Search Results (587)

Diabetes mellitus represents a global health concern, which is expected to worsen over the years. The prevalence is estimated to increase up to 642 million people by 2040. Almost half of diabetic patients are at a high risk of developing kidney involvement up to dialysis; moreover, macrovascular complication could be an obstacle to kidney transplant. Besides the classic albuminuric phenotype, non-albuminuric diabetic kidney disease was also discovered recently. Fortunately, compared with classic therapy with diet, oral hypoglycemic drugs, and insulin, current clinicians can rely on several new drugs that act with different pathways characterized by kidney and heart protection, as shown by several clinical trials and confirmed in clinical practice. Herein, we will review the therapies that nephrologist and diabetologist have available today and the future perspective. Full article

Background: The incidence of endometrial cancer (EC) is rising globally across all age groups. Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion that may progress to EC if untreated. A clinical model is needed to efficiently identify women requiring prompt evaluation while avoiding unnecessary invasive procedures. Obesity is a major risk factor, but whether Asian women require a lower body mass index (BMI) cutoff than the World Health Organization (WHO) definition remains debated. This study aimed to develop a multivariable risk prediction model to guide biopsy decisions and determine an appropriate BMI cutoff for predicting EIN/EC risk among Asian women. Methods: This study retrospectively reviewed 1192 women aged ≥18 years who underwent hysteroscopy between 2010 and 2023 at a tertiary hospital. Candidate predictors included patient age, parity, BMI, postmenopausal status, symptom of abnormal uterine bleeding (AUB), diabetes mellitus, hypertension, polycystic ovary syndrome (PCOS), use of oral contraceptives, intrauterine devices, or menopausal hormone therapy, tamoxifen treatment, presence of multiple polyps, and endometrial thickness (EMT) measured by transvaginal ultrasonography. Multivariable logistic regression with stepwise selection identified independent predictors, and model stability and calibration were assessed using 1000 bootstrap resamples. Results: EIN/EC was diagnosed in 55 patients (4.6%). Six independent predictors were identified: postmenopausal status (adjusted odds ratio [aOR] 5.93, 95% CI 2.92–12.04), AUB (aOR 4.07, 1.51–10.97), multiple polyps (aOR 2.49, 1.33–4.66), PCOS (aOR 2.37, 1.08–5.22), BMI (aOR 1.13 per kg/m²; 1.84 per +5 kg/m²), and EMT (aOR 1.07 per mm, 1.02–1.11). When using categorical cutoffs, Obese II (BMI ≥ 30 kg/m²) and markedly increased EMT (≥20 mm) remained significant. Predicted probabilities ranged from 0.3% with no risk factors to 90.9% with all six risk factors present. The final model demonstrated good discrimination (AUC 0.79, 95% CI 0.73–0.86) and excellent calibration on bootstrap validation (mean absolute error 0.005). Conclusions: This six-factor clinical model stratifies individual EIN/EC risk using readily available variables and may guide timely, risk-based biopsy decisions by identifying high-risk patients while minimizing unnecessary procedures in low-risk cases. BMI ≥ 30 kg/m² (WHO obesity threshold) was confirmed as a meaningful cutoff, but external validation is warranted to confirm its generalizability and clinical applicability. Full article

Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by insulin resistance and pancreatic β-cell dysfunction. While human umbilical cord mesenchymal stem cells (HUCMSCs) show therapeutic potential, their efficacy can be limited by the harsh in vivo microenvironment. 20(R)-Rg3, a ginsenoside with anti-inflammatory and antioxidant properties, may enhance HUCMSCs’ function, but the combined effect and mechanism of this “cell-molecule” strategy remain unclear. This study aimed to investigate the therapeutic effects and underlying mechanisms of a combination therapy using 20(R)-Rg3 and HUCMSCs in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mouse model. Diabetic mice were treated with PBS, HUCMSCs alone, or HUCMSCs pre-treated with 20(R)-Rg3. Fasting blood glucose and body weight were monitored. Insulin resistance was assessed via oral glucose tolerance tests (OGTTs) and intraperitoneal insulin tolerance tests (IPITTs). Serum biochemical parameters (lipids, liver and kidney function, insulin, C-peptide) were analyzed. Histopathological examination (H&E, PAS) of the liver, kidney, and pancreas was performed, alongside immunofluorescence for islet hormones. Transcriptomic analysis (RNA-seq) was conducted on HUCMSCs with or without 20(R)-Rg3 pretreatment to elucidate potential signaling pathways. Results demonstrated that the combination significantly reduced hyperglycemia and improved insulin sensitivity more effectively than HUCMSCs alone. It also ameliorated dyslipidemia, enhanced liver and kidney function, promoted glycogen synthesis, and facilitated pancreatic islet “regeneration”. Transcriptomic analysis indicated that the synergistic effect is primarily mediated through activation of the PI3K/Akt signaling pathway. These findings suggest that 20(R)-Rg3 potentiates the therapeutic efficacy of HUCMSCs, providing a promising combinatorial strategy for T2DM treatment. Full article

