Nutrient patterns and risk of diabetes mellitus type 2: a case-control study.

BACKGROUNDS: Although the significance of diet in preventing or managing diabetes complications is highlighted in current literature, there is insufficient evidence regarding the correlation between nutrient patterns and these complications. The objective of this case-control study is to investigate this relationship by analyzing the dietary intake of nutrients in participants with and without type 2 diabetes (T2D). METHODS: A case-control study was conducted at the Tabriz Center of Metabolism and Endocrinology to investigate the relationship between nutrient patterns and type 2 diabetes (T2D). The study enrolled 225 newly diagnosed cases of T2D and 225 controls. The dietary intake of nutrients was assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Principal component analysis using Varimax rotation was used to obtain nutrient patterns. Logistic regression analysis was performed to estimate the risk of T2D. RESULTS: The participants' mean (SD) age and BMI were 39.8 (8.8) years and 27.8 (3.6) kg/m2, respectively. The results identified three major nutrient patterns. The first nutrient pattern was characterized by high consumption of sucrose, animal protein, vitamin E, vitamin B1, vitamin B12, calcium, phosphorus, zinc, and potassium. The second nutrient pattern included fiber, plant protein, vitamin D, Riboflavin, Vitamin B5, copper, and Magnesium. The third nutrient pattern was characterized by fiber, plant protein, vitamin A, riboflavin, vitamin C, calcium, and potassium. Individuals in the highest tertile of nutrient pattern 3 (NP3) had a lower risk of T2D compared to those in the lowest tertile after adjusting for confounders. The odds ratio was 0.52 with a 95% confidence interval of 0.30-0.89 and a P_trend of 0.039. CONCLUSION: This study found that conforming to a nutrient pattern consisting of plant protein, vitamin C, vitamin A, vitamin B2, potassium, and calcium is linked to a lower likelihood of developing T2D.The initial results suggest that following a nutrient pattern that includes these nutrients may reduce the risk of T2D. However, further research is required to confirm the relationship between nutrient patterns and T2D.

Imperatorin from the aerial parts of Cleome viscosa L.: a characterization study and evaluation of the antibacterial activity.

Cleome viscosa L., a member of the family Cleomaceae, is a potential medicinal plant, known for several bioactive properties such as: anticancer, antidiabetic, antioxidant, anti-inflammatory, antimicrobial, wound healing, etc. Our study aimed to isolate a bioactive compound and assess its antibacterial activity. The crystal compound imperatorin was isolated and reported for the first time from the aerial parts of C. viscosa. The isolation was made using silica gel (100-200 mesh) column chromatography. The structure of imperatorin was investigated through single-crystal XRD, unit cell molecules, FTIR, and ESI-MS spectral analysis. The results validated imperatorin's triclinic crystal structure and P2i/c distance group. The electronic structure was also calculated (4.28/6.21 D) along with the frontier molecular orbital, dipole moment, atomic charges, and electrostatic map of particles in gaseous stage and active site. Imperatorin showed highest activity at 40 µg/mL concentration against Gram + ve bacteria: Staphylococcus aureus (3 ± 0.2 mm), Bacillus subtilis (3 ± 0.6 mm), and Gram -ve bacteria: Klebsiella pneumoniae (3 ± 0.2 mm), Escherichia coli (5 ± 0.2 mm). The study highlights that the compound can be isolated in larger quantities as the plant is easily available across the tropics.

Neuroprotective effects of riluzole in Alzheimer's disease: A comprehensive review.

BACKGROUND: Despite several hundred clinical trials of drugs that initially showed promise, there has been limited clinical improvement in Alzheimer's disease (AD). This may be attributed to the existence of at least 25 abnormal cellular pathways that underlie the disease. It is improbable for a single drug to address all or most of these pathways, thus even drugs that show promise when administered alone are unlikely to produce significant results. According to previous studies, eight drugs, namely, dantrolene, erythropoietin, lithium, memantine, minocycline, piracetam, riluzole, and silymarin, have been found to target multiple pathways that are involved in the development of AD. Among these drugs, riluzole is currently indicated for the treatment of medical conditions in both adult patients and children and has gained increased attention from scientists due to its potential in the excitotoxic hypothesis of neurodegenerative diseases. OBJECTIVE: The aim of this study was to investigate the effects of drugs on AD based on cellular and molecular mechanisms. METHODS: The literature search for this study utilized the Scopus, ScienceDirect, PubMed, and Google Scholar databases to identify relevant articles. RESULTS: Riluzole exerts its effects in AD through diverse pathways including the inhibition of voltage-dependent sodium and calcium channels, blocking AMPA and NMDA receptors and inhibiting the release of glutamic acid release and stimulation of EAAT1-EAAT2. CONCLUSION: In this review article, we aimed to review the neuroprotective properties of riluzole, a glutamate modulator, in AD, which could benefit patients with the disease.

Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis.

Background: An increasing number of studies have suggested the relationship between single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes and gastric cancer (GC) susceptibility; however, the available evidence is contradictory. This meta-analysis aimed to comprehensively evaluate whether the SNPs within the TLR family are related to GC development. Methods: PubMed, Scopus, and China National Knowledge Infrastructure (CNKI) were systematically searched up to May 2023 to obtain the pertinent publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were applied to examine the associations using the random-effects model. Results: A total of 45 studies with 25,831 participants (cases: 11,308; controls: 14,523) examining the relation of 18 different SNPs in the TLR family to GC were analyzed. Variations in TLR-4 rs4986790, TLR-4 rs4986791, TLR-5 rs5744174, and TLR-9 rs187084 were significantly associated with increased risk of GC in different genetic models. No significant association was detected for TLR-2-196 to -174de (Delta22), TLR-2 rs3804100, TLR-4 rs11536889, TLR-4 rs11536878, TLR-4 rs2770150, TLR-4 rs10116253, TLR-4 rs1927911, TLR-4 rs10983755, TLR-4 rs10759932, TLR-4 rs1927914, and TLR-10 rs10004195. Conclusion: These findings indicate that variations in TLR-4, TLR-5, and TLR-9 genes were found to be potential risk factors for GC.

Molecular pathways in the development of HPV-induced oropharyngeal cancer.

Oropharyngeal cancer, a subset of head and neck cancer, is increasingly recognized as a unique clinical entity primarily influenced by high-risk human papillomavirus (HPV) infections, particularly HPV-16. This review delves into the viral life cycle of HPV-16 and its interactions with host cells, with a specific focus on the crucial roles played by the viral oncoproteins E6 and E7. These oncoproteins drive cellular proliferation by targeting critical tumor suppressor proteins like p53 and Rb, resulting in uncontrolled cell growth and genomic instability. Furthermore, the significance of epigenetic modifications induced by HPV-16 and their implications is important for cancer progression. This comprehensive review provides valuable insights into the intricate molecular landscape of HPV-induced oropharyngeal cancer, shedding light on the development of targeted therapies and preventive strategies for this emerging global health concern. Video Abstract.

Exploring the phenolic profile, antibacterial, and antioxidant properties of walnut leaves (Juglans regia L.).

The aim of this study was to identify phenolic compounds in walnut leaves from northern Iraq and evaluate their ability to act as antibacterial and antioxidant agents. Phenolic compounds were determined by reversed-phase HPLC. Antibacterial activity was tested against various bacteria. Antioxidant properties were evaluated by various assays, including reducing power and DPPH radical scavenging activity. The HPLC profiles of walnut leaf fractions revealed quercetin, hydroquinone, 4-hydroxybenzoic acid, and caffeic acid in three fractions. The inhibitory activity of DPPH was determined as 47.66, 32.41, and 51.90 µg/mL for fractions I, II, and III, respectively. For ferric reducing power activity, fraction II > fraction III > fraction I and the FRAP activity was observed as 64.43, 73.19, and 68.18 µg/mL for fractions I, II, and III, respectively. All extracted fractions had antibacterial properties against all bacterial strains tested. Observations showed that fraction I was able to produce similar zones of inhibition as streptomycin in most cases. These results suggest that the fractions of this plant extract are plausible natural antioxidants that could be used as prime candidates for the synthesis of antioxidant drugs that can be used for the treatment of many oxidative stress-related diseases.

Combined oncolytic virotherapy gold nanoparticles as synergistic immunotherapy agent in breast cancer control.

Combining viruses and nanoparticles may be a way to successfully treat cancer and minimize adverse effects. The current work aimed to evaluate the efficacy of a specific combination of gold nanoparticles (GNPs) and Newcastle disease virus (NDV) to enhance the antitumor effect of breast cancer in both in vitro and in vivo models. Two human breast cancer cell lines (MCF-7 and AMJ-13) and a normal epithelial cell line (HBL-100) were used and treated with NDV and/or GNPs. The MTT assay was used to study the anticancer potentials of NDV and GNP. The colony formation assay and apoptosis markers were used to confirm the killing mechanisms of NDV and GNP against breast cancer cell lines. p53 and caspase-9 expression tested by the qRT-PCR technique. Our results showed that combination therapy had a significant killing effect against breast cancer cells. The findings demonstrated that NDV and GNPs induced apoptosis in cancer cells by activating caspase-9, the p53 protein, and other proteins related to apoptosis, which holds promise as a combination therapy for breast cancer.

