Search Results (187)

The oral cavity harbors one of the most diverse microbial ecosystems in the human body, second only to the gut. Periodontitis, a chronic inflammatory disease arising from oral microbiota dysbiosis, has been increasingly associated with systemic disorders such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and neurodegenerative conditions. Although hematogenous dissemination of oral pathogens and inflammatory mediators has long been proposed as a mechanistic link, emerging evidence identifies the oral–gut axis as a novel bidirectional pathway. Swallowed oral pathobionts, such as Porphyromonas gingivalis and Fusobacterium nucleatum, can colonize the gut, disrupt the intestinal barrier, and induce dysbiosis, immune imbalance, and metabolic alterations that aggravate systemic inflammation and disease progression. In contrast, gut dysbiosis, especially in obesity or high-fat-diet models, can exacerbate periodontal tissue destruction through hyperuricemia, altered bone metabolism, and Th17/Treg immune imbalance. Experimental and clinical studies further support this reciprocal relationship, implicating microbial, metabolic, and immune crosstalk in both oral and systemic pathology. Understanding this oral–gut–systemic axis offers a paradigm shift in diagnostics and therapeutics, focusing on precision interventions such as microbiome modulation, probiotics, and integrated oral care to mitigate systemic inflammatory burden and improve overall health outcomes. Full article

Iodine is an essential micronutrient that is required for thyroid hormone (TH) synthesis. However, adequate maternal thyroid function is critical for fetal growth and neurodevelopment. Pregnancy increases iodine requirements due to enhanced renal clearance, higher maternal TH production, and transplacental transfer, making pregnant women especially vulnerable to iodine deficiency. In this review, we examine the molecular mechanisms of TH synthesis and regulation, placental transport and metabolism, and the physiological adaptations of thyroid function during gestation. We also analyze the clinical and public health consequences of iodine imbalances, ranging from deficiency to excess. Evidence indicates that mild iodine deficiency—which is common even in developed countries—can lead to maternal thyroid overstimulation, increased thyroglobulin levels, altered T3/T4 ratios, and enlarged thyroid volume, while severe deficiency results in maternal and fetal hypothyroidism with irreversible neurocognitive impairment in the offspring. Conversely, excessive iodine intake may impair fetal thyroid function through mechanisms such as the Wolff–Chaikoff effect. In conclusion, ensuring balanced iodine intake through iodized salt, supplementation, and routine thyroid monitoring during pregnancy is essential to protect maternal health and optimize early neurodevelopment. Full article

Background/Objectives: Pregnancy-induced hypertension (PIH), including preeclampsia (PE), remains a significant cause of maternal and fetal morbidity. Immune imbalance involving T helper (Th17) and regulatory T (Treg) cells is increasingly recognized as contributing to the pathogenesis of PIH. This study aimed to assess the proportions of Th17 and Treg cells and intracellular cytokine expression (IL-17A, IL-17F, IL-21, and IL-22) in the peripheral blood of hypertensive versus normotensive pregnant women. Methods: A total of 108 pregnant women were included: 60 with hypertensive disorders and 48 normotensive controls. Peripheral blood mononuclear cells were analyzed using multiparametric flow cytometry to quantify CD4+CD25+FoxP3+ Treg and CD4+IL-17A+ Th17 cells, along with intracellular IL-17F, IL-21, and IL-22 co-expression. Correlations with clinical and obstetric parameters were evaluated. Results: Hypertensive patients showed significantly increased proportions of activated Th17 cells (CD4+IL-17A+) and Th17 subpopulations co-expressing IL-17F and IL-22, as well as IL-21 and IL-22 (p < 0.0001). Although Treg cell percentages were lower in the hypertensive group, the difference was not statistically significant. A pronounced Th17/Treg imbalance was observed. Positive correlations were found between Th17 subpopulations and gestational age, birth weight, and length, as well as maternal age. Conclusions: The immune profile in hypertensive pregnancies was characterized by a shift toward Th17-mediated proinflammatory responses, supporting the role of immune dysregulation in PIH. The increased frequency of Th17 cells co-expressing IL-21 and IL-22 may serve as a potential biomarker of disease severity and warrants further exploration. Full article