Food allergies are rising globally, posing a multifactorial public health challenge driven by complex interactions among diet, immune development, and environmental exposures. This review highlights emerging insights into the cellular and molecular mechanisms by which specific dietary components, particularly vitamin A, fibre, indole compounds, and proteins, promote intestinal homeostasis. These nutrients act through both microbiota-dependent and -independent pathways, primarily in the small intestine, enhancing epithelial barrier integrity and supporting tolerogenic immune responses. Two key signalling axes, mediated by retinoic acid (RA) and aryl hydrocarbon receptor (AhR) ligands, converge to regulate RORγt-expressing immune cells, including group 3 innate lymphoid cells, TCRγδ⁺CD8αα⁺ intraepithelial lymphocytes (IELs), and Th17 cells, which are essential for secondary lymphoid organ development and barrier reinforcement. RA and AhR also guide the homing and specialization of diverse regulatory T cell subsets and CD4⁺ IELs, which collectively sustain peripheral tolerance to dietary antigens. Recent findings implicate RORγt⁺ antigen-presenting cells in the induction of peripheral Tregs during early life, particularly at weaning, underscoring a critical window for tolerance establishment. Microbial metabolites and commensal-derived signals further shape these immune pathways, reflecting the intricate interplay between host, diet, and microbiota in the regulation of oral tolerance. Full article

Chagas disease (CD), caused by the parasite Trypanosoma cruzi, remains one of the most important neglected tropical diseases. Historically confined to rural areas of Latin America, the disease has now become a global health challenge due to increased migration, urbanization, and ecological changes. This review explores how patterns of transmission and endemicity have evolved, emphasizing the emergence of new geographic hotspots and non-traditional routes of transmission, such as congenital and oral infections. We integrate evidence from ecological studies showing how deforestation, urban sprawl, and climate change are reshaping vector habitats and influencing the spread of triatomine insects. Furthermore, we highlight advances made between 2020 and 2025 in key research areas, including vector genomics and climate-based predictive mapping, as well as digital surveillance strategies that leverage machine learning and citizen science. These innovations provide valuable insights for predicting future risks and improving disease control. By linking global epidemiological trends, ecological drivers, and cutting-edge scientific advances, this review underscores the urgent need for integrated, collaborative strategies to prevent further spread and to protect vulnerable populations worldwide. Full article

The World Health Organization’s Bangkok Declaration, ‘No health without oral health,’ recognizes oral health as a global public health priority. Despite being largely preventable, oral diseases affect nearly half of the global population, and India mirrors this crisis while facing persistent systemic challenges. This qualitative study explores India’s oral healthcare landscape from the perspective of public health dentists to inform context-sensitive reforms. Thirty-one in-depth interviews were conducted with public health dentists from dental colleges registered with the Dental Council of India, recruited across six regions. Interviews were conducted online via MS Teams using a piloted interview guide and video-recorded with consent. Subsequently, the interviews were transcribed verbatim, anonymized, and qualitative data was analyzed using Atlas.ti, following reflexive thematic analysis. Analysis yielded four main themes: facets of oral health inequalities, dental public health initiatives, strategies to mobilize and optimize dental workforce in rural areas, and recommendations to optimize oral healthcare. This study offers contextually grounded yet globally relevant perspectives on oral health reform. By bridging local insights with international priorities, this study proposes a sustainable, equity-driven framework for transforming oral health systems while laying the foundation for future research and policy action aimed at achieving universal oral health coverage. Full article

