Search Results (34,104)

Type 2 diabetes mellitus (T2DM) is a highly prevalent and devastating chronic metabolic disease worldwide, with pathogenesis centrally characterized by insulin resistance and pancreatic β-cell dysfunction. Accumulating evidence has demonstrated that glucose metabolic reprogramming represents an adaptive metabolic shift from oxidative phosphorylation to aerobic glycolysis in cells in response to a hyperglycemic microenvironment. This shift acts as an upstream important event driving the initiation and progression of T2DM. This review summarizes the characteristics of glucose metabolic reprogramming in insulin-sensitive target organs under T2DM conditions, including the liver, skeletal muscle, adipose tissue and pancreatic β-cells. It also discusses four major downstream effector mechanisms: mitochondrial energy metabolism disturbance, augmented oxidative stress, disruption of mitochondria-associated endoplasmic reticulum membranes (MAMs) coupled with calcium homeostasis imbalance, and systemic inflammatory response. On this basis, we summarize the intervention strategies targeting the above signaling pathways, including antioxidant therapy, restoration of MAMs integrity and calcium homeostasis, systemic anti-inflammatory intervention, and multi-target regulatory effects of traditional Chinese medicine. Current studies indicate that early intervention in downstream stress events is induced by glucose metabolic reprogramming. This is particularly true for the preservation of MAMs’ integrity; restoration of calcium homeostasis; and inhibition of NLRP3 inflammasome activation, the latter of which is expected to block or delay the progression from prediabetes to clinical T2DM. Nevertheless, substantial gaps still remain in the understanding of the dynamic regulatory mechanisms of MAMs, tissue-specific therapeutic targets, and relevant clinical translational research. Future integration of multi-omics technologies will provide novel therapeutic strategies and theoretical foundations for the early prevention and treatment of T2DM. Full article

Global climate change has intensified drought and increased nitrogen deposition, threatening forest tree seedling regeneration. To clarify how drought severity and nitrogen enrichment jointly affect seedling performance in Quercus wutaishanica, a dominant montane tree in northern China, we conducted a full two-factor pot experiment. We established three drought treatments (ambient precipitation [CK], chronic drought [CD], and intense drought [ID]), fully crossed with two nitrogen addition levels (0 and 10 g N m⁻² yr⁻¹), and measured functional traits related to growth, photosynthesis, and stress resistance. Our main results were threefold: (1) Both drought treatments significantly inhibited growth and biomass accumulation: total biomass decreased by 28% under CD and 38% under ID relative to CK, with suppression intensifying as drought severity increased. (2) Nitrogen addition increased total biomass by 12% under chronic drought, but this ameliorative effect fell to just 2% under intense drought. (3) As drought stress increased, the seedlings underwent a shift from stomatal to non-stomatal photosynthetic limitation, and from active physiological acclimation to irreversible metabolic damage. (4) Random forest modeling confirmed that biomass variation was primarily driven by traits related to water-use efficiency and resource acquisition. Overall, intensifying drought consistently constrains Q. wutaishanica seedling growth, and the beneficial effect of nitrogen addition declines sharply with increasing drought severity. These findings provide new empirical insights for predicting seedling regeneration and guiding sustainable forest nutrient management under ongoing climate change. Full article

Endometriosis is a long-term gynecological condition marked by the growth of endometrial-like tissue outside the uterus, which undergoes proliferation, bleeding, and regeneration. This disease is associated with disrupted steroid hormone signaling, notably progesterone (P4) resistance and estradiol (E2) dominance. P4 resistance has been associated with impaired activation of the progesterone receptor (PR) and reduced transcription of P4 target genes, while elevated E2 levels induce estrogen receptor (ER)-mediated signaling, enhancing estrogen-dependent lesion growth. This hormonal imbalance contributes to a pro-inflammatory microenvironment, chronic pelvic pain, infertility, and enhanced neuroangiogenesis. Emerging evidence indicates that the coordinated regulation of neurotrophins and sex hormones promotes nerve fibers and blood vessel growth and invasion within endometriotic lesions. P4 and E2 have been shown to modulate the expression of key neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). This review presents current evidence on the interplay between neurotrophins and ovarian steroids in endometriosis, with a specific focus on their contribution to neuroangiogenesis and pain pathophysiology. The review includes articles in English containing the Medical Subject Headings (MeSH) terms: “endometriosis”, “neurotrophins”, “nerve growth factor”, “brain-derived neurotrophic factor”, “neuroangiogenesis”, “progesterone”, and “estradiol”, found in the PubMed database published between 2000 and 24 May 2026. This review included a range of original research articles, systematic reviews, meta-analyses, prospective observational studies, case–control studies, and review papers, for a total of 122 articles. Full article

