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Pharmaceuticals (Basel, Switzerland) May 2024Osteoporosis is a global health challenge characterized by bone loss and microstructure deterioration, which urgently requires the development of safer and more...
Osteoporosis is a global health challenge characterized by bone loss and microstructure deterioration, which urgently requires the development of safer and more effective treatments due to the significant adverse effects and limitations of existing drugs for long-term treatment. Traditional Chinese medicine, like , offers fewer side effects and has been used to treat osteoporosis, yet its active compounds and pharmacological mechanisms remain unclear. In this study, 65 potential active compounds, 258 potential target proteins, and 488 pathways of were identified through network pharmacology analysis. Further network analysis and review of the literature identified six potential active compounds and HIF-1α for subsequent experimental validation. In vitro experiments confirmed that 2″-O-RhamnosylIcariside II is the most effective compound among the six potential active compounds. It can promote osteoblast differentiation, bind with HIF-1α, and inhibit both HIF-1α gene and protein expression, as well as enhance COL1A1 protein expression under hypoxic conditions. In vivo experiments demonstrated its ability to improve bone microstructures and reduce bone loss by decreasing bone marrow adipose tissue, enhancing bone formation, and suppressing HIF-1α protein expression. This study is the first to describe the therapeutic effects of 2-O-RhamnosylIcariside II on osteoporosis, which was done, specifically, through a mechanism that targets and inhibits HIF-1α. This study provides a scientific basis for the clinical application of and offers a new candidate drug for the treatment of osteoporosis. Additionally, it provides new evidence supporting HIF-1α as a therapeutic target for osteoporosis.
PubMed: 38931373
DOI: 10.3390/ph17060706 -
Pharmaceuticals (Basel, Switzerland) May 2024The prevalence of obesity, characterized by an excessive accumulation of adipose tissue and adipocyte hypertrophy, presents a major public health challenge. This study...
The prevalence of obesity, characterized by an excessive accumulation of adipose tissue and adipocyte hypertrophy, presents a major public health challenge. This study investigates the therapeutic potential of two probiotic strains, Probio65 and Probio-093, in the context of obesity. Utilizing 3T3-L1 cell-derived human adipocytes, we assessed Probio65's and Probio-093's capacity to mitigate triglyceride accumulation and influence adipocytokine production in vitro. Subsequently, an in vivo trial with male C57BL/6J mice examined the effects of both probiotic strains on adipose tissue characteristics, body weight, fat mass, and obesity-related gene expression. This study employed both live and ethanol-extracted bacterial cells. The results demonstrated significant reductions in the triglyceride deposition, body weight, and adipose tissue mass in the treated groups ( < 0.05). Furthermore, both strains modulated adipokine profiles by downregulating proinflammatory markers such as PAI-1, leptin, TNF-α, STAMP2, F4/80, resistin, and MCP-1, and upregulating the insulin-sensitive transporter GLUT4 and the anti-inflammatory adiponectin ( < 0.05). Our findings suggest that Probio65 and Probio-093 are promising agents for microbiome-targeted anti-obesity therapies, offering the effective mitigation of obesity and improvement in adipocyte function in a murine model.
PubMed: 38931347
DOI: 10.3390/ph17060676 -
Nutrients Jun 2024Immune system development during gestation and suckling is significantly modulated by maternal environmental and dietary factors. Breastfeeding is widely recognized as...
