Assessment of the muscular strength of the global handgrip and physical activity in patients treated with renal replacement therapy (RRT) by hemodialysis

Introduction Chronic Kidney Disease (CKD) is a social problem. Hemodialysis is the most common method of renal replacement therapy. At the beginning of hemodialysis treatment, physical activity is reduced by 50-60%. The aim of the study was to compare physical activity, handgrip strength and selected anthropometric parameters, and to assess the relationship between handgrip strength, selected anthropometric parameters and the level of physical activity. Material and methods The study included 30 patients aged 65.92 ± 14.65 treated by hemodialysis. The study consisted of patients completing a proprietary survey questionnaire, assessing physical activity using the International Physical Activity Questionnaire (IPAQ), handgrip strength, and performing selected anthropometric measurements. The examinations were performed at baseline (E0) and after three months of hemodialysis (E3) treatment and the results were compared. Results There were no significant differences in the study group for physical activity and global handgrip strength at baseline and after three months of the study. There was no statistically significant differences beetwen physical activity and handgrip strength in study and control group. Conclusions Patients treated with renal replacement present less physical activity compared to people with normal kidney function. The BMI value and level of physical activity does not affect the handgrip strength in hemodialysis patients

l-Ornithine-N5-monooxygenase (PvdA) Substrate Analogue Inhibitors for Pseudomonas aeruginosa Infections Treatment: Drug Repurposing Computational Studies

Pseudomonas aeruginosa is an opportunistic pathogen that can cause acute and severe infections. Increasing resistance to antibiotics has given rise to the urgent need for an alternative antimicrobial agent. A promising strategy is the inhibition of iron sequestration in the bacteria. The current work aimed to screen for inhibitors of pyoverdine-mediated iron sequestration in P. aeruginosa. As a drug target, we choose l-ornithine-N5-monooxygenase (PvdA), an enzyme involved in the biosynthesis of pyoverdine that catalyzes the FAD-dependent hydroxylation of the side chain amine of ornithine. As drug repurposing is a fast and cost-efficient way of discovering new applications for known drugs, the approach may help to solve emerging clinical problems. In this study, we use data about molecules from drug banks for screening. A total of 15 drugs that are similar in structure to l-ornithine, the substrate of PvdA, and 30 drugs that are sub-structures of l-ornithine were virtually docked against PvdA. N-2-succinyl ornithine and cilazapril were found to be the top binders with a binding energy of −12.8 and −9.1 kcal mol−1, respectively. As the drug-likeness and ADME properties of the drugs were also found to be promising, molecular dynamics studies were performed to further confirm the stability of the complexes. The results of this in silico study indicate that N-2-succinyl ornithine could potentially be explored as a drug for the treatment of P. aeruginosa infections

The Effects of Hypoxia on Threshold Food Concentrations in Different Daphnia Species

Numerous studies have revealed a negative correlation between the body size and temperature among a variety of aquatic ectotherms. Many studies at individual and population levels indicated that this mechanism may be explained by the decrease of competitive abilities of larger- over smaller-bodied individuals, as the production of larger-bodied individuals is more limited due to greater susceptibility to decreased oxygen concentrations (i.e., environmental hypoxia) at elevated temperatures. However, this hypothesis is still not tested at the community level. To test this, we performed several experiments on the food thresholds (which is a proxy for competitive ability) of 6 zooplankton (Daphnia) species varying in body size, at high or low oxygen concentrations. Contrary to the hypothesis tested, hypoxia increased threshold food concentrations to a relatively greater extent in smaller species than in larger ones. This may be attributed to the better evolutionary adaptations of larger-bodied daphnids to oxygen-poor environments manifested in higher production of haemoglobin. The results obtained in this study cannot exclude the possibility that environmental hypoxia is responsible for the temperature-size pattern in aquatic ectotherms, as our experiments did not take into account the long-term energetic costs of expedited haemoglobin synthesis, which could shift size-dependent competitive power

The Effects of Hypoxia on Threshold Food Concentrations in Different <i>Daphnia</i> Species

Numerous studies have revealed a negative correlation between the body size and temperature among a variety of aquatic ectotherms. Many studies at individual and population levels indicated that this mechanism may be explained by the decrease of competitive abilities of larger- over smaller-bodied individuals, as the production of larger-bodied individuals is more limited due to greater susceptibility to decreased oxygen concentrations (i.e., environmental hypoxia) at elevated temperatures. However, this hypothesis is still not tested at the community level. To test this, we performed several experiments on the food thresholds (which is a proxy for competitive ability) of 6 zooplankton (Daphnia) species varying in body size, at high or low oxygen concentrations. Contrary to the hypothesis tested, hypoxia increased threshold food concentrations to a relatively greater extent in smaller species than in larger ones. This may be attributed to the better evolutionary adaptations of larger-bodied daphnids to oxygen-poor environments manifested in higher production of haemoglobin. The results obtained in this study cannot exclude the possibility that environmental hypoxia is responsible for the temperature-size pattern in aquatic ectotherms, as our experiments did not take into account the long-term energetic costs of expedited haemoglobin synthesis, which could shift size-dependent competitive power

