Search Results (3,540)

Central lipid metabolism disorders are crucial for the development of Alzheimer’s disease (AD). Phlorizin (PHZ) improved lipid metabolism abnormalities in AD nematodes, but its mechanism of action in improving AD-related symptoms and whether it can alleviate AD cognitive impairment remain unclear. To elucidate the effects and mechanisms of PHZ on lipid metabolism disorders in an AD model, gavage administration of PHZ for 8 weeks improved cognitive dysfunction and lipid disorders in APPswe/PSEN1dE9 (APP/PS1) mice. Concurrently, in astrocytes induced by palmitic acid (PA)- mediated lipid metabolic disorder, PHZ treatment improved astrocytic lipid accumulation by upregulating the target peroxisome proliferator-activated receptor α (PPARα) and its downstream pathways, thereby promoting astrocytic fatty acid oxidation. We validated PHZ’s strong in vitro binding affinity with PPARα. Co-culture systems of lipid-metabolically disordered astrocytes and neurons further demonstrated that PHZ significantly improved neuronal cell viability and reduced intracellular lipid accumulation, thereby decreasing the expression of enzymes associated with β-amyloid protein (Aβ) production. This study demonstrates that gavage administration of PHZ for 2 months improves cognitive deficits and pathological markers in AD mice. Furthermore, at the cellular level, PHZ may exert its effects by enhancing astrocytic lipid metabolism, thereby preventing neuronal lipotoxicity and mitigating AD progression. Full article

Psoriasis and allergic contact dermatitis (ACD) are the most common chronic inflammatory diseases, which are accompanied by epithelial alterations and a T cell-mediated immunopathology. In this study, we investigated the anti-ACD and anti-psoriasis effects of sea anemone Heteractis magnifica peptide HCRG21, a blocker of the TRPV1 channel, in 2,4-dinitrofluorobenzene (DNFB)- and imiquimod (IMQ)-induced mouse models, respectively. We found that topical application of 0.005–0.1% HCRG21 gels normalized hematological and immunological blood parameters in mice, significantly reduced the severity of ACD- and psoriasiform-like skin lesions, and increased the rate of tissue repair. The use of 0.005 and 0.05% HCRG21 gels decreased the production of IL-23-A and macrophage-derived chemokine (MDC) proteins in blood plasma, reduced the expression of Tnf, Il1β, Il6, Il23a, and Il17a genes, but increased the levels of the Il10 gene in scabs and/or blood of IMQ-treated mice. On the other hand, topical application of 0.05 and 0.1% HCRG21 reduced the expression of Il6 and Il23a in the DNFB-treated mice’s blood and it had no significant effects on TNF-α and IL-1β production. Thus, HCRG21 has the potential to be a treatment for psoriasis and dermatitis due to its potent anti-inflammatory properties. This effect is achieved by reducing pro-inflammatory cytokines associated with TRPV1 and normalizing immune cell levels in the bloodstream. This, in turn, leads to a decrease in clinical symptoms and an improvement in skin healing. Full article

The study of molecular mechanisms underlying late-life depression (LLD) is increasingly important in light of population aging. To date, LLD-related molecular brain changes remain poorly understood. Furthermore, environmental factors such as climate change and geography contribute to LDD risks. One overlooked factor might be deuterium—a stable hydrogen isotope—whose concentration in drinking water can vary geographically (~90–155 ppm) and alter the incidence of mood disorders. Conversely, potential effects of natural variations in deuterium content in drinking water on LLD symptoms and brain gene expression remain unknown. We conducted Illumina gene expression profiling in the hippocampi and prefrontal cortexes of 18-month-old C57BL/6J mice, a model of LLD-like behaviors, compared to 3-month-old controls. Separately, aged mice were allowed to consume deuterium-depleted (DDW, ~90 ppm) or control (~140 ppm) water for 21 days and were studied for LLD-like behaviors and Illumina gene expression of the brain. Naïve old mice displayed ≥2-fold significant changes of 35 genes. Housing on DDW increased their hedonic sensitivity and novelty exploration, reduced helplessness, improved memory, and significantly altered brain expression of Egr1, Per2, Homer1, Gadd45a, and Prdx4, among others. These genes revealed significant alterations in several GO-BP and KEGG pathways implicated in inflammation, cellular stress, synaptic plasticity, emotionality, and regeneration. Additionally, we found that incubation of primary neuronal cultures in DDW-containing buffer ameliorated Ca²⁺ influx and mitochondrial potential in a toxicity model, suggesting the involvement of mitochondrial mechanisms in the effects of decreased deuterium levels. Thus, aging induced profound brain molecular changes that may at least in part contribute to LLD pathophysiology. Reduced deuterium intake exerted modest but significant effects on LLD-related behaviors in aged mice, which can be attributed to, but not limited by ameliorated mitochondrial function and changes in brain gene expression. Full article

