Search Results (6,421)

Kidney cells are exposed to a wide range of physiological and pathological stresses, including hormonal changes, mechanical forces, hypoxia, hyperglycemia, and inflammation. These insults can trigger adaptive responses, but when they persist, they can lead to organelle stress. Organelles such as mitochondria, the endoplasmic reticulum, and primary cilia sustain cellular metabolism and tissue homeostasis. When organelle stress occurs, it disrupts cellular processes and organelle communication, leading to metabolic dysfunction, inflammation, fibrosis, and progression of kidney disease. Sex and hormonal factors play a significant role in the development of renal disorders. Many glomerular diseases show distinct differences between the sexes. Chronic Kidney Disease is more common in women, while men often experience a faster decline in kidney function, partly due to the influence of androgens. Additionally, the loss of female hormonal protection after menopause highlights the importance of sex as a factor in renal susceptibility. This narrative review synthesizes preclinical evidence on how sexual dimorphism and sex hormones affect organelle stress in mitochondria, the endoplasmic reticulum, and primary cilia, from 33 studies identified through a non-systematic literature search of the PubMed database, to provide an overview of how these mechanisms contribute to sex-specific differences in kidney disease pathophysiology. Full article

Grapevine (Vitis vinifera L.) is a globally significant crop increasingly affected by a variety of biotic and abiotic stresses. Plant biostimulants offer a promising approach to enhance plant resilience by modulating key physiological and metabolic processes. This study aimed to demonstrate that the preventive application of a Fabaceae-based biostimulant can prime grapevine defense pathways, thereby improving plants’ ability to endure potential stress conditions. Indeed, resistance to both biotic and abiotic stresses in plants involves common pathways, including Ca²⁺ and ROS signaling, MAPK cascades, hormone cross-talk, transcription factor activation, and induction of defense genes. Grapevine leaves were subjected to high-throughput transcriptomic analysis coupled with qPCR validation 6 and 24 h following treatment application. Differentially expressed genes were visualized using MapMan to identify the major metabolic and signaling pathways responsive to the treatment. This integrative analysis revealed several defense-related pathways triggered by the biostimulant, with representative protein families showing both up- and downregulation across key functional categories. Overall, the results indicate that a wider array of pathways associated with stress tolerance and growth regulation were stimulated in treated plants compared to untreated controls. These findings support the conclusion that a preventive biostimulant application can effectively prime grapevine metabolism, enhancing its preparation to cope with forthcoming environmental challenges. Full article

The basic/helix-loop-helix (bHLH) transcription factors are crucial regulators of plant development and stress responses. In this study, we conducted a genome-wide analysis of the bHLH family in Rosa roxburghii, an economically important fruit crop. A total of 89 non-redundant RrbHLHs were identified and unevenly distributed across the seven chromosomes. Phylogenetic analysis classified them into 23 subfamilies and 7 Arabidopsis subfamilies were absent, indicating lineage-specific evolutionary trajectories. Conserved motif and gene structure analyses showed that members within the same subfamily generally shared similar architectures, yet subfamily-specific variations were evident, suggesting potential functional diversification. Notably, key residues involved in DNA-binding and dimerization were highly conserved within the bHLH domain. Promoter analysis identified multiple cis-acting elements related to hormone response, stress adaptation, and tissue-specific regulation, hinting at broad regulatory roles. Expression profiling across fruit developmental stages and in response to GA₃ treatment revealed dynamic expression patterns. Furthermore, 21 duplicated gene pairs (17 segmental and 4 tandem duplicated pairs) were identified, with most evolving under purifying selection. Detailed analysis of these pairs revealed that segmental duplication, coupled with structural variations such as exon indels, dissolution/joining, and exonization/pseudoexonization, substantially contributed to their functional divergence during evolution. Our results provide a basis for understanding the evolution and potential functions of the RrbHLHs. Full article