Oral diseases pose a significant global public health challenge, affecting 3.5 billion people and surpassing the prevalence of major noncommunicable diseases. There is a growing burden of oral diseases, including dental caries, periodontal diseases, and dentine hypersensitivity (DH) from several countries in Southeast Asia including Malaysia, the Philippines, Vietnam, Thailand, Indonesia, and Taiwan. The impact of oral diseases on quality of life and their association with systemic health emphasize the need for preventive strategies and early interventions. The objectives of the Oral Health Steering Committee were to gain insights and a comprehensive picture of the oral disease burden in the Southeast Asian region including Malaysia, the Philippines, Vietnam, Thailand, Indonesia, and Taiwan, to highlight the importance of early prevention of oral health diseases, as well as the importance of identifying early symptoms of oral discomfort associated with oral diseases and to examine the correlation between oral diseases and systemic health. The committee included nine experts from the region with significant expertise in dental health. A steering committee of nine dental experts from seven Southeast Asian countries reviewed evidence on the burden of oral diseases, the prevention of oral discomfort in early diagnosis and its impact on systemic health. The association between oral health and systemic health was discussed by the group. The committee highlighted that there is a need for comprehensive public health strategies, including population-level preventive measures, professional evaluations, and awareness programs to improve oral health outcomes and reduce treatment costs. The role in interprofessional collaboration between dental professionals and medical professionals in achieving early identification of oral diseases and increases referrals to dental professionals at early stages of diseases was highlighted. These insights stress the importance of early diagnosis, prevention and targeted interventions to mitigate the impact of oral health issues and improve overall public health outcomes in the region. Full article

Background/Objectives: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly evolved from a theoretical concept to a crucial component of modern metabolic care. This review explores the comprehensive development journey of semaglutide, drawing on evidence from medicinal chemistry, animal studies, initial human trials, the pivotal SUSTAIN and STEP programs, and real-world post-marketing surveillance. Methods: We conducted a detailed analysis of preclinical data sets, Phase I–III clinical trials, regulatory documents, and pharmaco-epidemiological studies published between 2008 and 2025. Results: Through strategic molecular modifications, such as specific amino-acid substitutions and the addition of a C18 fatty-diacid side chain to enhance albumin binding, the half-life of the peptide was extended to approximately 160 h, allowing for weekly dosing. Studies in rodents and non-human primates showed that semaglutide effectively lowered blood glucose levels, reduced body weight, and preserved β-cells while maintaining a favorable safety profile. Phase I trials confirmed consistent pharmacokinetics and tolerability, while Phase II trials identified 0.5 mg and 1.0 mg once weekly as the most effective doses. The extensive SUSTAIN program validated significant reductions in HbA1c levels and weight loss compared to other treatments, as well as a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). Subsequent STEP trials expanded the use of semaglutide to chronic weight management, revealing that nearly two-thirds of patients experienced a body weight reduction of at least 15%. Regulatory approvals from the FDA, EMA, and other regulatory agencies were obtained between 2017 and 2021, with ongoing research focusing on metabolic dysfunction-associated steatohepatitis, cardiovascular events, and chronic kidney disease. Conclusions: The trajectory of semaglutide exemplifies how intentional peptide design, iterative translational research, and outcome-driven clinical trial design can lead to groundbreaking therapies for complex metabolic disorders. Full article

Background: Malnutrition is a significant national health problem in countries with low and intermediate incomes and was announced in the United Nations’ 2030 Agenda for Sustainable Development Goals. Chemotherapy may have adverse effects on nutritional health issues and quality of life experience, particularly in patients with gastrointestinal (GIT) cancer. Our research’s objective was to determine the beneficial effects of oral nutrition supplements on nutritional status assessed by maintenance of whole-body composition and patient-generated subjective global assessment (PG-SGA) in all GIT cancer patients treated with chemotherapy medications. Methods: Among the patients, the nutrition support (NS) group (n = 75) received 500 kcal daily of a balanced oral nutrition supplement formula for 12 weeks, while the control (C) group (n = 75) did not. Anthropometric measures, whole-body composition, nutritional status biomarkers, and the PG-SGA questionnaire were assessed. Additionally, this study analyzed whole-body composition, skeletal mass, fat mass, laboratory data, the complete lipid profile, albumin, total protein, adverse effects, and therapy delays. Results: After 12 weeks, the NS group showed a significant increase in body weight, with a mean difference of 1.27 ± 3.39, while the C group showed a mean difference of only 0.15 ± 0.42. Moreover, fat mass increased in the NS group, showing a mean difference of 0.55 ± 3.69, while the C group showed a fat mass loss with a mean difference of −0.21 ± 2.93. The fat mass index (FMI) indicated statistical significance between the two groups. There was a statistically significant difference in the lean mass index between the two groups, favoring a steady increase in the NS group. The NS group showed improvements in the PG-SGA and nutritional biochemical markers, such as albumin. The initial findings from our study include data from a total of 150 patients, including 75 patients in the NS group and 75 patients in the C group. These results are consistent with earlier research. Conclusions: Early oral nutrition supplements for GIT cancer may enhance nutritional outcomes and reduce the delay of disease-related therapy. Additionally, they may help maintain body composition. Full article

Background/Objectives: Antimicrobial Resistance (AMR) remains a growing public health threat, underscoring the need for robust surveillance of Antimicrobial Consumption (AMC) and Antimicrobial Use (AMU). This study analysed AMC and AMU trends in Zambia’s human and animal health sectors, identifying priority areas for antimicrobial stewardship (AMS) under a One Health framework. Methods: A retrospective study was conducted in February 2025, utilising data from 2018 to 2023. Sources of data included the Zambia Medicines Regulatory Authority (ZAMRA) and the WOAH Animal Antimicrobial Use (ANIMUSE) Global Database platform. AMC was analysed using the WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) methodology. Antimicrobials were classified using the WHO Anatomical Therapeutic Chemical (ATC) system, and consumption was measured in Defined Daily Doses (DDDs) per 1000 inhabitants per day (DID). Antibiotics were further categorised using the WHO Access, Watch, and Reserve (AwaRe) classification. Data analysis was performed using IBM SPPS version 25.0. Results: In the human health sector, oral antibiotics accounted for 88% of total consumption. Penicillins (33%), cephalosporins (19.2%), and macrolides (12.4%) were the most consumed classes. In 2023, 98,651,882.42 DDDs per 1000 inhabitants/day were recorded, with amoxicillin, ceftriaxone, and sulfamethoxazole/trimethoprim leading as the most consumed antibiotics. According to the consumption of antibiotics by the WHO AwaRe classification, 47% were Access, 40% Watch, and 3% Reserve group antibiotics. In animal health, tetracyclines dominated (63%), followed by sulphonamides (26%) and penicillins (11%). AMU in animal health peaked in 2023. Conclusions: This study found high AMC and AMU, especially Watch-group antibiotics and tetracyclines, highlighting the need for strengthened antimicrobial stewardship, regulatory oversight, and integrated One Health surveillance to mitigate AMR risks in Zambia. Full article

Iron deficiency anaemia (IDA) affects 25% of the global population, with detrimental effects on the health of women and children. Treatments with iron supplements offer temporary relief but often yield adverse effects, hindering patient adherence. Additionally, IDA is associated with oxidative stress, which becomes significantly exacerbated during iron supplementation. Our study aimed to address this challenge by developing a plant-based nutritional formula rich in bioavailable iron and antioxidants devoid of adverse effects. Chemical analysis of edible plants, focused on the content of iron and iron absorption inhibitors, guided formula development. In vivo studies on rats with IDA evaluated iron bioavailability from the formulated plant-based nutraceuticals. Results of animal studies showed significant improvements in IDA-associated blood parameters after 28 days of oral administration of the nutraceuticals. Additionally, the nutraceuticals did not impede the benefits of iron supplementation. These findings strongly indicate that plant-based nutraceuticals can serve as an effective source of bioavailable iron, potentially improving treatment adherence and at the same time aligning with ongoing WHO and UNICEF initiatives to enhance IDA management. Full article

Background and objectives: Atherosclerotic cardiovascular disease (ASCVD) remains a major global cause of mortality, with chronic infections and systemic inflammation, including those arising from periodontal pathogens, contributing to vascular pathology. This study aims to investigate the presence of bacterial DNA from oral cavity microorganisms in atherosclerotic plaques of patients with abdominal aortic aneurysm (AAA) and to explore correlations with oral health indices and clinical variables. Materials and Methods: Forty patients (mean age 61 ± 6 years; 60% male) with periodontitis and AAA were included. Subgingival biofilm and arterial plaque samples were analyzed using PCR for A. actinomycetemcomitans, P. gingivalis, P. intermedia, T. forsythensis, and T. denticola. Dental indices (PI, GI, SBI, and PPD) were determined in all patients, and concordance of the findings was assessed by Cohen’s κ, and correlations were evaluated using Spearman’s coefficient. Results: P. gingivalis exhibited the highest concordance between oral and arterial plaques, followed by T. forsythensis and A. actinomycetemcomitans. T. denticola DNA was not detected in aortic samples. Positive correlations found between A. actinomycetemcomitans and P. gingivalis with dental indices were found to be statistically significant. Conclusions: The detection of periodontal pathogens, particularly P. gingivalis and T. forsythensis, in both oral and arterial plaques supports their potential role in atherosclerotic and aneurysmal changes. The findings highlight the relevance of periodontal health in cardiovascular risk prevention and the need for longitudinal studies to reveal causal mechanisms. Full article