Background/Objectives: Lithocarpus litseifolius (Hance) Chun, also known as sweet tea, is a traditional Chinese tea-making plant. Acute lung injury (ALI), a life-threatening syndrome with symptoms like hypoxemia and dyspnea, can be triggered by infection or trauma, with high morbidity and mortality. Whether the water extract of Lithocarpus litseifolius (WEL) has therapeutic effects on ALI remains unclear. This study aimed to analyze WEL’s components, establish in vitro cellular inflammation and mouse ALI models, and investigate WEL’s protective effects against LPS-induced ALI. Methods: LC-MS analysis identified 42 compounds in WEL and quantified three key ones. In an LPS-induced mouse ALI model, WEL significantly reduced lung injury severity, lung wet-to-dry ratio, pulmonary edema, and levels of NO, ROS, IL-1β, TNF-α, and MPO in lung tissues and bronchial alveolar lavage fluid. Immunohistochemical analysis showed WEL pretreatment inhibited the upregulation of NLRP3, Caspase-1, and GSDMD-NT expression, mitigated tissue oxidative stress and cell pyroptosis, and alleviated ALI severity in mice. Cellular experiments confirmed WEL’s protective effects via anti-inflammatory, antioxidant actions, and inhibiting cell pyroptosis, with phlorizin and trilobatin as potential key active ingredients. Conclusions: This research demonstrates sweet tea’s significant protective effects against ALI and its potential to alleviate inflammation by inhibiting pyroptosis, providing a theoretical basis for developing new health-promoting functions of sweet tea. Full article

Helper component-proteinase (HC-Pro), encoded by tobacco vein banding mosaic virus (TVBMV), can cause various viral symptoms and even abortion. HC-Pro counteracts host-mediated inhibition by interfering with the accumulation of microRNAs (miRNAs) and small interfering RNAs (siRNAs). However, it is unclear whether the abortion phenotype of transgenic plants expressing HC-Pro is related to the abnormal expression of TEOSINTE BRANCHED 1/CYCLOIDEA/PROLIFERATING cell factors (TCPs), which are involved in regulating fertility. In this study, the molecular mechanisms through which HC-Pro causes various sterile phenotypes in plants were investigated. Reverse transcription–quantitative polymerase chain reaction (RT–qPCR) and Northern blotting revealed that in HC-Pro transgenic plants, the expression levels of TCP4 and TCP24 significantly increased. The increased expression of TCP4 further upregulated LIPOXYGENASE2 (LOX2), a gene encoding a key enzyme in the synthesis of jasmonic acid (JA) precursors. Further studies confirmed that the aberrant expression of TCP3, TCP4 and TCP24 blocks the elongation of petals and anthers and that the aberrant expression of TCP4 and TCP24 blocks the release of pollen. This study demonstrated that HC-Pro affects the expression levels of the miR319-targeted genes TCP2, TCP3, TCP4, TCP10 and TCP24, thereby affecting the normal development of floral organs and resulting in plant abortion. Both tobacco and Arabidopsis thaliana were used as model systems in this study on virus-mediated fertility, which provides important information for understanding how viral pathogenicity affects the regulation of fertility in crops. Full article

