Search Results (4,554)

Caffeic acid (CA) is a phenolic compound commonly found in fruits, vegetables, and coffee, with preclinical evidence demonstrating its important role in disease management through different mechanisms of action. This review aimed to explore CA’s pharmacological effects in different pathological conditions, and sources were retrieved by using databases like PubMed, Scopus, Google Scholar, and Web of Science and based on preclinical studies. CA notably protects cells and tissues from oxidative stress and inflammation, highlighting its therapeutic role in the management of pathogenesis. The neuroprotective, cardioprotective, hepatoprotective, anti-microbial, and anti-obesity effects are reported through in vitro and in vivo studies. Moreover, its anticancer effects are linked to modulation of cell signaling pathways, together with angiogenesis, cell cycle, apoptosis, and the PI3K/Akt pathway. This article explores how caffeic acid influences health conditions, providing a comprehensive overview of its effects on disease processes. Reviewing the literature aims to enhance the understanding of caffeic acid’s role in disease management and as a natural therapeutic agent. Although several studies demonstrate the anticancer effects and its role in the management of various pathological conditions, most of the existing evidence is based on in vitro, in vivo, and xenograft models. Moreover, many natural compounds, including CA, that exhibit activity in preclinical settings fail to translate into clinical applications, due to restrictions of poor bioavailability, toxicity, rapid metabolism, and differences in the tumor microenvironment. Thus, future studies should emphasize well-designed in vivo studies as well as controlled clinical trials to better describe CA’s safety, efficacy, mechanism of action, and therapeutic application in humans. Further investigation of its interactions with other therapeutic agents may offer insights into synergistic effects that enhance treatment efficacy. Overall, a more comprehensive understanding of this compound will be indispensable for its development as a therapeutic agent in the treatment of chronic disease. Full article

Background: Obstructive sleep apnea (OSA) is common in individuals with obesity, largely due to increased soft tissue causing upper airway narrowing. However, mechanisms of OSA improvement following weight loss are incompletely understood, particularly in Asian population, where craniofacial and soft tissue characteristics differ. This study aimed to evaluate changes in upper airway anatomy before and six months after bariatric surgery. Methods: We prospectively evaluated Indian obese patients with OSA undergoing bariatric surgery. Magnetic resonance imaging (MRI) and polysomnography were performed at baseline and six months post-surgery to assess volumetric changes in upper airway structures and the apnea–hypopnoea index (AHI), respectively. Correlations between MRI-derived structural changes, weight loss, and AHI were also analyzed. Results: Ten obese patients with OSA were included. Bariatric surgery resulted in significant reductions in body weight, body mass index (BMI), Epworth Sleepiness Scale score, and AHI (p < 0.05). MRI demonstrated a significant reduction in overall pharyngeal soft tissue volume, soft palate, pterygoid and parapharyngeal fat pad volume and tongue fat fraction. However, no significant changes were observed in total upper airway volume, retroglossal and retropalatal airway volume. Furthermore, no significant correlation was noted between changes in upper airway anatomy and post-operative changes in AHI or body weight. Conclusions: Bariatric surgery was associated with significant weight loss and improvement in OSA severity, accompanied by reduction in soft tissue volumes without significant increase in airway volume in this pilot study. These findings suggest a possible role of factors other than structural airway changes in the observed improvement in OSA following bariatric surgery. Full article