Plant roots form highly specialized apoplastic barriers that regulate the exchange of water, ions, and solutes between the soil and vascular tissues, thereby protecting plant survival under environmental stress. Among these barriers, the endodermis and exodermis play essential roles, enhanced by suberin lamellae and lignin-rich Casparian strips (CS). Recent advances have shown that these barriers are not static structures but are dynamic systems, rapidly adapting in response to drought, salinity and nutrient limitation. The R2R3-MYB transcription factor (TF) family is essential to this adaptive plasticity. These TFs serve as key regulators of hormonal and developmental signals to regulate suberin and lignin biosynthesis. Studies across different species demonstrate both conserved regulatory structure and species-specific adaptations in barrier formation. Suberization provides a hydrophobic structure that limits water loss and ion toxicity, while lignification supports structural resilience and pathogen defense, with the two pathways exhibiting adaptive and interactive regulation. However, significant knowledge gaps remain regarding MYB regulation under combined abiotic stresses, its precise cell-type-specific activity, and the associated ecological and physiological trade-offs. This review summarizes the central role of root barrier dynamics in plant adaptation, demonstrating how MYB TFs regulate suberin and lignin deposition to enhance crop resilience to environmental stresses. Full article

Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis. Full article

Low social status leads to chronic social stress that predicts risk for physical and mental illness, especially when it starts early in life. To examine the longitudinal effects of low social status on the immune system, this study assessed the effects of low social status on developmental secretory patterns of pro- and anti-inflammatory markers under baseline conditions, as well as in response to an immune challenge (lipopolysaccharide (LPS)-induced activation of pro- and anti-inflammatory cytokines) in a translational rhesus monkey model of lifelong social subordination stress. Baseline blood samples were collected in 27 socially housed female rhesus monkeys (13 dominants, DOM, and 14 subordinates, SUB) during infancy (6 months), the juvenile pre-pubertal period (16 months), and adulthood (9–10 years) to examine the longitudinal effects of social status on inflammatory markers in unstimulated versus LPS-stimulated conditions mimicking exposure to bacterial infection. Basal levels of the stress hormone cortisol in blood were measured to examine associations between inflammation and activity of the hypothalamic–pituitary–adrenal (HPA) axis throughout the life span. Basal peripheral levels of inflammatory markers (e.g., IL-6) increased across development in both SUB and DOM animals with no significant differences. Basal cortisol levels were significantly higher in infancy as compared to adulthood, but no significant effects of social rank were detected. However, in adulthood, SUB animals showed a cytokine-specific immune response to ex vivo LPS stimulation with significantly higher secretions of IL-1β, IL-2, and IL-10 compared to DOM animals, whereas IL-8 response to LPS was lower in SUB animals than in DOMs. This cytokine-specific response to an immune challenge that mimics bacterial infection could reflect dysregulated immune cells that may have short-term adaptation, but at the cost of longer-term risks for low-grade chronic inflammation and accelerated immune aging for socially subordinate female macaques. Full article

Background: Mini-puberty is a transient but critical postnatal activation of the hypothalamic–pituitary–gonadal axis, essential for male gonadal maturation, penile and testicular growth, and future reproductive potential: this physiological hormonal surge is absent or blunted in congenital hypogonadotropic hypogonadism (CHH), often manifesting as micropenis, cryptorchidism, and impaired Sertoli cell proliferation. Objective: The aim of this review is to summarize current evidence on the impact of early gonadotropin therapy in male infants with CHH. Methods: We conducted a comprehensive literature review using PubMed, including studies reporting on male infants with confirmed or suspected CHH receiving gonadotropin therapy. Keywords included “mini-puberty and hypogonadism”, “gonadotropins and infancy,” and “gonadotropin therapy in CHH.” Eligible studies reported biochemical outcomes (luteinizing hormone, follicle-stimulating hormone, testosterone, inhibin B, anti-Müllerian hormone) and clinical measures (penile length, testicular volume, testicular descent). Data extraction focused on endocrine responses, genital growth, and safety. Results: Twelve studies including 95 infants were analyzed. Early gonadotropin therapy effectively restored postnatal hormonal levels, with consistent increases in testosterone, inhibin B, and anti-Müllerian hormone. Clinically, treatment induced significant penile growth, increased testicular volume and partial or complete testicular descent in the majority of cases. Both continuous infusion and intermittent injection regimens were effective, though hormone kinetics and growth responses varied. No serious adverse events were reported, and therapy was generally well tolerated. Conclusions: Early gonadotropin therapy during mini-puberty represents a safe and effective intervention to replicate the physiological postnatal hormonal surge in male infants with CHH. Prospective longitudinal studies are warranted to evaluate sustained effects on puberty, fertility, and adult reproductive function. Full article

