Pattern-recognition receptors (PRRs) in SARS-CoV-2.

Pattern recognition receptors (PRRs) are specific sensors that directly recognize various molecules derived from viral or bacterial pathogens, senescent cells, damaged cells, and apoptotic cells. These sensors act as a bridge between nonspecific and specific immunity in humans. PRRs in human innate immunity were classified into six types: toll-like receptors (TLR), C-type lectin receptors (CLRs), nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and cyclic GMP-AMP (cGAMP) synthase (cGAS). Numerous types of PRRs are responsible for recognizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is immensely effective in prompting interferon responses. Detection of SARS-CoV-2 infection by PRRs causes the initiation of an intracellular signaling cascade and subsequently the activation of various transcription factors that stimulate the production of cytokines, chemokines, and other immune-related factors. Therefore, it seems that PRRs are a promising potential therapeutic approach for combating SARS-CoV-2 infection and other microbial infections. In this review, we have introduced the current knowledge of various PRRs and related signaling pathways in response to SARS-CoV-2.

Combination of nicotinamide mononucleotide and troxerutin induces full protection against doxorubicin-induced cardiotoxicity by modulating mitochondrial biogenesis and inflammatory response.

BACKGROUND: Clinical application of doxorubicin (DOX) is restricted due to its cardiotoxicity, reinforcing the significance of exploring new strategies to counteract DOX-induced cardiotoxicity. The present work aimed to investigate the ameliorative impact of combination therapy with nicotinamide mononucleotide (NMN) and troxerutin (TXR) on DOX-induced cardiotoxicity, with mitochondrial function/biogenesis and inflammatory response approach. METHODS: Male Wistar rats (n = 30, 250-300 g) were divided into groups with/without DOX and/or NMN and TXR, alone or in combination. Rats underwent 6 consecutive intraperitoneal injections of DOX (cumulative dose: 12 mg/kg). NMN (100 mg/kg/day; intraperitoneally) and/or TXR (150 mg/kg/day; orally) were administered for 28 days before DOX challenge. Seven days following the last injection of DOX, evaluation of cardiac histopathological changes, BNP and LDH levels, mitochondrial function (membrane potential, ROS generation, and ATP levels), expression of proteins involved in mitochondrial biogenesis (PGC-1α, NRF1, and TFAM), and inflammatory cytokines (TNF-α, IL-1ß, and IL-6) was performed. RESULTS: Combination of NMN and TXR significantly decreased the severity of histopathological damages, and BNP and LDH levels (P < 0.01 to P < 0.001). It also restored mitochondrial functional endpoints, and expression of proteins involved in mitochondrial biogenesis (P < 0.05 to P < 0.001), and decreased inflammatory cytokines (P < 0.01 to P < 0.001). The positive impacts of this combination therapy were more potent as compared to monotherapies. CONCLUSIONS: These findings shed new light on the understanding of additive properties of NMN/TXR combination therapy in protecting against DOX-induced cardiotoxicity. The cardioprotective effect of this combination therapy may be mediated in part through the restoration of mitochondrial function/biogenesis associated with the PGC-1α/NRF1/TFAM pathway, and suppression of inflammatory response.