Serum lipid peroxidation potential as a biomarker for risk-stratification of coronary artery disease in patients with type 2 diabetes mellitus.

Aim: We examined the serum lipid peroxidation potential as an estimate of systemic oxidative stress levels in people with type 2 diabetes (T2D) for coronary artery disease (CAD) risk stratification.

Methods: We prospectively recruited patients and categorized them into four subgroups based on diabetes and severity of CAD [Gensini score <20, non-significant CAD; Gensini score >20, significant CAD]: non-diabetics with non-significant CAD, diabetics with non-significant CAD, non-diabetics with significant CAD and diabetics with significant CAD. Lipid profile, HbA1c, fasting blood glucose, and oxidized LDL were assessed.

Dysfunctional HDL Diagnostic Metrics for Cardiovascular Disease Risk Stratification: Are we Ready to Implement in Clinics?

Epidemiological studies have revealed that patients with higher levels of high-density lipoprotein cholesterol (HDL-C) were more resistant to cardiovascular diseases (CVD), and yet targeting HDL for CVD prevention, risk assessment, and pharmacological management has not proven to be very effective. The mechanistic investigations have demonstrated that HDL exerts anti-atherogenic functions via mediating reverse cholesterol transport, antioxidant action, anti-inflammatory activity, and anti-thrombotic activity. Contrary to expectations, however, adverse cardiovascular events were reported in clinical trials of drugs that raised HDL levels.

Dyslipidemia and hyperglycemia induce overexpression of Syndecan-3 in erythrocytes and modulate erythrocyte adhesion.

Erythrocytes are important vascular components that play vital roles in maintaining vascular homeostasis, in addition to carrying oxygen. Previously, we reported that the changes in the internal milieu (e.g.

Forced expression of microRNA-221-3p exerts protective effects against manganese-induced cytotoxicity in human lung epithelial cells.

Manganese (Mn)-induced pulmonary toxicity and the underlying molecular mechanisms remain largely enigmatic. Further, in recent years, microRNAs (miRNAs) have emerged as regulators of several pollutants-mediated toxicity. In this context, our study aimed at elucidating whether miRNAs are involved in manganese (II) chloride (MnCl) (Mn)-induced cytotoxicity in lung epithelial cells.

The effect of yoga on insomnia and quality of life among nursing professionals during COVID-19: A pre-post-test interventional study.

Background: The coronavirus disease 2019 (COVID-19) pandemic has taken a toll on the well-being and quality of life (QoL) of healthcare professionals, especially nurses. Insomnia, a common consequence of the pandemic, adds to the physical and mental strain on healthcare workers.

Aim: This study aimed to assess the impact of workplace yoga intervention on insomnia severity and QoL among female nursing and healthcare professionals during the pandemic.

Human papillomavirus-driven repression of NRF2 signalling confers chemo-radio sensitivity and predicts prognosis in head and neck squamous cell carcinoma.

Purpose: To investigate the role of NRF2 signalling in conferring superior prognosis in patients with HPV positive (HPV) head & neck squamous cell carcinomas (HNSCC) compared to HPV negative (HPV) HNSCC and develop molecular markers for selection of HPV HNSCC patients for treatment de-escalation trials.

Methods: NRF2 activity (NRF2, KEAP1, and NRF2-transcriptional targets), p16, and p53 levels between HPV HNSCC and HPV HNSCC in prospective and retrospective tumor samples as well as from TCGA database were compared. Cancer cells were transfected with HPV-E6/E7 plasmid to elucidate if HPV infection represses NRF2 activity and sensitizes to chemo-radiotherapy.

Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids.

Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-induced alveolar type II organoids (hiAT2). hiAT2 organoids were susceptible to infection by both viruses and had features of severe lung damage.

Development of as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems.

Pharmacological activation of nuclear factor erythroid 2 related factor 2 (NRF2) provides protection against several environmental diseases by inhibiting oxidative and inflammatory injury. Besides high in protein and minerals, leaves contain several bioactive compounds, predominantly isothiocyanate moringin and polyphenols, which are potent inducers of NRF2. Hence, leaves represent a valuable food source that could be developed as a functional food for targeting NRF2 signaling.

FMRP protects the lung from xenobiotic stress by facilitating the integrated stress response.

Stress response pathways protect the lung from the damaging effects of environmental toxicants. Here we investigate the role of the fragile X mental retardation protein (FMRP), a multifunctional protein implicated in stress responses, in the lung. We report that FMRP is expressed in murine and human lungs, in the airways and more broadly.

Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy.

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden.

Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses.

Using particulate matter (PM) mass as exposure metric does not reveal the intrinsic PM chemical characteristics or toxic potential, which is crucial for monitoring the sources of emission causing adverse health effects and developing risk mitigating strategies. Oxidative stress and ensuing lipid peroxidation (LPO) in the lung are crucial underlying mechanisms of action by which PM drives cardiorespiratory disease. In the current study, we have postulated and demonstrated that the intrinsic potential of PM to elicit LPO, defined as "LPO index" as a novel approach for characterizing oxidative potential of PM (PM) and predicting biological toxicity.

Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo.

Nuclear factor erythroid-2 related factor-2 (Nrf2) is an oxidative stress-response transcriptional activator that promotes carcinogenesis through metabolic reprogramming, tumor promoting inflammation, and therapeutic resistance. However, the extension of Nrf2 expression and its involvement in regulation of breast cancer (BC) responses to chemotherapy remain largely unclear. This study determined the expression of Nrf2 in BC tissues (n = 46) and cell lines (MDA-MB-453, MCF-7, MDA-MB-231, MDA-MB-468) with diverse phenotypes.

Antiviral, immunomodulatory, and anticoagulant effects of quercetin and its derivatives: Potential role in prevention and management of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a devastating health crisis worldwide. In this review, we have discussed that prophylactic phytochemical quercetin supplementation in the form of foods or nutraceuticals may help manage the COVID-19 pandemic. The following evidence supports our argument.

Circulating Secretoglobin Family 1A Member 1 (SCGB1A1) Levels as a Marker of Biomass Smoke Induced Chronic Obstructive Pulmonary Disease.

Secretoglobin family 1A member 1 (SCGB1A1) alternatively known as club cell protein 16 is a protective pneumo-protein. Decreased serum levels of SCGB1A1 have been associated with tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD). Exposure to biomass smoke (BMS) is an important COPD risk factor among women in low and lower-middle income countries.

Antiviral and immunomodulatory activity of curcumin: A case for prophylactic therapy for COVID-19.

Coronavirus disease-19 (COVID-19), a devastating respiratory illness caused by SARS-associated coronavirus-2 (SARS-CoV-2), has already affected over 64 million people and caused 1.48 million deaths, just 12 months from the first diagnosis. COVID-19 patients develop serious complications, including severe pneumonia, acute respiratory distress syndrome (ARDS), and or multiorgan failure due to exaggerated host immune response following infection.

Tannic acid alleviates experimental pulmonary fibrosis in mice by inhibiting inflammatory response and fibrotic process.

Pulmonary fibrosis (PF) is a chronic and irreversible scarring disease in the lung with limited treatment options. Therefore, it is critical to identify new therapeutic options. This study was undertaken to identify the effects of tannic acid (TA), a naturally occurring dietary polyphenol, in a mouse model of PF.

NRF2, p53, and p16: Predictive biomarkers to stratify human papillomavirus associated head and neck cancer patients for de-escalation of cancer therapy.

Patients with HPV associated (HPV) head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal cancer, show better treatment response, higher survival rates, and lower risks of recurrence as compared to HPV HNSCC patients. Despite increased sensitivity to treatment modality, HPV HNSCC patients are subjected to the same intensive anti-cancer therapy as HPV HNSCC patients and thus subjecting them to unwarranted long-term toxicity. To identify predictive biomarkers for risk-stratification, we have analyzed the mutational spectrum, and the evidence suggests that gain-of-function mutations in the NRF2 pathway are highly prevalent in HPV HNSCC.

Drug Discovery Platform Targeting M. tuberculosis with Human Embryonic Stem Cell-Derived Macrophages.

A major limitation in anti-tuberculosis drug screening is the lack of reliable and scalable models for homogeneous human primary macrophage cells of non-cancer origin. Here we report a modified protocol for generating homogeneous populations of macrophage-like cells from human embryonic stem cells. The induced macrophages, referred to as iMACs, presented similar transcriptomic profiles and characteristic immunological features of classical macrophages and were permissive to viral and bacterial infection, in particular Mycobacterium tuberculosis (Mtb).

Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD.

Background: Patients with chronic obstructive pulmonary disease (COPD) have high oxidative stress associated with the severity of the disease. Nuclear factor erythroid-2 related factor 2 (Nrf2)-directed stress response plays a critical role in the protection of lung cells to oxidative stress by upregulating antioxidant genes in response to tobacco smoke. There is a critical gap in our knowledge about Nrf-2 regulated genes in active smokers and former-smokers with COPD in different cell types from of lungs and surrogate peripheral tissues.

Tannic acid protects against experimental acute lung injury through downregulation of TLR4 and MAPK.

Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) remain a major cause of morbidity and mortality in critically ill patients, and no specific therapies are still available to control the mortality rate. Thus, we explored the preventive and therapeutic effects of tannic acid (TA), a natural polyphenol in the context of ALI. We used in vivo and in vitro models, respectively, using lipopolysaccharide (LPS) to induce ALI in mice and exposing J774 and BEAS-2B cells to LPS.

Immunomodulators targeting MARCO expression improve resistance to postinfluenza bacterial pneumonia.

Downregulation of the alveolar macrophage (AM) receptor with collagenous structure (MARCO) leads to susceptibility to postinfluenza bacterial pneumonia, a major cause of morbidity and mortality. We sought to determine whether immunomodulation of MARCO could improve host defense and resistance to secondary bacterial pneumonia. RNAseq analysis identified a striking increase in MARCO expression between and after influenza infection and indicated important roles for Akt and Nrf2 in MARCO recovery.

Correction: Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pone.

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

Background: COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).

Methods: This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers.