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JCI Insight Jun 2024
Topics: Diet, High-Fat; Animals; Bile Acids and Salts; Intestinal Mucosa; Mice; Cell Proliferation; Up-Regulation; Humans; Thrombospondins; Male
PubMed: 38855870
DOI: 10.1172/jci.insight.181492 -
Drug Design, Development and Therapy 2024Buch.-Ham. ex D. Don (), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component...
BACKGROUND
Buch.-Ham. ex D. Don (), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties.
MATERIALS AND METHODS
Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS.
RESULTS
Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins.
CONCLUSION
Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin's action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.
Topics: Animals; Diabetes Mellitus, Experimental; Rats; Hypoglycemic Agents; Male; Streptozocin; Rats, Sprague-Dawley; Metabolome; Blood Glucose; Diet, High-Fat; Drugs, Chinese Herbal
PubMed: 38855535
DOI: 10.2147/DDDT.S459931 -
Journal of Medical Cases Jun 2024Eosinophilic enteritis (EoN) poses a distinctive challenge, affecting individuals with various clinical presentations depending on the layer and extent of the bowel...
Eosinophilic enteritis (EoN) poses a distinctive challenge, affecting individuals with various clinical presentations depending on the layer and extent of the bowel wall. We present a case of a 19-year-old female with abdominal pain, vomiting, and loose stools for 1 month. Labs were significant for persistent leukocytosis with peripheral eosinophilia. A computed tomography of the abdomen/pelvis demonstrated moderate abdominal ascites and moderately diffuse mucosal thickening of jejunal loops. A diagnostic paracentesis unveiled low serum ascites albumin gradient and 92% eosinophils. Push enteroscopy resulted in no significant biopsy findings, though a laparoscopic full-thickness jejunal biopsy exhibited increased eosinophils in the bowel wall. Intravenous steroid, proton pump inhibitor, and dietary changes resolved the symptoms and normalized the labs within a week. Our case report highlights a variable presentation of eosinophilic jejunitis uncommon in this disease population. EoN is an easily missed diagnosis and mandates frequent follow-up to prompt relevant investigations. Atopic clinical features are not prevalent in each case. While rare, EoN requires a strong clinical suspicion, even if endoscopic biopsies are unremarkable, prompting timely laparoscopic full-thickness biopsy. Per protocol, physicians must do the infectious and eosinophilia workup to rule out other etiologies. Our case also highlights that worsening clinical condition in EoN warrants early intravenous steroids with a favorable prognosis and considers a psychosocial aspect of the disease on the patient's health.
PubMed: 38855296
DOI: 10.14740/jmc4196 -
Archives of Osteoporosis Jun 2024These guidelines aim to provide evidence-based recommendations for the supplementation of Vitamin D in maintaining bone health. An unmet need persists in Latin American...
Clinical Practice Guidelines of the Latin American Federation of Endocrinology for the use of vitamin D in the maintenance of bone health: recommendations for the Latin American context.
INTRODUCTION
These guidelines aim to provide evidence-based recommendations for the supplementation of Vitamin D in maintaining bone health. An unmet need persists in Latin American regarding the availability of clinical and real-world data for rationalizing the use of vitamin D supplementation. The objective of these guidelines is to establish clear and practical recommendations for healthcare practitioners from Latin American countries to address Vitamin D insufficiency in clinical practice.
METHODS
The guidelines were developed according to the GRADE-ADOLOPMENT methodology for the adaptation or adoption of CPGs or evidence-based recommendations. A search for high quality CPGs was complemented through a comprehensive review of recent literature, including randomized controlled trials, observational studies, and systematic reviews evaluating the effects of Vitamin D supplementation on bone health. The evidence to decision framework proposed by the GRADE Working Group was implemented by a panel of experts in endocrinology, bone health, and clinical research.
RESULTS
The guidelines recommend Vitamin D supplementation for individuals aged 18 and above, considering various populations, including healthy adults, individuals with osteopenia, osteoporosis patients, and institutionalized older adults. These recommendations offer dosing regimens depending on an individualized treatment plan, and monitoring intervals of serum 25-hydroxyvitamin D levels and adjustments based on individual results.
