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Background: Individuals with diabetes have an increased risk of infection-related hospitalization; however, whether type 1 diabetes (T1D) and type 2 diabetes (T2D) differentially influence outcomes following hospitalization remains unclear. We compared mortality, metabolic complications, and hospital outcomes among adults with T1D, T2D, or no documented diabetes admitted with urinary tract infection (UTI) or pneumonia. Methods: We performed a retrospective cohort study using electronic health records from a tertiary 1500-bed medical center (2018–2026). Eligible adult hospital admissions for UTI or pneumonia were classified according to documented T1D, T2D, or no diabetes. The study included 22,475 UTI admissions (211 with T1D, 9230 with T2D, and 13,034 without diabetes) and 32,703 pneumonia admissions (208 with T1D, 15,112 with T2D, and 17,383 without diabetes). Multivariable logistic regression was used to evaluate the association between diabetes status and 30-day mortality, with adjustment for age, sex, BMI, CCI, and MEWS. Because individuals could contribute multiple eligible admissions, the primary mortality models used patient-level cluster-robust standard errors to account for within-patient correlation. Results: T1D admissions involved substantially younger individuals than T2D or non-diabetes admissions but were associated with the greatest metabolic instability during hospitalization. Hypoglycemia occurred in 41.2% of T1D admissions for UTI and 19.7% for pneumonia, compared with 19.6% and 4.1% in T2D, respectively (both p < 0.001). Hyperglycemia was also markedly more frequent in T1D, affecting 88.6% of UTI and 72.6% of pneumonia admissions. ICU transfer was nearly threefold higher in T1D than T2D during UTI hospitalization (10.0% vs. 3.5%, p < 0.001). After adjustment, T1D was not independently associated with 30-day mortality, whereas T2D was associated with modestly lower adjusted odds of 30-day mortality compared with patients without documented diabetes. No significant mortality differences were observed between T1D and T2D. Conclusions: Diabetes type was not independently associated with higher short-term mortality following hospitalization for UTI or pneumonia after adjustment for measured confounders. However, T1D was associated with substantially greater glycemic instability and increased intensive care utilization, suggesting that diabetes type may influence the metabolic complexity and intensity of inpatient management more than short-term survival. Full article

Endometriosis is a chronic estrogen-dependent systemic inflammatory disorder characterized by ectopic implantation of endometrial-like tissue, primarily on the ovaries, pelvic peritoneum, and bowel. According to the World Health Organization (WHO) estimate updated in 2025, endometriosis affects approximately 10% (about 190 million) of reproductive-age women worldwide and is a major contributor to chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. Standard medical therapies focus on ovarian suppression, which alleviates symptoms but precludes conception and carries significant metabolic and skeletal adverse effects. Recent multi-omics research has raised interest in the gut microbiome and the estrobolome, defined as the microbial gene repertoire involved in estrogen metabolism, as potential modulators of systemic estrogen exposure and immune homeostasis. Altered microbiota composition and microbial β-glucuronidase activity may influence enterohepatic estrogen recirculation; however, endometriosis-specific evidence is predominantly associative or preclinical and does not establish a causal pathway. Dysbiosis and increased bacterial β-glucuronidase activity promote enterohepatic recirculation of estrogens, contributing to hyperestrogenism and ectopic lesion proliferation. Concurrently, oxidative stress, peritoneal inflammation, aberrant macrophage polarization, and neoangiogenesis sustain lesion survival and contribute to chronic pelvic pain. This comprehensive review synthesizes mechanistic, preclinical, and clinical evidence regarding microbiome-targeted interventions and nutritional compounds, including probiotics, prebiotics, N-acetyl cysteine (NAC), curcumin, resveratrol, epigallocatechin gallate (EGCG), omega-3 polyunsaturated fatty acids (PUFAs), and vitamin D, in modulating the estrobolome, immune responses, and oxidative microenvironment in endometriosis. We further discuss dietary patterns, bioavailability challenges, and the potential of precision nutrition to optimize reproductive outcomes. These approaches may be considered complementary or investigational adjuncts; current evidence is insufficient to demonstrate disease modification or improvements in spontaneous pregnancy, assisted reproductive technology (ART) outcomes, or live birth. Here, “fertility-sparing” denotes the absence of intentional ovulation suppression rather than proven fertility enhancement. Full article

