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BMC Musculoskeletal Disorders Jun 2024Increased intake of specific vitamins has been linked to a decreased prevalence of osteoporosis. However, the association between dietary folate intake and the risk of...
BACKGROUND
Increased intake of specific vitamins has been linked to a decreased prevalence of osteoporosis. However, the association between dietary folate intake and the risk of osteoporosis in the general population remains incompletely understood. Therefore, we aimed to determine the association between dietary folate intake and the risk of osteoporosis in the general population of the USA.
METHODS
In this cross-sectional study, data from the National Health and Nutrition Examination Survey (2017-2020) were collected. Osteoporosis was considered to be indicated by a bone mineral density greater than 2.5 standard deviations below the mean of the young adult reference group. Dietary folate intake was measured by a 24-hour dietary recall. Multivariate logistic regression models and restricted cubic spline models were used.
RESULTS
The study included 2297 participants (mean age: 63.69 ± 0.35 years), 49.92% of whom were female. In the general population, increased dietary folate intake was directly associated with a decreased risk of osteoporosis (P for trend = 0.005). In the age > 60 years and female subgroups, folate intake was inversely associated with the risk of osteoporosis (P for trend < 0.001). The dose‒response curve suggested that this association was nonlinear (P for nonlinearity = 0.015).
CONCLUSIONS
Our cross-sectional study provides initial insights into the inverse association between dietary folate intake and the risk of osteoporosis in the general U.S.
POPULATION
Further research is needed to confirm these associations.
Topics: Humans; Female; Cross-Sectional Studies; Male; Middle Aged; Osteoporosis; Folic Acid; Nutrition Surveys; Risk Factors; Bone Density; United States; Aged; Diet; Adult
PubMed: 38909178
DOI: 10.1186/s12891-024-07605-9 -
Journal of Agricultural and Food... Jul 2024Scaffold hopping and structural fine-tuning are important strategies for agrochemical innovation. Multidimensional optimization of the prevalidated antifungal lead was...
Scaffold hopping and structural fine-tuning are important strategies for agrochemical innovation. Multidimensional optimization of the prevalidated antifungal lead was conducted via the design, synthesis, and bioevaluation of 53 new compounds differing in either scaffold or substituent. The antifungal structure-activity relationship (SAR) revealed that a number of amides containing 2-(2-oxazolinyl) aniline (NHPhOx) or 2-(2-thiazolinyl) aniline (NHPhthiOx) demonstrated a more promising antifungal effect than both and the positive control boscalid. Specifically, compound (encoded ) shows an excellent antifungal effect against with an EC value lower than 0.11 μM. This small change leads to a significant improvement (over 1 order of magnitude) in bioactivity compared to that of either (EC = 1.41 μM) or boscalid (EC = 2.01 μM) and fluxapyroxad (EC = 4.35 μM). With much lower resistance factors, () was more efficacious against the two boscalid-resistant strains of TZ01 and NJBH2017. A combination of () and boscalid in a ratio of 1:3 showed synergistic effects against resistant TZ01 and NJBH2017, with SR values of 3.01 and 2.55, respectively. () has a curative efficacy (70.3%) more prominent than that of boscalid (51.2%) in controlling disease caused by . The molecular docking simulation of () with the SDH protein of displayed four hydrogen bonds with amino acid residues TYR144, ARG88, TRP81, and SER84, rationalizing a stronger affinity than boscalid. The scanning electron microscopy (SEM) characteristic revealed that it could cause an obvious collapse of mycelium. This work indicates that () has the potential to be further explored as a new antifungal agent.
Topics: Botrytis; Structure-Activity Relationship; Fungicides, Industrial; Plant Diseases; Niacinamide; Microbial Sensitivity Tests; Molecular Structure; Biphenyl Compounds
PubMed: 38907719
DOI: 10.1021/acs.jafc.4c00782 -
Cell Chemical Biology Jun 2024Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the biosynthesis of nicotinamide adenine dinucleotide (NAD), making it a potential target for cancer therapy....
Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the biosynthesis of nicotinamide adenine dinucleotide (NAD), making it a potential target for cancer therapy. Two challenges hinder its translation in the clinic: targeting the extracellular form of NAMPT (eNAMPT) remains insufficient, and side effects are observed in normal tissues. We previously utilized proteolysis-targeting chimera (PROTAC) to develop two compounds capable of simultaneously degrading iNAMPT and eNAMPT. Unfortunately, the pharmacokinetic properties were inadequate, and toxicities similar to those associated with traditional inhibitors arose. We have developed a next-generation PROTAC molecule 632005 to address these challenges, demonstrating exceptional target selectivity and bioavailability, improved in vivo exposure, extended half-life, and reduced clearance rate. When combined with nicotinic acid, 632005 exhibits safety and robust efficacy in treating NAPRT-deficient pan-cancers, including xenograft models with hematologic malignancy and prostate cancer and patient-derived xenograft (PDX) models with liver cancer. Our findings provide clinical references for patient selection and treatment strategies involving NAMPT-targeting PROTACs.
