Molecular Mechanisms of Dietary Bioactive Peptides in Treating Alzheimer's Disease and Mild Cognitive Impairment by Network Pharmacology and Molecular Docking Analysis.

Emerging evidence suggests that bioactive peptides from various foods have therapeutic potentials in improving cognitive function in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We aimed to explore the characteristics of these peptides and their mechanisms on AD/MCI using a network pharmacology approach. We compiled a dataset of cognition-enhancing peptides from literatures and identified shared targets between these peptides and AD/MCI using Swiss Target Predication, PharmMapper, OMIM, GeneCards, TTD, and Drugbank databases.

Telomere length mediates the causal effects of excess adiposity on cardiovascular risk: A two-step Mendelian randomization study.

Background And Aims: Excess adiposity correlate to cardiovascular diseases, inflammation, and telomere shortening, while the latter two are associated with cardiovascular risks. Whether inflammation and telomere length mediate the excess adiposity-cardiovascular relationship is unclear.

Methods And Results: We performed a two-step Mendelian randomization analysis utilizing data from the latest genome-wide association studies: body mass index (BMI, n = 681,275), waist-to-hip ratio (WHR, n = 697,734) and BMI adjusted WHR (WHRBMI, n = 694,649), telomere length (n = 472,174), C-reactive protein (n = 204,402), interleukin-6 and interleukin-1 receptor antagonist (n = 21,758), tumor necrosis factor-α (n = 3454), hypertension (n = 463,010), coronary artery disease (n = 547,261), heart failure (n = 977,323), stroke (n = 446,696), ischemic stroke (n = 440,328), intracerebral hemorrhage (n = 343,663), aortic aneurysm (n = 356,934), transient ischemic attack (n = 360,692), peripheral vascular disease (n = 463,010), systolic and diastolic blood pressure changes (n = 757,601).

Genetic correlation, pleiotropic loci and shared risk genes between major depressive disorder and gastrointestinal tract disorders.

Background: Major depressive disorder (MDD) is associated with gastrointestinal tract (GIT) disorders, while genetic correlation, pleiotropic loci and shared risk genes remain to be explored.

Methods: Leveraging genome-wide association study statistics for MDD (n = 170,756), peptic ulcer disease (PUD; n = 16,666), gastroesophageal reflux disease (GORD; n = 54,854), PUD and/or GORD and/or medications (PGM; n = 90,175), irritable bowel syndrome (IBS; n = 28,518), and inflammatory bowel disease (IBD; n = 7045), we determined global and local genetic correlations, identified pleiotropic loci, performed gene-level evaluations, and inferred causal associations using bidirectional Mendelian randomization.

Results: We found global correlation of MDD with PUD (r = 0.

Dietary Flavonoids Consumption and Health: An Umbrella Review.

Scope: The current evidence between dietary flavonoids consumption and multiple health outcomes is inadequate and inconclusive. To summarize and evaluate the evidence for dietary flavonoids consumption and multiple health outcomes, an umbrella review of meta-analyses and systematic reviews is conducted.

Methods And Results: PubMed, Ovid-EMBASE, and the Cochrane Database of Systematic Reviews are searched up to January 2024.

Sex- and time-specific associations of obesity with glycaemic traits: A two-step multivariate Mendelian randomization study.

Aim: To assess the sex- and time-specific causal effects of obesity-related anthropometric traits on glycaemic traits.

Materials And Methods: We used univariate and multivariate Mendelian randomization to assess the causal associations of anthropometric traits (gestational variables, birth weight, childhood body mass index [BMI], BMI, waist-to-hip ratio [WHR], BMI-adjusted WHR [WHR BMI]) with fasting glucose and insulin in Europeans from the Early Growth Genetics Consortium (n ≤ 298 142), the UK Biobank, the Genetic Investigation of Anthropometric Traits Consortium (n ≤ 697 734; females: n ≤ 434 794; males: n ≤ 374 754) and the Meta-Analyses of Glucose and Insulin-related traits Consortium (n ≤ 151 188; females: n ≤ 73 089; males: n ≤ 67 506), adjusting for maternal genetic effects, smoking, alcohol consumption, and age at menarche.

Results: We observed a null association for gestational variables, a negative association for birth weight, and positive associations for childhood BMI and adult traits (BMI, WHR, and WHR BMI).