DISCUSSION
The guidelines highlight the role of Vitamin D in bone health and propose a standardized approach for healthcare practitioners to address Vitamin D insufficiency across Latin America. The panel underscored the necessity for generating local data and stressed the importance of considering regional geography, social dynamics, and cultural specificities when implementing these guidelines.
Topics: Humans; Vitamin D; Latin America; Vitamin D Deficiency; Osteoporosis; Dietary Supplements; Adult; Aged; Female; Male
PubMed: 38850469
DOI: 10.1007/s11657-024-01398-z -
Drug Design, Development and Therapy 2024Natural medicines possess significant research and application value in the field of atherosclerosis (AS) treatment. The study was performed to investigate the impacts...
Notoginsenoside R1 Ameliorate High-Fat-Diet and Vitamin D3-Induced Atherosclerosis via Alleviating Inflammatory Response, Inhibiting Endothelial Dysfunction, and Regulating Gut Microbiota.
AIM
Natural medicines possess significant research and application value in the field of atherosclerosis (AS) treatment. The study was performed to investigate the impacts of a natural drug component, notoginsenoside R1, on the development of atherosclerosis (AS) and the potential mechanisms.
METHODS
Rats induced with AS by a high-fat-diet and vitamin D3 were treated with notoginsenoside R1 for six weeks. The ameliorative effect of NR1 on AS rats was assessed by detecting pathological changes in the abdominal aorta, biochemical indices in serum and protein expression in the abdominal aorta, as well as by analysing the gut microbiota.
RESULTS
The NR1 group exhibited a noticeable reduction in plaque pathology. Notoginsenoside R1 can significantly improve serum lipid profiles, encompassing TG, TC, LDL, ox-LDL, and HDL. Simultaneously, IL-6, IL-33, TNF-α, and IL-1β levels are decreased by notoginsenoside R1 in lowering inflammatory elements. Notoginsenoside R1 can suppress the secretion of VCAM-1 and ICAM-1, as well as enhance the levels of plasma NO and eNOS. Furthermore, notoginsenoside R1 inhibits the NLRP3/Cleaved Caspase-1/IL-1β inflammatory pathway and reduces the expression of the JNK2/P38 MAPK/VEGF endothelial damage pathway. Fecal analysis showed that notoginsenoside R1 remodeled the gut microbiota of AS rats by decreasing the count of pathogenic bacteria (such as and ) and increasing the quantity of probiotic bacteria (such as ).
CONCLUSION
Notoginsenoside R1, due to its unique anti-inflammatory properties, may potentially prevent the progression of atherosclerosis. This mechanism helps protect the vascular endothelium from damage, while also regulating the imbalance of intestinal microbiota, thereby maintaining the overall health of the body.
Topics: Animals; Gastrointestinal Microbiome; Ginsenosides; Rats; Atherosclerosis; Diet, High-Fat; Male; Cholecalciferol; Rats, Sprague-Dawley; Inflammation; Endothelium, Vascular
PubMed: 38845851
DOI: 10.2147/DDDT.S451565 -
BMC Cancer Jun 2024Hepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in...
BACKGROUND
Hepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait.
METHODS
Fifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient's clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were computed using the parameters' estimates of the final model and used for interpretation of the model.
RESULTS
The HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (OR = 41.6; 95% CI: 8.9-193.5; p < 0.001). The cases compared with the controls were more likely to have reported the history of heavy alcohol drinking (OR = 14.2; 95% CI: 1.2-173.4; p = 0.038). Furthermore, compared with the controls, the HCC cases tended to frequently consume milk and/or milk substitutes (≥ 3 glass/ week) (OR = 7.2; 95% CI: 1.2-43.4). Conversely however, there was a significant protective effect if the participants reportedly have had regularly used olive oil in their routine diet as a source of fat (OR = 0.17; 95% CI: 0.04-0.80) or regularly used non-steroid anti-inflammatory drugs (NSAIDs) (OR = 0.20; 95% CI: 0.05-0.71).
