Signal transducer and activator of transcription-3 (STAT-3) mediated signalling in relation to upregulated collagen expression in fibroblasts is well defined during cardiac hypertrophy. Recent findings from our laboratory have identified Heat shock protein 90 (Hsp90) as a critical modulator of fibrotic signalling in cardiac fibroblasts in this disease milieu. The present study was therefore intended to analyze the role of Hsp90 in the STAT-3 mediated collagen upregulation process. Our data revealed a significant difference between in vivo and in vitro results pointing to a possible involvement of myocyte-fibroblast crosstalk in this process. Cardiomyocyte targeted knockdown of Hsp90 in renal artery ligated rats (Rattus norvegicus) showed downregulated collagen synthesis. Furthermore, cardiac fibroblasts conditioned with Hsp90 inhibited hypertrophied myocyte supernatant pointed towards cardiomyocytes' role in regulation of collagen expression in fibroblasts during hypertrophy. Our study also revealed a novel signalling mechanism where myocyte derived Hsp90 not only orchestrates p65 mediated Interleukin-6 (IL-6) synthesis but also its release in exosomal vesicles. Such myocyte derived exosomes along with myocyte secreted IL-6 are responsible in unison for the biphasic activation of STAT-3 signalling in cardiac fibroblasts that culminates in excess collagen synthesis leading to severely compromised cardiac function during cardiac hypertrophy.

Influenza A virus (IAV) poses a global threat worldwide causing pandemics, epidemics, and seasonal outbreaks. Annual modification of vaccines is costly due to continual shifts in circulating genotypes, leading to inadequate coverage in low- and middle-income countries like India. Additionally, IAVs are evolving resistance to approved antivirals, necessitating a search for alternative treatments. In this study, the antiviral role of the FDA-approved antibiotic minocycline against IAV strains was evaluated in vitro and in vivo by quantifying viral gene expression by qRT-PCR, viral protein levels by Western blotting, and viral titers. Our findings demonstrate that minocycline at a non-toxic dose effectively inhibits IAV replication, regardless of viral strain or cell line. Its antiviral mechanism operates independently of interferon signaling by targeting the MEK/ERK signaling pathway, which is crucial for the export of viral ribonucleoproteins (vRNPs). Minocycline prevents the assembly and release of infectious viral particles by causing the accumulation of vRNPs within the nucleus. Moreover, minocycline also inhibits IAV-induced late-stage apoptosis, further suppressing viral propagation. The antiviral activity of minocycline against IAVs could offer a promising solution amidst the challenges posed by influenza and the limitations of current treatments.