COVID-19 is an evolving systemic inflammatory pandemic disease, predominantly affecting the respiratory system. Associated cardiovascular comorbid conditions result in severe to critical illness with mortality up to 14.8 % in octogenarians. The role of endothelial dysfunction in its pathogenesis has been proposed with laboratory and autopsy data, though initially it was thought of as only acute respiratory distress syndrome (ARDS). The current study on endothelial dysfunction in SARS CoV-2 infection highlights its pathophysiology through the effects of direct viral-induced endothelial injury, uncontrolled immune & inflammatory response, imbalanced coagulation homeostasis, and their interactions resulting in a vicious cycle aggravating the disease process. This review may provide further light on proper laboratory tests and therapeutic implications needed for better management of patients. The main objective of the study is to understand the pathophysiology of COVID-19 with respect to the role of endothelium so that more additional relevant treatment may be incorporated in the management protocol.
Supplementary figure 1: Hematoxylin and Eosin staining of rat kidney sections with. (a) 50 mg/kg bw Thymoquinone (Tq), (b) 100 mg/kg bw curcumin (Cur) showing no signs of toxicity in the kidney tissues.
Chronic obstructive pulmonary disease (COPD) is characterized by cigarette smoke‐induced emphysema. Herein, we demonstrate protective effects of Thymoquinone (Tq), an active constituent from Nigella sativa, against cigarette smoke extract (CSE)‐induced abnormalities in bronchial epithelial cells. Dose‐dependent reduction in cell viability was observed in BEAS‐2B cells when exposed to different CSE concentrations, which was significantly reversed by Tq evident by LDH release. Levels of SOD, CAT, GR, GSH, and mitochondrial membrane ATPases were significantly reduced upon CSE exposure, an event, again, antagonized in presence of Tq. Similarly, Tq treatment significantly blocked CSE‐induced 4HNE elevations. Further, Tq‐improved mitochondrial dysfunction caused by CSE and significantly decreased autophagy/mitophagy markers like LC3II and p‐Drp. Tq also reduced necroptosis markers such as p‐MLKL, RIP‐1, and RIP‐3, by stabilizing PINK‐1 levels. In summary, Tq possesses protective properties against human bronchial epithelial cell autophagy/mitophagy‐dependent necroptosis caused by CSE, which warrants considerable attention for further preclinical evaluations. Practical applications This study demonstrates Thymoquinone (Tq), a natural plant extract to possess protective properties against human bronchial epithelial cell autophagy/mitophagy‐dependent necroptosis caused by cigarette smoke extract. The demonstrated efficacy of Tq will throw light for further preclinical evaluation of this molecule in CSE‐mediated complications. A detailed in vivo research is recommended.
Interleukin (IL)‐7 acts via the IL‐7 receptor in metastatic tumor progression in prostate cancer (PC). The current study aimed to evaluate thymoquinone (Tq), an active constituent from Nigella sativa against IL‐7–driven tumor progression and metastatic invasion in PC cells. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to assess the proliferation of PC cells. Enzyme‐linked immunosorbent assay was used to detect the expression of IL‐7 and matrix metalloproteinases (MMPs). Tumor‐cell transendothelial, scratch wound and cell scatter assays were performed to mimic metastasis. Western immunoblotting was used to measure the level of proteins. Tq effectively controlled the proliferation of DU‐145, PC‐3, and LNCaP cells with GI50 of 10.18, 12.40, and 16.78 µM, respectively. IL‐7 and IL‐7R were natively expressed in all PC types, while maximal expression was detected in DU‐145. IL‐7 promoted metastatic events, such as transendothelial migration, cell scatter, and cell invasion of DU‐145 cells in a dose‐dependent manner that was inhibited by Tq. Furthermore, Tq also downregulated p‐Akt and NF‐κB in DU‐145 cells induced by IL‐7 antibody and reduced the levels of MMP‐3 and MMP‐7 in these cells in a dose‐dependent manner. Collectively, Tq has excellent efficacy in controlling tumor progression, migration, and invasion of DU‐145 cells that were driven by the activation of MMPs through IL‐7/Akt/NF‐κB signaling.
Background The etiology of prostate cancer (PCa) is multiple and complex. Among the causes recently cited are chronic infections engendered by microorganisms that often go unnoticed. A typical illustration of such a case is infection due to mollicutes bacteria. Generally known by their lurking nature, urogenital mollicutes are the most incriminated in PCa. This study was thus carried out in an attempt to establish the presence of these mollicutes by PCR in biopsies of confirmed PCa patients and to evaluate their prevalence. Methods A total of 105 Formalin-Fixed Paraffin-Embedded prostate tissues collected from 50 patients suffering from PCa and 55 with benign prostate hyperplasia were subjected to PCR amplification targeting species-specific genes of 5 urogenital mollicutes species, Mycoplasma genitalium, M. hominis, M. fermentans, Ureaplasma parvum, and U. urealyticum. PCR products were then sequenced to confirm species identification. Results significance was statistically assessed using Chi-square and Odds ratio tests. Results PCR amplification showed no positive results for M. genitalium, M. hominis, and M. fermentans in all tested patients. Strikingly, Ureaplasma spp. were detected among 30% (15/50) of PCa patients. Nucleotide sequencing further confirmed the identified ureaplasma species, which were distributed as follows: 7 individuals with only U. parvum, 5 with only U. urealyticum, and 3 co-infection cases. Association of the two ureaplasma species with PCa cases proved statistically significant (P < 0.05), and found to represent a risk factor. Of note, Ureaplasma spp. were mostly identified in patients aged 60 and above with prostatic specific antigen (PSA) level > 4 ng/ml and an invasive malignant prostate tumor (Gleason score 8–10). Conclusions This study uncovered a significant association of Ureaplasma spp. with PCa arguing in favour of their potential involvement in this condition. Yet, this finding, though statistically supported, warrants a thorough investigation at a much larger scale.
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