Diabetes mellitus and human immunodeficiency virus (HIV) infection in people with tuberculosis in Odisha, India.

BACKGROUND: Modelling studies have indicated that approximately 20% of all tuberculosis (TB) cases may suffer from diabetes mellitus (DM). DM increases the risk of developing active TB disease by 2-3 times. People living with HIV (PLHIV) are more likely to develop TB disease, and TB is a leading cause of hospitalization and death among PLHIV. Despite the substantial burden of DM and HIV in India, few studies have evaluated the prevalence of DM and HIV among active cases of TB, and its impact on the treatment outcome for TB. This study evaluated the burden of HIV and DM in TB cases from Odisha during 2019, and its impact on the TB treatment outcome. METHODS: The study utilized data on TB patients of Odisha during 2019, from the NIKSHAY portal, the health management information system (HMIS) of TB in India. This is a retrospective observational registry-based cohort study, which evaluated a linkage between socio-demographic predictors, clinical diagnostic and treatment predictors, time of treatment predictors, and co-morbidity with TB. Data were retrieved electronically in Microsoft-Excel and analysis was done using STATA 16 (StataCorp. 2019, College Station, TX: StataCorp LLC). RESULTS: Data for 47,831 TB cases of Odisha as study population was extracted from the Nikshay application for the year 2019. The highest prevalence (31.1%, 14,863/47,831) of TB was observed among young participants aged 15-30 years, whereas the prevalence was least among children <14 years (4.4%, 2124/47,831). Males had a higher prevalence of TB (66.7%, 31,878/47,831). Of the 47,831 TB cases included in the study, 7.6% (3659/47,831) had diabetes mellitus (DM), along with TB. 1.2% (571/47,831) had HIV along with TB, while only 0.08% (37/47,831) had both DM and HIV along with TB. 88.2% (3148/3569) of cases with DM and TB had a favorable outcome, compared to 82.3% (449/541) of cases with HIV and TB. People with TB who did not have DM had a significantly higher favorable outcome (OR 1.6, 95% CI 1.5-1.8) compared to those with TB and DM. Similarly, TB cases who did not have HIV infection had a significantly higher favorable outcome (OR 2.4, 95% CI 1.9-3.0) compared to those with TB and HIV. CONCLUSION: Our study showed that presence of DM and/or HIV in TB patients had an impact on the TB treatment outcome. There is a crucial need to prevent comorbidities such as DM and HIV from occurring and to prioritize early diagnosis and management of these conditions.

Impact of cartridge-based nucleic acid amplification test (CBNAAT) introduction on the detection of pulmonary and extra-pulmonary tuberculosis in Bhubaneswar, Odisha.

Background: Compared to conventional microscopy, the cartridge-based nucleic acid amplification test (CBNAAT, Xpert MTB/RIF, Cepheid, USA) has the dual advantage of higher sensitivity to detect Mycobacterium tuberculosis (M. tb), and the ability to detect rifampicin resistance. Aim: To evaluate the impact of the CBNAAT on the detection of pulmonary and extra-pulmonary tuberculosis from private and public healthcare facilities in Bhubaneswar, Odisha. Materials and Methods: The study included specimens received between June 2015 to February 2017 from public and private health sectors for tuberculosis diagnosis at a national reference laboratory for tuberculosis in Bhubaneswar, where the CBNAAT was initiated in February 2016. We retrospectively collected the patients' socio-demographic characteristics from their test request form, CBNAAT results from the CBNAAT register and PMDT culture and drug susceptibility testing (DST) register and validated the data by comparing the patient details and test results from the CBNAAT software. Results: From June 2015 to January 2016, 106 samples were received from Bhubaneswar at the reference laboratory, of which there were zero referrals from the private sector and zero referrals of extra-pulmonary tuberculosis (TB) samples. After initiation of the CBNAAT, from February 2016 to February 2017, 1262 specimens were received, of which 55.2% (696/1262), 17.8% (225/1262), 17.2% (217/1262), and 9.8% (124/1262) were from government hospitals and medical colleges, private hospitals, private practitioners, and district TB centers, respectively. Conclusion: The availability of TB diagnostics at public sector facilities to patients from private sectors and the rollout of the CBNAAT increased the referral of patients from private health facilities and the referral of paucibacillary non-sputum samples.