Stress is a predisposing factor for pulmonary diseases; however, its effects on the lungs of healthy individuals have not been fully elucidated. Since bovine lactoferrin (bLf) is a powerful immunomodulator, this study aimed to evaluate whether lactoferrin can modulate the effects of chronic stress on humoral and cellular immunity in the lungs. We performed chronic restraint stress (RS) and oral administration of bLf in a BALB/c model, assessing serum corticosterone, body weight, and various lung immunity parameters, including immunoglobulin concentrations in serum and tracheobronchial lavages (TBLs), secretory IgA (S-IgA) levels in TBLs, IgA-secreting plasma cells, relative expression of pIgR, CD4⁺ lymphocyte Th1 and Th2 populations, and antigen-presenting cell (APC) populations in the lungs. Our results demonstrate that stress increases corticosterone and production of total IgA and IgG, while decreasing levels of IgM and S-IgA, promotes a Th1/Th2 profile imbalance, and decreases APC populations. Interestingly, bLf modulates serum corticosterone levels and stress-induced weight loss, and it also modulates humoral and cellular effects produced by chronic stress. These results demonstrate that bLf should be considered a new therapeutic target for further studies, focusing on prophylactic and co-therapeutic administration to treat and prevent respiratory diseases. Full article

Background/Objectives: With the aging of the population, the number of patients with osteoporosis is increasing worldwide. Osteoporosis results from an imbalance in bone remodeling by osteoblasts and osteoclasts. This study investigated the effects of sake lees and rice koji, traditional Japanese rice-fermented products, on bone metabolism. Methods: Both sake lees extract and rice koji extract increased alkaline phosphatase (ALP) activity, extracellular collagen accumulation, and mineralization of MC3T3-E1 cells. In addition, the intracellular protein levels of Hsp47 and Sec23IP, which are required for collagen maturation and secretion, respectively, were increased during the differentiation. On the other hand, both extracts significantly inhibited osteoclastic differentiation. Furthermore, the effects of freeze-dried sake lees or rice koji extract on osteoporotic bones were examined using twelve-week-old female C3H/HeJ ovariectomized (OVX) mice. Results: The groups of mice fed 20% or 40% freeze-dried sake lees showed significant suppression of the loss in bone volume fraction (BV/TV) and trabecular volume (Tb.V) compared with those fed a normal diet as well as the 40% freeze-dried sake lees-fed group reduced in the loss of trabecular thickness (Tb.Th). Similarly, the rice koji extract-treated mice showed significant inhibition of the loss in BV/TV, Tb.V, and even trabecular number (Tb.N.). Folic acid and S-adenosylmethionine (SAM), which have been reported to be present in sake lees, promoted extracellular collagen production by osteoblasts. Conclusions: In OVX mice, the intake of freeze-dried sake lees or rice koji extract was associated with the attenuation of trabecular bone loss, suggesting potential beneficial effects on bone metabolism. Full article

The STAT (Signal Transducer and Activator of Transcription) signaling pathway plays a central role in immune regulation by mediating cytokine responses and orchestrating both innate and adaptive immunity. Although CD4+ T cell depletion is the main driver of HIV-1–induced immunodeficiency, the virus also exerts a significant and often underestimated impact by disrupting the function of STAT family members, thereby exacerbating immune imbalance and accelerating disease progression. Specifically, HIV-1 suppresses STAT1 activation, impairing the induction of antiviral genes; inhibits IL-23–driven STAT3 activation in CD4+ Th17 cells with a reduction in IL-17; alters STAT3-dependent functions in antigen-presenting cells; and imposes profound—and at times opposing—dysregulations of STAT5, including the induction of a truncated isoform that contributes to latency. Notably, pharmacological inhibition of the JAK/STAT axis, particularly with JAK2 inhibitors, has been shown to reduce integrated proviral DNA and viral replication in vitro and in early clinical studies. This review provides an updated overview of the roles of individual STAT proteins in HIV-1 infection and pathogenesis, emphasizing the intricate interplay between viral factors and host signaling, highlighting the potential therapeutic implications, and suggesting that immunological assessment in HIV-1 patients should extend beyond CD4+ T cell counts and the CD4/CD8 ratio to include functional analysis of STAT signaling for deeper insights into immune dysfunction and chronic inflammation. Full article

