Polycystic Ovarian Syndrome (PCOS) Among Nursing Students in Bhubaneswar, Odisha

Polycystic Ovary Syndrome (PCOS) is a common hormonal disorder among women of reproductive age, characterized by irregular menstruation, elevated androgen levels, and often ovarian cysts, which can lead to serious reproductive and metabolic complications such as infertility. This study aimed to evaluate the effectiveness of a structured teaching programme in enhancing knowledge about PCOS among adult girls at Hi-Tech School and College of Nursing, Bhubaneswar. The study employed a descriptive survey method and a pre-test post-test research design. A total of 50 adult girls were selected as the sample. Data was collected using a structured questionnaire administered before and after the educational intervention, which included an informative booklet on PCOS. The pre-test results revealed that only 44% of participants had average knowledge, with a mean score of 13.2 (SD ±5.6). After the structured teaching programme, the post-test mean score significantly increased to 23.34 (SD ±4.62), translating to a mean percentage of 77.8% and a knowledge gain of 33.8%. The decrease in standard deviation indicated more consistent knowledge levels among participants post-intervention. A t-value of 9.88 with 49 degrees of freedom and a p-value of 0.000 demonstrated that the improvement in knowledge was statistically highly significant. These findings confirm the effectiveness of structured teaching in increasing awareness and understanding of PCOS. The study suggests that health education interventions can play a crucial role in addressing knowledge gaps among young women, potentially leading to better health outcomes. It also recommends conducting further studies with larger samples and diversified methods such as interviews to enhance the depth and generalizability of the findings. In conclusion, the study highlights health education as an essential strategy in empowering young women with the knowledge to manage and prevent complications related to PCOS

Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in DMD, a Narrative Review

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. Objective: To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. Methods: In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. Results: Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. Conclusions: Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being.

Achieving impactful treatment for paediatric endocrine disorders in low- to middle-income countries (LMICs): a scoping review.

Endocrine disorders, such as hypo/hyperthyroidism and diabetes, affect over 5% of the world's population, with an additional 5% of cases remaining undiagnosed. Despite the increasing prevalence of endocrine disorders, especially in low- to middle-income countries (LMICs), limited research offers comprehensive guidance on treating this complex medical field. This scoping review aims to provide evidence-based recommendations for efficient, effective and accessible treatment of paediatric thyroid conditions and diabetes in LMICs. Scoping review guidelines outlined by the Preferred Reporting Items for Systematic and Meta-Analysis Extension for Scoping Reviews, using the Joanna Briggs Institute (JBI) methodology to analyse healthcare administration approaches in LMICs. PubMed, Google Scholar, MEDLINE, EconLit, Science Direct and Scopus were searched using a set of search terms from 19 December 2023 to 16 January 2024. An additional high-level search was performed in May 2025. Selection of a variety of peer-reviewed publications with a setting in LMICs. Articles were included if they described an intervention strategy related to select paediatric chronic diseases, endocrine conditions or non-communicable diseases. The treatment strategies in question were government initiatives, mobile health, specialised programmes and primary care. One reviewer manually reviewed articles and documented findings on Microsoft Excel. In accordance with JBI methodological guidelines, no risk of bias assessment or quality appraisal of included studies was conducted. After reviewing primary care, specialised care, government intervention programmes and mobile care initiatives within developing countries, primary care with an emphasis on task shifting emerged as the best approach for treating paediatric endocrine disorders. Despite recommendations favouring specialised care or government interventions, primary care proves to be the optimal method for treating endocrine conditions. Given limited healthcare funding in LMICs, implementing primary care initiatives can achieve significant health outcomes while maximising resources.

Cadmium exposure and health outcomes:An umbrella review of meta-analyses.

Cadmium exposure and health outcomes:An umbrella review of meta-analyses.

Structure activity relationship of Aristolochic acid analogues: Inhibitory effect on human and rat gonadal 3β-Hydroxysteroid dehydrogenases.

Structure activity relationship of Aristolochic acid analogues: Inhibitory effect on human and rat gonadal 3β-Hydroxysteroid dehydrogenases.

Phase Separation Regulates Metabolism, Mitochondria, and Diseases.