GC-MS, alpha-amylase, and alpha-glucosidase inhibition and molecular docking analysis of selected phytoconstituents of small wild date palm fruit (Phoenix pusilla).

Phoenix pusilla (Arecaceae), commonly known as "small wild date palm", is regarded as one of the underutilized fruit crops in South India. Methanol extract of P. pusilla ripened fruits (PPRF) was analyzed for in vitro porcine pancreatic alpha-amylase (PPAA) and rat small intestine alpha-glucosidase (RIAG) inhibition activities, and through gas chromatography-mass spectrometry (GC-MS) analysis. The GC-MS analysis showed the presence of 25 phytoconstituents from PPRF which was further assessed on the docking behavior of five targeted enzymes diabetes mellitus (DM) namely (i) human aldose reductase, (ii) protein tyrosine phosphatase 1B, (iii) pancreatic alpha-amylase, (iv) peroxisome proliferator-activated receptor gamma, and (v) dipeptidyl peptidase IV by using the AutoDock Vina method. In addition to this physicochemical, bioactivity score, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis was performed using the Molinspiration and pkCSM free online servers. Methanolic extract of PPRF showed 50% inhibition concentration (IC50) at 69.86 and 72.60 µg/mL levels against PPAA and RIAG enzymes activities, respectively. Interestingly in the present study, GC-MS analysis showed the presence of 25 phytoconstituents from PPRF. Physicochemical analysis of PPRF has exhibited that 13 ligands have complied well with Lipinski's Rule of Five (RoF). With regard to ADMET analysis, one ligand (9,12-octadecadienoic acid [Z,Z]) has predicated to possess both the hepatotoxicity (HT) and skin sensitization (SS) effect. The docking studies showed that 1-formyl-2,5-dimethoxy-6,9,10-trimethyl-anthracene exhibited the maximum atomic contact energy (ACE) for all the five target enzymes of DM. Thus, the current study suggested that the methanolic extract of PPRF and its phytoconstituents could be considered as potent antidiabetic agents.

A comprehensive insight into the role of small nucleolar RNAs (snoRNAs) and SNHGs in human cancers.

Long non-coding RNAs (lncRNAs), which comprise most non-coding RNAs (ncRNAs), have recently become a focus of cancer research. How many functional ncRNAs exist is still a matter of debate. Although insufficient evidence supports that most lncRNAs function as transcriptional by-products, it is widely known that an increasing number of lncRNAs play essential roles in cells. Small nucleolar RNAs (snoRNAs), 60-300 nucleotides in length, have been better studied than long non-coding RNAs (lncRNAs) and are predominantly present in the nucleolus. Most snoRNAs are encoded in introns of protein- and non-protein-coding genes called small nucleolar RNA host genes (SNHGs). In this article, we explore the biology and characteristics of SNHGs and their role in developing human malignancies. In addition, we provide an update on the ability of these snoRNAs to serve as prognostic and diagnostic variables in various forms of cancer.

Shining the light on mesenchymal stem cell-derived exosomes in breast cancer.

In women, breast cancer (BC) is the second most frequently diagnosed cancer and the leading cause of cancer death. Mesenchymal stem cells (MSCs) are a subgroup of heterogeneous non-hematopoietic fibroblast-like cells that have the ability to differentiate into multiple cell types. Recent studies stated that MSCs can migrate into the tumor sites and exert various effect on tumor growth and development. Multiple researches have demonstrated that MSCs can favor tumor growth, while other groups have indicated that MSCs inhibit tumor development. Emerging evidences showed exosomes (Exo) as a new mechanism of cell communication which are essential for the crosstalk between MSCs and BC cells. MSC-derived Exo (MSCs-Exo) could mimic the numerous effects on the proliferation, metastasis, and drug response through carrying a wide scale of molecules, such as proteins, lipids, messenger RNAs, and microRNAs to BC cells. Consequently, in the present literature, we summarized the biogenesis and cargo of Exo and reviewed the role of MSCs-Exo in development of BC.

The protective effects of quercetin on the physiological responses in malathion-exposed common carp, Cyprinus carpio.