Cytotoxic Potential of Bioactive Compounds from Aspergillus flavus, an Endophytic Fungus Isolated from Cynodon dactylon, against Breast Cancer: Experimental and Computational Approach

Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants and exhibit mutual benefits. Their interactions with the host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of Aspergillus flavus, an endophytic fungus isolated from the roots of the medicinal grass Cynodon dactylon, for its anticancer potential. An in vitro analysis of the Ethyl acetate extract from A. flavus showed significant cytostatic effects (IC50: 16.25 &mu;g/mL) against breast cancer cells (MCF-7). A morphological analysis of the cells and a flow cytometry of the cells with annexin V/Propidium Iodide suggested that the extract induced apoptosis in the MCF-7 cells. The extract of A. flavus increased reactive oxygen species (ROS) generation and caused a loss of mitochondrial membrane potential in MCF-7 cells. To identify the metabolites that might be responsible for the anticancer effect, the extract was subjected to a gas chromatography-mass spectrometry (GC-MS) analysis. Interestingly, nine phytochemicals that induced cytotoxicity in the breast cancer cell line were found in the extract. The in silico molecular docking and molecular dynamics simulation studies revealed that two compounds, 2,4,7-trinitrofluorenone and 3&alpha;, 5 &alpha;-cyclo-ergosta-7,9(11), 22t-triene-6beta-ol exhibited significant binding affinities (&minus;9.20, and &minus;9.50 Kcal/mol, respectively) against Bcl-2, along with binding stability and intermolecular interactions of its ligand-Bcl-2 complexes. Overall, the study found that the endophytic A. flavus from C. dactylon contains plant-like bioactive compounds that have a promising effect in breast cancer

Guanidine&ndash;Curcumin Complex-Loaded Amine-Functionalised Hollow Mesoporous Silica Nanoparticles for Breast Cancer Therapy

The current study focuses on developing a tumour-targeted functionalised nanocarrier that wraps hollow mesoporous silica nanoparticles. The guanidine carbonate and curcumin are immobilised on the surface of 3-aminopropyl-triethoxy silane (APTES)-decorated hollow mesoporous silica nanoparticles (HMSNP), as confirmed through XPS and NMR analysis. XPS analysis demonstrates that the shape of the hysteresis loops is modified and that pore volume and pore diameter are consequently decreased compared to control. Guanidine (85%) and guanidine&ndash;curcumin complex (90%) were successfully encapsulated in HMSNAP and showed a 90% effective and sustained release at pH 7.4 for up to 72 h. Acridine orange/ethidium bromide dual staining determined that GuC-HMNSAP induced more late apoptosis and necrosis at 48 and 72 h compared with Gu-HMNSAP-treated cells. Molecular investigation of guanidine-mediated apoptosis was analysed using western blotting. It was found that cleaved caspases, c-PARP, and GSK-3&beta; (Ser9) had increased activity in MCF-7 cells. GuC-HMSNAP increased the activity of phosphorylation of oncogenic proteins such as Akt (Ser473), c-Raf (Ser249), PDK1 (Ser241), PTEN (Ser380), and GSK-3&beta; (Ser9), thus inducing cell death in MCF-7 cells. Altogether, our findings confirm that GuC-HMNSAP induces cell death by precisely associating with tumour-suppressing proteins, which may lead to new therapeutic approaches for breast cancer therapy

Aphrodisiac Performance of Bioactive Compounds from Mimosa pudica Linn.: In Silico Molecular Docking and Dynamics Simulation Approach

Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Mimosa pudica Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research. The main goal of this study was to predict highly effective molecules from M. pudica Linn. for reaching and maintaining penile erection before and during sexual intercourse through in silico molecular docking and dynamics simulation tools. A total of 28 bioactive molecules were identified from this target plant through public repositories, and their chemical structures were drawn using Chemsketch software. Graph theoretical network principles were applied to identify the ideal target (phosphodiesterase type 5) and rebuild the network to visualize the responsible signaling genes, proteins, and enzymes. The 28 identified bioactive molecules were docked against the phosphodiesterase type 5 (PDE5) enzyme and compared with the standard PDE5 inhibitor (sildenafil). Pharmacokinetics (ADME), toxicity, and several physicochemical properties of bioactive molecules were assessed to confirm their drug-likeness property. Molecular dynamics (MD) simulation modeling was performed to investigate the stability of PDE5&ndash;ligand complexes. Four bioactive molecules (Bufadienolide (&minus;12.30 kcal mol&minus;1), Stigmasterol (&minus;11.40 kcal mol&minus;1), Isovitexin (&minus;11.20 kcal mol&minus;1), and Apigetrin (&minus;11.20 kcal mol&minus;1)) showed the top binding affinities with the PDE5 enzyme, much more powerful than the standard PDE5 inhibitor (&minus;9.80 kcal mol&minus;1). The four top binding bioactive molecules were further validated for a stable binding affinity with the PDE5 enzyme and conformation during the MD simulation period as compared to the apoprotein and standard PDE5 inhibitor complexes. Further, the four top binding bioactive molecules demonstrated significant drug-likeness characteristics with lower toxicity profiles. According to the findings, the four top binding molecules may be used as potent and safe PDE5 inhibitors and could potentially be used in the treatment of ED