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The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2'-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein-ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing.The cherry silverberry (Elaeagnus multiflora Thunb.) is a lesser-known plant species with high nutritional and therapeutic potential. Cherry silverberry contains numerous biologically active compounds. The cherry silverberry is a shrub growing up to 3 m. Its drupe-like fruit is ellipsoidal, up to 1 cm long, and set on stems. It is red in color, juicy, and sour, and its taste resembles that of red currants. According to the literature, cherry silverberry fruit contains carbohydrates, organic acids, and amino acids, as well as vitamin C, in addition to biominerals, polyphenols, flavonoids, carotenoids, chlorophylls, and tocopherols, which contribute to its high nutritional value. New biotypes of cherry silverberry cultivated in Poland can be used for the production of functional foods and direct consumption. In China, the cherry silverberry, known as goumi, has been used as a medicinal plant and a natural remedy for cough, diarrhea, itch, foul sores, and, even, cancer. This review article summarizes the scant research findings on the nutritional and therapeutic benefits of cherry silverberry.In this study, FeNi magnetic alloy nanoparticles (MANPs) were employed for the forensic analysis of four poisons-dimethametryn, napropamide, thiodicarb, and strychnine-using surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). FeNi MANPs were prepared via coprecipitation using two reducing agents, sodium borohydride (NaBH4) and hydrazine monohydrate (N2H4·H2O), to optimize the prepared MANPs and investigate their effect on the performance of SALDI-MS analysis. Thereafter, SALDI-MS analysis was carried out for the detection of three pesticides and a rodenticide. The prepared substrate offered sensitive detection of the targeted analytes with LOD values of 1 ng/mL, 100 pg/mL, 10 ng/mL, and 200 ng/mL for dimethametryn, napropamide, thiodicarb, and strychnine, respectively. The relative standard deviation (%RSD) values were in the range of 2.30-13.97% for the pesticides and 15-23.81% for strychnine, demonstrating the good spot-to-spot reproducibility of the FeNi substrate. Finally, the MANPs were successfully employed in the analysis of poison-spiked blood serum using a minute quantity of the sample with an LOD of 700 ng/mL dimethametryn and napropamide, 800 ng/mL thiodicarb, and 500 ng/mL strychnine. This study has great potential regarding the analysis of several poisons that may be found in human serum, which is significant in cases of self-harm.SIRT1, an NAD+-dependent deacetylase, catalyzes the deacetylation of proteins coupled with the breakdown of NAD+ into nicotinamide and 2'-O-acetyl-ADP-ribose (OAADPr). Selective SIRT1 activators have potential clinical applications in atherosclerosis, acute renal injury, and Alzheimer's disease. Here, we found that the activity of the potent SIRT1 activator CWR is independent of the acetylated substrate. It adopts a novel mechanism to promote SIRT1 activity by covalently bonding to the anomeric C1' carbon of the ribose ring in OAADPr. In addition, CWR is highly selective for SIRT1, with no effect on SIRT2, SIRT3, SIRT5, or SIRT6. The longer distance between the anomeric C1' carbon of the ribose ring in OAADPr and Arg274 of SIRT1 (a conserved residue among sirtuins) than that between the anomeric C1' carbon in OAADPr and the Arg of SIRT2, SIRT3, SIRT5, and SIRT6, should be responsible for the high selectivity of CWR for SIRT1. This was confirmed by site-directed mutagenesis of SIRT3. Consistent with the in vitro assays, the activator also reduced the acetylation levels of p53 in a concentration-dependent manner via SIRT1 in cells. Our study provides a new perspective for designing SIRT1 activators that does not rely on the chemical moiety immediately C-terminal to the acetyl-lysine of the substrate.The applications of bioactive compounds from medicinal plants as therapeutic drugs are largely increasing. The present study selected the bioactive compounds from Acacia concinna (A. concinna) and Citrus limon (C. limon) to assess their phytochemicals, proteins, and biological activity. The plant material was collected, and extraction performed as per the standard procedure. Qualitative analysis was undertaken, and identification of functional organic groups was performed by FTIR and HPLC. Antibacterial, anticancer, antioxidant, antihyperglycemic, antihyperlipidemic, and inhibition kinetics studies for enzymes were performed to assess the different biological activities. Flavonoids and phenols were present in a significant amount in both the selected plants. A. concinna showed significant antimicrobial activity against Z. mobilis, E. coli, and S. AY-22989 aureus, with minimum inhibition zones (MIZ) of 24, 22, and 20 mm, respectively. C. limon strongly inhibited all the tested pathogenic bacteria with maximum and minimum MIZ of 32 and 17 mm. A. concinna silver nanoparticles also exhibited potent antimicrobial activity. Both extracts showed substantial antioxidant, antihyperlipidemic, antidiabetic, anticancer (MCF-7), and anti-urease (antiulcer) properties. To conclude, these plants can