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Journal of Inflammation Research 2024It is unclear how the Chinese Visceral Adiposity Index (cVAI) relates to metabolic dysfunction-associated fatty liver disease (MAFLD) and alanine aminotransferase (ALT)...
Predictive Value of the Chinese Visceral Adiposity Index for Metabolic Dysfunction-Associated Fatty Liver Disease and Elevated Alanine Aminotransferase Levels in Nonobese Chinese Adults: A Cross-Sectional Study.
PURPOSE
It is unclear how the Chinese Visceral Adiposity Index (cVAI) relates to metabolic dysfunction-associated fatty liver disease (MAFLD) and alanine aminotransferase (ALT) in nonobese individuals. In this study, we evaluated the ability of the cVAI to predict MAFLD and elevated ALT in nonobese participants.
METHODS
This cross-sectional study recruited 541 nonobese subjects from March 2019 to January 2022 with the age range of 18-80 years. Hepatic steatosis was diagnosed by ultrasound. Participants were divided into four groups according to cVAI quartiles. To assess the associations between cVAI and MAFLD and elevated ALT, multivariate logistic regression was used. Receiver operating characteristic (ROC) curves were generated to evaluate the ability of the cVAI to predict MAFLD and elevated ALT.
RESULTS
Compared to the group with the lowest cVAI, the group with the highest cVAI was positively associated with nonobese MAFLD [16.173 (4.082-64.073), < 0.001] and elevated ALT [8.463 (2.859-25.049), < 0.001]. The area under the ROC curve (AUC) of the cVAI was greater than that of WC, waist-to-height ratio, or BMI for predicting nonobese MAFLD in the male, female, > 38 and ≤ 38 years old subgroups ( < 0.05), respectively. In addition, the ability of the cVAI to predict MAFLD was better in females, young individuals, and individuals with a higher education level ( < 0.05). The cVAI also had good predictive ability for elevated ALT levels [0.655 (0.602-0.708)], particularly in females, young people, and highly educated participants. Furthermore, the cVAI was strongly positively correlated with the liver fibrosis score ( < 0.05) and was also a strong indicator of concomitant metabolic syndrome in nonobese MAFLD patients [AUC = 0.688 (0.612-0.763)].
CONCLUSION
The cVAI was strongly related to nonobese MAFLD and elevated ALT. The cVAI may be a reliable and accessible predictor of nonobese MAFLD and elevated ALT.
PubMed: 38915805
DOI: 10.2147/JIR.S468093 -
Frontiers in Cardiovascular Medicine 2024The lymphatic vascular system spans nearly every organ in the body and serves as an important network that maintains fluid, metabolite, and immune cell homeostasis.... (Review)
Review
The lymphatic vascular system spans nearly every organ in the body and serves as an important network that maintains fluid, metabolite, and immune cell homeostasis. Recently, there has been a growing interest in the role of lymphatic biology in chronic disorders outside the realm of lymphatic abnormalities, lymphedema, or oncology, such as cardiovascular-kidney-metabolic syndrome (CKM). We propose that enhancing lymphatic function pharmacologically may be a novel and effective way to improve quality of life in patients with CKM syndrome by engaging multiple pathologies at once throughout the body. Several promising therapeutic targets that enhance lymphatic function have already been reported and may have clinical benefit. However, much remains unclear of the discreet ways the lymphatic vasculature interacts with CKM pathogenesis, and translation of these therapeutic targets to clinical development is challenging. Thus, the field must improve characterization of lymphatic function in preclinical mouse models of CKM syndrome to better understand molecular mechanisms of disease and uncover effective therapies.
PubMed: 38915742
DOI: 10.3389/fcvm.2024.1412857 -
BioRxiv : the Preprint Server For... Jun 2024Lynch syndrome (LS) is defined by inherited mutations in DNA mismatch repair genes, including and carries 60% lifetime risk of developing endometrial cancer (EC)....
