Predictors of morbidity and mortality in COVID-19.

The mortality of COVID-19 patients is increasing in logarithmic fashion and is mostly observed in older age people and patients having history of chronic ailments like chronic obstructive pulmonary disease (COPD), hypertension, diabetes, cardiovascular & cerebrovascular dysfunction, compromised immunity, renal comorbidities, hepatic, obesity problems etc., and recently investigated thrombotic complications. The molecular underpinnings linking the chronic human diseases with COVID-19 related morbidity and mortality are evolving and poorly understood. The aim of the present review is to discuss the mortality and morbidity in COVID-19 in relation to preexisting comorbidities across the globe, upcoming molecular mechanisms associated with expression profile of ACE2 and viral load, evolving pathophysiology of COVID-19 with special reference to thrombotic complication ('Storm of Blood Clots') and related predictive markers. The levels of plasminogen/plasmin in comorbid diseases of COVID-19 have been elaborated in the framework of risk and benefits of fibrinolysis in COVID-19. We have also attempted to discuss the puzzle of prescribing ARBs and ACEI drugs in COVID-19 management which are routinely prescribed for the management of hypertension in COVID-19 patients. A focused discourse on risk of cardiovascular complications and diabetes in concert with COVID-19 pathogenesis has been presented along with dynamics of SARS-CoV-2 induced immune dysfunctions in COVID-19 patients.

Compensatory angiogenesis and tumor refractoriness.

Since the establishment of tumor angiogenesis as a therapeutic target, an excitement in developing the anti-angiogenic agents was resulted in tailoring a humanized monoclonal antibody (Bevacizumab) against vascular endothelial growth factor (VEGF): a key factor in recruiting angiogenesis. The past three decades' research in the area of angiogenesis also invented a series of novel and effective anti-angiogenic agents targeting the VEGF signaling axis. Despite the demonstrable clinical benefits of anti-angiogenic therapy, the preclinical and clinical data of the current therapeutic settings clearly indicate the transient efficacy, restoration of tumor progression and aggressive recurrence of tumor invasion after the withdrawal of anti-angiogenic therapy. Therefore, the impact of this therapeutic regime on improving overall survival of patients has been disappointing in clinic. The recent advances in pathophysiology of tumor angiogenesis and related molecular and cellular underpinnings attributed the conspiracy of compensatory angiogenic pathways in conferring evasive and intrinsic tumor resistance to anti-angiogenic agents. The understandings of how these pathways functionally cross-talk for sustaining tumor angiogenesis during VEGF blockade is essential and perhaps may act as a basic prerequisite for designing novel therapeutic strategies to combat the growing arrogance of tumors toward anti-angiogenic agents. The present review offers a discourse on major compensatory angiogenic pathways operating at cellular and molecular levels and their attributes with resistance to anti-angiogenic agents along with strategic opinions on future setting in targeting tumor angiogenesis.

Flavonoids as a scaffold for development of novel anti-angiogenic agents: An experimental and computational enquiry.

Relationship between structural diversity and biological activities of flavonoids has remained an important discourse in the mainstream of flavonoid research. In the current study anti-angiogenic, cytotoxic, antioxidant and cyclooxygenase (COX) inhibitory activities of diverse class of flavonoids including hydroxyl and methoxy substituted flavones, flavonones and flavonols have been evaluated in the light of developing flavonoids as a potential scaffold for designing novel anti-antiangiogenic agents. We demonstrate anti-angiogenic potential of flavonoids using in vivo chorioallantoic membrane model (CAM) and further elaborate the possible structural reasoning behind observed anti-angiogenic effect using in silico methods. Additionally, we report antioxidant potential and kinetics of free radical scavenging activity using DPPH and SOR scavenging assays. Current study indicates that selected flavonoids possess considerable COX inhibition potential. Furthermore, we describe cytotoxicity of flavonoids against selected cancer cell lines using MTT cell viability assay. Structural analysis of in silico docking poses and predicted binding free energy values are not only in accordance with the experimental anti-angiogenic CAM values from this study but also are in agreement with the previously reported literature on crystallographic data concerning EGFR and VEGFR inhibition.

