HIF-1α contributing to COVID-19 infections and poor prognosis in cancer patients – A hypothesis

In 2019, a new coronavirus (SARS-CoV-2) infecting Humans first identified in Wuhan, China, has caused the worst pandemic of the 21st century. This virus infection leads to the clinical symptoms that may range from asymptomatic condition to life-threatening illness. The insights from the recent studies suggest that SARS-CoV-2 requires a host enzyme, Furin to activate receptor-binding domain (RBD) of its S protein. Upon binding of RBD to host cell membrane-bound Angiotensin Convertase Enzyme 2 (ACE2), it facilitates the entry of virus in the host cell. Evidence from the literature also suggests that HIF-1α (Hypoxia-inducible factor 1-α) is one of the factors regulating the expression of Furin. In addition, it is also well documented that the interior of solid tumours, which grow very fast, leads to the hypoxic tumour microenvironment, resulting in overexpression and release of HIF-1α. The SARS-CoV-2 infected patients with severe tissue damage and inflammatory injury also suffer from tissue hypoxia. So, we hypothesize that hypoxic condition due to tumour microenvironment in cancer patients upregulates the HIF-1α, leading to increased expression of Furin. Upon infection of cancer patients with SARS-CoV-2 having increased Furin expression in the cells due to upregulation of HIF-1α, leads to the entry of a greater number of SARS-CoV-2 virus in these cells resulting in severe infection. The vicious cycle of the virus infection in which virus is more easily invaded into surrounding tissue leads to the involvement of multiple organs and ultimately poor prognosis in the disease outcome. Therefore, we suggest evaluating the expression of HIF-1α in SARS-CoV-2 infections at an early phase of infection particularly in patients with comorbidities like solid malignancies as well as patients having signs and symptoms of hypoxia. It is also suggested that continuous monitoring of the SpO2 level and early institution of preventive O2 therapy at an early stage in these patients may lead to lesser morbidity as well as mortality in COVID-19 patients

HIF-1α contributing to COVID-19 infections and poor prognosis in cancer patients – A hypothesis

670-675In 2019, a new coronavirus (SARS-CoV-2) infecting Humans first identified in Wuhan, China, has caused the worst pandemic of the 21st century. This virus infection leads to the clinical symptoms that may range from asymptomatic condition to life-threatening illness. The insights from the recent studies suggest that SARS-CoV-2 requires a host enzyme, Furin to activate receptor-binding domain (RBD) of its S protein. Upon binding of RBD to host cell membrane-bound Angiotensin Convertase Enzyme 2 (ACE2), it facilitates the entry of virus in the host cell. Evidence from the literature also suggests that HIF-1α (Hypoxia-inducible factor 1-α) is one of the factors regulating the expression of Furin. In addition, it is also well documented that the interior of solid tumours, which grow very fast, leads to the hypoxic tumour microenvironment, resulting in overexpression and release of HIF-1α. The SARS-CoV-2 infected patients with severe tissue damage and inflammatory injury also suffer from tissue hypoxia. So, we hypothesize that hypoxic condition due to tumour microenvironment in cancer patients upregulates the HIF-1α, leading to increased expression of Furin. Upon infection of cancer patients with SARS-CoV-2 having increased Furin expression in the cells due to upregulation of HIF-1α, leads to the entry of a greater number of SARS-CoV-2 virus in these cells resulting in severe infection. The vicious cycle of the virus infection in which virus is more easily invaded into surrounding tissue leads to the involvement of multiple organs and ultimately poor prognosis in the disease outcome. Therefore, we suggest evaluating the expression of HIF-1α in SARS-CoV-2 infections at an early phase of infection particularly in patients with comorbidities like solid malignancies as well as patients having signs and symptoms of hypoxia. It is also suggested that continuous monitoring of the SpO2 level and early institution of preventive O2 therapy at an early stage in these patients may lead to lesser morbidity as well as mortality in COVID-19 patients

Analog and RF Performance Analysis of 22nm Modified Source/Drain Dual Gate FDSOI MOSFET