Circulating tumor DNA (ctDNA) has emerged as a transformative tool in cancer diagnostics, enabling the non-invasive detection of tumor-derived DNA fragments released into the bloodstream through cellular lysis or active secretion. ctDNA measurement has demonstrated its clinical usefulness, including early cancer detection, identification of resistance mechanisms, and screening of asymptomatic individuals. In addition to prognosis, ctDNA analysis is increasingly used to guide adaptive treatment strategies by detecting minimal residual disease and tracking tumor evolution in real time. Recent advances in artificial intelligence are poised to further enhance the clinical impact of ctDNA, transforming it from a passive monitoring biomarker into a dynamic molecular sensor integrated into predictive clinical decision models. However, broad implementation of ctDNA-based assays in routine practice requires rigorous prospective validation, cross-platform standardization, and regulatory approval to unlock its full potential in precision oncology. Full article

Cancer is a genetic disease driven by the accumulation of mutations that disrupt normal cellular growth. Among the most frequently mutated families are protein kinases, inositol polyphosphate kinases, and GTPases, which together function as central molecular switches controlling proliferation, survival, and metabolism. In cancer, activating mutations in protein kinases, such as EGFR and BRAF, lead to uncontrolled downstream signaling by locking these enzymes in a constitutively active state. Similarly, mutations affecting inositol kinases, notably PI3KCA, hyperactivate the PI3K/AKT pathway, promoting relentless cell survival and resistance to apoptosis. GTPases, particularly Ras family members (KRAS, NRAS, HRAS), are classical oncogenes where single amino acid substitutions impair their intrinsic GTP hydrolysis activity, trapping them in a persistently GTP-bound “on” state. This unleashes continuous mitogenic signaling independently of external growth factors. Collectively, these mutations are not random but converge on a limited set of core pathways, making them key drivers of tumor initiation and progression. Understanding the specific molecular consequences of kinase and GTPase mutations has directly informed the development of targeted therapies, including small molecule inhibitors and monoclonal antibodies, now used in routine clinical practice. Full article

Background/Objectives: Schistosomiasis, a parasitic disease caused by Schistosoma worms with freshwater snails as intermediate hosts, affects over 250 million people. The current control relies solely on praziquantel, which raises concerns on drug resistance and highlights the need for new therapeutic alternatives. Our bioprospection studies have focused on marine macroalgae as an unexplored source of antischistosomal metabolites with promising results. Guided by WHO recommendations to target both the parasite and its transmission vectors, this study aimed to investigate Ochtodes secundiramea to: (i) isolate active metabolites; (ii) evaluate the isolated compounds against adult worms and oviposition to identify leads for drug development; and (iii) perform an independent screening of their effects against the environmental transmission stages on cercariae and B. glabrata embryos. Methods: A dichloromethane extract of O. secundiramea was submitted to an NMR–biomonitored guided fractionation against Schistosoma mansoni adult worms. Active fractions were further purified through HPLC and characterized by ¹H and ¹³C NMR spectroscopy to identify the isolated compounds. Results: Three halogenated monoterpenes were isolated: ochtodene 1 (4-bromo-1,6,8-trichloro-2,3-ochtodene), ochtodene 2 (2-chloro-1,6,8-tribromo-3,8-ochtodene), and the novel natural product ochtodene 3 [2,6-dibromo-4-(2-chloroethylidene)-1,1dimethylcyclohexane]. Ochtodene 1 was the primary active metabolite against Schistosoma mansoni adult worms, with IC₅₀/96 h values of 47.2 and 46.1 µM for male and female worms respectively, and totally suppressed egg laying with 60 µM, while showing no toxicity toward human fibroblasts. Notably, all metabolites, including the novel ochtodene 3, caused 100% mortality in cercariae and embryos at low concentrations. Conclusions: The discovery of the novel ochtodene 3 and the identification of distinct leads for host treatment and transmission elimination position O. secundiramea as a promising source for integrated schistosomiasis control. Full article