Colorectal cancer (CRC) remains a major global challenge, with growing attention to its pathogenesis as mediated by the gut microbiome and epigenetic regulation. Despite therapeutic progress, clinical management remains difficult. CRC accounts for ~10% of cancers and is the second leading cause of cancer death worldwide. Romania bears a substantial burden, with many diagnoses at advanced stages. Etiology—Integrated Genetic, Environmental, and Microbial Determinants. Hereditary syndromes explain 10–15% of cases; most are sporadic, with hypermutated MSI/POLE (~15%), non-hypermutated chromosomal instability (~85%), and a CpG island methylator phenotype (~20%). GWAS implicate loci near SMAD7, TCF7L2, and CDH1; in Romania, SMAD7 rs4939827 associates with risk. Lifestyle exposures—high red/processed meat, low fiber, adiposity, alcohol, and smoking—shape susceptibility. Microbiome–Epigenome Interactions. Dysbiosis promotes carcinogenesis via genotoxins (e.g., colibactin), hydrogen sulfide, activation of NF-κB/STAT3, barrier disruption, and epigenetic remodeling of DNA methylation and microRNAs. Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and pks⁺ Escherichia coli exemplifies these links. Population-Specific Risk—Romania within Lifestyle–Microbiome Evidence. Incidence is rising, including early-onset disease. Romania lacks CRC-specific microbiome datasets. However, metabolic cohorts show loss of butyrate producers, enrichment of pathobionts, and SCFA imbalance—patterns that mirror European CRC cohorts—and exhibit regional heterogeneity. Beyond Fusobacterium nucleatum. Additional oncobacteria shape tumor biology. Peptostreptococcus stomatis activates integrin α6/β4→ERBB2–MAPK and can bypass targeted inhibitors, while Parvimonas micra enhances WNT/β-catenin programs and Th17-skewed immunity. Together, these data support a systems view in which microbial cues and host epigenetic control jointly drive CRC initiation, progression, metastasis, and treatment response. Full article

Thyroid hormones (THs) are essential for brain development, and their dysregulation is associated with cognitive deficits and neurodevelopmental disorders. Down syndrome (DS), caused by trisomy 21, is frequently associated with thyroid dysfunction and impaired neurogenesis. Here, we investigated THs signaling dynamics during neural differentiation using human induced pluripotent stem cells (hiPSCs) derived from individuals with DS and controls. We analyzed the gene expression of key THs regulators—deiodinases, transporters, and receptors—and downstream target genes in hiPSCs, hiPSC-derived neural progenitor cells (NPCs), hiPSC-derived astrocytes, and hiPSC-derived neurons. DS-derived hiPSCs, hiPSC-derived NPCs, and hiPSC-derived neurons exhibited 2- to 7-fold increases in the gene expression of DIO2 and 3- to 8-fold reductions in DIO3, alongside 1- to 3-fold downregulation of THRA and THRB isoforms. hiPSC-derived astrocytes showed a 4-fold decrease in the gene expression of DIO2, a 4-fold increase in DIO3, upregulation of SLC16A10 (2-fold), and downregulation of SLC7A5 (0.5-fold) and THs receptors (0.5- to 12-fold). hiPSC-derived neurons exhibited marked downregulation of the gene expression of HOMER1 (0.5-fold), GRIN3A (14-fold), and GRIN3B (4-fold), accompanied by impaired spontaneous activity in multi-electrode array recordings. These findings reveal a robust, cell-type-specific imbalance between THs availability and signaling competence in DS hiPSC-derived neural cells, providing mechanistic insight into THs-related contributions to the function of DS hiPSC-derived neural cells and identifying potential therapeutic targets. Full article