In this paper, 22nm FDSOI MOSFET having Modified Source/Drain with Dual Gate has been analyzed. This device, not only provides higher ON current but it has also a lower leakage current in order of pA. With the help of Dual Gate (DG) electrical characteristics and Short Channel Effects improved. Analysis parameters like Drain Induced Barrier Lowering (DIBL), Subthreshold Swing, Threshold roll-off, Carrier Concentration, Gate to drain Capacitance, Gate to Source Capacitance, cut-off frequency, Conduction and Valence Band Banding are analyzed using high-k spacers

The role of topical gel containing chitosan, 0.2% chlorhexidine, allantoin and dexpanthenol on the wound healing after surgical extraction of impacted mandibular third molar

Odontostomologic procedures like extractions especially surgical removal of impacted 3rd molars, implants, biopsies etc are often associated with post-operative pain and inflammation. Traditionally chlorhexidine was used in this regard. Recently, topical gel, Bexident Post (ISDIN, SPAIN) has been in use to control post-operative discomfort. The aim of this study is to clinically evaluate the efficacy of Bexident Post (ISDIN, SPAIN) that contains chitosan, dexpenthanol, allantoin and 0.2% chlorhexidine on wound healing after surgical extraction of mandibular impacted 3rd molars. A study sample of 10 patients with similar type of bilateral impacted mandibular 3rd molar was included in the study. Total of 10 extractions were assingned in one of the two groups. Only difference between the two sides in terms of surgical protocol will be the Experimental side applied 10 mL thrice daily for 10 days while Control side did not. All patients were aware of the purpose of present study and written consent was taken requiring their participation. Results showed that facial swelling, mouth opening and pain were all significant between the two groups. The groups were homogenous only in terms of infection as neither of the groups showed post-operative signs of infection

Analysis of industrial pollution in India

Barry Commoner, American biologist once said, “Environmental pollution is an incurable disease. It can only be prevented”. But instead of preventing we are aggravating it. Around 7.4 Lacks people die in India annually because of abnormal temperatures due to climate change according to a recent Lancets study.  51% of air pollution in India is due to industries. Indians are exposed to 25 micrograms per cubic metre above World Health Organisations limit of 10 micrograms per cubic metre of particulate matter. We know how much industrial pollution has been damaging our environment, but do we have effective laws in order to protect citizens of India against environmental offenders? Are existing laws and legislation efficient enough to punish the offenders and protect the victims? We do not have any systematic approach for making Industrial sector accountable and responsible towards proper management of waste effluents as it contributes around 50% of environment pollution. Industries like leather, cement, plastic, garments, sugar, steel and petroleum are the major polluting industries. The objective of this paper is to throw light on the important issue of mismanagement of our future and future of our generations so that some useful solutions can come out

The Role of Topical Gel Containing Chitosan, 0.2% Chlorhexidine, Allantoin and Dexpanthenol on the Wound Healing After Surgical Extraction of Impacted Mandibular Third Molar

Odontostomologic procedures like extractions especially surgical removal of impacted 3rd molars, implants, biopsies etc are often associated with post-operative pain and inflammation. Traditionally chlorhexidine was used in this regard. Recently, topical gel, Bexident Post (ISDIN, SPAIN) has been in use to control post-operative discomfort. The aim of this study is to clinically evaluate the efficacy of Bexident Post (ISDIN, SPAIN) that contains chitosan, dexpenthanol, allantoin and 0.2% chlorhexidine on wound healing after surgical extraction of mandibular impacted 3rd molars. A study sample of 10 patients with similar type of bilateral impacted mandibular 3rd molar was included in the study. Total of 10 extractions were assingned in one of the two groups. Only difference between the two sides in terms of surgical protocol will be the Experimental side applied 10 mL thrice daily for 10 days while Control side did not. All patients were aware of the purpose of present study and written consent was taken requiring their participation. Results showed that facial swelling, mouth opening and pain were all significant between the two groups. The groups were homogenous only in terms of infection as neither of the groups showed post-operative signs of infection

Ultrasensitive Detection of Multidrug-Resistant Mycobacterium tuberculosis Using SuperSelective Primer-Based Real-Time PCR Assays

