Search Results (287)

Obesity is a chronic disorder associated with serious comorbidities such as diabetes, cardiovascular disease, and cancer. Conventional pharmacological treatments often suffer from limited efficacy, poor selectivity, and undesirable side effects, highlighting the need for more effective alternatives. Nanomedicine offers a promising approach by overcoming these limitations through targeted drug delivery and enhanced therapeutic precision. This review examines key nanotechnological strategies in obesity management, including targeting white adipose tissue (WAT) and the vascular marker prohibitin, promoting WAT browning, and utilizing photothermal therapy and magnetic hyperthermia as nanotheranostic tools. We discuss major nanomedicine platforms—such as liposomes, nanoemulsions, and polymeric nanoparticles—alongside emerging applications in gene nanotherapy and herbal formulations. Potential toxicity concerns are also addressed. In summary, nanomedicine holds substantial potential to revolutionize obesity treatment through targeted, effective, and multifunctional therapeutic strategies. Full article

The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the metabolic level. The kinin B2 receptor (B2R) is involved in blood pressure regulation and glucose metabolism, promoting glucose uptake in skeletal muscle via bradykinin. Studies in B2R-KO mice demonstrate that the absence of this receptor predisposes animals to glucose intolerance under a high-fat diet and impairs adaptive thermogenesis, indicating a protective role for B2R in metabolic homeostasis and insulin sensitivity. In contrast, the kinin B1 receptor (B1R) is inducible under pathological conditions and is activated by kinin metabolites. Mouse models lacking B1R exhibit improved metabolic profiles, including protection against high-fat diet-induced obesity and insulin resistance, enhanced energy expenditure, and increased leptin sensitivity. B1R inactivation in adipocytes enhances insulin responsiveness and glucose tolerance, supporting its role in the development of insulin resistance. Moreover, B1R deficiency improves energy metabolism and thermogenic responses to adrenergic and cold stimuli, promoting the activation of brown adipose tissue and the browning of white adipose tissue. Collectively, these findings suggest that B1R and B2R represent promising therapeutic targets for the treatment of metabolic disorders. Full article

Background/Objectives: Estrogen deficiency contributes to dyslipidemia and visceral adiposity, increasing cardiovascular risk in postmenopausal women. Sargassum fulvellum (Sf), a brown seaweed rich in bioactive compounds, possesses lipid-regulating properties that may be enhanced by lactic acid bacteria fermentation. This study aimed to evaluate the effects of fermented S. fulvellum (SfLlLm), prepared using Lactococcus lactis and Leuconostoc mesenteroides, on lipid metabolism and adipose tissue remodeling in an ovariectomized (OVX) mouse model of estrogen deficiency. Methods: Female C57BL/6 mice underwent ovariectomy and were fed an AIN-76A diet supplemented with either unfermented Sf or SfLlLm for eight weeks. Sham-operated and 17β-estradiol-treated OVX groups served as controls. Serum lipid levels—total cholesterol, triglycerides, LDL-C, and HDL-C—were assessed, and histological analysis of visceral adipose tissue was conducted to evaluate adipocyte morphology. Results: OVX-induced estrogen deficiency led to increased total cholesterol, triglycerides, and LDL-C, along with hypertrophic changes in visceral adipocytes. Supplementation with fermented Sargassum fulvellum (SfLlLm) markedly improved these parameters, reducing total cholesterol by 6.7%, triglycerides by 9.3%, and LDL-C by 52.9%, while increasing HDL-C by 17.5% compared to the OVX controls. SfLlLm also normalized visceral adipocyte size and distribution. These effects were comparable to or exceeded those of 17β-estradiol treatment. Conclusions: Fermented SfLlLm ameliorated dyslipidemia and visceral adiposity under estrogen-deficient conditions. These findings support its potential as a functional dietary intervention for managing postmenopausal lipid disorders and associated metabolic complications. Full article