Urban livability and sustainable development remain major global challenges, yet the interplay between urban planning layouts and actual human activities has not been sufficiently examined. This study investigates this relationship in Beijing by integrating multi-source spatiotemporal data, including point of interest (POI), Land Use Cover Change (LUCC), remote sensing data, and the railway network. Defining urban functional units as “street + railway network”, we analyze the spatial–temporal evolution within the 6th Ring Road over the past four decades and propose targeted strategies for the urban functional layout. The results reveal the following: (1) The evolution of Beijing’s urban functions can be divided into four stages (1980–1990, 1990–2005, 2005–2015, and 2015–2020), with continuous population growth (+142%) driving the over-concentration of functions in central districts. (2) Between 2010 and 2020, the POI densities of medical services (+133.6%) and transport services (+130.48%) increased most rapidly, subsequently stimulating the expansion of other urban functions. (3) High-density functional facilities and construction land (+179.10%) have expanded significantly within the 6th Ring Road, while green space (cropland, forestland and grassland) has decreased by 86.97%, resulting in a severe imbalance among land use types. To address these issues, we recommend the following: redistributing high-intensity functions to sub-centers such as Tongzhou and Xiongan New Area to alleviate population pressure, expanding high-capacity rail transit to reinforce 30–50 km commuting links between the core and periphery, and establishing ecological corridors to connect green wedges, thereby enhancing carbon sequestration and environmental quality. This integrated framework offers transferable insights for other megacities, providing guidance for sustainable functional planning that aligns human activity patterns with urban spatial structures. Full article

Mast cells (MC) are key effector cells in allergic diseases and are increasingly recognized for their roles in the immunopathogenesis of tuberculosis (TB). In allergic conditions, MCs are hyperactivated, driving T-helper Type 2 (Th2)-skewed immune responses that may antagonize the T-helper Type 1 (Th1)-mediated immunity essential for controlling Mycobacterium tuberculosis (Mtb) infection. This immunological imbalance may contribute to increased TB susceptibility, altered granuloma dynamics, and accelerated fibrotic remodeling. Histopathological and in vivo studies have revealed that MCs are recruited to TB lesions, where they release a spectrum of mediators, including histamine, IL-17A, TNF-α, TGF-β, tryptase, and chymase. These mediators can either support initial immune defense or promote chronic inflammation and tissue damage, depending on context and regulation. Moreover, individuals with chronic allergic diseases such as asthma and allergic rhinitis may experience worse TB outcomes due to their baseline immune dysregulation. Environmental exposures (e.g., air pollution, smoking), genetic polymorphisms (e.g., IL-4 −589C/T, IL-13 R130Q), and gut-lung axis disturbances further modulate MC activity and TB pathogenesis. This review synthesizes current findings on MC involvement in TB, particularly in allergic settings, and highlights the need for epidemiological studies and mechanistic research. It also explores the promise of host-directed therapies (HDTs) that target MCs or their mediators, such as antihistamines, MC stabilizers, leukotriene inhibitors, and cytokine modulators, as novel adjuncts to standard TB treatment. Personalized approaches that consider immune profiles, genetic risk, and comorbid allergies may improve TB outcomes and inform future clinical guidelines. Full article

In response to China’s dual-carbon strategy, this study proposes a comprehensive analytical framework to identify the evolutionary pathways of key policy tasks in developing a new-type power system. A dual-channel data acquisition process was designed to extract, standardize, and segment policy documents and online texts into a unified corpus. A multi-label BERT classification model was then developed, incorporating domain-specific terminology injection, label-wise attention, dynamic threshold scanning, and imbalance-aware weighting. The model was trained and validated on 200 energy news articles, 100 official policy releases, and 10 strategic planning documents. By the 10th epoch, it achieved convergence with a Macro-F1 of 0.831, Micro-F1 of 0.849, and Samples-F1 of 0.855. Ablation studies confirmed the significant performance gain over simplified configurations. Structural label analysis showed “Build system-friendly new energy power stations” was the most frequent label (107 in plans, 80 in news, 24 in policies) and had the highest co-occurrence (81 times) with “Optimize and strengthen the main grid framework.” The label co-occurrence network revealed multi-layered couplings across generation, transmission, and storage. The Priority Evaluation Index (PEI) further identified “Build shared energy storage power stations” as a structurally central task (centrality = 0.71) despite its lower frequency, highlighting its latent strategic importance. Within the domain of national-level public policy and planning documents, the proposed framework shows reliable and reusable performance. Generalization to sub-national and project-level corpora is left for future work, where we will extend the corpus and reassess robustness without altering the core methodology. Full article