Background/Objectives: Chronic colitis presents a growing global health burden with rising incidence. This study investigated the ameliorative effect of Dendrobium officinale polysaccharide (DOP) against dextran sulfate sodium (DSS)-induced chronic colitis in mice, specifically examining its dual modulation of gut microbiota and metabolic pathways. Methods: DOP was extracted and purified from Dendrobium officinale stems and leaves. A chronic colitis model was established in male C57BL/6J mice via DSS induction. Eighty-four mice were randomized into seven groups: control, model, low/high-dose leaf-DOP, low/high-dose stem-DOP, and sulfasalazine positive control. We assessed body weight, disease activity index (DAI), colon length, splenic/thymic indices, inflammatory cytokines, and histopathology (Hematoxylin and Eosin/Alcian blue staining), with tight junction protein and tumor necrosis factor-alpha (TNF-α) expression quantified via immunofluorescence. 16S rRNA sequencing and untargeted metabolomics evaluated microbial and metabolic shifts. Results: DOP significantly attenuated colitis severity, restored colon histoarchitecture, elevated goblet cell counts, upregulated zonula occludens-1 (ZO-1) and occludin expression, and suppressed TNF-α. Crucially, DOP remodeled dysbiosis by enriching beneficial taxa (e.g., Candidatus_Saccharimonas, Lachnoclostridium) while reducing pathogens (Mucispirillum). Metabolomics further elucidated DOP-mediated regulation of purine and nicotinate/nicotinamide metabolism—pathways mechanistically linked to its anti-inflammatory and barrier-repair effects. Conclusions: DOP effectively alleviates symptoms of DSS-induced chronic colitis in mice, protects intestinal barrier integrity, and achieves therapeutic potential through simultaneous regulation of the gut microbiome and metabolome. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, most frequently metastasizing to the liver, peritoneum, and lungs. Intestinal metastases are exceptionally rare and easily misinterpreted as primary small-bowel tumors, typically presenting with acute complications such as obstruction, perforation, or bleeding. Methods: We combined a detailed case description with a narrative literature review. PubMed/MEDLINE and Embase (2000–2025) were searched for case reports and case series describing intestinal metastases from PDAC with histopathological and immunohistochemical confirmation. Case presentation: We report a female patient presenting with acute intestinal obstruction caused by a synchronous ileal metastasis from PDAC. Imaging revealed an ileal stenosing lesion and a pancreatic body mass. An exploratory laparotomy identified a 3 cm transmural ileal tumor with additional serosal nodules. Histopathology confirmed a moderately differentiated adenocarcinoma. Immunohistochemistry supported pancreatic origin (CK7+, CA19-9+, faint CDX2), with mutant-type p53 positivity, ultra-low HER2/Neu expression, and a Ki-67 index of ~50%. The patient underwent segmental enterectomy with terminal ileostomy, followed by systemic therapy. Conclusions: This represents an exceptional and rare clinical finding rather than a presentation from which broad conclusions can be drawn. Histopathological and immunohistochemical analysis supported pancreatic origin and helped avoid misclassification as a primary intestinal neoplasm. It underscores the importance of careful clinicopathological correlation and multidisciplinary evaluation in atypical metastatic scenarios, while illustrating how surgery can provide symptom control and enable systemic therapy. Given its rarity, these observations should be interpreted with caution and regarded as descriptive rather than generalizable. Full article

Preeclampsia (PE) is a major cause of maternal and perinatal morbidity, and early prediction is critical for timely intervention. This study aimed to identify predictive biomarkers for PE through transcriptomic analysis of second-trimester amniotic fluid supernatant (AFS) collected prior to clinical symptom onset. AFS samples from women who later developed PE (n = 7) and matched controls (n = 7) underwent RNA sequencing to identify differentially expressed genes (DEGs). Candidate genes were validated by real-time PCR in HTR-8/SVneo cells exposed to fluid shear stress at 3, 10, and 20 dyn/cm² for 24 h, mimicking the hemodynamic environment of PE, and siRNA-mediated knockdown was used to assess effects on trophoblast migration and invasion. RNA sequencing revealed 19 DEGs, with 3 upregulated and 16 downregulated genes in the PE group. HOOK2 emerged as the most significantly upregulated gene. Four candidate genes, including HOOK2, CCDC160, CKB, and PARP15, were selected for further validation. HOOK2 mRNA expression significantly increased with higher shear stress levels, consistent with sequencing data. Knockdown of HOOK2 led to a significant increase in trophoblast invasion, while migration showed no significant change. These findings suggest that HOOK2 may serve as a promising early biomarker for PE by modulating trophoblast invasiveness under altered hemodynamic conditions, with potential to improve risk stratification and personalized monitoring in pregnancy. Full article