Due to consumer needs and the prevalence of gluten-related disorders such as celiac disease, the gluten-free food market is expanding rapidly and is expected to surpass USD 2.4 billion by 2036. The objective of this study was to substitute wheat flour with oat, black rice, brown rice, buckwheat, and rice flours in the production of gluten-free scones, to assess consumer acceptability, and to identify factors contributing to consumer acceptability using check-all-that-apply questions. The 10 attributes of appearance, color, texture, grainy flavor, sweetness, familiar flavor, novelty, familiarity, moistness, and consistency exhibited statistically significant differences among the samples (p < 0.001). One hundred consumers evaluated 18 attributes using a nine-point hedonic scale, and all attributes demonstrated statistically significant differences across six samples (p < 0.001). The samples from buckwheat and wheat scored the highest in consumer acceptability. The results indicate a strong positive correlation between overall liking and purchase intention, with sensory attributes such as nutty flavor, cohesiveness, appearance, moistness, color, texture, and inner softness positively influencing consumer acceptability. The attributes affecting negatively were thick throat sensation, unique flavor, and stuffiness. This study is expected to provide data to aid in the development of better-tasting gluten-free products that meet customer and market needs. Full article

Peach fruit flesh spongy tissue disorder causes dry, porous, and brown areas in the flesh, severely compromising fruit quality and market value. While soil properties and calcium nutrition have been linked to the disorder, the role of rhizosphere microbial communities in disorder resistance remains unclear. This study investigated both the physicochemical properties and the root-associated microbiomes of disordered (CK) and healthy (TT) peach orchards to explore microbial mechanisms underlying disorder suppression. TT soils exhibited higher pH, greater organic matter, increased exchangeable calcium, and more balanced trace elements compared to CK. Microbial analysis revealed significantly higher diversity and enrichment of beneficial taxa in TT associated with plant growth and disorder resistance. Functional gene prediction showed TT was enriched in siderophore production, auxin biosynthesis, phosphate solubilization, and acetoin–butanediol synthesis pathways. Co-occurrence network analysis demonstrated that TT harbored a more complex and cooperative microbial community structure, with 274 nodes and 6013 links. Metagenomic binning recovered high-quality MAGs encoding diverse resistance and growth-promoting traits, emphasizing the ecological roles of Gemmatimonadaceae, Reyranella, Nitrospira, Bacillus megaterium, and Bryobacteraceae. These findings highlight the combined importance of soil chemistry and microbiome structure in disorder suppression and provide a foundation for microbiome-informed soil management to enhance fruit quality and promote sustainable orchard practices. Full article

Background: Melasma is an acquired hyperpigmentation disorder with multifactorial etiologies and limited response to conventional therapies. Recent evidence suggests that Botulinum Toxin A (BoNT-A) may modulate ultraviolet (UV)-induced pigmentation and offer therapeutic benefits. Objective: We sought to evaluate the efficacy and safety of two intradermal dilutions of Letibotulinum toxin A (LetiBoNT-A) in Thai patients with melasma. Methods: In this randomized, double-blind, split-face study, 30 participants aged 32–62 years received a single intradermal injection of LetiBoNT-A, with 20 units administered per cheek. A 1:5 dilution was injected on one side of the face, and a 1:10 dilution was injected on the contralateral side. Outcomes were evaluated over a 6-month period using the Hemi-modified Melasma Area and Severity Index (Hemi-mMASI), VISIA^® brown spot analysis, and quantitative assessments of skin texture. Results: Both dilutions significantly improved Hemi-mMASI scores (1:5, p = 0.043; 1:10, p = 0.002) and brown spots (1:5, p = 0.002; 1:10, p < 0.001). The 1:10 dilution showed earlier and more sustained improvements. Subgroup analysis revealed greater reductions in Hemi-mMASI scores among patients with telangiectatic melasma, particularly with the 1:10 dilution, though they were not statistically significant. Additionally, the 1:10 dilution significantly reduced pore volume, pore area, and sebum levels. One case of transient facial asymmetry was reported with the 1:5 dilution. Conclusions: LetiBoNT-A is a safe and effective adjunct in melasma treatment. The 1:10 dilution offered superior clinical outcomes. Full article