Topics: Nicotinamide Phosphoribosyltransferase; Humans; Animals; Niacin; Mice; Antineoplastic Agents; Male; Proteolysis; Cell Proliferation; Mice, Nude; Cytokines; Cell Line, Tumor; Female; Xenograft Model Antitumor Assays; Molecular Structure; Neoplasms
PubMed: 38906111
DOI: 10.1016/j.chembiol.2024.05.007 -
Science Immunology Jun 2024Intestinal inflammation shifts microbiota composition and metabolism. How the host monitors and responds to such changes remains unclear. Here, we describe a protective...
Intestinal inflammation shifts microbiota composition and metabolism. How the host monitors and responds to such changes remains unclear. Here, we describe a protective mechanism by which mucosal-associated invariant T (MAIT) cells detect microbiota metabolites produced upon intestinal inflammation and promote tissue repair. At steady state, MAIT ligands derived from the riboflavin biosynthesis pathway were produced by aerotolerant bacteria residing in the colonic mucosa. Experimental colitis triggered luminal expansion of riboflavin-producing bacteria, leading to increased production of MAIT ligands. Modulation of intestinal oxygen levels suggested a role for oxygen in inducing MAIT ligand production. MAIT ligands produced in the colon rapidly crossed the intestinal barrier and activated MAIT cells, which expressed tissue-repair genes and produced barrier-promoting mediators during colitis. Mice lacking MAIT cells were more susceptible to colitis and colitis-driven colorectal cancer. Thus, MAIT cells are sensitive to a bacterial metabolic pathway indicative of intestinal inflammation.
Topics: Animals; Mucosal-Associated Invariant T Cells; Colitis; Dysbiosis; Mice; Gastrointestinal Microbiome; Mice, Inbred C57BL; Mice, Knockout; Intestinal Mucosa; Riboflavin
PubMed: 38905325
DOI: 10.1126/sciimmunol.adi8954 -
PloS One 2024This study aims to evaluate the efficacy and safety of JAK inhibitors in the treatment of patients with RA. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to evaluate the efficacy and safety of JAK inhibitors in the treatment of patients with RA.
METHODS
The databases CNKI, VIP, Wanfang, CBM, and PubMed, Embase, Cochrane Library and Web of Science were searched to identify relevant randomized controlled trials (RCTs), all from the time of database creation to April 2024. Screening, data extraction, and risk of bias assessment (using Review Manager-5.3 software) were independently performed by at least two authors. The network meta-analysis was conducted using R 4.1.3 software. PROSPERO registration number: CRD42022370444.
RESULTS
Thirty-three RCTs included 15,961 patients The experimental groups involved six JAK inhibitors (filgotinib, tofacitinib, decernotinib, baricitinib, upadacitinib and peficitinib) and 12 interventions (different doses of the six JAK inhibitors), and the control group involved adalimumab (ADA) and placebo. Compared with placebo, all JAK inhibitors showed a significant increase in efficacy measures (ACR20/50/70). Compared with ADA, only tofacitinib, low-dose decernotinib, and high-dose peficitinib showed a significant increase in ACR20/50/70. Decernotinib ranked first in the SUCRA ranking of ACR20/50/70. In terms of safety indicators, only those differences between low-dose filgotinib and high-dose upadacitinib, low-dose tofacitinib and high-dose upadacitinib were statistically significant. Low-dose filgotinib ranked first in the SUCRA ranking with adverse events as safety indicators. Only the efficacy and safety of tofacitinib ranked higher among different SUCRA rankings.
CONCLUSION
Six JAK inhibitors have better efficacy than placebo. The superior efficacy of decernotinib and safety of low-dose filgotinib can be found in the SUCRA. However, there are no significant differences in safety between the different JAK inhibitors. Head-to-head trials, directly comparing one against each other, are required to provide more certain evidence.