Feminization is an important biotechnological approach in aquaculture for species in which females exhibit superior growth and higher market value. The long-whiskered catfish (Mystus gulio), a euryhaline species cultivated in both monoculture and co-culture systems, contributes to sustainable aquaculture by grazing on uneaten feed and maintaining pond cleanliness. This study evaluated the effects of dietary 17β-estradiol (E2) at 0, 10, 30, and 60 mg/kg, incorporated into conventional and microencapsulated feeds, on the feminization and early growth of M. gulio larvae. Treatments were administered during the weaning stage for 14 and 21 days under controlled rearing conditions. Results showed that larvae fed microencapsulated feed containing 60 mg/kg E2 achieved the highest specific growth rate (26.91 ± 1.92%/day), feed efficiency (164.76 ± 33.23%), and feminization success (99.73 ± 0.04%). Hormonal assays confirmed elevated estradiol and reduced testosterone levels, consistent with ovarian development observed in histological sections. Gene expression analysis further supported these findings through the significant upregulation of cyp19a, erb1, and erb2 mRNA levels. Overall, this study demonstrates that microencapsulated hormone feeding is an effective and environmentally responsible strategy for achieving monosex female populations in M. gulio, enhancing productivity, reproductive performance, and sustainability in aquaculture systems. Full article

Purpose: With the addition of palbociclib to endocrine therapy, many hormone receptor-positive (HR+) metastatic breast cancer (mBC) patients experience toxicities that can lead to dose reductions and cycle delays. We examined the actual doses of palbociclib received by patients and their treatment responses. These dose adjustments, made at the physician’s discretion, are not always consistent with pharmaceutical company recommendations. The aim of this study was to assess the influence of dose adjustments on dose intensity and treatment response in our patients. Methods: Records of patients with HR+ mBC treated with palbociclib between December 2016 and January 2019 at the Sainte-Catherine Institute were retrospectively reviewed. Dose intensity was defined as the total dose of palbociclib received by each patient during the first six months of treatment. Anticipated dose reductions and extended cycle delays were recorded. Treatment response at six months and survival were assessed using statistical analyses. Results: A total of 131 women were included; the median age was 67 years. Forty-six patients (35%) experienced an anticipated dose reduction or an extended cycle delay during the first six months of treatment. Logistic regression analysis showed that factors correlated with six-month treatment response included anticipated dose reduction or extended cycle delay (OR = 14.6, 95% CI 3.74–97.4, p < 0.001), cycle delay > 4 weeks (OR = 5.94, 95% CI 1.58–21, p = 0.01), initial dosage < 125 mg (OR = 4.09, 95% CI 1.13–13.7, p = 0.034), and six-month dose intensity < 14,250 mg (OR = 26.0, 95% CI 4.91–481, p < 0.001). Conclusions: In this real-world assessment of clinical outcomes in French patients with HR+ mBC treated with palbociclib, a palbociclib dose intensity lower than recommended—particularly due to cycle delays longer than four weeks—was associated with an increased risk of six-month disease progression. Full article