UNLABELLED
Lynch syndrome (LS) is defined by inherited mutations in DNA mismatch repair genes, including and carries 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, specific mechanisms for LS-associated endometrial carcinogenesis are not well understood. Here, we assessed the effects of MSH2 loss on EC pathogenesis using a novel mouse model (PR-Cre , abbreviated Msh2KO), primary cell lines established from this model, human tissues, and human EC cell lines with isogenic MSH2 knockdown. Beginning at eight months of age, 30% of Msh2KO mice exhibited endometrial atypical hyperplasia (AH), a precancerous lesion. At 12 to 16 months of age, 47% of Msh2KO mice exhibited either AH or ECs with histologic features similar to human LS-related ECs. Transcriptomic profiling of EC from Msh2KO mice revealed a transcriptomic signature for mitochondrial dysfunction. Studies and revealed mitochondrial dysfunction based upon two mechanisms: marked mitochondrial content reduction, along with pronounced disruptions to the integrity of retained mitochondria. Human LS-related ECs also exhibited mitochondrial content reduction compared with non-LS-related ECs. Functional studies revealed metabolic reprogramming of MSH2-deficient EC cells , including reduced oxidative phosphorylation and increased susceptibility to glycolysis suppression. We are the first to identify mitochondrial dysfunction and metabolic disruption as a consequence of MSH2 deficiency-related EC. Mitochondrial and metabolic aberrations should be evaluated as novel biomarkers for endometrial carcinogenesis or risk stratification and could serve as targets for cancer interception in women with LS.
SIGNIFICANCE
This is the first study to report mitochondrial dysfunction contributing to MSH2-deficient endometrial cancer development, identifying a noncanonical pathway for MSH2 deficient carcinogenesis, which also imparts vulnerability to metabolic targeting.
PubMed: 38915709
DOI: 10.1101/2024.06.10.596841 -
Frontiers in Pharmacology 2024Sishen Pill (SSP) has good efficacy in diarrhea with deficiency kidney-yang syndrome (DKYS), but the mechanism of efficacy involving intestinal microecology has not been...
BACKGROUND
Sishen Pill (SSP) has good efficacy in diarrhea with deficiency kidney-yang syndrome (DKYS), but the mechanism of efficacy involving intestinal microecology has not been elucidated.
OBJECTIVE
This study investigated the mechanism of SSP in regulating intestinal microecology in diarrhea with DKYS.
METHODS
Adenine combined with was used to construct a mouse model of diarrhea with DKYS and administered with SSP. The behavioral changes and characteristics of gut content microbiota and short-chain fatty acids (SCFAs) of mice were analyzed to explore the potential association between the characteristic bacteria, SCFAs, intestinal inflammatory and kidney function-related indicators.
RESULTS
After SSP intervention, the body weight and anal temperature of diarrhea with DKYS gradually recovered and approached the normal level. was significantly enriched, and propionic, butyric, isobutyric and isovaleric acids were elevated. Serum creatinine (Cr), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels of the mice were reduced, while serum blood urea nitrogen (BUN) and secretory immunoglobulin A (sIgA) in the colonic tissues were increased. Moreover, there were correlations between , SCFAs, intestinal inflammatory, and kidney function.
CONCLUSION
SSP might suppress the intestinal inflammation by regulating the "-propionic acid" pathway, thus achieving the effect of treating diarrhea with DKYS.
PubMed: 38915463
DOI: 10.3389/fphar.2024.1360589 -
Journal of Health, Population, and... Jun 2024Even after the peak of the COVID-19 pandemic, the number of mild cases remains high, requiring continuous control. Curcumin, owing to its anti-inflammatory properties,... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Even after the peak of the COVID-19 pandemic, the number of mild cases remains high, requiring continuous control. Curcumin, owing to its anti-inflammatory properties, can suppress vital proliferation and cytokine secretion in animal models. We developed a highly absorbable curcumin, curcuRouge (cR), which is approximately 100 times more orally bioavailable than conventional curcumin. We evaluated the effect of cR on the inhibition of disease progression in asymptomatic or mildly symptomatic COVID-19 patients.
METHODS
This study evaluated the effect of 7-day oral intake of cR (360 mg twice daily). Patients within 5 days of COVID-19 diagnosis were randomly assigned to a placebo or cR group in a double-blind manner.
RESULTS
Primary endpoint events [body temperature (BT) ≥ 37.5 °C and saturation of percutaneous oxygen (SpO2) < 96%] were fewer than expected, and the rate of these events was 2.8% in the cR group (2/71) and 6.0% in the placebo group (4/67); hazard ratio (HR) = 0.532, 95% confidence interval (CI) 0.097-2.902. Patients receiving cR tended to take fewer antipyretic medications than those receiving placebo (HR = 0.716, 95% CI 0.374-1.372). Among patients with a normal range of BT at baseline, the BT change rate was significantly (p = 0.014) lower in the cR group (- 0.34%) versus placebo (- 0.01%).
CONCLUSION
The relative suppression of event rates and antipyretic medications taken, and significant decrease of subclinical BT support the anti-inflammatory effects of cR in asymptomatic or mildly symptomatic patients with COVID-19.