Introduction: Thrombopoietin mimetics (TPOm) are known to increase blood cell counts, thereby ameliorating various diseases, including cardiomyopathy—a leading cause of mortality because of delayed radiotoxic effects. Previous preclinical studies demonstrated significant survival enhancement following lethal radiation exposure with a single dose of JNJ-26366821 in two mouse strains, CD2F1 and C57BL/6. Materials and Methods: In this study, a single dose of JNJ-26366821 (1.0 mg/kg) or saline was administered 24 h post-8.0 Gy total body irradiation (TBI) to male C57BL/6 mice. Mice were euthanized on days 1, 7, 15, and 30 post-TBI, and serum and heart samples were collected. Unirradiated mice treated with saline served as baseline controls. Inflammatory serum cytokines/chemokines, growth factors and multi-omics analyses, including proteomics, metabolomics, and lipidomics, were evaluated to assess therapeutic impacts. Results: JNJ-26366821 demonstrated overall positive effects, restraining radiation-induced inflammatory surges by 7 days post-TBI. Functional analysis revealed that JNJ-26366821 treatment in unirradiated mice activated cellular homeostasis, which persisted after post-exposure intervention in irradiated mice. The drug immediately reduced cell death, but networks supporting cardiovascular health, such as angiogenesis and vasculogenesis, remained inhibited 2 h post-intervention. By 7 days post-TBI, JNJ-26366821 mobilized molecules in heart tissue to reconstitute cellular development and maintenance. Protein synthesis and metabolism were activated between 15 and 30 days post-TBI, potentially compensating for radiation-induced muscle wasting. Conclusions: JNJ-26366821 demonstrated promising mitigating effects on cellular homeostasis and cardiovascular health when administered as a single dose at 24 h post-exposure. Full article

Background/Objectives: Electrolyte disturbances are common in patients with Acute Ischemic Stroke (AIS) and may influence clinical outcomes. However, the prognostic significance of peri-procedural electrolyte changes in patients undergoing mechanical thrombectomy remains insufficiently investigated. This study aimed to evaluate the associations of pre- and post-procedural serum electrolyte levels and peri-procedural electrolyte changes with 90-day mortality in patients with AIS treated with mechanical thrombectomy. Methods: This retrospective observational study included 274 adult patients with anterior circulation large-vessel occlusion who underwent mechanical thrombectomy between February 2017 and February 2026. Serum sodium (Na), potassium (K), chloride (Cl), and calcium (Ca) levels were recorded before thrombectomy and within the first hour after the procedure. Peri-procedural electrolyte changes (Δ) were calculated as post-procedural minus pre-procedural values. Clinical, imaging, laboratory, and procedural variables associated with 90-day mortality were evaluated using univariate and multivariable logistic regression analyses. Results: Of the 274 patients, 67 (24.5%) died within 90 days. Post-procedural serum Na levels were significantly lower in the mortality group than in the survival group (p = 0.030). No significant associations were observed between 90-day mortality and pre-procedural electrolyte levels or peri-procedural electrolyte changes. In the multivariable analysis, higher admission National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.001), symptomatic intracranial hemorrhage (p < 0.001), higher admission glucose levels (p = 0.003), and higher triglyceride levels (p = 0.046) were independently associated with increased 90-day mortality, whereas successful reperfusion (TICI 2b–3) (p = 0.011) and higher post-procedural serum Na levels (OR = 0.851, 95% CI: 0.749–0.968; p = 0.014) were independently associated with reduced odds of 90-day mortality. The addition of post-procedural serum Na to the base model resulted in a modest increase in discrimination (AUC 0.800 to 0.812; ΔAUC = 0.012), which was not statistically significant (DeLong p = 0.454). Conclusions: Among the peri-procedural electrolyte parameters evaluated, only post-procedural serum Na was independently associated with 90-day mortality after mechanical thrombectomy. However, adding post-procedural serum Na to established clinical, procedural, and metabolic predictors did not significantly improve model discrimination. These findings suggest that post-procedural serum Na may represent an associated prognostic marker, while its incremental predictive utility beyond established predictors remains unproven. Full article