The emergence of drug-resistant tuberculosis is a significant global health issue. The presence of heteroresistant Mycobacterium tuberculosis is critical to developing fully drug-resistant tuberculosis cases. The currently available molecular techniques may detect one copy of mutant bacterial genomic DNA in the presence of about 1–1000 copies of wild-type M. tuberculosis DNA. To improve the limit of heteroresistance detection, we developed SuperSelective primer-based real-time PCR assays, which, by their unique assay design, enable selective and exponential amplification of selected point mutations in the presence of abundant wild-type DNA. We designed SuperSelective primers to detect genetic mutations associated with M. tuberculosis resistance to the anti-tuberculosis drugs isoniazid and rifampin. We evaluated the efficiency of our assay in detecting heteroresistant M. tuberculosis strains using genomic DNA isolated from laboratory strains and clinical isolates from the sputum of tuberculosis patients. Results show that our assays detected heteroresistant mutations with a specificity of 100% in a background of up to 104 copies of wild-type M. tuberculosis genomic DNA, corresponding to a detection limit of 0.01%. Therefore, the SuperSelective primer-based RT-PCR assay is an ultrasensitive tool that can efficiently diagnose heteroresistant tuberculosis in clinical specimens and contributes to understanding the drug resistance mechanisms. This approach can improve the management of antimicrobial resistance in tuberculosis and other infectious diseases

A FACS-based novel isolation technique identifies heterogeneous CTCs in oral squamous cell carcinoma

PurposeIsolating circulating tumour cells (CTCs) from the blood is challenging due to their low abundance and heterogeneity. Limitations of conventional CTC detection methods highlight the need for improved strategies to detect and isolate CTCs. Currently, the Food and Drug Administration (FDA)-approved CellSearch™ and other RUO techniques are not available in India. Therefore, we wanted to develop a flexible CTC detection/isolation technique that addresses the limitation(s) of currently available techniques and is suitable for various downstream applications.MethodsWe developed a novel, efficient, user-friendly CTC isolation strategy combining density gradient centrifugation and immuno-magnetic hematogenous cell depletion with fluorescence-activated cell sorting (FACS)-based positive selection using multiple CTC-specific cell-surface markers. For FACS, a stringent gating strategy was optimised to exclude debris and doublets by side scatter/forward scatter (SSC/FSC) discriminator, remove dead cells by 4′,6-diamidino-2-phenylindole (DAPI) staining, and eliminate non-specific fluorescence using a “dump” channel. APC-labelled anti-CD45mAB was used to gate remaining hematogenous cells, while multiple epithelial markers (EpCAM, EGFR, and Pan-Cytokeratin) and an epithelial–mesenchymal transition (EMT) marker (Vimentin) labelled with fluorescein isothiocyanate (FITC) were used to sort cancer cells. The technique was initially developed by spiking Cal 27 cancer cells into the blood of healthy donors and then validated in 95 biopsy-proven oral squamous cell carcinoma (OSCC) patients. CTCs isolated from patients were reconfirmed by Giemsa staining, immuno-staining, and whole transcriptome amplification (WTA), followed by qRT-PCR. In vitro culture and RNA sequencing (RNA-Seq) were also performed to confirm their suitability for various downstream applications.ResultsThe mean detection efficiency for the Cal 27 tongue cancer cells spiked in the whole blood of healthy donors was 32.82% ± 12.71%. While ~75% of our patients (71/95) had detectable CTCs, the CTC positivity was independent of the TNM staging. The isolated potential cancer cells from OSCC patients were heterogeneous in size. They expressed different CTC-specific markers in various combinations as identified by qRT-PCR after WTA in different patients. Isolated CTCs were also found to be suitable for downstream applications like short-term CTC culture and RNA-Seq.ConclusionWe developed a sensitive, specific, flexible, and affordable CTC detection/isolation technique, which is scalable to larger patient cohorts, provides a snapshot of CTC heterogeneity, isolates live CTCs ready for downstream molecular analysis, and, most importantly, is suitable for developing countries