Folate-Mediated Paclitaxel Nanodelivery Systems: A Comprehensive Review.

Paclitaxel (PTX) is used as a viable cancer medication in the chemotherapy of breast, ovarian, lung, bladder, neck, head, and esophageal tumors. The focus of this review is to survey various folate-targeting PTX-loaded nanopreparations in both research and clinical applications. There are diverse nanopreparations, including liposomes, micelles, polymeric nanopreparations, lipid nanopreparations, lipoprotein nanocarriers, and other inorganic nanopreparations for folate-associated PTX tumor targeting. Here, the folate targeting PTX-loaded nanopreparations, which have promising results in the constructive treatment of cancer by reducing toxic side-effects and/or improving effectiveness, was mainly reviewed.

Changes in Mode of Oxygen Delivery and Physiological Parameters with Physiotherapy in COVID-19 Patients: A Retrospective Study.

Background: Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2, clinically presenting with common symptoms of fever, dry cough, and breathlessness within 14 days of exposure. Its severity ranges from mild to severe, latter manifesting into severe acute respiratory syndrome. As a part of multidisciplinary team, physiotherapy along with medical management was administered to patients with COVID-19 in an acute care setup. This retrospective study aims to explore various patient characteristics and will aid in identifying the impairments associated with the disease, giving a direction to the physiotherapy community in planning future management strategy to improve quality of life. Patients and methods: The present study is a unicentric study wherein prospective analysis of retrospective data of patients referred for physiotherapy from May 13 to July 31, 2020, was performed. (i) Characteristics of patients, (ii) associated comorbidities, (iii) hospital course since the time of admission to discharge, (iv) mode of oxygen delivery, (v) pre- and post-physiotherapy treatment values of oxygen saturation and heart rate, and (vi) physiotherapy treatment were recorded. The archived data were analyzed using the commercially available SPSS software version 24. Wilcoxon's matched pair test was used to compare pre- and post-treatment oxygen saturation and heart rate, and McNemar's test was used to compare mode of oxygen delivery and pre- and post-physiotherapy treatment. Results: Descriptive analysis of data showed a better outcome in terms of grade of dyspnea and rate of discharge on day 14 of physiotherapy treatment. Hence, a comparative analysis of day 1 and day 14 was performed for mode of oxygen delivery, oxygen saturation, and heart rate. A statistically significant improvement was observed in the heart rate (p = 0.001) and oxygen delivery (p = 0.000). However, no significant difference in the level of oxygen saturation was found (p = 0.6433). Conclusion: Physiotherapy treatment in conjunction with medical treatment can be effectively administered in patients with COVID-19 in acute care setup taking into consideration the health status and the hemodynamic stability of the patients. It emphasizes the role of physiotherapy in the alleviation of symptoms, facilitating early weaning and recovery enabling early discharge from the hospital. How to cite this article: Verma CV, Arora RD, Mistry HM, Kubal SV, Kolwankar NS, Patil PC, et al. Changes in Mode of Oxygen Delivery and Physiological Parameters with Physiotherapy in COVID-19 Patients: A Retrospective Study. Indian J Crit Care Med 2021;25(3):317-321.

BRG1 promotes hepatocarcinogenesis by regulating proliferation and invasiveness.

The chromatin remodeler complex SWI/SNF plays an important role in physiological and pathological processes. Brahma related gene 1(BRG1), a catalytic subunit of the SWI/SNF complex, is known to be mutated in hepatocellular carcinoma (HCC). However, its role in HCC remains unclear. Here, we investigate the role of BRG1 on cell growth and invasiveness as well as its effect on the expression of putative target genes. Expression of BRG1 was examined in human liver tissue samples and in HCC cell lines. In addition, BRG1 was silenced in human HCC cell lines to analyse cell growth and invasiveness by growth curves, colony formation assay, invasion assay and the expression of putative target genes. BRG1 was found to be significantly increased in HCC samples compared to non-HCC samples. In addition, a declined proliferation rate of BRG1-silenced human HCC cell lines was associated with a decrease of expression of cyclin family members. In line with a decreased invasiveness of BRG1-siRNA-treated human HCC cell lines, down-regulation of MMP7 was detected. These results support the hypothesis that overexpression of BRG1 increases cell growth and invasiveness in HCC. Furthermore, the data highlight cyclin B, E and MMP7 to be associated with BRG1 during hepatocarcinogenesis.