Background/Objectives: Eating disorders (EDs) frequently emerge during critical stages of childhood and adolescence, when identity development and emotional regulation are still maturing. Disturbances in self-concept clarity and identity integration may transform the body into a symbolic battlefield for autonomy, belonging, and self-worth. This review synthesizes developmental, psychosocial, neurocognitive, and therapeutic perspectives on the role of identity disturbance in EDs. Methods: A narrative review was conducted (2010–2025) using combinations of terms related to identity, self-concept clarity, self-discrepancy, objectification, interoception, and eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorder). Results: Findings indicate that identity vulnerability (expressed as low self-concept clarity, heightened self-discrepancies, and self-objectification) mediates the association between early adversity, sociocultural pressures, and ED symptoms. Neurocognitive studies reveal altered self-referential processing, default mode network connectivity, and interoceptive signaling. Clinically, comorbid borderline personality features further exacerbate identity disturbance and complicate recovery. Evidence-based treatments such as enhanced cognitive-behavioral therapy (CBT-E) effectively target core maintaining mechanisms, while adjunctive interventions (mentalization-based therapy, schema therapy, narrative approaches, and compassion- or acceptance-based methods) show promise in addressing identity-related processes and improving outcomes. Conclusions: Identity disturbance provides a unifying framework for understanding why ED symptoms become entrenched despite adverse consequences. Integrating identity-focused approaches with nutritional and medical care may enhance recovery and reduce chronicity in youth. Future research should adopt longitudinal and mechanistic designs to clarify pathways linking identity change to clinical improvement and test identity-specific augmentations to standard ED treatments. Full article

Background: The PRO-CTCAE provides patient-reported data on symptomatic AEs. A summary metric—the ACS—reflecting total AE burden can be calculated by averaging AE-level composite scores at a given timepoint for each participant. This study investigated the psychometric properties and interpretability of this PRO-CTCAE ACS in patients with breast, lung, or head/neck cancers. Methods: We conducted a secondary analysis of a PRO-CTCAE validation dataset comprising 940 adults undergoing chemotherapy or radiation therapy (clinicaltrials.gov: NCT02158637). We focused on empirically recommended symptom terms for three cancer sites. Analyses included Spearman’s correlations, coefficient alpha, and eigenvalues from the correlation matrices, confirmatory factor analysis (CFA), and principal component analysis (PCA). Latent profile analysis (LPA) was used to assess ACS interpretability in the lung cohort. Results: Mean composite score inter-correlations were moderate (0.30–0.35), and coefficient alphas were high (0.81–0.91). Eigenvalue ratios and CFA supported retention of a single factor/component, with suitable model fit indices. ACS correlated highly with factor scores and the first principal component from the PCA. Reduced sets of terms produced reliable scores that closely approximated the full set scores and aligned with external criteria. LPA in the lung subgroup identified four latent classes; ACS differentiated high vs. low symptom burden groups but did not distinguish the two groups expressing distinct symptom profiles. Conclusion: The ACS demonstrated structural validity through adequately fitting linear factor models and effectively summarized symptomatic AE burden. However, similar ACS values may mask clinically distinct symptomatic AE profiles, underscoring the value of both summary metrics and profile-based approaches. Full article