This study aimed to evaluate the protective effects of quercetin on the biochemical parameters, immunity, and growth performance in malathion-exposed common carp, Cyprinus carpio. The methods six experimental groups, including the control group, fish exposed to concentrations of 1.04 and 2.08 mg/l malathion, fish supplemented with quercetin (200 mg/kg diet), and fish treated with quercetin + malathion for 21 days, were considered for the experiment. After the feeding period, in results the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were significantly decreased in the hepatocyte, while malondialdehyde (MDA) content increased in response to malathion. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and glucose, cortisol, and urea levels significantly increased after exposure to malathion. Exposure of fish to malathion-induced decreases in protease, lysozyme, and alternative complement (ACH50) activities and total immunoglobulin (total Ig) in the mucosa. Changes in other parameters were different depending on malathion concentrations. The supplementation of fish with quercetin had no ameliorating effect on the malathion-related alternations of mucosal lysozyme and protease activities. However, quercetin ameliorated the depressing effects of malathion on biochemical and immunological parameters. Changes in the growth performance and hematological parameters indicated the toxic effect of malathion. In conclusion, quercetin could efficiently reduce the toxic effects of malathion on the biochemical, immune, and hematological parameters of the common carp.

Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes.

The present study aimed to develop potent carbonic anhydrase inhibitors (CAIs). The design of the target compounds was based on modifying the structure of the ureido-based carbonic anhydrase inhibitor SLC-0111. Six series of a substituted benzoylthioureido core were prepared featuring different zinc-binding groups; the conventional sulphamoyl group 4a-d and 12a-c, its bioisosteric carboxylic acid group 5a-d and 13a-c or the ethyl carboxylate group 6a-d and 14a-c as potential prodrugs. All compounds were assessed for their carbonic anhydrase (CA) inhibitory activity against a panel of four physiologically relevant human CA isoforms hCA I and hCA II, and hCA IX, and hCA XII. Compounds 4a, 4b, 4c, 4d, 5d, 12a, and 12c revealed significant inhibitory activity against hCA I that would highlight these compounds as promising drug candidates for the treatment of glaucoma.

The effect of flaxseed oil consumtion on blood pressure among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized clinical trials.

We systematically reviewed randomized clinical trials (RCTs) to elucidate the overall effects of flaxseed oil consumption on blood pressure (BP) in patients with metabolic syndrome and related disorders. PubMed, Scopus, Cochrane Library, and ISI Web of Science databases were systematically searched until March 31, 2020, to find RCTs that examined the effect of flaxseed oil consumption on BP. Weighed mean difference (WMD) was pooled using a random-effects model. Standard methods were used for the assessment of heterogeneity, sensitivity analysis, and publication bias. Meta-analysis of five trials (6 arms) showed significant reductions in systolic (WMD: -3.86 mmHg, 95% CI: -7.59 to -0.13, p = .04) BP (SBP) after flaxseed oil consumption. However, the overall effect illustrated no significant change in diastolic (WMD: -1.71 mmHg, 95% CI: -3.67 to 0.26, p = .09) BP (DBP) in the intervention group compared with the control group. Our findings revealed that flaxseed oil consumption has favorable effects on SBP in patients with metabolic syndrome and related disorders. However, further investigations are needed to provide more reliable evidence.

The deciphering of the immune cells and marker signature in COVID-19 pathogenesis: An update.

The precise interaction between the immune system and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical in deciphering the pathogenesis of coronavirus disease 2019 (COVID-19) and is also vital for developing novel therapeutic tools, including monoclonal antibodies, antivirals drugs, and vaccines. Viral infections need innate and adaptive immune reactions since the various immune components, such as neutrophils, macrophages, CD4+ T, CD8+ T, and B lymphocytes, play different roles in various infections. Consequently, the characterization of innate and adaptive immune reactions toward SARS-CoV-2 is crucial for defining the pathogenicity of COVID-19. In this study, we explain what is currently understood concerning the conventional immune reactions to SARS-CoV-2 infection to shed light on the protective and pathogenic role of immune response in this case. Also, in particular, we investigate the in-depth roles of other immune mediators, including neutrophil elastase, serum amyloid A, and syndecan, in the immunopathogenesis of COVID-19.

Design, synthesis and molecular docking of novel pyrazolo[1,5-a][1,3,5]triazine derivatives as CDK2 inhibitors.

Cyclin Dependent Kinases CDKs unpredictable activity has been accounted for a wide assortment of human malignancies, so it might be conceivable to design pharmacologically relevant ligands that go about as specific and potent inhibitors of CDK2 action. In this respect, a series of novel pyrazolo[1,5-a][1,3,5]triazine derivatives were designed, synthesized and evaluated for CDK2 enzyme inhibitory and anticancer activity. Compounds 9f and 10c showed best CDK2 inhibition among the newly synthesized compounds, with percent inhibition at 82.38%, and 81.96% against CDK2 and IC50 of 1.85 and 2.09 µM, respectively. Additionally, the newly synthesized compounds were tested for their antiproliferative activity against 60 NCI cell lines. Molecular docking revealed the binding mode of these new compounds into the roscovitine binding site of CDK2 enzyme (PDB code: 3ddq). Conclusively, pyrazolotriazine derivatives represent a talented starting point for further study as anticancer drug.