Primula nutans Georgi, a medicinal herb used in Mongolian and Tibetan medicine for treating respiratory ailments, is a natural agent with antiobesity potential. We investigated the antiobesity and insulin-sensitizing effects of P. nutans Georgi extract (PGE) using in vitro and in vivo models. In 3T3-L1 preadipocytes, PGE inhibited adipocyte differentiation and lipid accumulation without cytotoxicity, accompanied by the reduced expression of adipogenic transcription factors (PPARG, C/EBPA, and adiponectin) and lipogenic genes (FASN, SCD1, and ACC), particularly during the early stages of adipogenesis. Similar effects were observed in primary stromal vascular cells derived from mouse inguinal white adipose tissue. PGE upregulated C/EBP homologous protein and C/EBPB and was associated with altered cell cycle progression, increased G2/M phase distribution, and the potential disruption of mitotic clonal expansion during early adipogenesis. In HFD-induced obese mice, intraperitoneal administration of PGE (10 or 30 mg/kg) significantly reduced body weight gain, white adipose tissue mass, and hepatic steatosis, independent of food intake. PGE downregulated lipogenic and proinflammatory gene expression in adipose and hepatic tissues and increased AMPK phosphorylation in white adipose tissue. PGE improved glucose tolerance and was associated with enhanced insulin sensitivity, as evidenced by reduced areas under the curve in the glucose tolerance and insulin tolerance tests and increased circulating adiponectin levels. Feature-based molecular networking identified 61 compounds from PGE. Network pharmacology analysis revealed several antiobesity targets, including PPARG and AKT1. Molecular docking analyses suggested favorable binding affinities between major compounds and metabolic regulators. Collectively, these findings suggest that PGE may suppress adipogenesis and improve metabolic parameters in obese mice, supporting its potential as a natural candidate for obesity and related metabolic disorders. Full article

Background: Vitamin D deficiency is a common global health problem and remains highly prevalent in Türkiye, where limited food fortification and heterogeneous clinical practices contribute to variability in testing and supplementation strategies. Aims: To provide Türkiye-specific best practice recommendations for defining clinically relevant serum 25-hydroxyvitamin D [25(OH)D] thresholds, identifying adult risk groups for targeted testing, and recommending evidence-based prevention, treatment, and monitoring approaches while minimizing under-treatment and inappropriate high-dose use. Methods: This national expert consensus document was developed by endocrinologists from across Türkiye using a structured, modified Delphi methodology. Draft statements informed by systematic literature reviews were rated via online surveys using a 9-point Likert scale, followed by two Delphi rounds and a face-to-face consensus meeting in İstanbul in October 2025. Results: Recommendations addressed sun exposure, laboratory assessment, screening, supplementation, treatment, and follow-up. Serum 25(OH)D <20 ng/mL was defined as deficiency and <12 ng/mL as severe deficiency, with a target range of 20–50 ng/mL. Routine population-wide screening was not recommended; instead, targeted testing in high-risk adults and symptom-driven biochemical evaluation were endorsed. Empiric supplementation was recommended for selected high-risk groups, with cholecalciferol as the preferred agent. Higher individualized doses were suggested in obesity or malabsorption, while loading regimens were reserved for specific clinical indications, such as severe deficiency or certain medical conditions that impair vitamin D metabolism. Reassessment of 25(OH)D at 8–12 weeks was recommended. Conclusion: These consensus-based recommendations provide a practical, context-specific framework for assessing, preventing, treating, and monitoring vitamin D deficiency in adults in Türkiye. Full article

Background/Objectives: Gastrojejunal–ileal interposition with bipartition and sleeve gastrectomy (GJIB-SG) is a novel metabolic procedure developed to combine functional foregut exclusion with hindgut stimulation while preserving duodenal continuity and endoscopic biliary access. This study evaluated the medium-term glycemic, weight-loss, and nutritional safety outcomes of GJIB-SG in patients with obesity and long-standing type 2 diabetes (T2D). Methods: A retrospective single-center cohort of 30 consecutive patients with obesity and T2D who underwent GJIB-SG between January 2016 and August 2019 and reached at least 60 months of postoperative follow-up was analyzed at baseline and at 12, 24, 36, 48, and 60 months. Longitudinal data were analyzed by repeated-measures ANOVA with Greenhouse–Geisser correction and Bonferroni-adjusted pairwise comparisons. Diabetes remission was classified using the 2021 American Diabetes Association consensus definition (A1C < 6.5%, medication-free). Results: Mean body weight decreased from 102.4 ± 13.6 kg preoperatively to 73.5 ± 7.6 kg at 60 months (p < 0.001; mean %TWL 27.4%, mean %EWL 99.4%). Mean A1C decreased from 9.4 ± 1.6% to 6.0 ± 1.4% at 60 months (p < 0.001). Complete medication-free remission was achieved by 70.0% of patients at 12 months and 44.8% at 60 months; cumulatively, 25 of 30 (83.3%) achieved complete remission at one or more intervals, and 3 patients (10.0%) never achieved A1C < 6.5%. Triglycerides, total cholesterol, and LDL cholesterol decreased by 56%, 39%, and 35%, respectively. No protein–energy malnutrition or hypoalbuminemia occurred; however, a late rise in parathyroid hormone and a return of 25-OH vitamin D toward preoperative insufficient values by 60 months indicate the need for sustained micronutrient surveillance. One cardiovascular death at 24 months was not considered procedure related. Conclusions: In this single-center cohort, GJIB-SG was associated with durable weight loss, sustained glycemic improvement with cumulative complete remission in 83.3% of patients, and absence of severe nutritional complications over 60 months. Prospective comparative studies with longitudinal mixed-effects analysis are warranted to define the role of GJIB-SG within the metabolic–surgical armamentarium. Full article

