Biochemical Properties, In-Vitro Antimicrobial, and Free Radical Scavenging Activities of the Leaves of Annona muricata

Fifteen (15) male Wistar rats were completely randomized into three (3) groups. Group A was normal control, Group B received 200 mg/kg weight of ethyl acetate extract of Annona muricata leaves (AMLE) and Group C received 100 mg/kg b.weight AMLE. Single daily dose of AMLE was administered orally for twenty one (21) days after which the animals were sacrificed. The blood samples were taken for haematological and biochemical analysis. Antibacterial and antifungal activities of n-hexane, ethyl acetate and methanol extracts of Annona muricata leaves were carried out. These extracts exhibited satisfactory inhibitory activities against bacterial and fungal strains, which include; Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhi, Klebsiellae pneumonae, Candida albicans, Aspergillus niger, penicillium notatum and Rhizopus stolonifer. N-hexane extract of the plant exhibited antioxidant property by scavenging DPPH radicals with IC50 of 342.44 μg/mL. GC-MS analysis of nhexane, ethyl acetate and methanol extracts of the plant principally revealed the presence of Urs-12-ene (23.15%), Squalene (48.80%) and Clionasterol (15.88%) respectively. Keywords: biochemical properties, antimicrobial, antioxidant, urs-12-ene, squalene, clionastero

Chemical Quality and Hydrogeological Settings of the El-Farafra Oasis (Western Desert of Egypt) Groundwater Resources in Relation to Human Uses

In the Egyptian deserts, new land reclamation projects have been recently established to meet the increasing-population growth rate and food demand. These projects mainly depend on the different groundwater aquifers. El-Farafra Oasis is one of the "1.5-million-feddan reclamation project" areas recently established in the Western Desert of Egypt where the only available water source is the world's largest fossil freshwater reservoir "the Nubian Sandstone Aquifer System (NSAS)". Groundwater-dependent springs, and their artificial counterpart "drilled wells", are reliable water systems throughout the world. In the present study, hydrochemical parameters were collected in 2015 from 16 different springs and wells of the El-Farafra Oasis, and analyzed using the different water quality indices. The calculated water quality index (WQI), its correlations with the water quality parameters Gibbs, Piper, US Salinity-Lab Staff and Wilcox diagrams, and Principal Component Analysis (PCA) were used to evaluate the groundwater suitability for human drinking and irrigation purposes. WQI values revealed good-to-excellent groundwater quality for human drinking. In addition, the spring and well water samples investigated showed good indices for irrigation activities. Gibbs and Piper's diagrams were presented, with most samples falling into the rock-dominance category, and belonging to hydrogeochemical facies determining the following water types: Mg(HCO3)(2) type water (37.5% of the samples), no dominant ions (mixed water-type category; Ca/MgCl2) (50% of the samples), and, finally, NaCl water type (the remaining 12.5%). The groundwater chemistry in the study area is mainly controlled by rock-water interactions, particularly the dissolution of carbonate rocks and silicate weathering. The elevated nutrient concentrations, in particular nitrates, are most likely due to agricultural activities, indicating substantial anthropogenic activities in the area studied

Quantitative and Qualitative Assessment of Phytochemicals in Methanolic Extracts of Hurricane Weed ( Phyllanthus amarus Schumach. &Thonn) Plant

The phytocomponents of the leaf and root extracts of Phyllanthus amarus (Euphorbiaceae) were studied. The constituents of the leaves and roots were identified and quantified by using GC-MS. Result from the phytochemical analyses showed the presence of saponins, tannins, phenolics, anthocyanins, and glycosides in both leaves and root of the plant. Alkaloids and triterpenoids were, however only absent in the root of P. amarus but present in the leaves of the plant. Flavonoids, coumarins and steroids were absent in the leaves but present in the root part. The mean concentration of the phytochemicals investigated in leaves are 0.73\ub10.01%, 1.85\ub10.03%, 1.12\ub10.01%, 1.80\ub10.01%, 1.59\ub10.50%, 0.13\ub10.10%, and 0.86\ub10.01%, for saponins, tannins, phenolics, anthocyanins, alkaloids, triterpenoids, and glycosides respectively, while the mean concentration of the phytochemicals investigated in roots are 0.91\ub10.01%, 1.53\ub10.03%, 0.70\ub10.01%, 2.97\ub10.10%, 2.47\ub10.03%, 0.62\ub10.01%, 0.90\ub10.01% and 2.02\ub10.10% for saponins, tannins, phenolics, steroids, flavonoids, anthocyanins, glycosides and coumarins respectively. Furthermore, the GC-MS analysis of methanol extracts of the leaves and root of P. amarus revealed the presence of three medicinally important bioactive compounds, which are: 9-Octadecenoic acid which has percentage of abundance of 92.23% and 82.46% in leaves and roots of the plant respectively, followed by n-Hexadecanoic acid and Tetradecanoic acid with their corresponding percentage of abundance of 7.7% and 17.54% for leaves and root. These analytical results suggest the plantto possess a significant role in phyto-medicine. The importance of this plant was discussed in line with the role they play in ethnomedicinal life of the people