CONCLUSIONS
This study showed that heavy alcohol consumption, NAFLD history, and excessive consumption of milk/ milk substitutes were associated with a significantly increased HCC risk. Conversely however, regular use of olive oil in the diet as a source of fat or regular use of NSAIDs had a significantly protective effect against HCC risk. Adapting healthy dietary habits and preventing/ treating NAFLD may minimize the HCC risk. Future research with a larger sample size may contemplate validating the results of this study and unraveling additional risk factors contributing to HCC risk. The resultant data may help design and implement evidence-based educational programs for the prevention of HCC in this and other similar settings.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Female; Male; Case-Control Studies; Middle Aged; Risk Factors; Kuwait; Life Style; Diet; Aged; Comorbidity; Adult; Alcohol Drinking; Non-alcoholic Fatty Liver Disease
PubMed: 38844890
DOI: 10.1186/s12885-024-12409-0 -
Experimental Gerontology Aug 2024Ageing is associated with cognitive decline. This study investigated the individual and combined effects of resistance exercise (RE) and whey protein supplementation... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of resistance exercise and whey protein supplementation on cognitive function in older men: secondary analysis of a randomised, double-blind, placebo-controlled trial.
PURPOSE
Ageing is associated with cognitive decline. This study investigated the individual and combined effects of resistance exercise (RE) and whey protein supplementation (PRO) on cognitive function in older men.
METHODS
In a pooled-groups analysis, 36 older men (age: 67 ± 4 years) were randomised to either RE (2 x/week; n = 18) or no exercise (NE; n = 18), and either PRO (2 × 25 g/d whey protein isolate; n = 18) or control (CON, 2 × 23.75 g maltodextrin/d; n = 18). A sub-analysis was also conducted between RE + CON (n = 9) and RE + PRO (n = 9). At baseline and 12 weeks, participants completed a battery of neuropsychological tests (CANTAB; Cambridge Cognition, UK) and neurobiological, inflammatory, salivary cortisol and insulin sensitivity biomarkers were quantified.
RESULTS
PRO improved executive function z-score (+0.31 ± 0.08) greater than CON (+0.06 ± 0.08, P = 0.03) and there was a trend towards improved global cognitive function (P = 0.053). RE and RE + PRO did not improve any cognitive function domains (p ≥ 0.07). RE decreased tumor necrosis factor-alpha (P = 0.02) and interleukin-6 (P = 0.048) concentrations compared to NE, but changes in biomarkers did not correlate with changes in cognitive domains. Muscle strength (r = 0.34, P = 0.045) and physical function (ρ = 0.35-0.51, P < 0.05) outcomes positively correlated with cognitive function domains at baseline, but only Δskeletal muscle index correlated with Δepisodic memory (r = 0.34, P = 0.046) following the intervention.
CONCLUSION
In older men, PRO improved cognitive function, most notably executive functioning. RE did not improve any cognitive function domains but did decrease biomarkers of systemic inflammation. No synergistic effects were observed.
Topics: Humans; Male; Whey Proteins; Resistance Training; Aged; Double-Blind Method; Cognition; Dietary Supplements; Executive Function; Neuropsychological Tests; Middle Aged; Cognitive Dysfunction; Biomarkers; Hydrocortisone; Insulin Resistance
PubMed: 38844183
DOI: 10.1016/j.exger.2024.112477 -
Clinical and Experimental Hypertension... Dec 2024Fibroblast growth factor 21 (FGF21) has a protective effect against cardiovascular disease. However, the role of FGF21 in hypertension remains elusive.
BACKGROUND
Fibroblast growth factor 21 (FGF21) has a protective effect against cardiovascular disease. However, the role of FGF21 in hypertension remains elusive.
METHODS
Ten-week-old male C57BL/6 mice were randomly divided into normal-salt (NS) group, NS+FGF21 group, deoxycorticosterone acetate-salt (DOCA) group and DOCA+FGF21 group. The mice in NS group underwent uninephrectomy without receiving DOCA and 1% NaCl and the mice in DOCA group were subjected to uninephrectomy and DOCA-salt (DOCA and 1% NaCl) treatment for 6 weeks. At the same time, the mice were infused with vehicle (artificial cerebrospinal fluid, aCSF) or FGF21 (1 mg/kg) into the bilateral paraventricular nucleus (PVN) of mice.
RESULTS
Here, we showed that FGF21 treatment lowered DOCA salt-induced inflammation and oxidative stress in the PVN, which reduced sympathetic nerve activity and hypertension. Mechanistically, FGF21 treatment decreased the expression of HNF4α and inhibited the binding activity of HNF4α to the promoter region of ACE2 in the PVN of DOCA salt-treated mice, which further up-regulated ACE2/Ang (1-7) signals in the PVN. In addition, ACE2 deficiency abolished the protective effect of FGF21 in DOCA salt-treated mice, suggesting that FGF21-mediated antihypertensive effect was dependent on ACE2.