Background: Metabolic and bariatric surgery is an established therapeutic option for severe obesity and obesity-related medical problems. Although minimally invasive techniques and enhanced recovery pathways have reduced postoperative morbidity, infectious complications remain clinically relevant because they may lead to readmission, reoperation, prolonged antimicrobial therapy, and mortality. Methods: We conducted a narrative review of the literature on infectious complications after metabolic and bariatric surgery. Evidence was synthesized across five clinically relevant domains: host-related pathophysiology, microbial epidemiology, preoperative optimization, antimicrobial prophylaxis and pharmacokinetic considerations, and diagnosis and management of postoperative infectious complications. Results: Patients with obesity present specific infection-related vulnerabilities, including chronic low-grade inflammation, altered immune responses, impaired tissue oxygenation, obesity-related medical problems, and procedure-specific risks. Contemporary prevention relies on multidisciplinary preoperative optimization, appropriate skin antisepsis, weight-based antimicrobial prophylaxis, intraoperative redosing when indicated, and adherence to enhanced recovery principles. Anastomotic leaks and intra-abdominal abscesses represent the most severe organ/space infections and require early recognition, source control, antimicrobial therapy, nutritional support, and coordinated surgical, radiological, and endoscopic management. Conclusions: Infectious complications after metabolic and bariatric surgery result from the interaction between host physiology, microbial factors, pharmacological considerations, and surgical technique. A structured approach integrating prevention, early diagnosis, and multidisciplinary management may improve outcomes. Further bariatric-specific studies are needed to strengthen the evidence base for several preventive and therapeutic strategies. Full article

Acute respiratory failure (ARF) often leads to ICU admission, ventilatory support, illness, and death. The usual classification into hypoxemic and hypercapnic types does not capture its full complexity. Precision medicine uses the concept of “treatable traits” to guide care based on traits that are clinically relevant, identifiable, measurable, and possibly changeable. Arterial carbon dioxide pressure (PaCO₂) reflects factors like alveolar ventilation, dead space, respiratory mechanics, and how patients respond to ventilatory support. This makes it clinically relevant in selected situations. We carried out a scoping review using PRISMA-ScR and JBI guidelines to summarize evidence on hypocapnia and hypercapnia as prognostic, stratification, or clinically relevant variables during respiratory support. We searched PubMed/MEDLINE, ScienceDirect, and Web of Science (1994–2025), and checked references by hand. Thirty-four studies met our criteria and were grouped into four areas: pre-intubation or early acute presentation, non-invasive support (NIV/HFNC), invasive mechanical ventilation (IMV), and weaning or post-extubation. In summary, hypocapnia was linked to worse outcomes or failure of support in hypoxemic or cardiogenic cases. Hypercapnia helped identify patients who benefited from NIV, such as those with chronic obstructive pulmonary disease or obesity hypoventilation. For IMV, the effects depended on the presence and severity of acidosis and on its duration. Overall, PaCO₂ showed context-dependent clinical relevance, acting mainly as a prognostic or stratification marker and, in narrower settings, as a variable that may inform monitoring or support decisions. This review provides a pragmatic framework for interpreting PaCO₂ across respiratory support contexts and highlights the need for safe and clinically meaningful targets. Full article