Detergent induced structural perturbations in peanut agglutinin: insights from spectroscopic and molecular dynamic simulation studies.

The three dimensional structure of a protein is very important for its structure. Studies relating to protein structure have been numerous and the effect of denaturants on proteins can help understand the process of protein folding and misfolding. Detergents are important denaturants and play important roles in various fields. Here we explored the effect of sodium dodecyl sulphate (SDS) and cetyltrimethylammonium bromide (CTAB) on the structure of peanut agglutinin (PNA). The protein was purified from its natural source and impact of SDS and CTAB was studied by circular dichroism, intrinsic fluorescence, 8-anilino-1-napthalenesulfonic acid, molecular docking and molecular dynamics simulation. Pure peanut agglutinin showed a trough at 220 nm and positive ellipticity peak at 195 nm, specific for lectins. Results from the experimental and simulation studies suggest how oppositely charged detergents can interact differently and lead to varied structural perturbations in PNA. Both the surfactants induce all α protein-like circular dichroism in the protein, above its critical micelle concentrations, with significant change in accessible surface area that became more hydrophobic upon the treatment. Major interactions between the surfactants and protein, resulting in PNA conformational rearrangement, are electrostatic and van der Waals interactions. However, CTAB, a cationic surfactant, has similar effects as anionic surfactant (SDS) but at significantly very low concentration. Though the effects followed same pattern in both the surfactant treatment, i.e. above respective CMC, the surfactants were inducing all α protein-like conformation in PNA.Communicated by Ramaswamy H. Sarma.

Pleural tuberculosis in Bhubaneswar, Odisha, during 2016 to 2022.

We conducted a retrospective study to evaluate the burden of tuberculosis and rifampicin resistance in patients with pleural effusion in Bhubaneswar, Odisha, during February 2016, to December 2022, using cartridge-based nucleic acid amplification test (CBNAAT, Xpert MTB/RIF). Of the 1370 pleural fluid samples tested at the National Reference Laboratory for tuberculosis, 3.8% (52/1370) were positive for M.tuberculosis. Rifampicin resistance was detected in 3.8% (2/52) samples. The positivity was 5% in 2016, increased to 7.5% in 2020, and was 4.4% in 2022. The positivity varied across age groups, ranging from 1.5% in patients aged >60 years to 6.1% in 15-30 years.

Synthesis of Novel Pyrazole-Oxindole Conjugates with Cytotoxicity in Human Cancer Cells via Apoptosis.

A novel series of pyrazole-oxindole conjugates were prepared and characterized as potential cytotoxic agents by FT-IR, NMR and HR-MS. The cytotoxic activity of these compounds was tested in the Jurkat acute T cell leukemia, CEM acute lymphoblastic leukemia, MCF10 A mammary epithelial and MDA-MB 231 triple negative breast cancer cell lines. Among the tested conjugates, 5-methyl-3-((3-(1-phenyl)-3-(p-tolyl)-1H-pyrazol-4-yl)methylene)indolin-2-one 6h emerged as the most cytotoxic with a CC50 of 4.36+/-0.2 µM against Jurkat cells. The mechanism of cell death induced by 6h was investigated through the Annexin V-FITC assay via flow cytometry. Reactive oxygen species (ROS) accumulation, mitochondrial health and the cell cycle progression were also evaluated in cells exposed to 6h. Results demonstrated that 6h induces apoptosis in a dose-response manner, without generating ROS and/or altering mitochondrial health. In addition, 6h disrupted the cell cycle distribution causing an increase in DNA fragmentation (Sub G0-G1), and an arrest in the G0-G1 phase. Taken together, the 6h compound revealed a strong potential as an antineoplastic agent evidenced by its cytotoxicity in leukemia cells, the activation of apoptosis and restriction of the cell cycle progression.