Systemic inflammation mediates the association between environmental tobacco smoke and depressive symptoms: A cross-sectional study of NHANES 2009-2018.

Background: Depression is associated with both environmental tobacco smoke (ETS) and inflammation. However, whether systemic inflammation mediates the ETS-depression relationship is unclear.

Methods: We analyzed 19,612 participants from the 2009-2018 National Health and Nutrition Examination Survey (representing approximately 206,284,711 USA individuals), utilizing data of depressive symptoms (assessed by Patient Health Questionnaire-9), blood cotinine level (an ETS biomarker), dietary inflammatory index (DII, assessed by 24-h dietary recall) and inflammation, represented by immune-inflammation index (SII) and systemic inflammation response index (SIRI).

Description of Tellurirhabdus bombi sp. nov., Isolated from Bumblebee.

A Gram-stain-negative, aerobic, non-motile, and rod-shaped bacterium, designated IE-0392, was isolated from a bumblebee. The 16S rRNA gene sequence (highest 16S rRNA gene sequence similarity with the type strain of Tellurirhabdus rosea (90.0%) and phylogenetic analysis suggest that strain IE-0392 was a member of the genus Tellurirhabdus.

Differential effects of low and high temperature stress on pollen germination and tube length of mango (Mangifera indica L.) genotypes.

Mango flowering is highly sensitive to temperature changes. In this research, the maximum values of pollen germination rate (PGR), pollen tube length (PTL) and their cardinal temperatures (Tmin, Topt and Tmax) were estimated by using quadratic equation and modified bilinear model under the conditions of 14-36 °C. The pollen germination rate in four mango varieties ranged from 29.

Pd-Catalyzed Intramolecular Chemoselective C(sp2)-H and C(sp3)-H Activation of N-Alkyl- N-arylanthranilic Acids.

A controllable palladium-catalyzed intramolecular C-H activation of N-alkyl- N-arylanthranilic acids has been developed. The methodology allows selective synthesis of 1,2-dihydro-(4 H)-3,1-benzoxazin-4-ones and carbazoles from the same starting materials and palladium catalyst. The selectivity is controlled by the oxidant.

Detection of Bacterial Meningitis Pathogens by PCR-Mass Spectrometry in Cerebrospinal Fluid.

Background: Acute bacterial meningitis remains a life-threatening infectious disease with considerable morbidity and mortality. DNA-based detection methods are an urgent requisite for meningitis-causing bacterial pathogens for the prevention of outbreaks and control of infections.

Methods: We proposed a novel PCR-mass spectrometry (PCR-Mass) assay for the simultaneous detection of four meningitis-causing agents, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Mycobacterium tuberculosis in the present study.

Production of Human Cu,Zn SOD with Higher Activity and Lower Toxicity in via Mutation of Free Cysteine Residues.

Although, as an antioxidant enzyme, human Cu,Zn superoxide dismutase 1 (hSOD1) can mitigate damage to cell components caused by free radicals generated by aerobic metabolism, large-scale manufacturing and clinical use of hSOD1 are still limited by the challenge of rapid and inexpensive production of high-quality eukaryotic hSOD1 in recombinant forms. We have demonstrated previously that it is a promising strategy to increase the expression levels of soluble hSOD1 so as to increase hSOD1 yields in . In this study, a wild-type hSOD1 (wtSOD1) and three mutant SOD1s (mhSOD1s), in which free cysteines were substituted with serine, were constructed and their expression in soluble form was measured.

Expression, Purification, and Characterization of a Sucrose Nonfermenting 1-Related Protein Kinases 2 of in -Based Cell-Free System.

The plant-specific sucrose nonfermenting 1-related protein kinase 2 (SnRK2) family is considered an important regulator of plant responses to abiotic stresses such as drought, cold, salinity, and nutrition deficiency. However, little information is available on how SnRK2s regulate sulfur deprivation responses in Arabidopsis. Large-scale production of SnRK2 kinases can help to elucidate the biochemical properties and physiological functions of this protein family.

Enantioselective Synthesis of 3-Alkynyl-3-hydroxyindolin-2-ones by Copper-Catalyzed Asymmetric Addition of Terminal Alkynes to Isatins.