Background: Severe asthma exacerbations remain a major cause of pediatric intensive care unit (PICU) admissions, particularly in early childhood. Objective: To describe the demographic characteristics, clinical features, management strategies, and short-term outcomes of children admitted to the PICU with severe acute asthma exacerbations. Methods: A retrospective descriptive study was conducted of pediatric patients aged 1–14 years with severe acute asthma requiring PICU admission at King Salman Medical City, Madinah, Saudi Arabia (January 2023–October 2024). A total of 73 patients were included. Data included demographics, risk factors, medical history, clinical presentation, management, and outcomes. Results: The mean patient age was 4.6 years, with most (57.5%) aged 1–5 years. Males comprised 56.2% of cases. WHO BMI-for-age z-score assessment revealed a bimodal nutritional distribution: 27.9% of patients were underweight, including 20.6% with severe underweight, while 29.4% were overweight or obese; 42.6% had normal nutritional status. Severe undernutrition was concentrated in the 1–5-year age group, whereas obesity predominated in the 6–10-year age group. A family history of asthma was noted in 54.8% of patients; 16.4% had prior COVID-19 infection. Early symptom onset and delayed diagnosis were common. Poor asthma control was documented in 60.3%, with low medication adherence (9.6%) and limited aerochamber use (13.7%). The most frequent presenting symptoms were dyspnea, cough, and wheezing. Management followed evidence-based protocols: systemic corticosteroids and bronchodilators were first-line therapies. The mean PICU stay was 3.1 days and the mean hospital stay was 8.1 days. No mortality or major complications occurred; 93.2% of patients were discharged in good health. Conclusions: Severe pediatric asthma requiring PICU admission is associated with early symptom onset, a bimodal pattern of nutritional risk encompassing both undernutrition and overweight/obesity, family history of asthma, and inadequate outpatient management. These descriptive findings highlight the need for age-adjusted nutritional screening, enhanced medication adherence support, and targeted outpatient education to reduce avoidable PICU admissions. Full article

Background and Objectives: Obstructive sleep apnea (OSA) is a heterogeneous disease with diverse clinical presentations and high global prevalence. Obesity is a common comorbidity in OSA, but its relationship with symptom subtypes remains unclear. This study aimed to evaluate the association between OSA symptom subtypes and obesity in a clinical cohort. Methods: This observational study analyzed data from the Santiago Obstructive Sleep Apnea (SantOSA) prospective clinical cohort, including adults with OSA confirmed by home sleep apnea testing. Symptom subtypes were identified using latent class analysis. Associations between obesity and symptom subtypes were evaluated using multivariable regression models adjusted for age, sex, tobacco use, RDI, T90%, TST, hypertension, and diabetes. Statistical significance was set at p < 0.05. Results: A total of 1167 patients were included (943 men). Latent class analysis identified three symptom subtypes: non-sleepy, disturbed sleep, and excessive daytime sleepiness. Among obese patients, 30.7%, 50.0%, and 19.3% were classified into these subtypes, respectively. Obesity prevalence was 50.2%, and compared with non-obese OSA patients, obese patients showed a higher prevalence of severe OSA (46.1% vs. 26.9%), hypertension (54.4% vs. 34.9%), and diabetes (37.2% vs. 19.4%), as well as higher ESS scores and higher RDI and T90% values (all p < 0.01). In adjusted analyses, obesity remained independently associated with the excessive daytime sleepiness subtype after controlling for age, sex, tobacco use, RDI, T90%, TST, and comorbidities. Conclusions: Obesity is highly prevalent in OSA and is associated with specific symptom-defined phenotypes, particularly excessive daytime sleepiness and disturbed sleep. These findings support the relevance of considering symptom profiles alongside traditional severity metrics. Full article

Of the many clinical phenotypes of obesity, the most prevalent are metabolically “healthy” (MHO) and metabolically “unhealthy” (MUO) obesities, the latter being associated with a range of comorbidities, including type 2 diabetes mellitus (T2DM). The underlying causes of different obesity phenotypes and the mechanisms of conversion of one phenotype into another have yet to be fully elucidated. However, increasing evidence suggests the key role of low-grade metabolic inflammation (metaflammation) in the pathogenesis of obesity and metabolic dysfunction. The review presents a comprehensive description of changes in immune cell populations and pro-inflammatory mediators, as well as a detailed comparative mapping of the adipose tissue immune landscape during MHO/MUO transition. Based upon a conceptual model for the intensification of metaflammation during MHO progression and conversion to MUO, a pattern of dynamical changes that accompany MHO/MUO transition is described. Though many parameters demonstrate significant differences in multiple cross-sectional and some longitudinal studies, only a few of them (CRP, IL-6, IL-17A, absolute counts of leukocytes and neutrophils) meet the criteria of a validated biomarker in clinical setting. A lack of standardization in MHO definition and heterogeneity in the severity of MUO make the search for predictive biomarkers a challenge. The review also discusses the mechanisms underlying metabolic memory and the incomplete reversibility of metabolic disturbances after bariatric surgery. Full article

