Association of a single-nucleotide polymorphism in C12orf43 region with the risk of coronary artery disease.

The genetics of organisms play a vital role in the development of coronary artery disease (CAD), with its heritability estimated at approximately 50-60%. For this purpose, we examined the relationship between CAD risk and C12orf43/rs2258287 polymorphisms in the Pakistani population. In this study based on the genetic approach to dyslipidemia, a total of 200 subjects were included from the southern Punjab. The biochemical analysis of parameters (total cholesterol, triglycerides, blood glucose, high-density lipoprotein, and low-density lipoprotein) was carried out along with molecular analysis using an ARMS-PCR-based assay for single-nucleotide polymorphism (SNP) C12orf43/rs2258287 to identify the genotype. Genotypes showed a substantial correlation with both family history and metabolic markers. The cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides and blood glucose levels were higher while the high-density lipoprotein cholesterol (HDL-C) level was lower significantly (p<0.05) in cases than in controls. Age, pulse rate, diabetes, physical activity, smoking, family history, and dietary habits were also significantly associated (p<0.05) with CAD individuals. The SNP C12orf43/rs2258287 also showed an association with CAD in the population of southern Punjab. Based upon this study, it could be concluded that CAD is characterized by an unfavorable lipid profile in association with SNP C12orf43/rs2258287.

Anticancer and anti-metastasis activity of 1,25 dihydroxycholecalciferols and genistein in MCF-7 and MDA-MB-231 breast cancer cell lines.

A powerful steroid hormone precursor, 1,25 dihydroxycholecalciferols (1,25(OH)2D3), and dietary phytoestrogen (genistein) are essential compounds that act by binding to nuclear receptors and altering gene expression. They have many biological benefits, some of which have anticancer properties. We studied the impact of 1,25(OH)2D3 and genistein on the proliferation, progression, and metastasis of MCF-7 and MDA-MB-231 cells when they were used alone or in combination and investigated whether there was a synergistic effect between genistein and 1,25(OH)2D3. To achieve these goals, a variety of assays, including flow cytometry, cell invasion assays, cell adhesion assays, Western blotting, and RT‒PCR, were used. Our findings showed that genistein, 1,25(OH)2D3, and the two combined all effectively declined the growth of MCF-7 and MDA-MB-231 cells by arresting the cells in the G0/G1 phase and inducing an apoptotic pathway. Stimulation of apoptosis was achieved by upregulating the expression of BAX and CASP3 genes and downregulating the expression levels of BCL-2 gene. Furthermore, both compounds suppress metastasis by reducing cell adhesion and cell migration/invasion by elevating the expression level of E-cadherin and reducing the expression level of P-cadherin and N-cadherin. Additionally, both genistein and 1,25(OH)2D3 increased the expression level of ERK1 and reduced the expression levels of JNK, p38, Ras, and MEK proteins, which reduced metastasis, enhanced the response to cancer treatment, and improved overall survival. Thus, genistein and 1,25(OH)2D3 can both be considered key candidates in the search for new breast cancer treatments.

Exploring the hidden treasures of Nitella hyalina: a comprehensive study on its biological compounds, nutritional profile, and unveiling its antimicrobial, antioxidative, and hypoglycemic properties.