Effect of Common Medications on the Expression of SARS-CoV-2 Entry Receptors in Kidney Tissue

Besides the respiratory system, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection was shown to affect other essential organs such as the kidneys. Early kidney involvement during the course of infection was associated with worse outcomes, which could be attributed to the direct SARS-CoV-2 infection of kidney cells. In this study, the effect of commonly used medications on the expression of SARS-CoV-2 receptor, angiotensin-converting enzyme (ACE)2, and TMPRSS2 protein in kidney tissues was evaluated. This was done by in silico analyses of publicly available transcriptomic databases of kidney tissues of rats treated with multiple doses of commonly used medications. Of 59 tested medications, 56% modified ACE2 expression, whereas 24% modified TMPRSS2 expression. ACE2 was increased with only a few of the tested medication groups, namely the renin-angiotensin inhibitors, such as enalapril, antibacterial agents, such as nitrofurantoin, and the proton pump inhibitor, omeprazole. The majority of the other medications decreased ACE2 expression to variable degrees with allopurinol and cisplatin causing the most noticeable downregulation. The expression level of TMPRSS2 was increased with a number of medications, such as diclofenac, furosemide, and dexamethasone, whereas other medications, such as allopurinol, suppressed the expression of this gene. The prolonged exposure to combinations of these medications could regulate the expression of ACE2 and TMPRSS2 in a way that may affect kidney susceptibility to SARS-CoV-2 infection. Data presented here suggest that we should be vigilant about the potential effects of commonly used medications on kidney tissue expression of ACE2 and TMPRSS2

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

Identifying Immunological and Clinical Predictors of COVID-19 Severity and Sequelae by Mathematical Modeling

Since its emergence as a pandemic in March 2020, coronavirus disease (COVID-19) outcome has been explored via several predictive models, using specific clinical or biochemical parameters. In the current study, we developed an integrative non-linear predictive model of COVID-19 outcome, using clinical, biochemical, immunological, and radiological data of patients with different disease severities. Initially, the immunological signature of the disease was investigated through transcriptomics analysis of nasopharyngeal swab samples of patients with different COVID-19 severity versus control subjects (exploratory cohort, n=61), identifying significant differential expression of several cytokines. Accordingly, 24 cytokines were validated using a multiplex assay in the serum of COVID-19 patients and control subjects (validation cohort, n=77). Predictors of severity were Interleukin (IL)-10, Programmed Death-Ligand-1 (PDL-1), Tumor necrosis factors-α, absolute neutrophil count, C-reactive protein, lactate dehydrogenase, blood urea nitrogen, and ferritin; with high predictive efficacy (AUC=0.93 and 0.98 using ROC analysis of the predictive capacity of cytokines and biochemical markers, respectively). Increased IL-6 and granzyme B were found to predict liver injury in COVID-19 patients, whereas interferon-gamma (IFN-γ), IL-1 receptor-a (IL-1Ra) and PD-L1 were predictors of remarkable radiological findings. The model revealed consistent elevation of IL-15 and IL-10 in severe cases. Combining basic biochemical and radiological investigations with a limited number of curated cytokines will likely attain accurate predictive value in COVID-19. The model-derived cytokines highlight critical pathways in the pathophysiology of the COVID-19 with insight towards potential therapeutic targets. Our modeling methodology can be implemented using new datasets to identify key players and predict outcomes in new variants of COVID-19

Azelaic acid and Melaleuca alternifolia essential oil co-loaded vesicular carrier for combinational therapy of acne

Aim: Azelaic acid (AzA), a comedolytic, antibacterial, anti-inflammatory anti-melanogenic agent, prescribed against acne vulgaris is safe on skin. Its combination with another widely used anti-acne agent, tea tree oil (EO) whose delivery is limited by volatility, instability and lipophilicity constraints was attempted. Method: Solvent injection was used to prepare AzA-EO integrated ethosomes. Result: Ethosomes were transformed into carbopol hydrogel, which exhibited pseudo-plastic properties with appreciable firmness, work of shear, stickiness and work of adhesion. The hydrogel showed better permeation and retention characteristics vis-a-vis commercial formulation (AzidermTM), when evaluated in Wistar rat skin. Further, ethosome hydrogel composite was better tolerated with no side effects. Conclusion: The findings suggests that the aforementioned strategy could be a potential treatment used for acne management. </jats:p