Immune system development during gestation and suckling is significantly modulated by maternal environmental and dietary factors. Breastfeeding is widely recognized as the optimal source of nutrition for infant growth and immune maturation, and its composition can be modulated by the maternal diet. In the present work, we investigated whether oral supplementation with and short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) to rat dams during gestation and lactation has an impact on the immune system and microbiota composition of the offspring at day 21 of life. On that day, blood, adipose tissue, small intestine (SI), mesenteric lymph nodes (MLN), salivary gland (SG), cecum, and spleen were collected. Synbiotic supplementation did not affect the overall body or organ growth of the pups. The gene expression of , , , and were upregulated in the SI, and the increase in IgA gene expression was further confirmed at the protein level in the gut wash. Synbiotic supplementation also positively impacted the microbiota composition in both the small and large intestines, resulting in higher proportions of genus, among others. In addition, there was an increase in butanoic, isobutanoic, and acetic acid concentrations in the cecum but a reduction in the small intestine. At the systemic level, synbiotic supplementation resulted in higher levels of immunoglobulin IgG2c in plasma, SG, and MLN, but it did not modify the main lymphocyte subsets in the spleen and MLN. Overall, synbiotic maternal supplementation is able to positively influence the immune system development and microbiota of the suckling offspring, particularly at the gastrointestinal level.
Topics: Animals; Gastrointestinal Microbiome; Synbiotics; Female; Bifidobacterium breve; Pregnancy; Oligosaccharides; Rats; Animals, Suckling; Dietary Supplements; Maternal Nutritional Physiological Phenomena; Lactation; Immune System; Male; Animals, Newborn
PubMed: 38931246
DOI: 10.3390/nu16121890 -
Nutrients Jun 2024This study investigates the role of body composition parameters in patients with pancreatic cancer undergoing surgical treatment. The research involved 88 patients...
This study investigates the role of body composition parameters in patients with pancreatic cancer undergoing surgical treatment. The research involved 88 patients diagnosed with pancreatic cancer who underwent surgery at the Modena Cancer Center between June 2015 and October 2023. Body composition parameters were obtained from CT scans performed before and after surgery. The percentage of sarcopenic patients at the time of diagnosis of pancreatic cancer is 56.82%. Of the patients who died between the first and second CT evaluated, 58% were sarcopenic, thus confirming the role of sarcopenia on outcome. The study found that all body composition parameters (TAMA, SMI, VFI, and SFI) demonstrated a trend towards reduction between two examinations, indicating an overall depletion in muscle and adipose tissue. We then evaluated the relationships between fat-related parameters (VFI, SFI and VSR) and survival outcomes: overall survival and progression-free survival. Cox univariate regression model show significant parameter related to outcomes was adipose tissue, specifically VFI. The study found that higher VFI levels were associated with greater survival rates. This research holds promise for advancing our understanding of the link between body composition and the prognosis of pancreatic cancer patients.
Topics: Humans; Pancreatic Neoplasms; Body Composition; Male; Female; Aged; Sarcopenia; Middle Aged; Adipose Tissue; Tomography, X-Ray Computed; Prognosis
PubMed: 38931189
DOI: 10.3390/nu16121834 -
Nutrients Jun 2024Morphofunctional assessment was developed to evaluate disease-related malnutrition. However, it can also be used to assess cardiometabolic risk, as excess adiposity... (Review)
Review
Morphofunctional assessment was developed to evaluate disease-related malnutrition. However, it can also be used to assess cardiometabolic risk, as excess adiposity increases this risk. Phenylketonuria (PKU) is the most prevalent inherited metabolic disease among adults, and obesity in PKU has recently gained interest, although fat mass correlates better with cardiometabolic risk than body mass index. In this systematic review, the objective was to assess whether adult patients with PKU have higher fat mass than healthy controls. Studies of adult PKU patients undergoing dietary treatment in a metabolic clinic reporting fat mass were included. The PubMed and EMBASE databases were searched. Relevance of articles, data collection, and risk of bias were evaluated by two independent reviewers. Ten articles were evaluated, six with a control group, including 310 subjects with PKU, 62 with mild hyperphenylalaninemia, and 157 controls. One study reported a significant and four a tendency towards an increased fat mass in all patients or only females with PKU. Limitations included not having a healthy control group, not reporting sex-specific results and using different techniques to assess fat mass. Evaluation of fat mass should be included in the morphofunctional assessment of cardiometabolic risk in adult patients with PKU.
