Accumulating Impact of Smoking and Co-morbidities on Severity and Mortality of COVID-19 Infection: A Systematic Review and Meta-analysis.

Background: High prevalence, severity, and formidable morbidity have marked the recent emergence of the novel coronavirus disease (COVID-19) pandemic. The significant association with the pre-existing co-morbid conditions has increased the disease burden of this global health emergency, pushing the patients, healthcare workers and facilities to the verge of complete disruption. Methods: Meta-analysis of pooled data was undertaken to assess the cumulative risk assessment of multiple co-morbid conditions associated with severe COVID-19. PubMed, Scopus, and Google Scholar were searched from January 1st to June 27th 2020 to generate a well-ordered, analytical, and critical review. The exercise began with keying in requisite keywords, followed by inclusion and exclusion criteria, data extraction, and quality evaluation. The final statistical meta-analysis of the risk factors of critical/severe and non-critical COVID-19 infection was carried out on Microsoft Excel (Ver. 2013), MedCalc (Ver.19.3), and RevMan software (Ver.5.3). Results: We investigated 19 eligible studies, comprising 12037 COVID-19 disease patients, representing the People's Republic of China (PRC), USA, and Europe. 18.2% (n = 2200) of total patients had critical/severe COVID-19 disease. The pooled analysis showed a significant association of COVID-19 disease severity risk with cardiovascular disease (RR: 3.11, p < 0.001), followed by diabetes (RR: 2.06, p < 0.001), hypertension (RR: 1.54, p < 0.001), and smoking (RR: 1.52, p < 006). Conclusion: The review involved a sample size of 12037 COVID-19 patients across a wide geographical distribution. The reviewed reports have focussed on the association of individual risk assessment of co-morbid conditions with the heightened risk of COVID-19 disease. The present meta-analysis of cumulative risk assessment of co-morbidity from cardiovascular disease, diabetes, hypertension, and smoking signals a novel interpretation of inherent risk factors exacerbating COVID-19 disease severity. Consequently, there exists a definite window of opportunity for increasing survival of COVID-19 patients (with high risk and co-morbid conditions) by timely identification and implementation of appropriately suitable treatment modalities.

Genipin crosslinked curcumin loaded chitosan/montmorillonite K-10 (MMT) nanoparticles for controlled drug delivery applications.

Here, we have reported the influence of MMT and genipin in releasing curcumin from the Genipin crosslinked Chitosan/MMT nanoparticles, prepared by ionic gelation method. The nanoparticles were characterised using Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffractometry (XRD), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM). Zeta potential and average diameter of the nanoparticles were found in the range 32-47 mV and 430-560 nm. Swelling and release of curcumin from the nanoparticles increased with the decrease in pH of the medium, MMT, and genipin content. Curcumin released from the nanoparticles reduced the viability of MCF-7 and Hep G2 cells as compared to untreated cells. The nanoparticles increased the level of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase level in human PBMCs and decreased the level of Lipid peroxidation suggesting an enhanced protection against cellular damage. Lower pH and higher MMT concentration in the nanoparticles improved the mucoadhesive properties.

Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity.

Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa. Accordingly, we assessed whether NOX activity in PCa cells could be inhibited by Graviola pulp extract (GPE) that contains unique acetogenins with strong anti-cancer effects. GPE (1-5 µg/ml) treatment strongly inhibited the hypoxia-induced NOX activity in PCa cells (LNCaP, 22Rv1 and PC3) associated with a decrease in the expression of NOX catalytic and regulatory sub-units (NOX1, NOX2 and p47(phox)). Furthermore, GPE-mediated NOX inhibition was associated with a strong decrease in nuclear HIF-1α levels as well as reduction in the proliferative and clonogenic potential of PCa cells. More importantly, GPE treatment neither inhibited NOX activity nor showed any cytotoxicity against non-neoplastic prostate epithelial PWR-1E cells. Overall, these results suggest that GPE could be useful in the prevention of PCa progression via inhibiting NOX activity.

Carboxymethyl starch-chitosan-coated iron oxide magnetic nanoparticles for controlled delivery of isoniazid.

CONTEXT: The coating material of magnetic nanoparticles plays a great role in drug delivery application. The coatings not only increase the stability of the nanoparticles but also improve the drug release pattern, biocompatibility and mucoadhesivity. OBJECTIVE: Montmorillonite (MMT) containing magnetic iron oxide nanoparticles coated with polyelectrolyte complex (PEC) of carboxymethyl starch-chitosan were prepared for controlled release applications. METHOD: The PEC-coated nanoparticles were characterised by Fourier Transmission Infra-red spectroscopy and X-ray diffraction, scanning electron microscope, transmission electron microscope, and dynamic light scattering. Cytotoxicity study was performed by MTT assay analysis. Mucoadhesivity test was performed by using in vitro wash off and ex vivo method. RESULT: The coating of PEC showed good stability, biocompatibility and mucoadhesivity of the iron oxide magnetic nanoparticles. MMT addition enhanced the swelling, drug loading and release and also the cytotoxicity and mucoadhesivity of the nanoparticles. CONCLUSION: This study revealed that the MMT incorporated PEC of CMS-CS can be effectively used for coating of iron oxide nanoparticles.

Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules.