A Coumarin-Imidazothiadiazole Derivative, SP11 Abrogates Tumor Growth by Targeting HSP90 and Its Client Proteins.

Despite several treatment options for blood cancer, mortality remains high due to relapse and the disease's aggressive nature. Elevated levels of HSP90, a molecular chaperone essential for protein folding, are associated with poor prognosis in leukemia and lymphoma. HSP90 as a target for chemotherapy has been met with limited success due to toxicity and induction of heat shock. This study tested the activity of an HSP90 inhibitor, SP11, against leukemic cells, mouse lymphoma allograft, and xenograft models. SP11 induced cytotoxicity in vitro in leukemic cell lines and induced cell death via apoptosis, with minimal effect on normal cells. SP11 induced cell death by altering the status of HSP90 client proteins both in vitro and in vivo. SP11 reduced the tumor burden in allograft and xenograft mouse models without apparent toxicity. The half-life of SP11 in the plasma was approximately 2 h. SP11 binding was observed at both the N-terminal and C-terminal domains of HSP90. C-terminal binding was more potent than N-terminal binding of HSP90 in silico and in vitro using isothermal calorimetry. SP11 bioavailability and minimal toxicity in vivo make it a potential candidate to be developed as a novel anticancer agent.

Bacterial AsmA-Like Proteins: Bridging the Gap in Intermembrane Phospholipid Transport.

In eukaryotic cells, nonvesicular lipid transport between organelles is mediated by lipid-transfer proteins. Recently, a new class of these lipid transporters has been described to facilitate the bulk of inter-organelle lipid transport at contact sites by forming bridge-like structures with a hydrophobic groove through which lipids travel. Because their predicted structure is composed of repeating ß-groove (RBG) domains, they have been named the RBG protein superfamily. Early studies on RBG proteins VPS13 and ATG2 recognized the resemblance of their predicted structures to that of the bacterial Lpt system, which transports newly synthesized lipopolysaccharides (LPS) between the inner and the outer membranes (IMs and OMs) of Gram-negative bacteria. In these didermic bacteria, the IMs and OMs are separated by an aqueous periplasmic compartment that is traversed by a bridge-like structure built with ß-jelly roll domains from several Lpt proteins that provides a hydrophobic groove for LPS molecules to travel across the periplasm. Despite structural and functional similarities between RBG proteins and the Lpt system, the bacterial AsmA-like protein family has recently emerged as the likely ancestor of RBG proteins and long sought-after transporters that facilitate the transfer of phospholipids from the IM to the OM. Here, we review our current understanding of the structure and function of bacterial AsmA-like proteins, mainly focusing on recent studies that have led to the proposal that AsmA-like proteins mediate the bulk of phospholipid transfer between the IMs and OMs.

Pattern of InhA and KatG mutations in isoniazid mono resistant Mycobacterium tuberculosis isolates from Odisha.

We conducted a retrospective analysis of the line probe assay (LPA) data during January to December 2019, from 8 districts of Odisha. The prevalence of Hr-TB (isoniazid resistance only) was 1.53% (50/3272) with a range of 0-3.4% in the 8 districts. Of the 50 Hr-TB strains, katG mutation and inhA mutations were seen in 74% (37/50) and 26% (13/50) strains respectively. S315T1 and C15T were common mutations in katG and inhA respectively. Since these mutations are closely related to high- or low degree resistance to INH, it has therapeutic implications.

Chloride Ions Are Required for Thermosipho africanus MurJ Function.