The global obese population accounts for approximately 30% of the total population and continues to increase. White adipocytes, which accumulate in the body for energy storage, are associated with obesity. Mechanisms that activate browning of white adipocytes are an attractive therapeutic target for obesity and metabolic disorders. Exosomes are nano-sized biovesicles that play a role in cell-to-cell communication though the transfer of cargos such as microRNAs. Although milk exosomes contain many endogenous microRNA molecules, the role of microRNAs in milk exosomes is limited. Therefore, the aim of this study was to investigate the effects of milk exosomes on the browning of white adipocyte. Mouse pre-adipocytes (3T3-L1) and human adipose-derived stem cells (hADSCs) were differentiated and exposed to milk exosomes. Compared to control, milk exosomes promoted the expression of thermogenic genes and cellular mitochondrial energy metabolism in both 3T3-L1 cells and hADSCs. Additionally, milk exosomes were orally administered to mice fed a high-fat diet. As the intake of milk exosomes increased, the mice’s body weight decreased. Milk exosomes also increased the protein levels of thermogenic genes and mitochondrial-related genes in mouse adipose tissue. The overexpression of miR-11987, which is abundant in milk exosomes, in both 3T3-L1 cells and hADSCs led to the increased expression of thermogenic genes and mitochondrial activity. Our results support that bovine-specific miR-11987 in milk exosomes promotes the browning of white adipocytes. Therefore, milk exosome and milk exosomal miR-11987 could have significant clinical implications for obesity and metabolic syndrome. Full article

Alginate oligosaccharide (AOS), a degradation product of alginate derived from marine brown algae, has attracted significant attention due to its potent ability to modulate gut microbiota and enhance human health. This review aims to systematically introduce current evidence on the interactions between AOS and gut microbial communities, focusing on how AOS improves health through regulating gut microbiota. Initially, the structural factors of AOS that influence their functions are highlighted, including molecular weight, monomer composition, terminal structure, and chemical modifications. Importantly, AOS primarily exerts beneficial effects by adjusting gut microbiota community and outputs, which include the promotion of probiotics, the inhibition of pathogens, the balance of microbiota composition, and the increase of short-chain fatty acid production. Moreover, the discovered mechanisms underlying AOS-mediated health promotion via microbiota modulation are detailed comprehensively, specifically emphasizing intestinal barrier maintenance, antioxidation, dual-regulation of immune and inflammatory responses, pathogenic infection inhibition, metabolic improvement, uric acid excretion promotion, anti-tumor effects, and anti-skin aging. Such beneficial effects make AOS valuable in keeping healthy, preventing disorders, and intervening in diseases. Despite these findings and research progress, there are yet limitations in studying AOS–gut microbiota interactions, such as precise microbiota-targeted structural optimization, personalized nutritional interventions based on microbial characteristics, and broadening the horizon of microbiota-derived metabolic metabolomic profiles. In conclusion, advancing our understanding of the gut microbiota-centered mechanisms of AOS would probably facilitate novel nutritional strategy development for health promotion. Full article