Salinity is a major constraint that compromises safflower performance by disrupting redox balance and metabolic homeostasis. Although hormonal mechanisms for improving plant resilience to abiotic stresses have been reported, the mechanistic role of gibberellic acid (GA₃)-induced regulation of safflower tolerance to salinity remains unclear. This study aimed to investigate the impact of exogenous GA₃ application under normal and saline conditions to evaluate its effects on growth, physiology, redox regulation, and flavonoid biosynthesis in safflower. Using phenotypic, physiological, biochemical, and gene expression analysis, it is suggested that GA₃ significantly alleviates salt stress by integrating antioxidant defense and flavonoid biosynthesis. The results of phenotypic and physiological assessments showed that GA₃ at 400 mg/L GA₃ in safflower seedlings suggests enhanced vegetative growth and photosynthetic performance. Under salt stress, GA₃ significantly alleviated oxidative damage by reducing H₂O₂, ${\mathrm{O}}_2^{-}$, and malondialdehyde (MDA) levels, while enhancing osmoprotective compounds such as proline, soluble sugars, proteins, and chlorophyll. GA₃ also significantly increased the activity of antioxidant enzymes (SOD, POD, CAT, APX, GST, DHAR, and Prx), accompanied by the transcriptional upregulation of their corresponding genes, indicating GA₃-mediated regulation of redox homeostasis at both biochemical and molecular levels. In parallel, GA₃ enhanced the accumulation of major flavonoids, particularly hydroxy safflor yellow A (HSYA), with strong induction of key HSYA biosynthetic genes (CtF6H, CtCGT, Ct2OGD1), whereas salinity alone suppressed their expression. In contrast, the quercetin branch displayed a regulatory bottleneck at CtF3H, which remained suppressed under all treatments, although upstream genes were GA₃-responsive. Together, these findings demonstrate that GA₃ enhances salinity tolerance in safflower by simultaneously activating antioxidant defenses and stimulating flavonoid biosynthesis, providing mechanistic insight with practical implications for developing salt-resilient safflower varieties. Full article

Women exhibit a higher prevalence of depression, anxiety, stress-related disorders, and autoimmune conditions compared to men, yet the biological mechanisms underlying this sex difference remain incompletely understood. Growing evidence identifies neuroinflammation as a central mediator of psychiatric vulnerability in women, shaped by interactions between sex hormones, immune activation, and neural circuit regulation. Throughout the female lifespan, fluctuations in estrogen and progesterone, such as those occurring during puberty, the menstrual cycle, pregnancy, postpartum, and perimenopause, modulate microglial activity, cytokine release, and neuroimmune signaling. These hormonal transitions create windows of heightened sensitivity in key brain regions involved in affect regulation, including the amygdala, hippocampus, and prefrontal cortex. Parallel variations in systemic inflammation, mitochondrial function, and hypothalamic–pituitary–adrenal (HPA) axis responsivity amplify stress reactivity and autonomic imbalance, contributing to increased risk for mood and anxiety disorders in women. Emerging data also highlight sex-specific interactions between the immune system and monoaminergic neurotransmission, gut–brain pathways, endothelial function, and neuroplasticity. This review synthesizes current neuroscientific evidence on the sex-dependent neuroinflammatory mechanisms that bridge hormonal dynamics, brain function, and psychiatric outcomes in women. We identify critical periods of vulnerability, summarize converging molecular pathways, and discuss novel therapeutic targets including anti-inflammatory strategies, estrogen-modulating treatments, lifestyle interventions, and biomarkers for personalized psychiatry. Understanding neuroinflammation as a sex-specific process offers a transformative perspective for improving diagnosis, prevention, and treatment of psychiatric disorders in women. Full article