Determination of mutagenicity of the precipitate formed by sodium hypochlorite and chlorhexidine using the Ames test.

The aim of this study was to determine the direct mutagenic potential of any precipitate formed by combining sodium hypochlorite (NaOCl) and chlorhexidine (CHX). The precipitates formed by NaOCl and CHX were dissolved in 100% dimethyl sulfoxide and cultured with mutant Salmonella Typhimurium strains. The cells were observed for reverse mutation. The numbers of positive/mutated wells were statistically compared with those in the background plates using the two-sample proportion independent t-test. The precipitates were not found to be significantly more mutagenic than the background plates. Within the limitations of this study, the results suggest that the precipitates formed when sodium hypochlorite and chlorhexidine contact did not show mutagenic (and are therefore carcinogenic) potential.

Effect of Water-miscible Organic Solvents on CYP450-mediated Metoprolol and Imipramine Metabolism in Rat Liver Microsomes.

The catalytic activity of cytochrome P450 enzymes is known to be affected by presence of organic solvents in in vitro assays. However, these effects tend to be variable and depend on the substrate and CYP450 isoform in question. In the present study, we have investigated effect of ten water miscible organic solvents (methanol, ethanol, propanol, isopropanol, acetone, acetonitrile, dimethylsulphoxide, dimethylformamide, dioxane and PEG400) on water soluble substrates of CYP450, metoprolol and imipramine, at 0, 0.1, 0.25, 0.5, 0.75 and 1% v/v concentration in rat liver microsomes. Organic solvents studied had a concentration dependent inhibitory effect on the metoprolol and imipramine metabolism activity. Metoprolol metabolism was found to be more susceptible to the organic solvents, almost all the ten solvents had more or less inhibitory effect compared to imipramine metabolism. Except acetone, PEG400 and dimethylsulphoxide, all solvents had ~50% inhibition of total metoprolol metabolism activity, while in case of imipramine metabolism activity, only n-propanol, isopropanol and PEG400 had ~50% inhibition at 1% v/v. Interestingly, methanol, dimethylsulphoxide and acetonitrile had negligible effect on the imipramine metabolism (less than 10% inhibition at 1% v/v) while, total metoprolol metabolism activity was substantially inhibited by these solvents (MeOH 52%, DMSO 29% and ACN 47% at 1% v/v). In both cases, dioxane was found to be the most inhibitory solvent (~90% inhibition at 1% v/v).

Effect of Water Miscible Organic Solvents on p-Nitrophenol Hydroxylase (CYP2E1) Activity in Rat Liver Microsomes.

Organic solvents used for solubilization of the substrates/NCEs are known to affect the activity of cytochrome P450 enzymes. Further, this effect varies with the solvents used, the substrates and CYP450 isoforms in question. In the present study, we have investigated the effect of ten commonly used water miscible organic solvents (methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, acetone, dimethyl sulphoxide, N,N-dimethyl formamide, dioxane and polyethylene glycol 400) on p-nitrophenol hydroxylase activity at 0, 0.1, 0.25, 0.5, 0.75 and 1% v/v concentration in rat liver microsomes. All the solvents studied showed concentration dependent inhibition of the p-nitrophenol hydroxylase activity except acetonitrile which showed activation of the activity at concentration range studied. Out of ten solvents studied, dioxane was found to be the most inhibitory solvent (inhibition >90% at 0.25% v/v concentration). Overall, solvents like dimethyl sulphoxide, dimethyl formamide and dioxane appeared to be unsuitable for characterizing p-nitrophenol hydroxylase (CYP2E1-mediated) reactions due to a high degree of inhibition. On the other hand, methanol and acetonitrile at concentrations <0.5% v/v appeared to be appropriate solvents for substrate solubilization while evaluating CYP2E1-mediated catalysis. The results of this study imply that caution should be exercised while choosing solvents for dissolution of substrate during enzyme studies in liver microsomes.