This study compared the metabolic consequences of fecal microbiota transplantation (FMT) from donor mice that had been either administered pulsed electromagnetic field (PEMF) therapy or exercised to recipient mice fed a high-fat diet (HFD). Eight weeks of PEMF treatment (10 min/week) enhanced PGC-1α-associated mitochondrial and metabolic gene expression in white and brown adipose to a greater degree than eight weeks of exercise (30–40 min/week). FMT from PEMF-treated donor mice recapitulated these adipogenic adaptations in HFD-fed recipient mice more faithfully than FMT from exercised donors. Direct PEMF treatment altered hepatic phospholipid composition, reducing long-chain ceramides (C16:0) and increasing very long-chain ceramides (C24:0), which could be transferred to PEMF-FMT recipient mice. FMT from PEMF-treated mice was also more effective at recovering glucose tolerance than FMT from exercised mice. PEMF treatment also enhanced bone density in both donor and HFD recipient mice. The gut Firmicutes/Bacteroidetes (F/B) ratio was lowest in both the directly PEMF-exposed and PEMF-FMT recipient mouse groups, consistent with a leaner phenotype. PEMF treatment, either directly applied or via FMT, enhanced adipose thermogenesis, ceramide levels, bone density, hepatic lipids, F/B ratio, and inflammatory blood biomarkers more than exercise. PEMF therapy may represent a non-invasive and non-strenuous method to ameliorate metabolic disorders. Full article

Background: Misdiagnosis, defined as the incorrect identification of a condition or the failure to identify a condition altogether, can lead to delayed treatment, unnecessary interventions, and avoidable morbidity and mortality. Ehlers–Danlos Syndrome (EDS) is a complex pain disorder that is often misdiagnosed or underdiagnosed due to lack of awareness among healthcare providers and variability in diagnostic criteria. Objectives: This study aimed to determine the misdiagnosis rate of hypermobile EDS (hEDS) with psychiatric disorders by physicians who are not board-certified in psychiatry. Methods: Between January 2010 and December 2018, the medical records of 429 patients who were diagnosed with hEDS were reviewed and analyzed. During the process of taking a history, patients were asked if they had previously been told by physicians who were not board-certified in psychiatry that their symptoms were “in their head”, that they were “making it up” or seeking attention, or that they might suffer from Munchausen syndrome by proxy or a factitious disorder, or if such physicians had diagnosed them with conversion disorder. The Brown University Human Research Protection Program determined that the proposed activity was not research involving human subjects. Results: A retrospective chart review was conducted. Among the 429 patients, 405 patients (94.4%) said yes to at least one of the questions, with only 24 patients (5.6%) not having been misdiagnosed with psychiatric illnesses. A total of 378 patients (88%) were told that they were “making it up”, 326 patients (76%) were told that they were attention-seeking, 286 patients (67%) were diagnosed with conversion disorder, 255 patients (60%) were told that “it was in their head”, and 16 patients (4%) were diagnosed with Munchausen syndrome by proxy or a factitious disorder. Conclusions: Misdiagnosis of Ehlers–Danlos Syndrome is a pervasive issue with profound implications for patients’ physical, mental, and economic well-being. By addressing the underlying causes of misdiagnosis and implementing strategies for improved recognition, the healthcare system can significantly enhance outcomes for individuals who are affected by these complex disorders. Full article

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are major contributors to the rise in metabolic disorders, particularly in developed countries. Despite the need for effective therapies, natural product-based interventions remain underexplored. This study investigated the therapeutic effects of Endarachne binghamiae, a type of brown algae, hot water extract (EB-WE) in ameliorating obesity and MASLD using high-fat diet (HFD)-induced ICR mice for an acute obesity model (4-week HFD feeding) and C57BL/6 mice for a long-term MASLD model (12-week HFD feeding). EB-WE administration significantly reduced body and organ weights and improved serum lipid markers, such as triglycerides (TG), total cholesterol (T-CHO), HDL (high-density lipoprotein), LDL (low-density lipoprotein), adiponectin, and apolipoprotein A1 (ApoA1). mRNA expression analysis of liver and skeletal muscle tissues revealed that EB-WE upregulated Ampkα and Cpt1 while downregulating Cebpα and Srebp1, suppressing lipogenic signaling. Additionally, EB-WE activated brown adipose tissue through Pgc1α and Ucp1, contributing to fatty liver alleviation. Western blot analysis of liver tissues demonstrated that EB-WE enhanced AMPK phosphorylation and modulated lipid metabolism by upregulating PGC-1α and UCP-1 and downregulating PPAR-γ, C/EBP-α, and FABP4 proteins. It also reduced oxidation markers, such as OxLDL (oxidized low-density lipoprotein) and ApoB (apolipoprotein B), while increasing ApoA1 levels. EB-WE suppressed lipid peroxidation by modulating oxidative stress markers, such as SOD (superoxide dismutase), CAT (catalase), GSH (glutathione), and MDA (malondialdehyde), in liver tissues. Furthermore, EB-WE regulated the glucose regulatory pathway in the liver and muscle by inhibiting the expression of Sirt1, Sirt4, Glut2, and Glut4 while increasing the expression of Nrf2 and Ho1. Tentative liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis for EB-WE identified bioactive compounds, such as pyropheophorbide A and digiprolactone, which are known to have antioxidant or metabolic regulatory activities. These findings suggest that EB-WE improves obesity and MASLD through regulation of metabolic pathways, glucose homeostasis, and antioxidant activity, making it a promising candidate for natural product-based functional foods and pharmaceuticals targeting metabolic diseases. Full article