Background/Objectives: Healthcare workers often experience chronic psychological stress, which may affect up to 71% of nurses, leading to mental outcomes, namely, depressive symptoms and a chronic state of physical and emotional depletion followed by burnout syndrome. Emotional exhaustion, depersonalization and poor personal accomplishment are three core features responsible for the development of burnout. Given sleep quality as a mediator is likely to play a key role in forecasting the potential impingement of burnout both directly and indirectly, this cross-sectional study aimed to explore any possible association between sleep disorders and burnout in a cohort of Lithuanian clinical nurses. Methods: During a six-week period in October–November 2024, a total of 269 female nurses ranging between 22 and 67 years old were recruited for a cross-sectional study. The Pittsburgh Sleep Quality Index (PSQI) tool and the Maslach Burnout Inventory (MBI) were applied to assess the level of subjective sleep quality over the last month and the self-perceived occupational burnout experienced by clinical nurses, respectively. Results: This study highlighted a worrying proportion of nurses found to be at an increased risk of occupational burnout syndrome after more than 60% of nurses had experienced the symptoms of emotional exhaustion and depersonalization. A similar proportion of nurses was exposed to the risk of sleep disorders, which, as a potential trigger, played an important role in maintaining burnout syndrome. More specifically, the global PSQI score was related to the expression of depersonalization (β 0.5, 95% confidence interval (CI) 0.2; 0.9, p = 0.002, R² = 0.27). The higher levels of both emotion exhaustion (β 2.5, 95% CI 1.5; 3.5, p < 0.001, R² = 0.26) and depersonalization (β 1.9, 95% CI 0.8; 3.0, p = 0.001, R² = 0.28) were associated with perceived daily disturbances (in terms of sleep disturbances and daytime dysfunction) in nurses. Conclusions: Healthcare professionals should focus further attention on reducing high-level depersonalization expression and potential risk factors, namely sleep disturbances and daytime dysfunction associated with this burnout symptom in a population of clinical nurses. Therefore, by targeted integration of efficient sleep interventions, healthcare institutions could promote employee-friendly workplaces, and, eventually, improve not only the indicators of burnout syndrome but also nurses’ performance and patient safety as well as satisfaction with perceived nursing care. Full article

Background/Objectives: Neck-specific pain and disability are common and burdensome for survivors of oropharyngeal squamous cell carcinoma (OPSCC), yet the biological mechanisms underlying these symptoms remain poorly understood. While patient-reported outcomes (PROs) offer valuable insight into pain and function, their limited integration with molecular data restricts the development of targeted interventions. The purpose of this study was to explore transcriptomic differences associated with neck pain and disability in OPSCC survivors. Methods: Bulk RNA sequencing was performed on blood samples collected from OPSCC survivors either pre-radiation or more than one year post treatment. DESeq2 was used to determine differentially expressed genes between survivors reporting no versus any neck-related pain, as measured by the validated Neck Disability Index. Ingenuity Pathway Analysis was used to explore interaction among the genes. Results: We identified 24 significantly differentially expressed genes (adjusted p < 0.05) linked to hematopoietic, immune, and neuronal functions. Pathway analysis of the top 50 differentially expressed genes revealed overlap in interferon signaling, iron homeostasis, and blood cell development, suggesting molecular connectivity in hematologic and immunologic disease, cellular movement, and connective tissue disorders. Conclusions: These findings suggest the existence of molecular phenotypes associated with patient-reported neck pain and disability in OPSCC survivors and highlight the importance of integrating PROs with molecular profiling to better understand survivorship burden. Full article

Background/Objectives: Tubo-ovarian high-grade serous carcinoma (HGSC) is a highly lethal malignancy, usually diagnosed at an advanced stage due to the lack of early symptoms and biomarkers. Contraceptive hormone use is associated with a reduced risk of HGSC, but the relative contributions of natural versus synthetic progestins, and their interaction with estrogens, are poorly understood. Methods: We evaluated the chemo-preventive efficacy of a synthetic progestin medroxyprogesterone acetate (MPA), progesterone (P4), and combined 17β-estradiol-progesterone (E2 + P4) in a well-characterized genetically engineered mouse model (GEMM) of oviductal HGSC based on the conditional inactivation of one or both alleles of the Brca1, Trp53, Rb1, and Nf1 tumor suppressor genes (BPRN-het and BPRN-homo mice, respectively). Mice received hormones or placebo via slow-release pellets implanted subcutaneously. After induction of tumor formation, the mice were monitored for tumor development, progression, and survival. Tumor incidence was assessed histologically, and hormone effects were further explored via RNA-seq analysis of oviductal tissues. Results: MPA significantly reduced HGSC incidence and delayed tumor progression compared to the placebo, P4, and P4 + E2 in both BPRN-homo and BPRN-het mice, with up to 78% tumor-free survival in the MPA-treated BPRN-het cohort. P4 monotherapy did not provide significant protection vs. the placebo, but the effects of P4 could have been impacted by a failure to achieve sustained release of the hormone beyond 4–8 weeks. The E2 + P4 combination accelerated tumorigenesis and reduced survival (p < 0.0001 in BPRN-homo and p = 0.0004 in BPRN-het mice). MPA did not affect tumorigenesis in a colon cancer GEMM, or the growth of mouse HGSC-derived cells in vivo, suggesting the role of MPA in the early stages of HGSC development. Gene expression analyses showed that P4 and MPA downregulated cholesterol homeostasis, early and late estrogen response, and epithelial–mesenchymal transition pathways, though only MPA afforded tumor protection. Conclusions: These findings demonstrate that a synthetic progestin, specifically MPA, confers robust protection against HGSC development, while a combination including E2 (E2 + P4) increases risk. This work also illustrates how HGSC GEMMs can be used to compare the chemo-preventive effects of various synthetic progestins on HGSC development in order to prioritize the most effective ones for use in preventing HGSC in both general and high-risk populations. Full article