Most bacteria have a peptidoglycan cell wall that determines their cell shape and helps them resist osmotic lysis. Peptidoglycan synthesis depends on the translocation of the lipid-linked precursor lipid II across the cytoplasmic membrane by the MurJ flippase. Structure-function analyses of MurJ from Thermosipho africanus (MurJTa) and Escherichia coli (MurJEc) have revealed that MurJ adopts multiple conformations and utilizes an alternating-access mechanism to flip lipid II. MurJEc activity relies on membrane potential, but the specific counterion has not been identified. Crystal structures of MurJTa revealed a chloride ion bound to the N-lobe of the flippase and a sodium ion in its C-lobe, but the role of these ions in transport is unknown. Here, we investigated the effect of various ions on the function of MurJTa and MurJEc in vivo. We found that chloride, and not sodium, ions are necessary for MurJTa function, but neither ion is required for MurJEc function. We also showed that murJTa alleles encoding changes at the crystallographically identified sodium-binding site still complement the loss of native murJEc, although they decreased protein stability and/or function. Based on our data and previous work, we propose that chloride ions are necessary for the conformational change that resets MurJTa after lipid II translocation and suggest that MurJ orthologs may function similarly but differ in their requirements for counterions. IMPORTANCE The biosynthetic pathway of the peptidoglycan cell wall is one of the most favorable targets for antibiotic development. Lipid II, the lipid-linked PG precursor, is made in the inner leaflet of the cytoplasmic membrane and then transported by the MurJ flippase so that it can be used to build the peptidoglycan cell wall. MurJ functions using an alternating-access mechanism thought to depend on a yet-to-be-identified counterion. This study fills a gap in our understanding of MurJ's energy-coupling mechanism by showing that chloride ions are required for MurJ in some, but not all, organisms. Based on our data and prior studies, we propose that, while the general transport mechanism of MurJ may be conserved, its specific mechanistic details may differ across bacteria, as is common in transporters. These findings are important to understand MurJ function and its development as an antibiotic target.

SARS-CoV-2 Omicron Variant Genomic Sequences and Their Epidemiological Correlates Regarding the End of the Pandemic: In Silico Analysis.

Background: Emergence of the new SARS-CoV-2 variant B.1.1.529 worried health policy makers worldwide due to a large number of mutations in its genomic sequence, especially in the spike protein region. The World Health Organization (WHO) designated this variant as a global variant of concern (VOC), which was named "Omicron." Following Omicron's emergence, a surge of new COVID-19 cases was reported globally, primarily in South Africa. Objective: The aim of this study was to understand whether Omicron had an epidemiological advantage over existing variants. Methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on the Global Initiative on Sharing Avian Influenza Data (GISAID) database to analyze the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period from October 1 to November 29, 2021) with matched epidemiological data (new COVID-19 cases and deaths) from South Africa. Results: Compared with the current list of global VOCs/variants of interest (VOIs), as per the WHO, Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with the Alpha variant for the complete sequence and the RBM. The mutations were found to be primarily condensed in the spike region (n=28-48) of the virus. Further mutational analysis showed enrichment for the mutations decreasing binding affinity to angiotensin-converting enzyme 2 receptor and receptor-binding domain protein expression, and for increasing the propensity of immune escape. An inverse correlation of Omicron with the Delta variant was noted (r=-0.99, P<.001; 95% CI -0.99 to -0.97) in the sequences reported from South Africa postemergence of the new variant, subsequently showing a decrease. There was a steep rise in new COVID-19 cases in parallel with the increase in the proportion of Omicron isolates since the report of the first case (74%-100%). By contrast, the incidence of new deaths did not increase (r=-0.04, P>.05; 95% CI -0.52 to 0.58). Conclusions: In silico analysis of viral genomic sequences suggests that the Omicron variant has more remarkable immune-escape ability than existing VOCs/VOIs, including Delta, but reduced virulence/lethality than other reported variants. The higher power for immune escape for Omicron was a likely reason for the resurgence in COVID-19 cases and its rapid rise as the globally dominant strain. Being more infectious but less lethal than the existing variants, Omicron could have plausibly led to widespread unnoticed new, repeated, and vaccine breakthrough infections, raising the population-level immunity barrier against the emergence of new lethal variants. The Omicron variant could have thus paved the way for the end of the pandemic.