Hypoxic conditions in prostate cancer (PCA) are associated with poor prognosis; however, precise mechanism/s through which hypoxia promotes malignant phenotype remains unclear. Here, we analyzed the role of exosomes from hypoxic PCA cells in enhancing the invasiveness and stemness of naïve PCA cells, as well as in promoting cancer-associated fibroblast (CAF) phenotype in prostate stromal cells (PrSC). Human PCA LNCaP and PC3 cells were exposed to hypoxic (1% O2 ) or normoxic (21% O2 ) conditions, and exosomes secreted under hypoxic (Exo(Hypoxic) ) and normoxic (Exo(Normoxic) ) conditions were isolated from conditioned media. Nanoparticle tracking analysis revealed that Exo(Hypoxic) have smaller average size as compared to Exo(Normoxic) . Immunoblotting results showed a higher level of tetraspanins (CD63 and CD81), heat shock proteins (HSP90 and HSP70), and Annexin II in Exo(Hypoxic) compared to Exo(Normoxic) . Co-culturing with Exo(Hypoxic) increased the invasiveness and motility of naïve LNCaP and PC3 cells, respectively. Exo(Hypoxic) also promoted prostasphere formation by both LNCaP and PC3 cells, and enhanced α-SMA (a CAF biomarker) expression in PrSC. Compared to Exo(Normoxic) , Exo(Hypoxic) showed higher metalloproteinases activity and increased level of diverse signaling molecules (TGF-ß2, TNF1α, IL6, TSG101, Akt, ILK1, and ß-catenin). Furthermore, proteome analysis revealed a higher number of proteins in Exo(Hypoxic) (160 proteins) compared to Exo(Normoxic) (62 proteins), primarily associated with the remodeling of epithelial adherens junction pathway. Importantly, Exo(Hypoxic) targeted the expression of adherens junction proteins in naïve PC3 cells. These findings suggest that Exo(Hypoxic) are loaded with unique proteins that could enhance invasiveness, stemness, and induce microenvironment changes; thereby, promoting PCA aggressiveness.

Physical and biophysical assessment of highly fluorescent, magnetic quantum dots of a wurtzite-phase manganese selenide system.

Combining fluorescence and magnetic features in a non-iron based, select type of quantum dots (QDs) can have immense value in cellular imaging, tagging and other nano-bio interface applications, including targeted drug delivery. Herein, we report on the colloidal synthesis and physical and biophysical assessment of wurtzite-type manganese selenide (MnSe) QDs in cell culture media. Aiming to provide a suitable colloidal system of biological relevance, different concentrations of reactants and ligands (e.g., thioglycolic acid, TGA) have been considered. The average size of the QDs is ∼7 nm, which exhibited a quantum yield of ∼75% as compared to rhodamine 6 G dye(®). As revealed from time-resolved photoluminescence (TR-PL) response, the near band edge emission followed a bi-exponential decay feature with characteristic times of ∼0.64 ns and 3.04 ns. At room temperature, the QDs were found to exhibit paramagnetic features with coercivity and remanence impelled by TGA concentrations. With BSA as a dispersing agent, the QDs showed an improved optical stability in Dulbecco's Modified Eagle Media(®) (DMEM) and Minimum Essential Media(®) (MEM), as compared to the Roswell Park Memorial Institute(®) (RPMI-1640) media. Finally, the cell viability of lymphocytes was found to be strongly influenced by the concentration of MnSe QDs, and had a safe limit upto 0.5 µM. With BSA inclusion in cell media, the cellular uptake of MnSe QDs was observed to be more prominent, as revealed from fluorescence imaging. The fabrication of water soluble, nontoxic MnSe QDs would open up an alternative strategy in nanobiotechnology, while preserving their luminescent and magnetic properties intact.

Flower extract of Nyctanthes arbor-tristis modulates glutathione level in hydrogen peroxide treated lymphocytes.

BACKGROUND: Nyctanthes arbor-tristis Linn (Oleaceae) is a well-known traditional medicinal plant used throughout the India as an herbal remedy for treating various infectious and non-infectious diseases. OBJECTIVE: To evaluate the antioxidative activity of hydro-alcoholic extract of flower in the lymphocytes exposed to oxidative stress induced by H(2)O(2) . MATERIALS AND METHODS: Isolated lymphocytes were treated in vitro with extract or extract+H(2)O(2,) and the level of reduced glutathione (GSH) as well as the activity of glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) were measured. RESULTS: Treatment of lymphocyte with flower extract (50, 100, and 200 µg/ ml) significantly increased the level of GSH and decreased the activity of GST. The LDH activity measured in the cell-free medium decreased significantly. Pre-treatment of lymphocyte with flower extract protects the lymphocyte from the H(2)O(2) induced oxidative stress by significantly increasing the levels of GSH as compared to the cells treated only with H(2)O(2). Pre-treatment also reduced the activity of LDH significantly as compared to the cells treated only with H(2)O(2). The LDH activity in cell-free medium is associated with membrane damage, the decreased levels of LDH activity reflects the reduced level of membrane damage due to H(2)O(2). CONCLUSION: The present findings suggest the protective role of the hydro-alcoholic extracts of the flower of Nyctanthes arbor-tristis against membrane damage induced by H(2)O(2). The results also suggest that the extract might be rich in phytochemicals with antioxidant/radical scavenging potentials, which might find application in antioxidant therapy.