We developed a machine-learning model for the International Classification of Diseases, 10th Revision (ICD-10) classification using data from 5108 patients. Nine features, including age, gender, BMI, and vital signs, were extracted to classify the top three ICD-10 categories: intestinal infections, tuberculosis, and other bacterial diseases. Decision trees, random forest, and XGBoost models were tested using the synthetic minority over-sampling technique (SMOTE) and class weights to minimize class imbalance. Five-fold cross-validation was used using the training and testing datasets in a data ratio of 80:20. The random forest model with class weights showed the best performance. Shapley additive explanations (SHAP) analysis highlighted body-mass index (BMI), gender, and pulse as key features. The developed model showed potential for enhancing ICD-10 classification through real-time and personalized medical applications. Full article

Type 2 diabetes mellitus (T2DM) is known to increase the risk of fragility fractures; however, the underlying mechanism is still elusive. Reduced miR-155 and elevated RHOA are known to drive bone resorption, but their role in T2DM remains unclear. This study investigates bone remodeling imbalances in T2DM through miR-155 and RHOA expression profiling. Three-month-old female Wistar rats were fed a high-calorie diet for 3 weeks, followed by intraperitoneal injections of two lower doses of streptozotocin at weekly intervals to induce T2DM. Bone analysis from diabetic rats tested using qRT-PCR showed significantly reduced miR-155 levels and elevated RHOA. Histological analysis showed a 12.65% increase in Tb.Sp, 10.07% decrease in Tb.Th, and significant increase (p < 0.05) in apoptotic osteocytes. The bone turnover marker CTx-1 level was increased by 20.84%, and RANKL levels were significantly increased in T2DM. IL-1β and TNF-α were increased in T2DM. Bone resorption is more likely to occur in T2DM as both IL-1β and TNF-α work synergistically to promote osteoclastogenesis. MiR-155 could be an important modulator of bone remodeling in T2DM and a potential therapeutic target for diabetic osteopathy. Full article

Atopic dermatitis (AD) is a chronic inflammatory disorder with immune imbalance, including elevated IgE levels and mast cell activation mediated by Th2 cytokines, leading to allergic inflammation and impaired skin barrier function. Current treatment limitations highlight the need for safer and more effective AD alternatives. We aimed to evaluate the therapeutic effects of multi-strain probiotics, BCL-2 (comprising Lactiplantibacillus plantarum LRCC5264 and Bifidobacterium longum RAPO), in alleviating AD clinical signs and elucidate its underlying immunomodulatory mechanisms. In vitro, BCL-2 treatment significantly reduced IL-4 secretion in RBL-2H3 cells, with higher inhibitory effects than single-strain treatment. In vivo, BCL-2 (10⁶–10⁸ CFU/day) was orally administered for 28 days to AD-induced Nc/Nga mice. BCL-2 treatment improved the clinical signs and histopathological features of AD, including epidermal hypertrophy, hyperkeratosis, and mast cell infiltration (p < 0.05). It also reduced neutrophil and eosinophil counts and modulated cytokine and chemokine profiles, notably decreasing IL-17, IL-5, IL-6, TNF-α, IL-1β, TARC, and eotaxin, while increasing IL-10, IFN-γ, and IL-12 (p < 0.05). Among the tested concentrations, 10⁷ CFU exhibited the most effective immune modulation with no adverse effects on body weight. These findings demonstrate the therapeutic potential of BCL-2 in AD; however, further studies are required to validate its clinical relevance. Full article

Lipid hormone imbalances involving glucocorticoids, thyroid hormones (THs), and sex hormones have widespread metabolic consequences, contributing to the global increase in obesity and insulin resistance. This review examines the complex role of disrupted lipid hormone pathways in the development of metabolic disorders, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Endocrine disorders such as hypercortisolism, hypothyroidism, and polycystic ovary syndrome (PCOS) are closely linked to MASLD through shared metabolic pathways. Mechanisms include glucocorticoid-induced gluconeogenesis and lipolysis, impaired lipid clearance in hypothyroidism, and the hyperandrogenism-induced downregulation of hepatic low-density lipoprotein (LDL) receptors. PCOS-related factors—such as central obesity, adipocyte hypertrophy, low adiponectin levels, and genetic predisposition—further promote hepatic steatosis. Thyroid dysfunction may also impair the hepatic deiodination of T4, contributing to lipid accumulation and inflammation. Given the overlapping pathophysiology among endocrine, hepatic, and reproductive disorders, multidisciplinary collaboration is essential to optimize diagnosis, treatment, and long-term cardiometabolic outcomes. Full article