Topics: Humans; Arthritis, Rheumatoid; Janus Kinase Inhibitors; Bayes Theorem; Pyrimidines; Piperidines; Network Meta-Analysis; Azetidines; Purines; Pyrroles; Pyrazoles; Sulfonamides; Randomized Controlled Trials as Topic; Treatment Outcome; Heterocyclic Compounds, 2-Ring; Niacinamide; Benzamides; Heterocyclic Compounds, 3-Ring; Antirheumatic Agents; Triazoles; Adamantane; Pyridines; Valine
PubMed: 38905267
DOI: 10.1371/journal.pone.0305621 -
International Journal For Vitamin and... Jun 2024Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder that begins before age 12. Given the role of B group vitamins in cell... (Meta-Analysis)
Meta-Analysis Review
Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder that begins before age 12. Given the role of B group vitamins in cell metabolism, synthesis of nucleotides, and neurotransmitters, the present study systematically investigated the plasma levels of vitamins B and B in children with ADHD. We searched electronic databases including Web of Science, MEDLINE, EMBASE, Scopus, Iran MEDEX, Cochran database, and SID from conception to June 2023. Full-text case-control or cross-sectional studies were included in this study. Participants in the case group were children with ADHD aged 6-12 years. Review Manager Software (RevMan 5.4) was used for statistical analyses. Standardized mean differences (SMD) with 95% CIs were used to determine the differences between the two groups. Six studies were included in the present meta-analysis. They included 982 children, of whom, 204 were girls and 744 were boys. The mean age of the children was 8.86±2.03 years. The level of vitamin B was significantly different between children with and without ADHD [SMD -0.80, 95% CI (-1.55, -0.04)]. Vitamin B was significantly lower in children with ADHD [SMD -0.29, 95% CI (-0.42, -0.16)]. However, due to high heterogeneity (I = 93%), sensitivity analysis was used, I fell to 21%, and significant difference was observed between the two groups [SMD -0.19, 95% CI (-0.34, -0.04)]. The results of this systematic review showed that the level of vitamins B and B in children with ADHD was significantly lower than that in healthy children.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Vitamin B 12; Child; Female; Male; Pantothenic Acid; Cross-Sectional Studies; Case-Control Studies
PubMed: 38904980
DOI: 10.1024/0300-9831/a000809 -
Advances in Therapy Jun 2024Perimenopause is a time of transition in a woman's life that links her reproductive years to the cessation of ovulation, or menopause. For many women, this time is...
INTRODUCTION
Perimenopause is a time of transition in a woman's life that links her reproductive years to the cessation of ovulation, or menopause. For many women, this time is characterized by a variety of physiological and lifestyle changes, including increasing irregularity in menstrual bleeding, frequency and severity of vasomotor symptoms, etc. Therapies evaluated specifically for the perimenopausal women are very limited. This study aimed to evaluate the effectiveness and safety of Amberen (a succinate-based non-hormonal supplement) combined with a Smart B (vitamin B) complex in women with typical (without complications) mild to moderate climacteric syndrome during perimenopause.
METHODS
Women up to 50 years of age, in perimenopause, with vasomotor and psychosomatic symptoms of the climacteric syndrome were enrolled for the study. The trial was randomized, double-blinded, placebo-controlled, comparative, and prospective.
RESULTS
A total of 106 participants were enrolled in the trial and, per protocol, 105 completed the trial. We observed statistically significant improvements in most of the Greene Climacteric Scale symptoms, State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS), and Well-being, Activity, and Mood (WAM) scores. The intervention was well tolerated with few adverse effects reported to be mild and transient.
CONCLUSION
The use of this dietary supplement is safe and eliminates or improves vasomotor and psychosomatic symptoms of climacteric symptoms in perimenopausal women: it improves sleep and cognitive abilities, lowers depression and anxiety, improves mood and well-being, and positively affects quality of life.
GOV IDENTIFIER
NCT03897738.
PubMed: 38904899
DOI: 10.1007/s12325-024-02910-0 -
International Journal of Biological... 2024Renal fibrosis is the common pathway in the progression of chronic kidney disease (CKD). Acyloxyacyl hydrolase (AOAH) is expressed in various phagocytes and is highly...
Renal fibrosis is the common pathway in the progression of chronic kidney disease (CKD). Acyloxyacyl hydrolase (AOAH) is expressed in various phagocytes and is highly expressed in proximal tubular epithelial cells (PTECs). Research shows that AOAH plays a critical role in infections and chronic inflammatory diseases, although its role in kidney injury is unknown. Here, we found that AOAH deletion led to exacerbated kidney injury and fibrosis after folic acid (FA) administration, which was reversed by overexpression of in kidneys. ScRNA-seq revealed that mice exhibited increased subpopulation of CD74 PTECs, though the percentage of total PTECs were decreased compared to WT mice after FA treatment. Additionally, exacerbated kidney injury and fibrosis seen in mice was attenuated via administration of methyl ester of (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (ISO-1), an inhibitor of macrophage inhibition factor (MIF) and CD74 binding. Finally, AOAH expression was found positively correlated with estimated glomerular filtration rate while negatively correlated with the degree of renal fibrosis in kidneys of CKD patients. Thus, our work indicates that AOAH protects against kidney injury and fibrosis by inhibiting renal tubular epithelial cells CD74 signaling pathways. Targeting kidney AOAH represents a promising strategy to prevent renal fibrosis progression.