Macroalgae has the potential to be a precious resource in food, pharmaceutical, and nutraceutical industries. Therefore, the present study was carried out to identify and quantify the phyco-chemicals and to assess the nutritional profile, antimicrobial, antioxidant, and anti-diabetic properties of Nitella hyalina extracts. Nutritional composition revealed0.05 ± 2.40% ash content, followed by crude protein (24.66 ± 0.95%), crude fat (17.66 ± 1.42%), crude fiber (2.17 ± 0.91%), moisture content (15.46 ± 0.48%) and calculated energy value (173.50 ± 2.90 Kcal/100 g). 23 compounds were identified through GC-MS analysis in ethyl acetate extract, with primary compounds being Palmitic acid, methyl ester, (Z)-9-Hexadecenoic acid, methyl ester, and Methyl tetra decanoate. Whereas 15 compounds were identified in n-butanol extract, with the major compounds being Tetra decanoic acid, 9-hexadecanoic acid, Methyl pentopyranoside, and undecane. FT-IR spectroscopy confirmed the presence of alcoholic phenol, saturated aliphatic compounds, lipids, carboxylic acid, carbonyl, aromatic components, amine, alkyl halides, alkene, and halogen compounds. Moreover, n-butanol contains 1.663 ± 0.768 mg GAE/g, of total phenolic contents (TPC,) and 2.050 ± 0.143 QE/g of total flavonoid contents (TFC), followed by ethyl acetate extract, i.e. 1.043 ± 0.961 mg GAE/g and 1.730 ± 0.311 mg QE/g respectively. Anti-radical scavenging effect in a range of 34.55-46.35% and 35.39-41.79% was measured for n-butanol and ethyl acetate extracts, respectively. Antimicrobial results declared that n-butanol extract had the highest growth inhibitory effect, followed by ethyl acetate extract. Pseudomonas aeruginosa was reported to be the most susceptible strain, followed by Staphylococcus aureus and Escherichia coli, while Candida albicans showed the least inhibition at all concentrations. In-vivo hypoglycemic study revealed that both extracts exhibited dose-dependent activity. Significant hypoglycemic activity was observed at a dose of 300 mg/kg- 1 after 6 h i.e. 241.50 ± 2.88, followed by doses of 200 and 100 mg/kg- 1 (245.17 ± 3.43 and 250.67 ± 7.45, respectively) for n-butanol extract. In conclusion, the macroalgae demonstrated potency concerning antioxidant, antimicrobial, and hypoglycemic properties.

Aconitum lycoctonum L. (Ranunculaceae) mediated biogenic synthesis of silver nanoparticles as potential antioxidant, anti-inflammatory, antimicrobial and antidiabetic agents.

In this study, a polar extract of Aconitum lycoctonum L. was used for the synthesis of silver nanoparticles (AgNPs), followed by their characterization using different techniques and evaluation of their potential as antioxidants, amylase inhibitors, anti-inflammatory and antibacterial agents. The formation of AgNPs was detected by a color change, from transparent to dark brown, within 15 min and a surface resonance peak at 460 nm in the UV-visible spectrum. The FTIR spectra confirmed the involvement of various biomolecules in the synthesis of AgNPs. The average diameter of these spherical AgNPs was 67 nm, as shown by the scanning electron micrograph. The inhibition zones showed that the synthesized nanoparticles inhibited the growth of Gram-positive and negative bacteria. FRAP and DPPH assays were used to demonstrate the antioxidant potential of AgNPs. The highest value of FRAP (50.47% AAE/mL) was detected at a concentration of 90 ppm and a DPPH scavenging activity of 69.63% GAE was detected at a concentration of 20 µg/mL of the synthesized AgNPs. 500 µg/mL of the synthesized AgNPs were quite efficient in causing 91.78% denaturation of ovalbumin. The AgNPs mediated by A. lycoctonum also showed an inhibitory effect on α-amylase. Therefore, AgNPs synthesized from A. lycoctonum may serve as potential candidates for antibacterial, antioxidant, anti-inflammatory, and antidiabetic agents.

Synthesis, DFT Studies, Molecular Docking and Biological Activity Evaluation of Thiazole-Sulfonamide Derivatives as Potent Alzheimer's Inhibitors.