Background: Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by chronic anemia, recurrent pain episodes, and multi-organ complications, which collectively impact patients’ quality of life and functional capacity. Exercise and physical activity are recognized as essential components of general health and well-being; however, their role in individuals with SCD remains underexplored due to concerns regarding safety, tolerance, and the potential to precipitate vaso-occlusive crises. This study aimed to assess the patterns and frequency of exercise and physical activity among patients with sickle cell disease using a validated questionnaire. Methods: We conducted a cross-sectional study on patients diagnosed with sickle cell disease at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. After obtaining ethical approval, we contacted the patients by phone or met them in person and administered the Global Physical Activity Questionnaire (GPAQ). Data on age, gender, comorbid conditions, disease-related variables, and weekly physical activity were collected. Total physical activity was expressed in metabolic equivalent of task (MET)-minutes per week, and participants achieving ≥600 MET-minutes per week were classified as meeting the World Health Organization (WHO) recommendation. Results: Of the 97 patients, males represented 52.6% of the participants, with a median age of 33 years. Overall, 70.1% of the patients were on hydroxyurea, and 14.4% had undergone splenectomy. More than half of the patients (56.7%) reported difficulties with exercise. According to the findings, 39% of the patients were getting enough physical activity each week, as recommended by the WHO. Male patients were significantly more likely to meet the WHO physical activity recommendation (p = 0.003), whereas no statistically significant associations were observed for age, nationality, body mass index, hemoglobin level, hydroxyurea use, splenectomy, hospital admissions, transfusion history, comorbidities, or exercise-related symptoms (all p > 0.05). Conclusions: Our data suggest that a significant proportion of patients with SCD did not achieve the WHO-recommended physical activity level, with adherence observed in only about forty percent of participants, and that adherence was more common in male patients (adjusted odds ratio 3.30, 95% CI 1.36–8.52, after multivariable adjustment for age, body mass index, hemoglobin, and transfusion status). This association was concentrated in occupational rather than recreational activity and was not explained by the clinical variables measured. Because no comparison group was studied, the extent to which this shortfall is attributable to SCD itself, rather than to the population-level inactivity already documented in Saudi Arabia, cannot be determined from these data. These findings identify a potential area for targeted intervention, particularly among women, and underscore the need for further research into disease-specific and sociocultural barriers before tailored programs can be developed. Further larger, controlled, multi-center studies are necessary to clarify the specific contribution of SCD to inactivity and to guide individualized physical activity promotion in this population. Full article

Newborn screening (NBS) is a critical component of the three-tiered prevention strategy for birth defects, reducing congenital disorder burden and improving long-term child health outcomes. Over the past 45 years, NBS in China has evolved into a nationwide quality-controlled network driven by policy support and technological advances. Currently, phenylketonuria and congenital hypothyroidism are included in universal NBS across the country, and several provinces have expanded to encompass congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase deficiency, and additional inherited metabolic disorders identified through tandem mass spectrometry. The application of next-generation sequencing and other technologies has further enhanced detection capacity and expanded detectable disease spectra. Meanwhile, the National Quality Management System for NBS (QMS-NBS) has realized the visualization and standardization of screening quality and performance. Despite these advances, challenges remain, including regional disparities, inadequate follow-up, and long-term management. This review summarizes the historical evolution and policy framework of NBS in China, outlines the development of screening institutions, the spectrum and incidence of screened disorders, advances in detection technologies, and the establishment of QMS-NBS. It also highlights future priorities: expanding screened conditions, strengthening follow-up and long-term care, promoting regional equity, and advancing novel technologies to improve child health and foster precision public health. Full article