Background/Objectives: The aim of this study was to investigate the experiences of Swedish patients with inflammatory bowel disease (IBD) regarding intimacy and sexuality-related issues, and to explore both patients’ and healthcare professionals’ perspectives on discussing these topics. Methods: This cross-sectional cohort study used two internet-based questionnaires: one targeting patients and the other healthcare professionals. The patient survey examined the impact of IBD and its treatment on relationships and sexuality, as well as expectations on healthcare support. The survey of healthcare professionals focused on experiences of discussing sexuality-related topics with IBD patients. Responses were analyzed using both quantitative and content analysis. Results: A total of 556 IBD patients and 118 healthcare professionals responded. Among patients, 78% reported difficulties related to relationships and sexuality, with physical symptoms like pain, fecal urgency, and bloating, and psychological problems such as fear of leakage and reduced sexual desire. Over half wished for these issues to be addressed in routine care, yet 84% had never initiated such discussions themselves. Among healthcare professionals, 23% never addressed issues of relationship and sexuality with patients, and another 50% did so only occasionally. Only 15% had access to qualified sexologists for referrals, and just 8% offered sexual rehabilitation after pelvic surgery. Conclusions: Sexual health is frequently compromised in IBD patients, especially in women, but remains insufficiently addressed in clinical practice. Both patients and healthcare professionals expressed a need for more open discussions about relationships and sexuality. Improving care requires routine screening, multidisciplinary support, and the development of guidelines for managing sexual dysfunction in IBD. Full article

Background/Objectives: Menopause is a significant, universal hormonal transition, with symptoms impacting ~80% of women. Research shows that menopause can be professionally disruptive, contributing to decreased productivity, absenteeism, and early exit from the workplace. The objective of this study was to describe the landscape of menopause among Canadian women physicians and explore its potential impact on work performance, job satisfaction, and absenteeism. Methods: In this exploratory cross-sectional study, Canadian physicians self-identifying as women and peri-menopausal or menopausal were invited to participate in an online survey between May–September 2023. Demographic and practice characteristics data were collected. A modified Menopause Rating Scale (MRS) was used to quantify symptom burden. Qualitative data describing the menopausal experience were collected as well. Primary outcome was self-reported work performance. Secondary outcomes included perceived impact of menopause on promotional opportunities, absenteeism, and job satisfaction. Multivariable regression was used to examine associations between MRS scores and outcomes of interest. Results: Among 217 respondents, 47.7% reported a severe menopausal symptom burden; 40% felt menopause negatively impacted work performance, and 16.1% expressed job dissatisfaction. However, fewer than 10 respondents (4.6%) ever took time off for menopausal symptoms. Increasing MRS scores were significantly associated with negative perceived work performance (p < 0.001), fewer promotional opportunities (p < 0.001), and lower job satisfaction (p = 0.006) when controlling for confounders. Qualitative responses were provided by 43 participants, 6 of whom reported positive aspects of the menopausal transition, whereas 20 elaborated on the challenges. Conclusions: Canadian women physicians can experience severe menopausal symptoms, often without support. This needs assessment highlights an important occupational health issue and suggests that opportunities remain for medical institutions and employers to formally recognize and study this life stage of women physicians to improve well-being for this valuable workforce. Full article