Background/Objectives: Compulsive rituals in Obsessive–Compulsive Disorder (OCD) are characterized by a specific motor structure, built upon the fragmentation of action flow, obtained through act repetitions and the intrusion of non-functional acts. No study to date has adopted a hierarchical analysis to subtype OCD according to specific behavioral patterns, nor has a possible association between motor profiles and psychopathology been investigated. Methods: This study involved 31 OCD patients (11 female, 35%) and 31 healthy controls (11 female, 35%). The participants were asked to provide videotapes of their behaviors (OCD compulsions for patients and corresponding normal behaviors for healthy controls). BORIS software version 2.84.1 was adopted to analyze the recorded videos. Psychopathology was assessed through the Yale–Brown Obsessive–Compulsive Scale, the Childhood Trauma Questionnaire, the Frankfurt Complaint Questionnaire, and the Social and Occupational Functioning Assessment Scale. Results: Hierarchical analysis revealed three behavioral clusters based on motor profile: Cluster 1 included OCD compulsions structurally characterized by act repetitions (“iterative” rituals); Cluster 2 was represented by OCD compulsions mainly built upon non-functional acts (“idiosyncratic” rituals); and Cluster 3 comprised routinized and normative behaviors, without behavioral ritualization (no act repetitions and few non-functional acts). No significant differences were found in age, age at onset, and OCD severity between “iterative” and “idiosyncratic” rituals. However, patients with “iterative” rituals showed both more severe pre-psychotic symptoms and childhood trauma experiences than patients with “idiosyncratic” rituals. Conclusions: These findings may have significant clinical implications as they hint at a relationship between specific behavioral patterns of OCD compulsions and different underlying psychopathologies and/or vulnerabilities. Full article

Obesity, marked by excessive white adipose tissue (WAT) accumulation, worsens metabolic disorders, and inducing WAT browning is a promising therapy. This study examined the synergistic effects of moderate-intensity aerobic training and resveratrol (RES) on WAT browning and its underlying mechanisms in obese male rats. Methods: Male Sprague Dawley rats were divided into a normal diet control group (n = 8) and a high-fat-diet modeling group (n = 32), with the rats in the latter group being further divided randomly in groups of eight into a high-fat group; a high-fat, exercise group; a high-fat, RES group; and a high-fat, exercise-combined-with-RES group. The rats in the exercise intervention groups underwent moderate-intensity aerobic treadmill exercise for one hour daily, six days a week, while those in the RES groups received a 50 mg/kg/d RES solution via gavage before exercise, once daily, six days a week. Both interventions lasted eight weeks. Results: The combined intervention synergistically suppressed weight gain and visceral fat accumulation. WAT browning was enhanced, evidenced by upregulated UCP1 and CIDEA expression. Mitochondrial biogenesis was activated via the SIRT1-PGC-1α-NRF-1-TFAM pathway, accompanied by elevated mitochondrial enzyme activity and improved lipid mobilization (reduced serum free fatty acids and triglycerides). Conclusions: The combination of aerobic exercise and RES promotes WAT browning and lipolysis by enhancing mitochondrial biogenesis and stimulating mitochondrial thermogenesis through the modulation of the SIRT1-PGC-1α-NRF-1-TFAM pathway. Full article