As a physicochemical mechanism, phase separation is a spatial and temporal regulator of specific molecules within a cell, and it provides a new perspective for understanding cellular pathophysiology. Phase separation is closely associated with multiple metabolic processes in the body, including the regulation of key metabolic enzymes and the physiology of mitochondria. Mitochondria also regulate multiple physiological functions through phase separation, including protecting healthy mitochondria and mRNAs in oocytes and regulating crosstalk between nuclear and mitochondrial. Importantly, abnormal phase separation in vivo is associated with the development of diseases, including cancer, neurodegenerative diseases, endocrine disorders, skeletal system diseases, and infectious diseases. This review summarizes the relationship between phase separation and metabolism under both physiological and pathological conditions, as well as the therapeutic potential of phase separation in the treatment of relevant diseases, aiming to explore the possibility of treating diseases by regulating phase separation.

Comparing the metabolomic landscape of polycystic ovary syndrome within urban and rural environments

BackgroundPolycystic Ovary Syndrome (PCOS) affects up to 10% of women of reproductive age, characterized by hormonal imbalances and metabolic complications. Environmental factors potentially influence the biochemical expression of this condition. This study aims to examine the impact of urban versus rural environments on metabolite profiles in women with PCOS.MethodsThirty women aged between 18 and 40, diagnosed with PCOS according to the Rotterdam 2003 criteria, were recruited from June 2022 to May 2023, 16 from urban settings and 14 from rural settings. Serum samples were analyzed using liquid chromatography-tandem mass spectrometry. Principal component analysis and orthogonal partial least squares discriminant analysis were performed to identify metabolic patterns and differences between the two groups.ResultsThis study reveals significant differences in metabolite profiles between women with PCOS from various environmental backgrounds. Rural participants exhibit higher levels of lipid-related metabolites, especially Palmitone, indicating specific dietary influences. Urban participants show distinct changes in carbohydrate and nucleotide metabolism pathways, likely due to processed food consumption. Multivariate analyses demonstrate a clear separation between the groups, emphasizing the environmental impact on PCOS expression.ConclusionsThis research highlights potential environment-related biomarkers for PCOS, emphasizing the importance of developing tailored treatment strategies considering environmental factors. The distinct metabolic profiles observed between urban and rural women provide new insights into the syndrome’s complex mechanisms, indicating that environmental influences play a critical role in its biochemical expression and may affect its clinical manifestations.

FSH, LH, lipid and adipokines in Polycystic Ovary Syndrome: Clinical biochemistry insights for diagnosis and management.

FSH, LH, lipid and adipokines in Polycystic Ovary Syndrome: Clinical biochemistry insights for diagnosis and management.

Integrating network pharmacology and transcriptomics reveals that Bushen Huoxue recipe ameliorates ferroptosis and apoptosis in granulosa cells by regulating PI3K/Akt signaling pathway in premature ovarian insufficiency mice.

Integrating network pharmacology and transcriptomics reveals that Bushen Huoxue recipe ameliorates ferroptosis and apoptosis in granulosa cells by regulating PI3K/Akt signaling pathway in premature ovarian insufficiency mice.

Assessment of Serum ACTH, Melatonin, and Cortisol Levels in Patients with Hormone Imbalance and Multiple Sclerosis.

Introduction: Multiple sclerosis (MS) is a long-term inflammatory disease that affects the central nervous system due to an abnormal immune response. Hormonal and enzyme changes in these patients can influence the progression and prognosis of the disease. In this research, the levels of cortisol, adrenocorticotropic hormone (ACTH), melatonin, and lactate dehydrogenase (LDH) in the blood of MS patients were studied. Methods: This study involved 50 MS patients and 50 healthy individuals. The levels of ACTH, melatonin, and cortisol in the blood were measured using specific ELISA kits. The data obtained were then analyzed statistically using SPSS software. Results: The findings revealed a significant increase in the levels of cortisol and LDH in MS patients (P&lt;0.05), while the levels of melatonin and ACTH showed a significant decrease (P&lt;0.05). The elevated cortisol levels may be attributed to chronic stress and inflammation associated with MS. An increase in LDH levels can indicate tissue damage caused by myelin destruction. On the other hand, decreased melatonin levels may lead to sleep disturbances and increased stress in these patients, while decreased ACTH levels may be linked to disruptions in the hypothalamic-pituitary-adrenal (HPA) axis. Conclusion: The hormonal and enzyme changes observed in MS patients illustrate the wide-ranging impact of the disease on various body systems. The increase in cortisol and LDH as well as the decrease in melatonin and ACTH could serve as useful biomarkers for predicting disease progression and managing the condition. These findings align with previous studies and contribute to a deeper understanding of the pathological mechanisms of MS.