A highly efficient copper-catalyzed asymmetric addition of terminal alkynes to isatins has been developed. In the presence of a catalytic amount of copper iodide and a chiral phosphine ligand, the reaction gave the corresponding chiral 3-alkynyl-3-hydroxyindolin-2-ones in high yields with high enantioselectivity. This methodology has a broad substrate scope, and the synthetic utility of the present protocol was further demonstrated by the transformation of chiral alkynylation products.

Reduction of PCN biosynthesis by NO in Pseudomonas aeruginosa.

Pyocyanin (PCN), a virulence factor synthesized by Pseudomonas aeruginosa, plays an important role during clinical infections. There is no study of the effect of nitric oxide (NO) on PCN biosynthesis. Here, the effect of NO on PCN levels in Pseudomonas aeruginosa strain PAO1, a common reference strain, was tested.

A pH-induced, intein-mediated expression and purification of recombinant human epidermal growth factor in Escherichia coli.

Human epidermal growth factor (hEGF) is a cellular factor that promotes cell proliferation and has been widely used for the treatment of wounds, corneal injuries, and gastric ulcers. Recombinant hEGF (rhEGF) has previously been expressed using the pTWIN1 system with pH-induced intein and a chitin-binding domain. The rhEGF protein can be purified by chitin affinity chromatography because of the high affinity between the chitin-binding domain fusion-tag and the column.

Expression, purification, and characterization of scar tissue neovasculature endothelial cell-targeted rhIL10 in Escherichia coli.

Interleukin 10 (IL10) plays a pivotal role in the anti-inflammatory response and immunosuppressive reactions. It has also been identified as a new promising therapy for scar formation. Treatment of scars with IL10 has significant effects, but there are some shortcomings, including poor tissue-binding specificity and low effectiveness.

[Cloning, expression and screening tandem repeats of the Z domain of Staphylococcus aureus protein A].

To screen an efficient recombinant Staphylococcus aureus protein A (SpA) for preparing matrix for affinity purification of immunoglobulin G (IgG), a genetic engineering approach was used to obtain monomer, two, three, four and five tandem repeats genes of the Z domain of SpA, then the genes were cloned into expression vector pET-22b and subsequently expressed in Escherichia coli BL21 (DE3). After induction with lactose, the target proteins were purified by Ni2+ affinity chromatography. The proteins with two, three, four and five tandem repeats of the Z domain were then coupled to CNBr-activated Sepharose 4B as an affinity chromatography matrix for affinity purification of human IgG.

Effects of CYP2C9*3 and CYP2C9*13 on Diclofenac Metabolism and Inhibition-based Drug-Drug Interactions.

Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of many important drugs, including diclofenac. CYP2C9*3 and CYP2C9*13 are the principal variant alleles found in the Chinese population. CYP2C9*3 has been reported to reduce the metabolism of diclofenac and alter the extent of drug-drug interactions (DDIs).

Evaluation of the effects of cytochrome P450 nonsynonymous single-nucleotide polymorphisms on tanshinol borneol ester metabolism and inhibition potential.

Nonsynonymous single-nucleotide polymorphisms (nsSNPs) in cytochrome P450 (P450) genes may affect drug metabolism and drug-drug interactions (DDIs), potentially leading to adverse drug reactions. Functional characterization of the nsSNPs in P450 genes is important to help us understand the impact of genetic factors on P450-mediated drug metabolism and DDIs. To evaluate the effects of P450 nsSNPs on the metabolism and inhibition potential of a candidate drug, tanshinol borneol ester (DBZ), we obtained and experimentally validated eight yeast-expressed human P450 isoforms and their nsSNP variants and tested DBZ using these recombinant P450 enzymes.

Metabolism of tanshinol borneol ester in rat and human liver microsomes.

Tanshinol borneol ester (DBZ) is an experimental drug that exhibits efficacious anti-ischemic activity in rats. Although the specific metabolic properties of DBZ are still unknown, previous studies in rats have strongly suggested that DBZ is extensively metabolized after administration and thus probably acts as a prodrug. Because the enzymes involved in drug metabolism differ between humans and rats in isoform composition, expression, and catalytic activity, the pharmacokinetics of the same drug in the two species may also differ.