Modifications to daily sedentary behavior (SB) and participation in moderate-to-vigorous physical activity (MVPA) may provide beneficial results in the prevention and management of mental disorders, such as Major Depressive Disorder (MDD). This cross-sectional research investigated the minimum number of follow-up days needed to reliably estimate the time spent in SB and MVPA from accelerometer data in people with MDD. SB and physical activity (PA) were assessed using an accelerometer, and classified as time spent in SB and in different PA intensities (light—LPA, moderate—MPA, vigorous—VPA, MVPA, or total—TPA). The minimum days of use were calculated using Spearman–Brown analyses, considering only variables with an ICC > 0.8 (cut point-considered acceptable). In the results, 98 people with MDD showed no differences between the days of the week, and an ICC > 0.8 for SB, MPA, and MVPA (for 2-3-4-5-6 vs. 7). Thus, Spearman–Brown analyses were performed considering 2 days (minimum days with ICC > 0.8) and 7 days (maximum days of original test with ICC > 0.8). Our results suggest that a minimum of 3 days of accelerometer use is necessary to reliably estimate the time of SB, MPA, and MVPA. This finding has a significant practical application, allowing data collection using a reduced duration of accelerometer wear. The optimization of time needed in this context permits the utilization of accelerometers among a greater number of individuals, possibly affecting the sample size of MDD patients in research and decreasing acquisition costs in this scientific area. Full article

Introduction: Alkaptonuria is an autosomal-recessive disorder affecting the metabolism of tyrosine and phenylalanine which results in accumulation of homogentisic acid in connective tissues. The joints are most commonly affected, while the most common cardiac damage is aortic valve stenosis. The treatment focuses on reducing the symptoms. Aortic stenosis in alkaptonuria is treated with surgical aortic valve replacement; however, transcatheter aortic valve implantation procedures are increasing in number with excellent outcomes. Case presentation: We report a case of a 67-year-old female with chronic back pain and large-joint arthralgia, who was recently diagnosed with alkaptonuria. She reported a long-known heart murmur and intermittent dark-brown staining of her underwear since childhood. Bilateral dark-brown pigmentation of the sclera and both ear cartilages were visualised. ECG confirmed atrial fibrillation and left ventricular hypertrophy. Cardiac ultrasonography showed severe aortic stenosis, reduced global longitudinal strain and preserved ejection fraction. According to the latest recommendations, the choice between surgical and transcatheter intervention must be based upon careful evaluation of clinical, anatomical and procedural factors by the Heart Team, weighing the risks and benefits of each approach for an individual patient. The advantages and disadvantages of both procedures were explained to the patient. It was emphasised that the genetic disease present has no etiopathogenetic definitive treatment and the pigment may continue to deposit on the biological valve (in transcatheter aortic valve implantation) and less likely on the mechanical valve prosthesis (in Surgical Aortic Valve Replacement), highlighting the fact that in the literature worldwide, there are only single reports of ochronosis and severe aortic stenosis. At this stage of knowledge, it is difficult to give the patient clear guarantees when choosing a methodology for performing a valve correction. Along with the standard therapy the patient underwent transcatheter aortic valve implantation with Boston Scientific prosthesis with a very good post-procedural outcome. Conclusions: There is scarce information on transcatheter aortic valve implantation success rate in patients with alkaptonuria. In the population, transcatheter aortic valve implantation outcome is generally good; however, the individual success in alkaptonuria patients depends on the severity of their heart valve damage and overall health. Full article