Screening of Optimal Phytoconstituents through in silico Docking, Toxicity, Pharmacokinetic, and Molecular Dynamics Approach for Fighting against Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a hormonal disorder caused by excessive secretion of male sex hormones in females. Herbal remedies for PCOS are lightning up as they bypass the adverse effects and are profoundly safe on prolonged usage. The present study included a selection of 34 herbs pursuing biological effects on the uterus, and their major chemical constituents were subjected to a series of in silico techniques using different software. The proteins contributing majorly to the hormonal functions like Human cytochrome P450 CYP17A1 (3RUK), Progesterone (1E3K), and estrogen receptor (1X7R) were selected for the study. Molecular docking studies were performed using AutoDock 1.5.7. The pharmacokinetic properties were predicted using the SwissADME online tool, while toxicity parameters were assessed with OSIRIS toxicity explorer and pkCSM. Molecular dynamics simulations and free energy calculations were performed using the Schrödinger suite. Constituents with a basic steroidal nucleus demonstrated high binding energy values. An analysis of all the in silico techniques showed that Sarsasapogenin from Asparagus racemosus exhibited strong binding energies of -10.88 kcal/mol, -10.51 kcal/mol, and -9.79 kcal/mol with the selected specific proteins. In molecular dynamics simulations, Sarsasapogenin displayed ideal stability, with RMSD fluctuations below 3 Å and RMSF slightly higher than the corresponding peak of apoprotein. Additionally, it showed a favorable druglikeness profile and non-toxic effects across all screened parameters. From the list of the selected constituents, sarsasapogenin was found to be ideal, and further research on it for targeting PCOS is expected to yield promising results.

Disproportionality analysis of adverse events associated with ipilimumab and nivolumab combination therapy based on FAERS database

The combination of immune checkpoint inhibitors (ICIs), such as ipilimumab and nivolumab, has revolutionized cancer treatment, particularly for advanced melanoma and other solid tumors. However, rare adverse events (AEs) associated with this combination are often underreported in clinical trials. This study aimed to investigate the safety profile of these drugs using the FDA Adverse Event Reporting System (FAERS) database. A retrospective analysis of data from 2015 to the first quarter of 2024 was conducted, focusing on AEs submitted by healthcare professionals. Disproportionality analysis, using algorithms like Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN), identified AE signals. A total of 19,462 reports related to the combination therapy were retrieved, spanning 20 System Organ Classes (SOCs), with endocrine and hepatobiliary disorders being most affected. Additionally, 125 unexpected significant AEs were identified, including thyrotoxic crisis, diabetes insipidus, immune-mediated optic neuritis, cystitis, eyelid ptosis, complete atrioventricular block, etc. The highest frequency of AEs occurred within the first 30 days of treatment (38.1%), with a decrease in incidence over time, as indicated by the Weibull Shape Parameter (WSP) test. These findings highlight the importance of continuous monitoring of ICIs in clinical practice.

Adropin mitigates reproductive and metabolic dysfunctions in streptozotocin induced hyperglycemic mouse.

Hyperglycemia is the predominant endocrine and metabolic disorder, resulting in infertility in males. Adropin, a hepatokine, is a well-known insulin sensitizer that regulates glucose and lipid homeostasis. Our recent reports demonstrated the vital role of adropin in the regulation of testicular activity but its role in testicular function during pathological condition like hyperglycemia is not yet studied. Therefore, this study aimed to explore the effect of adropin treatment on reproductive and metabolic dysfunctions in hyperglycemic mice. Hyperglycemia was induced by streptozotocin (55 mg/kg body weight; i.p.) treatment followed by treatment with either adropin (450 nmol/kg body weight; i.p.) or metformin (500 mg/kg body weight; orally) for a period of 15 days. Treatment to hyperglycemic mice enhanced insulin sensitivity by increasing insulin receptor expression in the testis and decreasing HOMA-IR and circulating glucose level. Adropin treatment to hyperglycemic mice increased the production of testicular testosterone by promoting the expression of steroidogenic proteins. Moreover, adropin treatment also enhanced the proliferation and survival of testicular germ cells by increasing PCNA expression and decreasing BAX/Bcl2 ratio and TUNEL positive cells in the testis of hyperglycemic mice. Flow-cytometric analysis revealed the increased number of advance germ cells in adropin treated hyperglycemic mice. Notably, adropin treatment is more effective than metformin in restoring reproductive functions in hyperglycemic mice that is evident by the reestablishment of the testicular histoarchitecture and increased synthesis of testosterone in the testes. These findings suggest that adropin may serve as a viable therapeutic alternative to mitigate the hyperglycemia-associated testicular dysfunction.