TRIAL REGISTRATION
Japan Registry of Clinical Trials (CRB5200002).
Topics: Humans; Curcumin; Double-Blind Method; Male; Female; Middle Aged; COVID-19 Drug Treatment; Administration, Oral; Adult; COVID-19; Aged; Treatment Outcome; SARS-CoV-2; Biological Availability
PubMed: 38915116
DOI: 10.1186/s41043-024-00584-6 -
BMC Endocrine Disorders Jun 2024Metabolic syndrome (MetS) is a cluster of risk factors and the Framingham risk score (FRS) is a useful metric for measuring the 10-year cardiovascular disease (CVD) risk...
Framingham risk scores for determination the 10-year risk of cardiovascular disease in participants with and without the metabolic syndrome: results of the Fasa Persian cohort study.
BACKGROUND
Metabolic syndrome (MetS) is a cluster of risk factors and the Framingham risk score (FRS) is a useful metric for measuring the 10-year cardiovascular disease (CVD) risk of the population. The present study aimed to determine the 10-year risk of cardiovascular disease using the Framingham risk score in people with and without MetS in a large Iranian cohort study.
METHODS
This cross-sectional study was done using the Fasa cohort. Participants aged ≥ 35 years old were recruited to the study from 2015 to 2016. The FRS was calculated using age, sex, current smoking, diabetes, systolic blood pressure (SBP), total cholesterol, and high-density lipoprotein (HDL) cholesterol. MetS was defined as the presence of three or more of the MetS risk factors including triglyceride (TG) level ≥ 150 mg dl, HDL level < 40 mg dl in men and < 50 mg dl in women, systolic/diastolic blood pressure ≥ 130/≥85 mmHg or using medicine for hypertension, fasting blood sugar (FBS) level ≥ 100 mg dl or using diabetes medication and abdominal obesity considered as waist circumference (WC) ≥ 88 cm for women and ≥ 102 cm for men. Multiple logistic regressions were applied to estimate the 10- year CVD risk among people with and without MetS.
RESULTS
Of 8949 participants, 1928 people (21.6%) had MetS. The mean age of the participants with and without Mets was 50.4 ± 9.2 years and 46.9 ± 9.1 years respectively. In total 15.3% of participants with MetS and 8.0% of participants without MetS were in the high-risk category of 10-year CVD risk. Among participants with MetS gender, TG, SBP, FBS and in people without MetS gender, TG, SBP, FBS, and HDL showed strong associations with the predicted 10-year CVD risk.
CONCLUSION
Male sex and increased SBP, TG, and FBS parameters were strongly associated with increased 10-year risk of CVD in people with and without MetS. In people without MetS, reduced HDL-cholestrol was strongly associated with increased 10-year risk of CVD. The recognition of participant's TG, blood pressure (BP), FBS and planning appropriate lifestyle interventions related to these characteristics is an important step towards prevention of CVD.
Topics: Humans; Metabolic Syndrome; Male; Female; Cardiovascular Diseases; Middle Aged; Iran; Cross-Sectional Studies; Adult; Risk Factors; Cohort Studies; Follow-Up Studies; Prognosis; Risk Assessment
PubMed: 38915041
DOI: 10.1186/s12902-024-01621-5 -
Gynecological Endocrinology : the... Dec 2024To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age.
OBJECTIVE
To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age.
METHOD
This was a cross-sectional study in which 288 women with PCOS and 180 women without PCOS between the ages of 20 and 40 years were evaluated. All women had serum total testosterone, androstenedione, DHEA-S, fasting glucose, total cholesterol, HDL-C, LDL-C, and triglyceride levels analyzed. The McCoy Female Sexual Questionnaire (MFSQ) was applied to all studied women. Exploratory factor analysis and reliability analysis were done after data collection. The factor loadings of MFSQ domains were compared between women with PCOS and controls.
RESULTS
Average factor loadings of the MFSQ sexuality domain and MFSQ sexual partner domain were significantly lower in the PCOS group when compared to controls. There was no correlation between the two sexual function domains of the MFSQ and the PCOS features either in the PCOS group or the controls.
CONCLUSION
PCOS is a heterogeneous disease with different metabolic components, such as insulin resistance, obesity, and hyperandrogenism. Although sexual function among women with PCOS was lower than controls, no differences were found in metabolic features of the PCOS and non-PCOS groups with relation to sexual function determined by the MFSQ.