COVID-19 vaccination may enhance hippocampal neurogenesis in adults.

Emerging evidence suggests a detrimental impact of COVID-19 illness on the continued hippocampal neurogenesis in adults. In contrast, the existing literature supports an enhancing effect of COVID-19 vaccination on adult hippocampal neurogenesis. Vaccines against respiratory infections, including influenza, have been shown to enhance hippocampal neurogenesis in adult-age animals. We propose that a similar benefit may happen in COVID-19 vaccinated adults. The vaccine-induced enhancement of the hippocampal neurogenesis in adults thus may protect against age-related cognitive decline and mental disorders. It alsohints at an added mental health benefit of the COVID-19 vaccination programs in adults.

Synthesis of tetracyclic 4H-benzo[5,6]chromeno[3,4-d]oxazoles via palladium-catalyzed intramolecular direct heteroarylation.

We report a palladium-catalyzed intramolecular direct heteroarylation of oxazole tethered ß-naphthols to access corresponding tetracyclic 4H-benzo[5,6]chromeno[3,4-d]oxazoles. Various functional groups are well tolerated and furnished the desired products in good to excellent yields under the present reaction conditions. The scale-up reaction and synthetic utility of the resulting molecules have been demonstrated. Moreover, UV/vis absorption and fluorescence emission properties have been evaluated for these polyheterocyclic compounds.

Flow cytometric measurable residual disease in adult acute myeloid leukemia: a preliminary report from Eastern India.

Presence of measurable residual disease (MRD) in acute myeloid leukemia (AML) is considered to be an independent predictor of relapse and poorer survival outcomes. MRD can be measured by flow cytometric, quantitative PCR, and NGS-based assays at varying sensitivities. There is scant Indian data on different aspects of MFC-MRD in AML including analysis strategies as well as molecular spectrum, clinical correlation, etc. This retrospective observational study included all newly diagnosed patients of acute myeloid leukemia in whom complete baseline diagnostic workup was available including flow cytometry and cytogenetic and molecular studies. Among patients with cytogenetic abnormalities (n = 25), no statistically significant correlation was observed between flow cytometric MRD positivity and presence of ≥ 3 mutations as well as relapsed disease. However, in AML patients with normal karyotype (n = 32), MRD positivity correlated strongly with relapsed status (p = 0.02), although no significant correlation was found with respect to FLT3 mutation, IDH mutation, NPM1 mutation, or complex genotype. Interestingly, 90.5% of MRD-positive patients belonged to ELN (2017) intermediate to high-risk category unlike only 9.5% in the good risk category (p = 0.0002). Median relapse-free survival was 8.5 months with a follow-up range of 3-24 months. On the basis of the observations of the present study, it can be clearly inferred that MRD status affects relapse status in the normal karyotype subgroup and can delineate patients who require stem cell transplantation in addition to molecular signatures.

Impact of COVID-19 vaccination: a global perspective.