Theranostics is a novel approach that integrates diagnostic and therapeutic efficacy on a single platform, holding great promise for precision medicine by enabling real-time monitoring of disease progression and therapeutic response. Despite significant advances, the successful development and delivery of theranostic systems are critically limited by multiple biological barriers present at systemic, tissue, cellular, anatomical, and immunological levels. These barriers restrict bioavailability, target accessibility, and therapeutic efficacy, while often increasing off-target accumulation and adverse effects. This review provides a comprehensive overview of the major biological barriers encountered in theranostic development, including physiological barriers such as plasma protein binding, renal clearance, and hepatic metabolism; anatomical barriers like endothelial linings, the blood–brain barrier (BBB), and the tumor microenvironment; cellular barriers involving membrane permeability, intracellular trafficking, and endo-lysosomal entrapment; and immunological barriers such as immune recognition, inflammatory responses, and complement activation. Special emphasis is placed on the BBB, highlighting its structural complexity, transport mechanisms, and strategies such as molecular Trojan-horse technology, receptor-mediated and adsorptive-mediated transcytosis, and nanocarrier-based approaches to enhance central nervous system delivery. The review further discusses targeted delivery challenges, including receptor heterogeneity and multidrug resistance, and critically evaluates current strategies to overcome these barriers through surface functionalization, stimuli-responsive systems, biomimetic carriers, and controlled-release mechanisms. Finally, recent advances, clinical challenges, and future perspectives—including personalized theranostics, artificial intelligence—assisted design, and next-generation barrier-penetrating systems—are explored. Overall, this review aims to provide a structured understanding of biological barriers in theranostics and highlight innovative approaches to improve their translational potential. Full article

Prostate cancer (PCa) is among the highest incidence malignancies in men, with high rates of inevitable resistance development, relapse, and mortality. Castration-resistant prostate cancer (CRPC) continued to pose substantial therapeutic challenges, highlighting the urgent need for effective treatment options. This study assessed the marine cembranoid sarcophine activity against the progression and recurrence of the metastatic CRPC (mCRPC) in mouse xenograft models. Protein and phosphorylation levels were assessed by immunoblotting and mRNA expression by qPCR and RNA sequencing. The in vivo efficacy was evaluated through tumor progression over 3 weeks followed by primary tumor excision and recurrence monitoring over an 8-week course. Sarcophine significantly reduced the mCRPC CWR-R1ca tumor volume by 74.1% and suppressed the epigenetic regulators EZH2 and SMYD2; lineage plasticity factors ASCL1 and BRN2; Wnt/stemness signaling markers β-catenin and LGR6; AKT total expression and activation; and invasion-associated proteins TRPC4 and MMP2 in primary tumors. Sarcophine effectively prevented the mCRPC locoregional recurrence, as well as lung and spleen distant recurrences, and effectively reduced recurrence in other organs. Transcriptomics-RNA-Seq analysis of primary tumors identified 2697 downregulated and 3534 upregulated genes, indicating broad transcriptional reprogramming following sarcophine treatments. These findings demonstrate coordinated suppression of multi-oncogenic pathways and validate the therapeutic potential of sarcophine to control mCRPC. Full article

Adipose tissue remodeling is a dynamic process essential for metabolic homeostasis, enabling tissue expansion, extracellular matrix (ECM) turnover, angiogenesis, and coordinated immune adaptation. In obesity, however, maladaptive remodeling characterized by fibrosis, chronic low-grade inflammation, and hypoxia disrupts adipose plasticity and promotes systemic insulin resistance. Central to these processes is the tightly regulated homeostasis between proteases and their inhibitors, in which the serine protease inhibitor (serpin) superfamily represents an important yet underappreciated regulatory axis. Beyond their classical roles in coagulation and fibrinolysis, serpins regulate ECM remodeling, macrophage recruitment and polarization, cytokine signaling, angiogenic responses, adipokine activity, and insulin sensitivity, thereby orchestrating immune–metabolic crosstalk within adipose depots. Emerging evidence indicates that individual serpins exert distinct and context-dependent effects, with some promoting fibrosis, inflammation, and metabolic dysfunction, whereas others preserve adipose tissue homeostasis and metabolic function. This review synthesizes current knowledge on the structural and functional diversity of the serpin superfamily and examines their mechanistic roles in adipose tissue remodeling during obesity, with particular emphasis on how adipose-associated serpins regulate adipose tissue homeostasis, depot-specific remodeling, and immune–metabolic crosstalk. The review further discusses the experimental and translational applications of emerging single-cell and spatial transcriptomics, multi-omics, and computational approaches that may advance the understanding of serpin biology, improve the investigation of human adipose tissue, and accelerate the identification of clinically relevant serpin-related biomarkers and therapeutic targets for obesity and related metabolic disorders. By positioning serpins as key regulators of adipose tissue remodeling and immune–metabolic integration, this review highlights protease–antiprotease balance as a central determinant of metabolic health and identifies serpins as promising biomarkers and therapeutic targets for obesity and related metabolic disorders. Full article