Topics: Humans; Phenylketonurias; Adult; Female; Male; Malnutrition; Adiposity; Body Mass Index; Obesity; Cardiometabolic Risk Factors; Adipose Tissue
PubMed: 38931188
DOI: 10.3390/nu16121833 -
Nutrients Jun 2024In order to better understand which metabolic differences are related to insulin resistance in metabolic syndrome (MetSyn), we used hyperinsulinemic-euglycemic (HE)...
CONTEXT/OBJECTIVE
In order to better understand which metabolic differences are related to insulin resistance in metabolic syndrome (MetSyn), we used hyperinsulinemic-euglycemic (HE) clamps in individuals with MetSyn and related peripheral insulin resistance to circulating biomarkers.
DESIGN/METHODS
In this cross-sectional study, HE-clamps were performed in treatment-naive men (n = 97) with MetSyn. Subjects were defined as insulin-resistant based on the rate of disappearance (Rd). Machine learning models and conventional statistics were used to identify biomarkers of insulin resistance. Findings were replicated in a cohort with n = 282 obese men and women with (n = 156) and without (n = 126) MetSyn. In addition to this, the relation between biomarkers and adipose tissue was assessed by nuclear magnetic resonance imaging.
RESULTS
Peripheral insulin resistance is marked by changes in proteins related to inflammatory processes such as IL-1 and TNF-receptor and superfamily members. These proteins can distinguish between insulin-resistant and insulin-sensitive individuals (AUC = 0.72 ± 0.10) with MetSyn. These proteins were also associated with IFG, liver fat (rho 0.36, = 1.79 × 10) and visceral adipose tissue (rho = 0.35, = 6.80 × 10). Interestingly, these proteins had the strongest association in the MetSyn subgroup compared to individuals without MetSyn.
CONCLUSIONS
MetSyn associated with insulin resistance is characterized by protein changes related to body fat content, insulin signaling and pro-inflammatory processes. These findings provide novel targets for intervention studies and should be the focus of future in vitro and in vivo studies.
Topics: Humans; Insulin Resistance; Metabolic Syndrome; Male; Female; Cross-Sectional Studies; Middle Aged; Adult; Biomarkers; Proteome; Glucose Clamp Technique; Obesity; Adipose Tissue; Insulin; Intra-Abdominal Fat
PubMed: 38931177
DOI: 10.3390/nu16121822 -
Nutrients Jun 2024The global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown...
The global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown to reduce blood glucose, in a rat model of diet-induced obesity and T2D. Over 12 weeks, we hypothesized that allulose supplementation would improve body weight, insulin sensitivity, and glycemic control. Our results showed that allulose mitigated the adverse effects of high-fat, high-sugar diets, including reduced body weight gain and improved insulin resistance. The allulose group exhibited lower food consumption and increased levels of glucagon-like peptide-1 (GLP-1), enhancing glucose regulation and appetite control. Additionally, allulose prevented liver triglyceride accumulation and promoted mitochondrial uncoupling in adipose tissue. These findings suggest that allulose supplementation can improve metabolic health markers, making it a promising dietary component for managing obesity and T2D. Further research is needed to explore the long-term benefits and mechanisms of allulose in metabolic disease prevention and management. This study supports the potential of allulose as a safe and effective intervention for improving metabolic health in the context of dietary excess.
Topics: Animals; Fructose; Male; Obesity; Diabetes Mellitus, Type 2; Insulin Resistance; Blood Glucose; Rats; Diet, High-Fat; Liver; Glucagon-Like Peptide 1; Triglycerides; Rats, Sprague-Dawley; Adipose Tissue; Weight Gain; Disease Models, Animal
PubMed: 38931176
DOI: 10.3390/nu16121821 -
Microorganisms May 2024Given the recognized involvement of the gut microbiome in the development of obesity, considerable efforts are being made to discover probiotics capable of preventing...