Background/Objectives: Maternal obesogenic diets may produce persistent developmental alterations in offspring, with response patterns that may differ between males and females. We investigated whether propolis supplementation from preconception through lactation modified metabolic and hepatic outcomes in offspring exposed to a maternal cafeteria diet. Methods: Thirty-two Wistar rat dams received a control diet (CON), cafeteria diet (CAF), or either diet with propolis in drinking water (CONP and CAFP; target exposure, 200 mg/kg/day). One male and one female per litter (n = 8/sex/group) received standard chow after weaning. This design isolated maternal exposure because offspring received no propolis after weaning. At 18 weeks, metabolic and inflammatory biomarkers, liver histopathology, and hepatic lipid-metabolism gene expression were evaluated using groupwise tests and two-way ANOVA. Results: Final body weights were comparable across groups. In males, maternal diet affected glucose (p = 0.034) and HOMA-IR (p = 0.023), with a diet × propolis interaction for glucose (p = 0.042). CAF males had higher TNF-α than CAFP and CONP males. In females, diet × propolis interactions were detected for insulin, total cholesterol, triglycerides, and leptin (all p ≤ 0.049); CAF females had higher triglycerides than CON and CAFP females. Hydropic degeneration was greater in CAF dams than all other groups and in CAF than CONP male offspring; female histopathology did not differ. Male hepatic gene expression did not differ among groups, whereas female PPAR-β and FADS2 showed propolis main effects (p = 0.046 and p = 0.009, respectively). Conclusions: Maternal cafeteria-diet exposure was associated with persistent metabolic and hepatic alterations despite comparable offspring body weights, with different response patterns observed in the separate male and female analyses. Maternal propolis supplementation selectively modified some inflammatory, lipid-related, and histopathological outcomes; however, these effects were heterogeneous and did not consistently normalize the cafeteria-associated phenotype. Overall, the findings support partial, endpoint-specific, and context-dependent modulation rather than uniform metabolic or hepatic protection. Full article

Background: Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age and are associated with abnormal uterine bleeding, infertility, and impaired implantation and endometrial receptivity. However, the contribution of the myometrial microbiome (MM) to fibroid biology and the broader uterine environment remains poorly understood. Materials and Methods: We characterized the paired MM of UF tissue and adjacent healthy myometrium (HM) from 21 women undergoing surgery and integrated serum free fatty acid (FFA) and cytokine profiling. Results: Taxonomic composition and microbial diversity were highly similar between tissues, with no differentially abundant taxa after multiple-testing correction. In contrast, PICRUSt2-based functional prediction indicated tissue-specific differences in microbial metabolic potential: UF tissue showed higher predicted representation of pathways related to L-tyrosine biosynthesis and aromatic amine degradation, whereas HM showed higher predicted representation of coenzyme A and arginine biosynthesis pathways. Patients also exhibited distinct circulating FFA profiles compared with healthy women, and integrative analyses identified phenotype-specific associations among microbial taxa, FFAs, and inflammatory mediators, particularly in women with heavy menstrual bleeding or specific fibroid localizations. Conclusions: These findings suggest that UFs are associated with potential functional remodeling of the MM rather than major taxonomic alterations, which may contribute to changes in the uterine environment relevant to implantation, endometrial receptivity, and reproductive health. Full article

Somatic cell count (SCC) is routinely used as an indicator of mammary gland health, but the SCC level at which coordinated inflammatory and systemic changes become apparent remains uncertain. This study aimed to characterize biological changes across increasing SCC and identify the SCC range associated with a coordinated transition. The study included 580 clinically healthy Polish Holstein–Friesian cows without detectable intramammary infection (IMI), classified according to milk SCC as <100, 100–199, 200–399, or ≥400 × 10³ cells/mL. Milk was analyzed for composition, inflammatory cytokines, and mammary innate-defense proteins, while blood was assessed for metabolic and hepatic indicators and oxidative-status markers, including malondialdehyde (MDA), total antioxidant status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GluRed). Relatively little variation occurred between the two SCC groups below 200 × 10³ cells/mL, whereas SCC ≥ 200 × 10³ cells/mL was associated with increased pro-inflammatory activity, significant changes in mammary innate-defense proteins, oxidative and metabolic changes, lower body condition, and reduced milk yield. Interleukin-8 showed the strongest independent association with SCC ≥ 200 × 10³ cells/mL. Independently estimated breakpoints for 12 inflammatory, innate-defense, and oxidative variables converged within 198–228 × 10³ cells/mL. Among the evaluated thresholds, 200 × 10³ cells/mL provided 88.0% sensitivity and 82.0% specificity for discrimination of the inflammatory phenotype. These findings identify the region around 200 × 10³ cells/mL as a coordinated biological transition rather than a universal diagnostic threshold for mastitis or intramammary infection. Full article