Profile of aldose reductase inhibition, anti-cataract and free radical scavenging activity of selected medicinal plants: an attempt to standardize the botanicals for amelioration of diabetes complications.

Phytotherapy has played an important role in the management of diabetes and related complications. In the present study different fractions of Catharanthus roseus L. (Apocynaceae), Ocimum sanctum L. (Labiatae), Tinospora cordifolia Willd. (Menispermaceae), Aegle marmelos L. (Rutaceae), Ficus golmerata L. (Moraceae), Psoralea corlifolia L. (Fabaceae), Tribulus terrestris L. (Zygophyllaceae), and Morinda cetrifolia L. (Rubiaceae) were evaluated as possible inhibitors of aldose reductase (AR: a key enzyme implicated in cataractogenesis) and antioxidant agents. Anti-cataract activity of the selected plants was demonstrated using 'sugar induced lens opacity model' and the cytotoxicity studies were carried out using MTT assay. Among the tested plants, water extract of M. cetrifolia (IC50 0.132 mg/ml) exhibited maximum AR inhibitory activity as compared to other phytofractions which showed the activity in an IC50 range of 0.176-0.0.82 mg/ml. All the plant fractions showed considerable antioxidant potential. Sugar induced lens opacity studies revealed that, M. cetrifolia possess significant anti-cataract potential to maintain lens opacity as compared to glucose induced lens opacity in bovine lens model. The extract of the selected plants showed moderate cytotoxicity against HeLa cell line. Results of the present studies may find useful in converting botanicals into therapeutic modalities.

Aldose reductase inhibitory, anti-cataract and antioxidant potential of selected medicinal plants from the Marathwada region, India.

The water, ethanol and chloroform extracts of selected plants such as Adhatoda vasica (L.) (Acanthaceae), Caesalpinia bonduc (L.), Cassia fistula (L.) (Caesalpiniaceae) and Biophytum sensitivum (L.) (Oxalidaceae) were evaluated for rat lens aldose reductase inhibitory (RLAR) potential, anti-cataract and antioxidant activities. All the samples inhibited the aldose reductase considerably and exhibited anti-cataract activity, while C. fistula (IC(50), 0.154 mg mL(-1)) showed significant RLAR inhibitory activity as compared to the other tested samples, and was further found to be more effective in maintaining sugar-induced lens opacity in the rat lens model. The antioxidant potential of plant extracts was determined using DPPH (2,2-diphenyl-1-picryl hydrazine), hydroxyl (OH), nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) scavenging activities, along with determination of reducing power, ferrous ion chelating ability and inhibition of polyphenol oxidase (PPO). The extracts of the tested plant showed significant free radical scavenging activities and inhibited the activity of enzyme PPO, a model oxidising enzyme. The plant samples were found to possess considerable amounts of vitamin C, total polyphenols and flavonoids.

Kinetics of Inhibition of Monoamine Oxidase Using Cymbopogon martinii (Roxb.) Wats.: A Potential Antidepressant Herbal Ingredient with Antioxidant Activity.

The study was designed to evaluate the antioxidant activity and effect of Cymbopogon martinii (Roxb.) Wats. (Poaceae) leaves on the activity of monoamine oxidase and kinetics of enzyme inhibition. Ethanol extract of C. martinii and rat brain mitochondrial monoamine oxidase preparation ware used to study the kinetics of enzyme inhibition using double reciprocal Lineweaver-Burk plot. The DPPH was used as a source of free radical to evaluate antioxidant potential. It is observed that, the ethanolic extract of C. martinii inhibits the monoamine oxidase activity with competitive mode of inhibition. The V(max) (0.01 mM/min) remained constant while, K(m) varied from 21.00 ± 1.1, 43.33 ± 1.5 and 83.33 ± 1.4 mM for 100-500 µg/ml concentration of C. martinii. The K(i) values were calculated to be 90.00 ± 0.87, 75.00 ± 0.69, 68.18 ± 0.68 µg for 100-500 µg/ml concentration of C. martini. It also shows a significant DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavenging (IC(50) = 0.34 ± 0.05 mg/ml) and reducing activity (IC(50) = 0.70 ± 0.22 mg/ml). The C. martini can be considered as a possible source of MAO inhibitor used in the treatment of depression and other neurological disorders.

