Pandemic coronavirus disease-2019, commonly known as COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious disease with a high mortality rate. Various comorbidities and their associated symptoms accompany SARS-CoV-2 infection. Among the various comorbidities like hypertension, cardiovascular disease and chronic obstructive pulmonary disease, diabetes considered as one of the critical comorbidity, which could affect the survival of infected patients. The severity of COVID-19 disease intensifies in patients with elevated glucose level probably via amplified pro-inflammatory cytokine response, poor innate immunity and downregulated angiotensin-converting enzyme 2. Thus, the use of ACE inhibitors or angiotensin receptor blockers could worsen the glucose level in patients suffering from novel coronavirus infection. It also observed that the direct β-cell damage caused by virus, hypokalemia and cytokine and fetuin-A mediated increase in insulin resistance could also deteriorate the diabetic condition in COVID-19 patients. This review highlights the current scenario of coronavirus disease in pre-existing diabetic patients, epidemiology, molecular perception, investigations, treatment and management of COVID-19 disease in patients with pre-existing diabetes. Along with this, we have also discussed unexplored therapies and future perspectives for coronavirus infection.

Context: The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood-brain barrier. Objective: Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route. Methodology: Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsionsolvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed for in vitro release kinetics, ex vivo permeation and in situ nasal perfusion. Cytotoxic potential of CPCs in vitro was evaluated on LN229 human glioblastoma cells. Results and discussion: The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6 ± 4.7 nm and zeta potential À16.3 ± 3.7 mV exhibited percentage entrapment efficiency of 27.95 ± 4.21. In vitro drug release showed initial burst release followed by slow and continues release indicating biphasic pattern. The ex vivo permeation pattern through sheep nasal mucosa also exhibited a similar release pattern as for in vitro release studies. In situ nasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution. In vitro cytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone. Conclusion: CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery.

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Reactive oxygen species (ROS) induced oxidative stress is believed to be a primary causative factor of various inflammatory diseases. ROS has been linked with cancer, coronary heart disease, and neurodegenerative diseases, and their presence in the body causes damage to the DNA of cells. Antioxidants exert their effects by scavenging or preventing the generation of ROS, which can protect the formation of free radicals and retard the progress of many chronic diseases, including cancer, inflammation, and car- A series of novel 5-alkyl/aryl thiadiazole substituted thiazolidin-4-ones were synthesized by a two-step process. In the first step, 5-alkyl/aryl substituted 2-aminothiadiazoles were synthesized, which on reaction with substituted aromatic aldehydes and thioglycolic acid in the presence of dicyclohexylcarbodiimide afforded thiazolidin-4-ones. All the compounds were synthesized in fairly good yields and their structures were confirmed by spectral and physical data. The title compounds were screened for in vitro anti-proliferative activity on human breast adenocarcinoma cells (MCF-7) by MTT assay. Most of the derivatives showed an IC 50 less than 150 µmol L -1 . Among the compounds tested, 2-(2-nitrophenyl)-3-(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3f), 2-(3-fluorophenyl)-3-(5-methyl-1,3,4-thiadiazol-2--yl)-thiazolidin-4-one (3b), and 2-(4-chlorophenyl)-3--(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3c) were found to be the most active derivatives with IC 50 values of 46.34, 66.84, and 60.71 µmol L -1 , respectively. Antioxidant studies of all the synthesized compounds were carried out by diphenylpicrylhydrazyl (DPPH) assay. Among the compounds tested, 2-phenyl-3-(5-styryl--1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3s) elicited superior antioxidant activity with IC 50 of 161.93 µmol L -1 .

Atrophy of the quadriceps musculature is frequently associated with chronic knee instability. This atrophy may persist despite the patient's ability to return to athletic competition. When open biopsies of the quadriceps muscle from unstable knees were compared with those from normal acutely injured knees, it was found that clinical evidence of atrophy correlated with a relative decrease in the size of Type II or fast twitch muscle fibers. This supports the subjective, clinical impression that the unstable knee is less effective in explosive push-off. The findings also indicate the necessity of including exercise specific for the training of Type II fast twitch fibers in any program designed to rehabilitate the injured knee.