Introduction: The COVID-19 pandemic has caused widespread morbidity, mortality, and socio-economic disruptions worldwide. Vaccination has proven to be a crucial strategy in controlling the spread of the virus and mitigating its impact. Objective: The study focuses on assessing the effectiveness of COVID-19 vaccination in reducing the incidence of positive cases, hospitalizations, and ICU admissions. The presented study is focused on the COVID-19 fully vaccinated population by considering the data from the first positive case reported until 20 September 2021. Methods: Using data from multiple countries, time series analysis is deployed to investigate the variations in the COVID-19 positivity rates, hospitalization rates, and ICU requirements after successful vaccination campaigns at the country scale. Results: Analysis of the COVID-19 positivity rates revealed a substantial decline in countries with high pre-vaccination rates. Within 1-3 months of vaccination campaigns, these rates decreased by 20-44%. However, certain countries experienced an increase in positivity rates with the emergence of the new Delta variant, emphasizing the importance of ongoing monitoring and adaptable vaccination strategies. Similarly, the analysis of hospitalization rates demonstrated a steady decline as vaccination drive rates rose in various countries. Within 90 days of vaccination, several countries achieved hospitalization rates below 200 per million. However, a slight increase in hospitalizations was observed in some countries after 180 days of vaccination, underscoring the need for continued vigilance. Furthermore, the ICU patient rates decreased as vaccination rates increased across most countries. Within 120 days, several countries achieved an ICU patient rate of 20 per million, highlighting the effectiveness of vaccination in preventing severe cases requiring intensive care. Conclusion: COVID-19 vaccination has proven to be very much effective in reducing the incidence of cases, hospitalizations, and ICU admissions. However, ongoing surveillance, variant monitoring, and adaptive vaccination strategies are crucial for maximizing the benefits of vaccination and effectively controlling the spread of the virus.

Bronchiectasis without lower respiratory symptoms in the presence of multisystem anomalies - a clinical clue to diagnose esophageal lung anomaly.

Esophageal lung is a type of Group-II communicating bronchopulmonary foregut malformations (CBPFM) usually diagnosed beyond neonatal period during investigation for recurrent respiratory symptoms and persistent radiographic features suggesting pneumonia or bronchiectasis. In our case, we noticed bronchiectasis and disproportionately severe volume loss in an infant with associated multisystem anomalies in the absence of "significant" lower respiratory tract symptoms. A detailed evaluation with repeat imaging confirmed a Group-II CBPFM, a congenital pathology instead of an infective cause. Pneumonectomy is a more prudent option instead of undertaking major airway reconstruction for the dysplastic "dysfunctional" tissue. Amongst the various associated anomalies reported till now, the associated rib and renal anomalies noted by us have not been described earlier to the best of our knowledge.

Prognostic Role of Interim 18-Fluorodeoxyglucose-PET in Diffuse Large B Cell Lymphoma: Experience from a Tertiary Care Centre in North India.

This study was done to investigate the role of Interim 18-FDG-PET/CT (i-PET) in predicting the outcome of Diffuse Large B Cell Lymphoma (DLBCL) patients. The Lymphoma registry data base of the Department of Haematology was reviewed for all newly diagnosed DLBCL patients treated with R-CHOP-21 (n = 63). The PET-CT data of these patients at pre-defined time points (baseline, interim and end of treatment) was systematically collected. The predictive accuracy of i-PET-CT (done after 4 cycles R-CHOP-21 chemotherapy) was analysed to define their prognostic importance. 47 patients were eligible for final analysis in this study. According to Deauville's criteria 15 patients (31%) were positive on i-PET. The positive predictive value (PPV) of i-PET by DS was 73.3%. At a median follow up of 21 months, DS based i-PET negative and positive cases showed significant differences in 2-year OS (81.2% vs 46.7%, p = 0.007) and PFS (75% vs 26.7%, p = 0.005). Combined analysis of i-PET (by DS) and IPI showed negative predictive value (NPV) of 92.3% in Low IPI while PPV of 76.9% in high IPI subgroup of DLBCL. On a multivariate analysis of all prognostic variables, i-PET was found to be independent prognostic marker predicting outcome in DLBCL patients. i-PET is an independent prognostic marker for outcome in DLBCL patients. Combined analysis of Interim PET along with IPI score at diagnosis improves the predictive accuracy of i-PET (both PPV & NPV) and may guide tailoring of therapy in these patients.

Deciphering the Role of S-adenosyl Homocysteine Nucleosidase in Quorum Sensing Mediated Biofilm Formation.