This study evaluated the effects of replacing alfalfa (Medicago sativa) with Sesbania cannabina hay on growth performance, nutrient digestibility, and ruminal microecology in fattening lambs. Forty 3-month-old Aohu crossbred lambs (initial BW: 22.08 ± 0.31 kg) received five isoenergetic, isonitrogenous diets in which S. cannabina hay replaced 0% (CON), 25%, 50%, 75%, or 100% of alfalfa during a 60-day trial. Growth traits, nutrient digestibility, rumen fermentation, enzyme activities, serum biochemical parameters, ruminal microbiota, and metabolomic profiles were evaluated. Substitution did not affect final body weight, average daily gain, or feed conversion ratio (p > 0.05), but nutrient utilization and ruminal fermentation differed among replacement treatments. The 50–100% replacement groups showed higher digestibility of crude protein, ether extract, and fiber, together with higher ruminal protease, cellulase, hemicellulase, and α-amylase activities (p < 0.05). Total volatile fatty acid concentrations were higher in the 50–100% replacement groups, whereas the acetate-to-propionate ratio was lower in all substituted groups. Serum biochemical parameters indicated changes related to protein metabolism without evidence of adverse health effects. Multi-omics analyses revealed distinct differences in ruminal bacterial communities and metabolic profiles among replacement treatments. The 25% replacement group showed relatively limited microbial and metabolic changes. The 75% replacement group exhibited greater bacterial diversity, enrichment of Prevotellaceae_NK3B31_group and Streptococcus, coordinated microbe–metabolite associations, and changes in bile acid and cholesterol metabolism. Complete substitution was associated with more extensive microbial remodeling and lower abundances of several functional metabolites, without additional benefits to growth performance. Full article

Over the years, metabolic syndrome (MetS) has emerged as one of the most significant public health challenges, driven by the global increase in obesity, physical inactivity, unhealthy dietary patterns, and population aging. Ellagitannins are a class of hydrolysable tannins that have emerged as promising natural bioactive compounds, owing to their broad spectrum of biological activities. Increasing evidence suggests that some ellagitannins and their metabolites modulate several pathogenic mechanisms underlying metabolic syndrome, including oxidative stress, chronic inflammation, insulin resistance, endothelial dysfunction, and dysregulated lipid metabolism. This work reviews the pharmacological activities and therapeutic prospects of ellagitannins in the management of metabolic syndrome-related disorders. It further provides a critical and comparative analysis of the pharmacological profiles of reported ellagitannins, offering insights into their therapeutic efficacy and potential synergistic applications in the management of MetS-related disorders. Overall, Punicalagin and Geraniin currently possess the strongest preclinical evidence, supported by multiple independent studies employing both cellular and animal models that consistently demonstrate beneficial effects across several components of MetS. Chebulagic acid, Corilagin, Chebulinic acid, and Punicalin also show considerable promise but require further validation in diverse experimental systems. Potential synergistic interactions among ellagitannins when administered in combination should be investigated for enhanced therapeutic efficacy and broader multifaceted pharmacological effects. Full article

Population aging, the rising burden of chronic non-communicable diseases, and environmental degradation are increasingly recognized as interconnected global challenges, underscoring the need for integrated strategies that simultaneously promote human and planetary health. The Planetary Health Diet (PHD), originally proposed to address these challenges, has emerged as a promising dietary framework for supporting healthy aging. Although its health benefits are increasingly supported by epidemiological and clinical evidence, the biological mechanisms underlying these effects remain incompletely understood. This narrative review synthesizes evidence on the interplay among the PHD, the gut microbiome, and biological aging, with emphasis on microbiome-mediated pathways connecting sustainable nutrition with healthspan. Adherence to PHD-consistent dietary patterns is associated with greater microbial diversity and functional capacity, increased production of bioactive microbial metabolites, and more favorable intestinal barrier, immune, and metabolic profiles. These adaptations may modulate several hallmarks of aging and contribute to the preservation of physiological resilience. Evidence from prospective cohort studies, randomized controlled trials, and systematic reviews further indicates that dietary patterns consistent with the PHD are associated with lower risks of cardiometabolic diseases, frailty, cognitive decline, and premature mortality. By integrating findings from nutritional science, microbiome research, geroscience, and public health, this review positions the gut microbiome as an important, although not exclusive, biological interface through which sustainable dietary patterns may support healthspan while contributing to environmental sustainability. Full article