CONCLUSIONS
The results demonstrate that FGF21 protects against salt-sensitive hypertension via regulating HNF4α/ACE2/Ang (1-7) axis in the PVN of DOCA salt-treated mice via multi-organ crosstalk between liver, brain and blood vessels.
Topics: Animals; Paraventricular Hypothalamic Nucleus; Fibroblast Growth Factors; Male; Mice; Hypertension; Mice, Inbred C57BL; Angiotensin-Converting Enzyme 2; Hepatocyte Nuclear Factor 4; Desoxycorticosterone Acetate; Oxidative Stress; Blood Pressure; Sodium Chloride, Dietary
PubMed: 38841901
DOI: 10.1080/10641963.2024.2361671 -
BMC Neurology Jun 2024Myasthenia gravis (MG) is a long-term autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue as its primary clinical features....
BACKGROUND
Myasthenia gravis (MG) is a long-term autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue as its primary clinical features. Vitamin D is crucial for both the autoimmune response and skeletal muscle function.
CASE PRESENTATION
Here, we presented a case report documenting the substantial improvement in symptoms experienced by a patient who underwent subtotal gastrectomy for gastric cancer following high-dose Vitamin D supplementation. The patient developed generalized MG two months after the surgery and did not respond adequately to pyridostigmine therapy, experiencing a progressive deterioration of the condition. A significant reduction in vitamin D concentration was observed following subtotal gastrectomy. In response, high-dose vitamin D supplementation was administered to the patient. Within one week of treatment, swallowing symptoms improved, enabling the consumption of a small amount of liquid food. By the second week, substantial swallowing and neck function improvements were evident. After one month, the patient regained the ability to straighten the neck while walking and consumed a regular diet despite persistent difficulties chewing hard food.
CONCLUSIONS
This case underscores the therapeutic potential of vitamin D in alleviating MG symptoms, particularly in individuals with compromised vitamin D levels following gastrectomy. The observed improvements present a new perspective on the possible involvement of vitamin D supplementation in the management of postoperative MG cases.
Topics: Humans; Gastrectomy; Myasthenia Gravis; Vitamin D; Stomach Neoplasms; Male; Female; Aged; Middle Aged; Dietary Supplements
PubMed: 38840065
DOI: 10.1186/s12883-024-03687-z -
FASEB Journal : Official Publication of... Jun 2024Selenoprotein I (Selenoi) is highly expressed in liver and plays a key role in lipid metabolism as a phosphatidylethanolamine (PE) synthase. However, the precise...
Selenoprotein I (Selenoi) is highly expressed in liver and plays a key role in lipid metabolism as a phosphatidylethanolamine (PE) synthase. However, the precise function of Selenoi in the liver remains elusive. In the study, we generated hepatocyte-specific Selenoi conditional knockout (cKO) mice on a high-fat diet to identify the physiological function of Selenoi. The cKO group exhibited a significant increase in body weight, with a 15.6% and 13.7% increase in fat accumulation in white adipose tissue (WAT) and the liver, respectively. Downregulation of the lipolysis-related protein (p-Hsl) and upregulation of the adipogenesis-related protein (Fasn) were observed in the liver of cKO mice. The cKO group also showed decreased oxygen consumption (VO), carbon dioxide production (VCO), and energy expenditure (p < .05). Moreover, various metabolites of the steroid hormone synthesis pathway were affected in the liver of cKO mice. A potential cascade of Selenoi-phosphatidylethanolamine-steroid hormone synthesis might serve as a core mechanism that links hepatocyte-specific Selenoi cKO to biochemical and molecular reactions. In conclusion, we revealed that Selenoi inhibits body fat accumulation and hepatic steatosis and elevates energy consumption; this protein could also be considered a therapeutic target for such related diseases.
Topics: Animals; Mice; Obesity; Mice, Knockout; Hepatocytes; Fatty Liver; Selenoproteins; Diet, High-Fat; Male; Liver; Energy Metabolism; Lipid Metabolism; Mice, Inbred C57BL; Adipose Tissue, White
PubMed: 38837270
DOI: 10.1096/fj.202400575RR