In-vitro evaluation of selected chalcones for antioxidant activity.

Synthetic chalcones (SCs) having different side chains on the 1-(2-Hydroxy-3-(2-hydroxy-cyclohexyl)-4,6 dimethoxy-phenyl(-methanone structure were examined in-vitro for their antioxidant abilities by DPPH (2,2-diphenyl-1-picryl hydrazine) radical scavenging activity, reducing ability, OH radical scavenging activity, inhibition of polyphenol oxidase (PPO) and formation of diene conjugates. Overall, with few exceptions, all the SCs showed moderate biological activity in all the parameters examined. The SCs were found to be reactive towards DPPH radical and had considerable reducing ability. With few exceptions, all the test compounds under study were found to possess moderate to poor OH radical scavenging activity and inhibited PPO significantly and all were found to be effective inhibitors of hydroperoxide formation. These findings suggest that these SCs can be considered as potential antioxidant agents which might be further explored for the design of lead antioxidant drug candidates.

Coumarin Schiff-bases: as antioxidant and possibly anti-inflammatory agents.

Coumarin Schiff-bases (CSB) possessing different substituents on the 4-methyl-2-substituted phenyl imino-2H-chromene-7-ol molecule were evaluated for their in-vitro antioxidant and plausible anti-inflammatory potential. The antioxidant studies of selected CSB were carried out by determining their reducing power, OH* radical scavenging activity, scavenging of stable 2,2-diphenyl-l-picrylhydrazine (DPPH*) radical and inhibition of the polyphenol oxidase (PPO) enzyme. The assessment of possible anti-inflammatory potential was performed by trypsin inhibition assay and inhibition of beta-glucuronidase. All the CSBs under study showed significant reducing effects. The majority of the tested CSB were found to be effective scavengers of DPPH* radical with moderate to low OH* scavenging ability and significantly inhibited the activity of PPO. With few exceptions, results from the inhibition assay of trypsin and beta-glucuronidase were not encouraging, however they may be helpful in defining structure-activity relationships in further optimization of the lead molecules.

Glutathione and cinnamic acid: natural dietary components used in preventing the process of browning by inhibition of Polyphenol Oxidase in apple juice.

Consumer demands for 'freshness' in processed foods has been given increasing attention by food processing industries by searching for minimally processed products. Polyphenol Oxidase (PPO) mediated browning is a major cause of undesirable flavors and nutritional losses in fruit juices. Here the anti-browning efficiency of glutathione (GSH, reduced form) and cinnamic acid (CA) in apple juice is evaluated. It was observed that the rate of the browning reaction could be efficiently delayed using GSH and CA, which act as inhibitors of PPO. Kinetic studies confirm that GSH and CA are non-competitive and competitive inhibitors of PPO respectively.

Kinetics of inhibition of polyphenol oxidase mediated browning in apple juice by beta-cyclodextrin and L-ascorbate-2-triphosphate.

Polyphenol Oxidase (PPO) mediated browning in raw fruits and vegetables is a major cause of quality deterioration in fruits and vegetables and derived food products. Here the rate of browning reaction in apple juice treated individually and in combination (1:1) of beta-Cyclodextrin (beta-CD) and L-Ascorbate-2-triphosphate (L-AATP) is described. It was observed that the rate of quinone formation can be minimized using a combination of beta-CD and L-AATP as compared to individual treatment with these agents. Kinetic experiments revealed that both compounds are non-competitive inhibitors of PPO.