Both 2′-fucosyllactose (2′-FL) and Bifidobacterium can modulate gut health; however, whether their combination provides strain-dependent protection against colitis remains unclear. This study aimed to compare the protective effects of 2′-FL alone and in combination with Bifidobacterium longum subsp. infantis M63 or Bifidobacterium breve M16V in dextran sulfate sodium (DSS)-induced colitis. Forty-eight male C57BL/6J mice were randomly assigned to six groups: negative control, DSS model control, 5-aminosalicylic acid positive control, 2′-FL, 2′-FL + M63, and 2′-FL + M16V. The interventions were administered for two weeks, with 2.5% DSS supplied in the drinking water during the second week. Colitis-related indices, colonic histopathology, inflammatory cytokines, oxidative-stress markers, intestinal barrier-associated gene expression, gut microbiota composition, lactate, and short-chain fatty acids (SCFAs) were evaluated. Compared with the model control, 2′-FL and both synbiotic combinations ameliorated colonic tissue injury and goblet-cell loss. Both combinations significantly reduced IL-1β, whereas 2′-FL and both combinations reduced IL-6 and TNF-α. The combinations also increased catalase and glutathione peroxidase activities and decreased malondialdehyde levels. 2′-FL alone increased Occludin and RELMβ expression, whereas 2′-FL + M63 showed the strongest effects on tight-junction and mucus-barrier restoration, including increased Claudin-1, Claudin-2, ZO-1, TFF3, and MUC2 expression. All 2′-FL-containing interventions increased microbial diversity, while 2′-FL + M63 increased Bacteroidota, reduced Proteobacteria, and enriched Muribaculaceae and Ruminococcaceae. Both synbiotic combinations increased lactate and all measured SCFAs; 2′-FL + M63 produced the highest acetate level, whereas 2′-FL + M16V produced the highest propionate level, and both combinations markedly increased butyrate. These findings demonstrate strain-dependent protective effects, with 2′-FL + M63 showing the greatest overall efficacy in restoring intestinal barrier function and microbial metabolism, supporting its development as a candidate functional synbiotic food formulation. Full article

This study evaluated the efficacy of graded dietary sanguinarine as a phytobiotic alternative for mitigating Clostridium perfringens-induced enteric challenge in broiler chickens. A total of 360 newly hatched Ross 308 broiler chicks were randomly assigned to six treatments: a non-challenged negative control, a challenged positive control, a challenged group supplemented with avilamycin at 0.10 g/kg, and three challenged groups supplemented with sanguinarine at 0.06, 0.09, or 0.12 g/kg diet. Birds were reared for 35 days, and all challenged groups received repeated oral inoculations with Clostridium perfringens following an initial Eimeria spp. challenge. Compared with the positive control, all sanguinarine doses improved cumulative average daily gain, feed conversion ratio, and European production efficiency factor to levels comparable with the negative control and avilamycin groups. Sanguinarine at 0.09 and 0.12 g/kg restored dressing percentage, whereas all doses improved breast yield and increased relative bursa weight beyond both control and avilamycin values. All sanguinarine treatments normalized serum total protein, glucose, total antioxidant capacity, and superoxide dismutase activity, with stronger recovery of superoxide dismutase than avilamycin. In the ileum, all sanguinarine doses increased villus length above the avilamycin and negative control groups, while maintaining comparable villus width. Sanguinarine also improved immune status by restoring serum immunoglobulin Y, interleukin-2, and interferon-gamma concentrations, reducing interleukin-1 and interleukin-6 more effectively than avilamycin, and fully restoring immunoglobulin A at the highest dose. Moreover, sanguinarine reduced harmful bacterial populations and promoted beneficial ileal bacteria across the tested inclusion levels. Overall, dietary sanguinarine, especially at 0.09–0.12 g/kg, may serve as a promising non-antibiotic nutritional strategy for improving broiler resilience under enteric challenge conditions. Full article