Background: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with the risk of several chronic and acute diseases. However, updated data on vitamin D status in Mediterranean countries, including Italy, remain limited, hindering effective public health strategies. Objective: To assess serum 25(OH)D levels and their seasonal variation in healthy blood donors aged 18–65 years living in Northern Italy and not taking vitamin D supplements. Given the latitude and the high levels of environmental pollution, cutaneous vitamin D synthesis may be impaired in this population. Recent Italian guidelines on supplementation emphasize the need for updated data on the prevalence of hypovitaminosis D and seasonal variation in endogenous vitamin D synthesis. Methods: In this exploratory retrospective cross-sectional study, 534 blood donors (268 men and 266 women) attending the Transfusion Medicine Unit of the Verona University Hospital were enrolled between April 2016 and May 2018. Serum 25(OH)D concentrations were analyzed by season. Clinical, lifestyle, pharmacological and dietary characteristics were also collected. Results: Among healthy, normal-weight individuals, the prevalence of vitamin D insufficiency (25(OH)D < 50 nmol/L) was low and limited to one-two months per year. Overweight and obesity significantly reduced the likelihood of achieving adequate 25(OH)D levels through cutaneous synthesis for several months. Mean 25(OH)D concentrations were higher than those previously reported in the same area, while seasonal variation remained preserved. Conclusions: In a relatively small non-supplemented population of blood donors living in a high polluted urban area of Northern Italy, seasonal vitamin D synthesis seems to be preserved. These updated data show higher 25(OH)D levels compared to past findings. Although these data certainly warrant further validation through a national survey involving other regions of Italy and in not selected population, they appear to be in line with the SIOMMMS recommendations against indiscriminate serum 25(OH)D testing and against routine supplementation for healthy normal-weight individuals under 70 years. Full article

Background/Objectives: Two diagnostic approaches for sleep studies are commonly used worldwide: in-laboratory polysomnography [PSG] and home sleep apnea testing [HSAT]. Although HSAT has gained increasing acceptance due to its convenience and lower cost, clinical criteria for HSAT use remain complex and cannot be inferred directly from AHI/ODI severity indices alone. The aim of the present exploratory study was to examine associations between routinely collected demographic, clinical, and symptom-related variables and objective indices of disease severity, namely the apnea–hypopnea index [AHI] and oxygen desaturation index [ODI] as an initial, hypothesis-generating step toward future patient-level model development and validation. Methods: A retrospective observational analysis was conducted in 1100 individuals who previously underwent in lab-polysomnography [PSG] at the University Hospital of Thessaly, Greece, between 2006 and 2023. Specific demographic, clinical and symptom-related variables were included in this study [six continuous and fifteen categorical], which were analyzed in relation to AHI and ODI values. A three-step process was carried out: variable selection followed a screening and backward elimination process. Multivariable linear regression models were subsequently estimated within a Bayesian framework using Hamiltonian Monte Carlo methods. Results: Out of 1100 individuals, the mean age was 51.9 years with the predominant gender being male [76%]. Obesity [65.6%] and hypertension [40.5%] were the most common comorbidities. For AHI, male gender, body mass index [BMI], Epworth Sleepiness Scale [ESS] score, reported breathing interruptions during sleep, and chronic obstructive pulmonary disease [COPD] were significant predictors. For ODI, significant predictors included male gender, BMI, ESS score, breathing interruptions during sleep, daytime sleepiness, obesity, and COPD. COPD showed an inverse association with both indices. Conclusions: These findings support the feasibility of integrating routinely available clinical variables within a Bayesian probabilistic framework to estimate disease severity pre-test probability. The current analysis may not constitute a validated tool for HSAT versus PSG selection; however, it is an initial, hypothesis-generating step toward future model development. Full article