be used to treat hyperlipidemia, diabetes, cancer, and gastrointestinal ulcers. They can also serve as antimicrobial and antioxidant agents. Thus, the studied plants must be exploited cost-effectively to generate therapeutic drugs for various diseases.Collagen peptide (CP) and collagen tripeptide (CTP) are supplementary health foods that exhibit several biological effects. However, the effects of collagen on age-associated sarcopenia and its underlying mechanisms are unclear. C57BL/6J mice (n = 24, 12 months old) were divided into three dietary groups and administered AIN93G (aging control, AC; JA BIO, Suwon, Korea), AIN93G plus 0.2% CP, and AING93G plus 0.2% CTP supplement for 12 weeks. The results indicated that the CP and CTP supplements significantly increased the weight of the quadriceps tibialis anterior and gastrocnemius muscles and reduced body fat. A morphological analysis revealed that the spaces within the muscle cells were tight with attenuated fibrosis following CP and CTP supplementation. Immunohistochemistry was applied and a Western blot analysis was performed to determine the underlying mechanisms. The CTP supplement increased the expression of IGF-1, PI3K/AKT, and mTOR, whereas the CP supplement increased the expression of IGF-1 and AMPK in the gastrocnemius of aging mice. CP and CTP ameliorate age-associated sarcopenia through different mechanisms.This study aimed to determine the chemical composition of different types of tissue of Cedrus brevifolia Henry (Pinaceae) methanolic extracts, namely needles, twigs, branches, and bark. Cedrus brevifolia is a narrow endemic coniferous tree species of Cyprus, growing in a sole population in the mountainous area of Paphos Forest. Chemical analysis of the extracts was performed using liquid chromatography combined with time-of-flight high-resolution mass spectrometry (LC/Q-TOF/HRMS). The majority of the 36 compounds tentatively identified belonged to the flavonoids family. The extract of needles was the richest extract in terms of secondary metabolites. The extracts were studied for their antioxidant activity using the DPPH free radical scavenging assay. Additionally, the antibacterial activity was evaluated by determining both the minimum inhibitory concentration and the minimum bactericidal concentration against Staphylococcus aureus and Escherichia coli. All extracts demonstrated antioxidant property, while bark gave the highest antioxidant capacity (IC50 value of 0.011 mg/mL) compared to the other tissues. Antibacterial activity was observed against both types of bacteria, with the extract of branches presenting the strongest activity against S. aureus (MIC, 0.097 mg/mL and MBC, 0.195 mg/mL). This is the first time that extracts of needles, twigs, branches, and bark of C. brevifolia are compared regarding their chemical composition as well as their antimicrobial and antioxidant properties.Ferritin is an iron storage protein that plays a key role in iron homeostasis and cellular antioxidant activity. Ferritin has many advantages as a tumor immunotherapy platform, including a small particle size that allows for penetration into tumor-draining lymph nodes or tumor tissue, a unique structure consisting of 24 self-assembled subunits, cavities that can encapsulate drugs, natural targeting functions, and a modifiable outer surface. In this review, we summarize related research applying ferritin as a tumor immune vaccine or a nanocarrier for immunomodulator drugs based on different targeting mechanisms (including dendritic cells, tumor-associated macrophages, tumor-associated fibroblasts, and tumor cells). In addition, a ferritin-based tumor vaccine expected to protect against a wide range of coronaviruses by targeting multiple variants of SARS-CoV-2 has entered phase I clinical trials, and its efficacy is described in this review. Although ferritin is already on the road to transformation, there are still many difficulties to overcome. Therefore, three barriers (drug loading, modification sites, and animal models) are also discussed in this paper. Notwithstanding, the ferritin-based nanoplatform has great potential for tumor immunotherapy, with greater possibility of clinical transformation.
(
) is known to exhibit a beneficial effect for anti-inflammatory, anti-oxidant, and anti-hyperlipidemic effects. However, no sufficient research data are available on the cardiovascular effect of
. Thus, in this study, we investigate whether
extract has direct effects on vascular reactivity.
To examine whether
extract affects vascular functionality, we measured isometric tension in rat mesenteric resistance arteries using a wire myograph. After arteries were pre-contracted with high-K
(70 mM), phenylephrine (5 µM), or U46619 (1 µM),
extract was treated.
extract induced vasodilation in a concentration-dependent manner, and this effect was endothelium independent. To further investigate the mechanism, we incubated arteries in a Ca
-free and high-K
solution, followed by the cumulative addition of CaCl
(0.01-2.5 mM) with or without
extract (30 µg/mL). Pre-treatment of
extract reduced the contractile responses induced by cumulative administration of Ca
, which suggests that extracellular Ca
influx was inhibited by the treatment of
extract.
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