S-adenosylhomocysteine nucleosidase (MTAN) is a protein that plays a crucial role in several pathways of bacteria that are essential for its survival and pathogenesis. In addition to the role of MTAN in methyl-transfer reactions, methionine biosynthesis, and polyamine synthesis, MTAN is also involved in bacterial quorum sensing (QS). In QS, chemical signaling autoinducer (AI) secreted by bacteria assists cell to cell communication and is regulated in a cell density-dependent manner. They play a significant role in the formation of bacterial biofilm. MTAN plays a major role in the synthesis of these autoinducers. Signaling molecules secreted by bacteria, i.e., AI-1 are recognized as acylated homoserine lactones (AHL) that function as signaling molecules within bacteria. QS enables bacteria to establish physical interactions leading to biofilm formation. The formation of biofilm is a primary reason for the development of multidrug-resistant properties in pathogenic bacteria like Enterococcus faecalis (E. faecalis). In this regard, inhibition of E. faecalis MTAN (EfMTAN) will block the QS and alter the bacterial biofilm formation. In addition to this, it will also block methionine biosynthesis and many other critical metabolic processes. It should also be noted that inhibition of EfMTAN will not have any effect on human beings as this enzyme is not present in humans. This review provides a comprehensive overview of the structural-functional relationship of MTAN. We have also highlighted the current status, enigmas that warrant further studies, and the prospects for identifying potential inhibitors of EfMTAN for the treatment of E. faecalis infections. In addition to this, we have also reported structural studies of EfMTAN using homology modeling and highlighted the putative binding sites of the protein.

Low expression of TMPRSS2-a SARS-CoV-2 internalization protease-associates with basal subtype of head and neck squamous cell carcinoma.

SARS-CoV-2 is a single-stranded RNA virus that has caused the ongoing COVID-19 pandemic. ACE2 and other genes utilized by SARS-CoV-2 to enter human cells have been shown to express in Head and Neck Squamous Cell Carcinoma (HNSCC) patients. However, their expression pattern in different subtypes has not been investigated. Hence, in the current study, we have analyzed the expression of ACE2, TMPRSS2 and FURIN in 649 HNSCC patients from two independent cohorts. Our analysis showed significantly lower expression of TMPRSS2 while significantly increased expression of ACE2 and FURIN in HPV-negative HNSCC. Comparison of expression of these genes in the three subtypes of HNSCC patients (basal, classical and inflamed/mesenchymal) showed no significant difference in the expression of ACE2 among the three subtypes; however, the basal subtype showed significantly reduced expression of TMPRSS2 but significantly increased expression of FURIN. Comparison of expression of these genes between the HPV-negative patients of basal subtype vs all others confirmed significantly lower expression of TMPRSS2 in HPV-negative patients of basal subtype as compared to all others. Our study shows that the different subtypes of HNSCC patients have different expression patterns of genes utilized by the SARS-CoV-2 to enter human cells, and hence, their susceptibility to SARS-CoV-2 may also be different. As the expression of TMPRSS2 is significantly lower in the HNSCC patients of the basal subtype, we predict that these patients would be less susceptible to SARS-CoV-2 infection than the patients of other subtypes. However, these findings need to be further validated.

Therapeutic approaches for the treatment of head and neck squamous cell carcinoma-An update on clinical trials.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common non-skin cancer with a tobacco consumption and infection with high-risk human papillomavirus (HPV) being major risk factors. Despite advances in numerous therapy modalities, survival rates for HNSCC have not improved considerably; a vast number of clinical outcomes have demonstrated that a combination strategy (the most well-known docetaxel, cisplatin, and 5-fluorouracil) is the most effective treatment choice. Immunotherapy that targets immunological checkpoints is being tested in a number of clinical trials, either alone or in conjunction with chemotherapeutic or targeted therapeutic drugs. Various monoclonal antibodies, such as cetuximab and bevacizumab, which target the EGFR and VEGFR, respectively, as well as other signaling pathway inhibitors, such as temsirolimus and rapamycin, are also being studied for the treatment of HNSCC. We have reviewed the primary targets in active clinical studies in this study, with a particular focus on the medications and drug targets used.