Targeting complement cascade: an alternative strategy for COVID-19

The complement system is a stakeholder of the innate and adaptive immune system and has evolved as a crucial player of defense with multifaceted biological effects. Activation of three complement pathways leads to consecutive enzyme reactions resulting in complement components (C3 and C5), activation of mast cells and neutrophils by anaphylatoxins (C3a and C5a), the formation of membrane attack complex (MAC) and end up with opsonization. However, the dysregulation of complement cascade leads to unsolicited cytokine storm, inflammation, deterioration of alveolar lining cells, culminating in acquired respiratory destructive syndrome (ARDS). Similar pathogenesis is observed with the middle east respiratory syndrome (MERS), severe acquired respiratory syndrome (SARS), and SARS-CoV-2. Activation of the lectin pathway via mannose-binding lectin associated serine protease 2 (MASP2) is witnessed under discrete viral infections including COVID-19. Consequently, the spontaneous activation and deposits of complement components were traced in animal models and autopsy of COVID-19 patients. Pre-clinical and clinical studies evidence that the inhibition of complement components results in reduced complement deposits on target and non-target tissues, and aid in recovery from the pathological conditions of ARDS. Complement inhibitors (monoclonal antibody, protein, peptide, small molecules, etc.) exhibit great promise in blocking the activity of complement components and its downstream effects under various pathological conditions including SARS-CoV. Therefore, we hypothesize that targeting the potential complement inhibitors and complement cascade to counteract lung inflammation would be a better strategy to treat COVID-19.N/

Anti-oxidant effect of gold nanoparticles restrains hyperglycemic conditions in diabetic mice

<p>Abstract</p> <p>Background</p> <p>Oxidative stress is imperative for its morbidity towards diabetic complications, where abnormal metabolic milieu as a result of hyperglycemia, leads to the onset of several complications. A biological antioxidant capable of inhibiting oxidative stress mediated diabetic progressions; during hyperglycemia is still the need of the era. The current study was performed to study the effect of biologically synthesized gold nanoparticles (AuNPs) to control the hyperglycemic conditions in streptozotocin induced diabetic mice.</p> <p>Results</p> <p>The profound control of AuNPs over the anti oxidant enzymes such as GSH, SOD, Catalase and GPx in diabetic mice to normal, by inhibition of lipid peroxidation and ROS generation during hyperglycemia evidence their anti-oxidant effect during hyperglycemia. The AuNPs exhibited an insistent control over the blood glucose level, lipids and serum biochemical profiles in diabetic mice near to the control mice provokes their effective role in controlling and increasing the organ functions for better utilization of blood glucose. Histopathological and hematological studies revealed the non-toxic and protective effect of the gold nanoparticles over the vital organs when administered at dosage of 2.5 mg/kilogram.body.weight/day. ICP-MS analysis revealed the biodistribution of gold nanoparticles in the vital organs showing accumulation of AuNPs in the spleen comparatively greater than other organs.</p> <p>Conclusion</p> <p>The results obtained disclose the effectual role of AuNPs as an anti-oxidative agent, by inhibiting the formation of ROS, scavenging free radicals; thus increasing the anti-oxidant defense enzymes and creating a sustained control over hyperglycemic conditions which consequently evoke the potential of AuNPs as an economic therapeutic remedy in diabetic treatments and its complications.</p

Exopolysaccharides from Lactobacillus acidophilus modulates the antioxidant status of 1,2–dimethyl hydrazine-induced colon cancer rat model

The aim of the current study is to ascertain the anticancer activity of exopolysaccharides (EPS) from probiotic Lactobacillus acidophilus in the 1, 2–dimethyl hydrazine (DMH)-induced colon cancer rat model and to determine the antioxidant status. Rats were divided into five groups of six animals each. Group I served as control, group II served as cancer control (DMH alone administered), group III as standard drug control (5-FU along with DMH) and group IV and V received EPS in two doses (200 mg/kg body weight and 400 mg/kg body weight along with DMH). EPS administration was found to reduce the number of polyps formed (Group IV—8.25 ± 1.258 and Group V—8.50 ± 1.732 vs Group II—14.50 ± 2.380) and to increase the levels of antioxidant enzymes viz. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and antioxidants like vitamin C (Vit. C), reduced glutathione (GSH) which was found to be reduced in colon cancer control rats. The status of lipid peroxidation (LPO) was also evaluated. All the values which were affected by the supplementation of DMH were brought to near normal levels by the treatment with EPS. The well-preserved histology of colon and the biochemical evaluation also show that EPS could be a potential agent for the prevention and treatment of colon cancer

DNA-based nanowires and nanodevices

DNA (deoxyribonucleic acid) is a highly versatile biopolymer that has been a recent focus in the field of nanomachines and nanoelectronics. DNA exhibits many properties, such as high stability, adjustable conductance, vast information storage, self-organising capability and programmability, making it an ideal material in the applications of nanodevices, nanoelectronics and molecular computing. Even though native DNA has low conductance, it can easily be converted into a potential conductor by doping metal ions into the base pairs. Nickel ions have been employed to tune DNA into conducting polymers. Doping of nickel ions within DNA (Ni-DNA) increases the conductivity of DNA by at least 20 folds compared with that of native DNA. Further studies showed that Ni-DNA nanowires exhibit characteristics of memristors, making them a potential mass information storage system. In summary, DNA molecules have promising applications in a variety of fields, including nanodevices, nanomachines, nanoelectronics, organic solar cells, organic light emitting diodes and biosensors

Exopolysaccharides from Lactobacillus acidophilus modulates the antioxidant status of 1,2–dimethyl hydrazine-induced colon cancer rat model

The aim of the current study is to ascertain the anticancer activity of exopolysaccharides (EPS) from probiotic Lactobacillus acidophilus in the 1, 2 – dimethyl hydrazine (DMH) induced colon cancer rat model and to determine the antioxidant status. Rats were divided into five groups of six animals each. Group I served as control, group II served as cancer control (DMH alone administered), group III as standard drug control [Fluorouracil (5-FU) along with DMH} and group IV and V received EPS in two doses (200 mg/kg body weight and 400 mg/kg body weight along with DMH). EPS administration was found to reduce the number of polyps formed (Group IV - 8.25±1.258 & Group V - 8.50±1.732 vs Group II - 14.50±2.380) and to increase the levels of antioxidant enzymes viz. superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and antioxidants like vitamin C (Vit. C), reduced glutathione (GSH) which was found to be reduced in colon cancer control rats. The status of lipid peroxidation (LPO) was also evaluated. All the values which were affected by the supplementation of DMH were brought to near normal levels by the treatment with EPS. The well preserved histology of colon and the biochemical evaluation also show that EPS could be a potential agent for the prevention and treatment of colon cancer.Science and Engineering Research Boar

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