Congenital heart disease (CHD) is the most common anatomical malformation occurring in live-born infants and an increasing cause of morbidity and mortality all over the world. Population-based observations have described associations between maternal cardiometabolic disorders and the risk of CHD in offspring. The present article is a narrative review. The aim of this study was to review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD in offspring, with particular attention paid to first trimester disturbances of fetal cardiac development and the influence of genetic, epigenetic and environmental factors. Studies have shown that maternal diabetes is a risk factor associated with nearly all subtypes of CHDs in offspring, while obesity and overweight are associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. Diabetes and obesity share several phenotypes, which could be transmissible from mother to fetus via the placenta. This means that an increase in maternal glucose could be responsible for the prevalence of CHD in newborns of obese women. On the other hand, maternal diabetes may induce epigenetic modifications in the developing fetus. DNA methylation changes can impact gene expression patterns relevant to heart development. The abovementioned studies are heterogenous, express different opinions and are often difficult to compare. Therefore, the results from these meta-analyses must be interpreted with caution. Optimal diabetes control is responsible for the prevention of oxidative stress in diabetic pregnancies, and a deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHDs by identifying at-risk pregnancies and primary prevention of diseases by improving preconception management. Full article

Although risk factors for Alzheimer’s disease (AD) involve obesity and elevated low-density lipoprotein (LDL) cholesterol levels, and Lonicera caerulea has been reported to improve lipid metabolism disorders (LMDs), it remains unknown whether Lonicera caerulea can simultaneously modulate the progression of both AD and LMDs. In this study, an integrative strategy combining network pharmacology, Mendelian randomization (MR), molecular docking, and molecular dynamics simulations was employed to explore potential targets, pathways, and causal relationships. Network pharmacology and molecular docking results revealed that several blood–brain barrier (BBB)-permeable active components of Lonicera caerulea, including Naringenin and Palmatine, may be associated with targets involved in the lipid and atherosclerosis pathway, such as HSP90AA1, SRC and TNF. These associations indicate a potential link between the modulation of lipid metabolism and AD-related processes, although further validation is required. Molecular dynamics simulations were conducted to support the stability of key docking complexes. Given that elevated LDL is a central feature of LMDs and a key indicator of cholesterol imbalance, MR analysis was conducted to assess its causal relationship with AD. The results provided genetic evidence supporting a causal role of elevated LDL in AD risk, reinforcing the epidemiological link between lipid metabolism and neurodegeneration. These findings imply that BBB-permeable constituents of Lonicera caerulea may exert multi-target effects relevant to AD and LMDs. Enrichment analysis further indicates a possible involvement of pathways associated with lipid and atherosclerosis, supporting its potential as a dietary strategy for at-risk populations. Full article

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition frequently associated with psychiatric comorbidity, including disordered eating. Adult women remain under-recognized and underrepresented in ADHD research, and emerging evidence suggests that symptom expression may be shaped by gendered social factors, ovarian hormone fluctuations, and metabolic health. In this manuscript, we provide a gender-focused theoretical overview of the literature linking ADHD to binge eating symptoms in adult women, with attention to underdiagnosis, menstrual cycle-related symptom variability, and obesity-related metabolic risk, and empirically test the association between a self-reported ADHD diagnosis and binge eating symptoms in an online cross-sectional sample of adult women. Women reporting an ADHD diagnosis (n = 140) were compared with a random subsample of n = 140 women without ADHD drawn from the same survey; comparability between groups on age, education, and employment was formally verified; and binge eating symptoms were assessed with the Binge Eating Scale (BES) as a continuous outcome and as an ordered three-category variable. Women reporting an ADHD diagnosis showed significantly higher BES scores than controls (rank-biserial r = 0.28, 95% CI 0.15–0.41), and a higher proportion of severe binge eating symptomatology (BES ≥ 27; 22.1% vs. 11.4%; OR = 2.20, 95% CI 1.14–4.25) than controls. The association remained significant in a sensitivity analysis adjusting for age and BMI. Taken together, our findings support the need for routine, gender-sensitive screening for binge eating symptoms in women with ADHD, as well as ADHD screening in women presenting with binge eating and obesity. Full article