In this study, we report the results of the structural characterization and electrochemical evaluation of novel cobalt-free layered Ruddlesden–Popper (RP) oxides, La₂SrFe₂O_7−δ and La₂SrFe_1.8Ga_0.2O_7−δ, as electrode materials for intermediate-temperature solid oxide cells. X-ray diffraction confirmed the formation of RP phases and phase stability after reducing treatment. The materials showed compatible thermal expansion behavior, with slightly lower thermal expansion coefficients for the Ga-doped composition. Oxygen pressure relaxation measurements demonstrated that the oxygen surface exchange coefficient increases with temperature and pO₂, while Ga substitution slightly reduces the O₂/oxide exchange rate, which may be associated with a lower concentration of oxygen vacancies. The electrical conductivity in air was higher for La₂SrFe₂O_7−δ than for the Ga-doped sample, while both compositions showed much lower conductivity under reducing conditions. Symmetrical cell impedance spectroscopy showed high polarization resistance for the electrodes, which was substantially reduced by applying a Ag current collector (0.43 Ω cm² for La₂SrFe₂O_7−δ and 0.73 Ω cm² for La₂SrFe_1.8Ga_0.2O_7−δ at 800 °C), consistent with the limited electronic conductivity of the oxide layers. Overall, both oxides exhibit structural stability, acceptable thermomechanical compatibility, and measurable oxygen exchange activity, making them promising candidates for further development as cobalt-free electrodes in solid oxide cells. Full article

Fatty acid-binding protein 7 (FABP7) is a multifunctional lipid chaperone that is enriched in radial glia and astrocytes within the central nervous system (CNS) and is frequently upregulated in glioma. Beyond its established roles in glial development, lipid homeostasis, and circadian regulation, growing evidence positions FABP7 at the intersection of tumor metabolism, neuronal activity, and immune modulation in the brain. In this review, we integrate the physiological functions of FABP7 in glial cells with its tumor-intrinsic and microenvironmental roles in glioma. We summarize how gliomas co-opt FABP7-dependent metabolic, transcriptional, and post-transcriptional programs to promote stemness, lipid remodeling (e.g., altered fatty acid composition, lipid droplet formation, and lipid peroxidation resistance), inflammatory signaling, and invasive growth, including nuclear FABP7-mediated transcriptional activation linked to oncogene status. Furthermore, we discuss the role of FABP7 in shaping the tumor–neuro–immune interface, including regulating immunosuppressive gene networks, pro-tumoral macrophage polarization, resistance to T-cell-induced ferroptosis and immunotherapy, and tumor microtube-mediated integration into neuronal circuits to support glioma progression. Finally, we highlight therapeutic opportunities and challenges, including small-molecule FABP7 inhibitors, brain-directed delivery strategies, chronotherapeutic considerations, and combination approaches with immunotherapy. Collectively, this work positions FABP7-centered metabolic, circadian, and neuro-immune networks as potential vulnerabilities in glioma, linking fundamental glial biology to glioma therapeutics. Full article

Brucellosis and tuberculosis (TB) are chronic infectious diseases of international public health importance, with developing countries being most affected. The diagnosis of brucellosis and tuberculosis co-infection remains challenging because both diseases present with overlapping nonspecific clinical manifestations, such as prolonged fever, fatigue, and weight loss, and elicit similar cell-mediated immune and inflammatory responses, which can complicate differential diagnosis, particularly in endemic regions. Recently, it has been shown that chronic infections affect cell stress pathways such as oxidative stress and telomere function. The current literature review provides an overview of the relationship between brucellosis and TB at a molecular level, focusing on telomere biology, oxidative stress and the mechanisms of antimicrobial resistance. Due to chronic immune response in brucellosis and TB patients, an increase in reactive oxygen species (ROS) levels is observed, leading to DNA damage and subsequent telomere shortening and alteration of telomerase activity. These alterations might be responsible for immune senescence, weakened defense response and persistent infection. In addition, different methods of drug resistance have been discovered among brucellae and mycobacteria, such as mutation in target sites, efflux systems and intracellular persistence, making their eradication difficult. Finally, the potential role of telomere-related genes and biomarkers of oxidative stress in diagnosis and prognosis is also highlighted. Insights into these interrelated pathways would allow us to have a better understanding of host–pathogen interactions and hence offer a possible means of developing new strategies in the fight against co-infection by finding new biomarkers. Full article