In recent years, heavy metal emissions in Lhasa have been increasing, which has an impact on the local water environment. The negative effects of copper (Cu²⁺) on aquatic ecosystems have attracted much attention, as even low concentrations of Cu²⁺ can exert toxic effects on aquatic organisms. However, the impact of Cu²⁺ on native fish species from the Lhasa River remains poorly understood. In this study, Schizopygopsis younghusbandi (S. younghusbandi) larvae were exposed to Cu²⁺ at concentrations of 0. 5, 5, 50, and 500 μg/L for 7 or 14 days to evaluate its toxic effects on thyroid function and the antioxidant system. The results indicate that whole-body total thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased following Cu²⁺ exposure. This decrease was accompanied by a marked increase in dio1 and dio2 gene expression and decreased expression of thyroid hormone synthesis genes (nis, tg, ttf1 and pax8) after exposure to Cu²⁺. Furthermore, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) and the content of lipid peroxidation were increased, while the content of glutathione (GSH) was decreased. In addition, the survival rates and body lengths of S. younghusbandi larvae were significantly reduced following 7- and 14-day Cu²⁺ exposure. The Integrated Assessment of Biomarker Response (IBR) analysis further revealed dose- and time-dependent effects of Cu²⁺ on the larvae. In conclusion, the findings demonstrate that Cu²⁺ exposure induced disruption of thyroid endocrine and antioxidant systems and caused developmental toxicity in S. younghusbandi larvae. Full article

Background: Lung adenocarcinoma in non-smoking women represents a distinct clinical entity that cannot be fully explained by traditional exposure-centered carcinogenic models. Although ambient air pollution is a recognized risk factor, sex-specific vulnerability suggests the involvement of additional biological modulators shaping inflammatory, immune, and proliferative responses. Main body: In this conceptual review, we integrate epidemiological, experimental, and mechanistic evidence to propose a multisystem framework of lung carcinogenesis in non-smoking women. We delineate a central carcinogenic spine encompassing lung epithelial injury, chronic inflammation, growth factor signaling activation—particularly epidermal growth factor receptor (EGFR) pathways—and tumor microenvironment remodeling. Within this framework, three interacting domains function as biological modulators that amplify carcinogenic processes: chemosensory–neural–immune modulation, hormonal–endocrine signaling including estrogen–EGFR crosstalk, and psychosocial stress–hypothalamic–pituitary–adrenal (HPA) axis dysregulation. These domains converge through feedback mechanisms that reinforce systemic dysregulation and tumor-promoting microenvironments. Implications: This integrative model provides a biologically grounded perspective on female-specific vulnerability to lung adenocarcinoma and informs precision prevention, risk stratification, and ESG-informed public health strategies beyond conventional exposure reduction. Full article

Sustainable food production for a growing population requires farming practices that reduce chemical inputs while maintaining soil as a living, renewable foundation for productivity. This review synthesizes current advances in understanding how endophytic fungi (EFs) interact with the soil microbiome and contribute to the physicochemical and biological dimensions of soil health in arable ecosystems. We examine evidence showing that EFs enhance plant nutrition through phosphate solubilization, siderophore-mediated micronutrient acquisition, and improved nitrogen use efficiency while also modulating plant hormones and stress-responsive pathways. EFs further increase crop resilience to drought, salinity, and heat; suppress pathogens; and influence key soil properties including aggregation, organic matter turnover, and microbial network stability. Recent integration of multi-omics, metabolomics, and community-level analyses has shifted the field from descriptive surveys toward mechanistic insight, revealing how EFs regulate nutrient cycling and remodel rhizosphere communities toward disease-suppressive and nutrient-efficient states. A central contribution of this review is the linkage of EF-mediated plant functions with soil microbiome dynamics and soil structural processes framed within a translational pipeline encompassing strain selection, formulation, delivery, and field scale monitoring. We also highlight current challenges, including context-dependent performance, competition with native microbiota, and formulation and deployment constraints that limit consistent outcomes under field conditions. By bridging microbial ecology with agronomy, this review positions EFs as biocontrol agents, biofertilizers, and ecosystem engineers with strong potential for resilient, low-input, and climate-adaptive cropping systems. Full article

Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (−0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements. Full article