Given the recognized involvement of the gut microbiome in the development of obesity, considerable efforts are being made to discover probiotics capable of preventing and managing obesity. In this study, we report the discovery of GBCC_F0227, isolated from fermented food, which exhibited superior triglyceride catabolism efficacy compared to WCSF1. Molecular analysis showed elevated expression levels of α/β hydrolases with lipase activity (abH04, abH08_1, abH08_2, abH11_1, and abH11_2) in GBCC_F0227 compared to WCFS1, demonstrating its enhanced lipolytic activity. In a high-fat-diet (HFD)-induced mouse obesity model, the administration of GBCC_F0227 mitigated weight gain, reduced blood triglycerides, and diminished fat mass. Furthermore, GBCC_F0227 upregulated adiponectin gene expression in adipose tissue, indicative of favorable metabolic modulation, and showed robust growth and low cytotoxicity, underscoring its industrial viability. Therefore, our findings encourage the further investigation of GBCC_F0227's therapeutic applications for the prevention and treatment of obesity and associated metabolic diseases.
PubMed: 38930468
DOI: 10.3390/microorganisms12061086 -
Microorganisms May 2024The human microbiome, a complex ecosystem of bacteria, viruses, and protozoans living in symbiosis with the host, plays a crucial role in human health, influencing... (Review)
Review
The human microbiome, a complex ecosystem of bacteria, viruses, and protozoans living in symbiosis with the host, plays a crucial role in human health, influencing everything from metabolism to immune function. Dysbiosis, or an imbalance in this ecosystem, has been linked to various health issues, including diabetes and gestational diabetes (GD). In diabetes, dysbiosis affects the function of adipose tissue, leading to the release of adipokines and cytokines, which increase inflammation and insulin resistance. During pregnancy, changes to the microbiome can exacerbate glucose intolerance, a common feature of GD. Over the past years, burgeoning insights into the gut microbiota have unveiled its pivotal role in human health. This article comprehensively reviews literature from the last seven years, highlighting the association between gut microbiota dysbiosis and GD, as well as the metabolism of antidiabetic drugs and the potential influences of diet and probiotics. The underlying pathophysiological mechanisms discussed include the impact of dysbiosis on systemic inflammation and the interplay with genetic and environmental factors. By focusing on recent studies, the importance of considering microbial health in the prevention and treatment of GD is emphasized, providing insights into future research directions and clinical applications to improve maternal-infant health outcomes.
PubMed: 38930451
DOI: 10.3390/microorganisms12061070 -
Materials (Basel, Switzerland) Jun 2024Gelatin-based photo-crosslinkable hydrogels are promising scaffold materials to serve regenerative medicine. They are widely applicable in additive manufacturing, which...
Gelatin-based photo-crosslinkable hydrogels are promising scaffold materials to serve regenerative medicine. They are widely applicable in additive manufacturing, which allows for the production of various scaffold microarchitectures in line with the anatomical requirements of the organ to be replaced or tissue defect to be treated. Upon their in vivo utilization, the main bottleneck is to monitor cell colonization along with their degradation (rate). In order to enable non-invasive visualization, labeling with MRI-active components like -(2,2-difluoroethyl)acrylamide (DFEA) provides a promising approach. Herein, we report on the development of a gelatin-methacryloyl-aminoethyl-methacrylate-based biomaterial ink in combination with DFEA, applicable in digital light processing-based additive manufacturing towards bone tissue regeneration. The fabricated hydrogel constructs show excellent shape fidelity in line with the printing resolution, as DFEA acts as a small molecular crosslinker in the system. The constructs exhibit high stiffness ( = 36.9 ± 4.1 kPa, evaluated via oscillatory rheology), suitable to serve bone regeneration and excellent MRI visualization capacity. Moreover, in combination with adipose tissue-derived stem cells (ASCs), the 3D-printed constructs show biocompatibility, and upon 4 weeks of culture, the ASCs express the osteogenic differentiation marker Ca.
PubMed: 38930365
DOI: 10.3390/ma17122996