Obesity is a major global health challenge strongly associated with increased cardiometabolic morbidity and mortality. In men, obesity is characterized by a predominance of visceral adiposity, which is metabolically active and closely linked to systemic inflammation, hormonal dysregulation, and adverse cardiovascular outcomes. Despite its clinical relevance, male obesity remains underrecognized as a distinct pathophysiological condition. This study aimed to analyze the inflammatory mechanisms underlying male obesity and their relationship with cardiometabolic risk. A structured narrative review was conducted based on a PICo-guided research question, with literature searches performed in PubMed/MEDLINE, Scopus, Web of Science, Embase, and ScienceDirect, covering publications from 2015 to 2026. Studies focusing on male obesity, inflammatory pathways, and cardiometabolic outcomes were included. Evidence indicates that visceral adipose tissue acts as an active endocrine organ, releasing pro-inflammatory cytokines such as TNF-α and IL-6, contributing to chronic low-grade inflammation. This inflammatory state is associated with insulin resistance (IR), endothelial dysfunction, and oxidative stress, mediated by intracellular pathways including NF-κB and JNK. Additionally, adipokine imbalance, characterized by reduced adiponectin and increased leptin levels, further exacerbates metabolic and vascular impairment. Hormonal alterations, particularly reduced testosterone levels, play a key role in amplifying visceral fat accumulation and inflammation, creating a bidirectional relationship between hypogonadism and metabolic dysfunction. Clinically, these mechanisms highlight the importance of integrating inflammatory biomarkers, body composition assessment, and hormonal evaluation into the management of male obesity. Emerging therapies, including GLP-1 receptor agonists and immunometabolic interventions, offer promising strategies for reducing cardiometabolic risk. In conclusion, male obesity represents a complex, inflammation-driven condition requiring a comprehensive and mechanism-based approach to improve clinical outcomes and guide future therapeutic developments. Full article

Background/Objectives: Motor impairments, including reduced muscular strength and coordination, are commonly reported in children with autism spectrum disorder (ASD) and may negatively affect functional mobility and participation in daily activities. Despite increasing recognition of these challenges, structured resistance training programs for children with ASD remain limited. This study aimed to examine the effects of a 12-week resistance training program on muscular strength and functional performance in children aged 9–11 years with mild ASD. Methods: A selected-group repeated-measures design was employed. Twenty-eight children with specialist-confirmed mild ASD were allocated to an exercise (n = 14) or control group (n = 14) using a strength-matched allocation procedure. The intervention followed established exercise guidelines for youth. Assessments were conducted at baseline, week 6, and week 12 and included handgrip strength, vertical jump height, and 10-m walk time. Non-parametric Friedman tests assessed changes over time, followed by Durbin–Conover post hoc comparisons where appropriate. Effect sizes (r) were calculated. Results: No significant overall time effect was observed for handgrip strength, although a between-group difference favoring the exercise group was observed at week 6. Vertical jump height demonstrated a significant effect over time, with improvements observed in the exercise group from baseline to week 6 and a between-group difference at week 6. Walking time improved significantly across the study period, with improvements observed in both the exercise and control groups. Conclusions: These findings suggest that structured resistance training is a feasible intervention that may support improvements in physical function in children with mild ASD. Resistance training may therefore represent a useful component of exercise programs aimed at improving functional mobility and participation in children with developmental conditions. Full article

Background: The global emergence of antibiotic resistance highlights the urgent need for novel therapeutic strategies, including adjuvants and potentiating compounds, against multidrug-resistant bacteria. Pseudomonas aeruginosa is classified by the World Health Organization (WHO) as a critical priority pathogen due to its high resistance potential and its ability to cause severe nosocomial infections. Beauvericin (BEA), a frequently detected mycotoxin, has been reported to exhibit various bioactive properties, including potential antibacterial and potentiating effects. Methods: The interaction between BEA and a last-resort antibiotic, colistin (COL), was evaluated in seven multidrug-resistant P. aeruginosa isolates using a microplate-based growth assay after preliminary MIC tests. Results: BEA at non-inhibitory concentrations (2.5–10 µg/mL) significantly enhanced the antibacterial activity of COL (1 and 2 µg/mL) in six out of seven isolates, resulting in a marked reduction in residual bacterial growth. Conclusions: BEA exhibited no measurable antibacterial activity at the concentrations used in the combination experiments but acted as a strain-dependent potentiator of colistin activity against multidrug-resistant P. aeruginosa. The observed enhancement of colistin-mediated growth inhibition supports the potential of BEA as an antibiotic adjuvant at clinically relevant colistin concentrations and provides a basis for further mechanistic investigation. Full article