Alzheimer's disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer's treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer's disease without many side effects. In this research project, we report the synthesis and biological activities of some new thiazole-bearing sulfonamide analogs (1-21) as potent anti-Alzheimer's agents. Suitable characterization techniques were employed, and the density functional theory (DFT) computational approach, as well as in-silico molecular modeling, has been employed to assess the electronic properties and anti-Alzheimer's potency of the analogs. All analogs exhibited a varied degree of inhibitory potential, but analog 1 was found to have excellent potency (IC50 = 0.10 ± 0.05 µM for AChE) and (IC50 = 0.20 ± 0.050 µM for BuChE) as compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 µM and 4.5 ± 0.11 µM). The structure-activity relationship was established, and it mainly depends upon the nature, position, number, and electron-donating/-withdrawing effects of the substituent/s on the phenyl rings.

Synthesis of New Triazole-Based Thiosemicarbazone Derivatives as Anti-Alzheimer's Disease Candidates: Evidence-Based In Vitro Study.

Triazole-based thiosemicarbazone derivatives (6a-u) were synthesized then characterized by spectroscopic techniques, such as 1HNMR and 13CNMR and HRMS (ESI). Newly synthesized derivatives were screened in vitro for inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives (except 6c and 6d, which were found to be completely inactive) demonstrated moderate to good inhibitory effects ranging from 0.10 ± 0.050 to 12.20 ± 0.30 µM (for AChE) and 0.20 ± 0.10 to 14.10 ± 0.40 µM (for BuChE). The analogue 6i (IC50 = 0.10 ± 0.050 for AChE and IC50 = 0.20 ± 0.050 µM for BuChE), which had di-substitutions (2-nitro, 3-hydroxy groups) at ring B and tri-substitutions (2-nitro, 4,5-dichloro groups) at ring C, and analogue 6b (IC50 = 0.20 ± 0.10 µM for AChE and IC50 = 0.30 ± 0.10 µM for BuChE), which had di-Cl at 4,5, -NO2 groups at 2-position of phenyl ring B and hydroxy group at ortho-position of phenyl ring C, emerged as the most potent inhibitors of both targeted enzymes (AChE and BuChE) among the current series. A structure-activity relationship (SAR) was developed based on nature, position, number, electron donating/withdrawing effects of substitution/s on phenyl rings. Molecular docking studies were used to describe binding interactions of the most active inhibitors with active sites of AChE and BuChE.

Effect of treatment with vitamin D plus calcium on oxidative stress in streptozotocin-induced diabetic rats.

BACKGROUND: In diabetes mellitus, uncontrolled hyperglycemia has been reported to induce oxidative stress, which may lead to health complications. Vitamin D, however, acts as a non-enzymatic antioxidant to protect cells against oxidative stress and damage. OBJECTIVE: To investigate the antioxidative effect of vitamin D combined with calcium in streptozotocin (STZ)-induced diabetic rats. METHODS: Rats were divided into four groups (ten rats in each group). The first group (control) received a normal diet and water. The second group, including STZ-induced diabetic rats (diabetic controls), received a normal diet and water. The third group, also including STZ-induced diabetic rats, received vitamin D (2000 IU/day) with calcium (500 mg/kg/day) orally for 28 consecutive days. The fourth group consisted of STZ-induced diabetic rats that received insulin treatment for 28 consecutive days. Activities of superoxide dismutase (SOD), glutathione peroxidase (GPO) and catalase were measured in the liver tissues. The level of malonaldehyde (MDA) was measured in the plasma. RESULTS: Diabetic rats showed a significant decrease in the activities of SOD, GPO and catalase compared to normal rats. Oral administration of vitamin D with calcium to diabetic rats caused a significant increase in the activities of SOD, GPO and catalase compared with the untreated group. Furthermore, the plasma level of MDA was significantly elevated in diabetic rats compared to normal rats. Diabetic rats treated with vitamin D and calcium had a significantly reduced level of MDA, suggesting that vitamin D with calcium played a vital role in the protection of tissues from damage by free radicals. CONCLUSION: Oral supplementation with vitamin D and calcium may be a useful treatment for diabetic patients to reduce/prevent the pathological complications of diabetes.