Background: As the global incidence of diabetes continues to rise, expanding the scope of practice for primary healthcare professionals is essential in addressing the type 2 diabetes (T2D) epidemic. Oral health is bidirectionally linked to systemic health, and dentists are in a unique position to engage in preventative activities, such as disease screening. The aim of this study was to investigate first-year dental students’ perceptions of screening for diabetes, and to explore their intentions to implement screening on graduation. Methods: First-year dental students (n = 98) were asked to write an essay about their views and attitudes to diabetes screening in the dental setting. Consent was provided by 51 students for their essays to be thematically analysed. Results: The study found that students’ intentions to perform screening after graduation are shaped by their diabetes knowledge, views on screening protocols, awareness of professional roles, and experience with interprofessional collaboration. Conclusions: The dental setting is an ideal location for increasing opportunistic diabetes screening in primary care. Most first-year dental students viewed diabetes screening favourably and intended to implement after graduation. However, the study indicates changes in dental education and practice are required to equip students with the skills and knowledge needed for diabetes screening. The dental students that participated in this study represent the future dental professionals whose knowledge and attitudes to diabetes and disease screening will determine the future uptake of this initiative. Full article

Background: Hyperuricemia (HUA), a metabolic disorder characterized by high serum uric acid (UA) level, presents a growing global health challenge. Method: In this study, a stable murine model of HUA was established by orally administering adenine (100 mg/kg) and potassium oxonate (600 mg/kg) in C57BL/6J mice, resulting in significant elevation of serum UA and xanthine oxidase (XOD) activity, as well as renal pathological alterations. Given the anti-hyperuricemia potential of Lactiplantibacillus plantarum WLPL04, a strain from a human breast milk was evaluated. Conclusions: Oral administration of L. plantarum WLPL04 significantly reduced serum UA level and XOD activity in a dose-dependent manner. Moreover, L. plantarum WLPL04 treatment enhanced UA excretion by upregulating ABCG2 and downregulating URAT1 and GLUT9 expression. It ameliorated renal injury and suppressed inflammation via downregulation of the NLRP3 inflammasome pathway. 16S rRNA gene sequencing revealed that L. plantarum WLPL04 restored gut microbial diversity and promoted the enrichment of beneficial genera such as Bacteroides, which was negatively correlated with UA in serum, creatinine, and inflammatory cytokines. Moreover, transcript analysis revealed upregulation of purine salvage genes (hpt and xpt), suggesting enhanced salvage pathway recycling of purine bases and reduced urate production. Those findings suggest that L. plantarum WLPL04 exerted multi-targeted anti-hyperuricemia effects through coordinated regulation of host purine metabolism, urate transport, inflammation, and gut microbiota composition, providing a promising probiotic candidate for HUA management. Full article

Invasive group A streptococcal (iGAS) infections are increasingly recognized as a global public health concern, with a notable resurgence observed among pediatric populations in high-income countries following the relaxation of COVID-19-related restrictions. While the most commonly implicated emm types in invasive disease are emm1 and emm3, the global distribution of Streptococcus pyogenes strains is highly diverse, posing challenges for surveillance and vaccine development. We describe a 3-year-old boy with a femoral subperiosteal abscess, a rare clinical manifestation of iGAS, caused by an emm6.10 S. pyogenes strain. The diagnosis was confirmed by positive blood cultures and magnetic resonance imaging. Antibiotic therapy included intravenous ceftriaxone followed by oral amoxicillin, and then prolonged oral clindamycin was introduced due to the deep-seated nature of the infection. Molecular typing was performed by the national reference center as part of routine surveillance of invasive strains. This case emphasizes the importance of recognizing atypical clinical presentations of iGAS in children and the crucial role of strain typing in epidemiological monitoring. It also illustrates how the remarkable emm-type diversity of S. pyogenes remains a major obstacle to effective vaccine design, despite ongoing efforts with multivalent M-protein-based candidates and alternative strategies targeting conserved antigens. Enhanced global surveillance and inclusive vaccine design are urgently needed to address the full spectrum of circulating GAS strains. Full article