Topics: Humans; Female; Polycystic Ovary Syndrome; Adult; Cross-Sectional Studies; Turkey; Young Adult; Insulin Resistance; Sexual Dysfunction, Physiological; Testosterone; Surveys and Questionnaires; Case-Control Studies; Hyperandrogenism; Sexual Behavior; Androstenedione; Dehydroepiandrosterone Sulfate; Obesity
PubMed: 38913084
DOI: 10.1080/09513590.2024.2362249 -
Heliyon Jun 2024Therapeutic vaccinations are designed to prevent cancer by inducing immune responses against tumor antigens. in cancer cells, tumor-associated antigens (TAA) or... (Review)
Review
Therapeutic vaccinations are designed to prevent cancer by inducing immune responses against tumor antigens. in cancer cells, tumor-associated antigens (TAA) or tumor-specific (mutated) derived peptides are presented within the clefts of main histocompatibility complex (MHC) class I or class II molecules, they either activate cytotoxic T-lymphocytes (CTLs), CD4 T or CD8 T lymphocytes, which release cytokines that can suppress tumor cells growth. In cancer immunotherapies, CD8 T lymphocytes are a major mediator of tumor repression. The effect of peptide-based vaccinations on cytokines in the activating CD8 T cell against targeted tumor antigens is the subject of this review. It is believed that peptide-based vaccines increased IFN-γ, TNF-α, IL-2, and IL-12, secreting CTL line by interacting with dendritic cell (DC), supposed to stimulate immune system. Additionally, mechanisms of CTL activation and dysfunction were also studied. According to most of the data resulted from in vivo and in vitro research works, it is assumed that peptide-based vaccines increased IFN-γ, TNF-α, IL-2, and IL-12.
PubMed: 38912474
DOI: 10.1016/j.heliyon.2024.e32249 -
PeerJ 2024(Thunb.) Makino, a well-known edible and medicinal plant, has anti-aging properties and is used to treataging-associated conditions such as diabetes, metabolic...
BACKGROUND
(Thunb.) Makino, a well-known edible and medicinal plant, has anti-aging properties and is used to treataging-associated conditions such as diabetes, metabolic syndrome, and cardiovascular diseases. Gypenosides (GYPs) are the primary constituents of . Increasing evidence indicates that GYPs are effective at preserving mitochondrial homeostasis and preventing heart failure (HF). This study aimed to uncover the cardioprotective mechanisms of GYPs related to mitochondrial regulation.
METHODS
The bioactive components in GYPs and the potential targets in treating HF were obtained and screened using the network pharmacology approach, followed by drug-disease target prediction and enrichment analyses. The pharmacological effects of GYPs in cardioprotection, mitochondrial function, mitochondrial quality control, and underlying mechanisms were further investigated in Doxorubicin (Dox)-stimulated H9c2 cardiomyocytes.
RESULTS
A total of 88 bioactive compounds of GYPs and their respective 71 drug-disease targets were identified. The hub targets covered MAPK, EGFR, PI3KCA, and Mcl-1. Enrichment analysis revealed that the pathways primarily contained PI3K/Akt, MAPK, and FoxO signalings, as well as calcium regulation, protein phosphorylation, apoptosis, and mitophagy process. In Dox-stimulated H9c2 rat cardiomyocytes, pretreatment with GYPs increased cell viability, enhanced cellular ATP content, restored basal oxygen consumption rate (OCR), and improved mitochondrial membrane potential (MMP). Furthermore, GYPs improved PINK1/parkin-mediated mitophagy without influencing mitochondrial fission/fusion proteins and the autophagic LC3 levels. Mechanistically, the phosphorylation of PI3K, Akt, GSK-3β, and the protein level of Mcl-1 was upregulated by GYP treatment.
CONCLUSION
Our findings reveal that GYPs exert cardioprotective effects by rescuing the defective mitophagy, and PI3K/Akt/GSK-3/Mcl-1 signaling is potentially involved in this process.
Topics: Gynostemma; Mitophagy; Glycogen Synthase Kinase 3 beta; Signal Transduction; Myeloid Cell Leukemia Sequence 1 Protein; Proto-Oncogene Proteins c-akt; Cardiotonic Agents; Plant Extracts; Phosphatidylinositol 3-Kinases; Animals; Rats; Myocytes, Cardiac; Cell Line
PubMed: 38912051
DOI: 10.7717/peerj.17538 -
Frontiers in Immunology 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient's overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.
Topics: Humans; COVID-19; SARS-CoV-2; Angiotensin-Converting Enzyme 2; Pandemics
PubMed: 38911850
DOI: 10.3389/fimmu.2024.1363572