Topics: Animals; Mice; Macrophages; Carboxylic Ester Hydrolases; Humans; Antigens, Differentiation, B-Lymphocyte; Renal Insufficiency, Chronic; Mice, Inbred C57BL; Male; Histocompatibility Antigens Class II; Folic Acid; Kidney Tubules; Fibrosis; Mice, Knockout; Epithelial Cells
PubMed: 38904010
DOI: 10.7150/ijbs.91237 -
Journal of Nanobiotechnology Jun 2024Repeated and widespread use of single chemical pesticides raises concerns about efficiency and safety, developing multi-component synergistic pesticides provides a new...
Repeated and widespread use of single chemical pesticides raises concerns about efficiency and safety, developing multi-component synergistic pesticides provides a new route for efficient control of diseases. Most commercial compound formulations are open systems with non-adjustable released rates, resulting in a high frequency of applications. Meanwhile, although nano pesticide delivery systems constructed with different carrier materials have been extensively studied, realizing their actual scale-up production still has important practical significance due to the large-scale field application. In this study, a boscalid and pyraclostrobin dual-loaded nano pesticide system (BPDN) was constructed with industrial-grade carrier materials to facilitate the realization of large-scale production. The optimal industrial-scale preparation mechanism of BPDN was studied with surfactants as key factors. When agricultural emulsifier No.600 and polycarboxylate are used as the ratio of 1:2 in the preparation process, the BPDN has a spherical structure with an average size of 270 nm and exhibits superior physical stability. Compared with commercial formulation, BPDN maintains rate-stabilized release up to 5 times longer, exhibits better dispersion and spreading performance on foliar, has more than 20% higher deposition amounts, and reduces loss. A single application of BPDN could efficiently control tomato gray mold during the growing period of tomatoes due to extended duration and combinatory effectiveness, reducing two application times and labor costs. Toxicology tests on various objects systematically demonstrated that BPDN has improved safety for HepG2 cells, and nontarget organism earthworms. This research provides insight into creating safe, efficient, and environmentally friendly pesticide production to reduce manual operation times and labor costs. Accompanied by production strategies that can be easily scaled up industrially, this contributes to the efficient use of resources for sustainable agriculture.
Topics: Pesticides; Humans; Strobilurins; Drug Carriers; Animals; Carbamates; Surface-Active Agents; Nanoparticles; Particle Size; Solanum lycopersicum; Biphenyl Compounds; Niacinamide
PubMed: 38902761
DOI: 10.1186/s12951-024-02628-9 -
Clinical Nutrition ESPEN Aug 2024Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of metformin is often associated...
Effect of calcium supplementation on reversing metformin-based inhibition of vitamin B bioavailability in healthy adults using a [C] cyanocobalamin tracer - A pilot study.
BACKGROUND & AIMS
Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of metformin is often associated with a decrease in vitamin B (B) levels in patients with DM. Few studies have shown that this effect could be mitigated with calcium supplementation. In the present study, we quantified the effect of metformin, and metformin co-administered with calcium on B absorption using a novel stable isotope [C] cyanocobalamin tracer.
METHODS
A pilot crossover study was conducted to estimate the bioavailability of B in healthy subjects, using [C] cyanocobalamin as a tracer. In the study, [C] cyanocobalamin was administered orally to the participants followed by hourly venous sampling to measure the concentration of the tracer and estimate bioavailability. This protocol was followed for three experiment days, each separated by a one month wash out period. As part of the study, all participants received the tracer alone for the control day (C), metformin 850 mg along with the tracer for the metformin day (M) and metformin 850 mg with calcium 500 mg and the tracer for the metformin calcium day (MC).
RESULTS
Seven participants completed all three experiment days. The mean B bioavailability (±SD, n = 7) was 42.6 ± 10.2% for the control day (C), 30.8 ± 15.3% for the metformin day (M) and 46.4 ± 8.6% for the metformin-calcium day (MC). Repeated measures ANOVA was done and the pairwise comparison showed a significant difference in the B bioavailability between control and metformin day (C vs M p = 0.010), and between the metformin and metformin with calcium day (M vs MC p = 0.003).
CONCLUSION
B bioavailability reduced significantly from baseline (C) when metformin (M) was administered and this reduction was reversed when calcium was co-administered (MC) in healthy participants. In patients using metformin, calcium supplementation as a strategy to prevent B deficiency needs to be further studied.
Topics: Humans; Metformin; Vitamin B 12; Pilot Projects; Cross-Over Studies; Male; Biological Availability; Female; Adult; Dietary Supplements; Carbon Isotopes; Vitamin B 12 Deficiency; Middle Aged; Hypoglycemic Agents; Calcium; Young Adult; Diabetes Mellitus, Type 2
PubMed: 38901951
DOI: 10.1016/j.clnesp.2024.04.024