Prac
Hydroxychloroquine attenuates sepsis-induced acute respiratory distress syndrome in rats
https://x.com/Scorcher78/status/2067405187535323232
https://pmc.ncbi.nlm.nih.gov/articles/PMC11331349/
Hydroxychloroquine (HCQ) demonstrates therapeutic efficacy in a rat model of sepsis-induced acute respiratory distress syndrome (ARDS) through pleiotropic immunomodulatory, anti-inflammatory, and antioxidant mechanisms. In this preclinical model, HCQ significantly improved arterial oxygenation (elevated PaO₂), reduced hypercapnia (decreased PaCO₂), and attenuated lactic acidosis—parameters critical in the hemodynamic assessment and management of septic patients. At the cellular level, HCQ functioned as a lysosomal autophagy inhibitor, thereby mitigating pathogen-induced cytokine storm and endothelial hyperpermeability; notably, post-exposure administration enhanced bacterial clearance while concomitantly reducing vascular leakage. The agent suppressed key pro-inflammatory mediators, specifically tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), via intracellular alkalinization and inhibition of lysosomal proteolysis in antigen-presenting cells. This cascade limited major histocompatibility complex (MHC) class II-dependent antigen presentation to T lymphocytes, attenuating T-cell and B-cell activation, differentiation, and downstream cytokine expression. Additionally, HCQ reduced systemic oxidative stress, as evidenced by decreased malondialdehyde (MDA) concentrations, a surrogate marker of lipid peroxidation. Histopathologically, treatment correlated with reduced leukocytic infiltration, perivascular and interstitial edema, alveolar hemorrhage, hyaline membrane deposition, and alveolar congestion—findings consistent with preserved pulmonary microarchitecture. Collectively, these mechanisms position HCQ as a promising candidate for further investigation in sepsis-induced ARDS, though translation to clinical practice necessitates prospective human clinical trials, as these findings are derived exclusively from experimental animal studies.
Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model
https://x.com/Scorcher78/status/2067402442551992643
https://x.com/Scorcher78/status/2067406208567230713
New Applications of Old Drugs as Novel Therapies in Idiopathic Pulmonary Fibrosis. Metformin, Hydroxychloroquine, and Thyroid Hormone
https://pmc.ncbi.nlm.nih.gov/articles/PMC7051474/
https://x.com/Scorcher78/status/2067407399607017660
Hydroxychloroquine (HCQ), originally developed as an antimalarial agent and now widely used to manage autoimmune disorders, has emerged as a potential antifibrotic therapy. Prior research has shown that HCQ can suppress fibroblast activation in fibrotic skin conditions, and more recent evidence indicates it may slow disease progression in pediatric interstitial lung disease.
In a novel approach, Liu and colleagues developed a cholesterol-modified variant of HCQ (Chol-HCQ) specifically for treating pulmonary fibrosis. The cholesterol modification enables the drug to anchor to cell membranes, which extends its half-life, allows for lower dosing, and minimizes adverse effects. The researchers encapsulated Chol-HCQ into liposome-based nanocarriers and administered them intravenously to rats with bleomycin-induced lung injury.
The results demonstrated multiple therapeutic benefits. Chol-HCQ suppressed the proliferation of lung fibroblasts by blocking Nf-κB and ERK1/2 signaling cascades. It also reduced pulmonary inflammation, evidenced by markedly decreased neutrophil infiltration in lung tissue. Furthermore, the treatment substantially lessened lung fibrosis by downregulating connective tissue growth factor (CTGF) and ERK1/2 activity. Additionally, Chol-HCQ lowered levels of TNF-α—a cytokine linked to rapidly advancing pulmonary fibrosis—in both lung macrophages and blood plasma. Importantly, comprehensive serologic and pathologic assessments showed no significant organ toxicity from the treatment.
This study represents the first demonstration of HCQ's mechanistic antifibrotic action in the lung and establishes a foundation for future clinical translation of Chol-HCQ in humans. Both cholesterol modification and nanocarrier delivery systems have previously improved the pharmacokinetic profiles of chemotherapeutic agents. Given the long history of failed drug trials for idiopathic pulmonary fibrosis, advances in drug delivery are critical for maximizing therapeutic efficacy. The combination of cholesterol modification with nanocarrier technology offers a promising new strategy, especially for HCQ, which has a wide therapeutic window but carries a risk of toxic accumulation. Careful evaluation of its therapeutic index in an IPF-specific formulation will be essential for advancing to human trials—a principle also reflected in recent investigations of HCQ for childhood interstitial lung disease.
MIA×PUS rat model reveals developmental timing-dependent hippocampal reprogramming: prenatal immune activation ↑GluN1 protein & glycine; peripubertal stress ↑MAGL, shifts Grin2a/Grin2b ratio & enhances PPI intensity-dependently. Combined insults synergistically ↑taurine. GABA, glutamate, nNOS spared—targeted, not global, disruption.
https://www.biorxiv.org/content/10.64898/2026.06.13.732070v1.full.pdf
https://x.com/Scorcher78/status/2066925583372579322
Surveillance bias, since vaccinated children were followed for a median of nearly three years compared to just fifteen months for unvaccinated children, giving far more time and opportunity for chronic conditions to be diagnosed.
Healthcare utilization bias, because vaccinated children had substantially more medical encounters where conditions could be detected.
Baseline imbalance, as the vaccinated group had higher rates of preterm birth and respiratory distress at birth, which independently increase risk for neurodevelopmental and chronic conditions.
Immature follow-up, since conditions like ADHD and asthma are typically diagnosed after age four or five, yet half of the unvaccinated cohort was only tracked to fifteen months, meaning the comparison groups were not observed through equivalent developmental windows.
https://x.com/Scorcher78/status/2065827800188121150
Relevant article could translate to Vaccine induced IgG4 and worse prognosis in pancreatic cancer….
https://x.com/Scorcher78/status/2060428543192953304/photo/1
Carcinogenic effects of long-term exposure from prenatal life to glyphosate and glyphosate-based herbicides in Sprague-Dawley rats
https://x.com/Scorcher78/status/2055338351146754350/photo/1
https://pubmed.ncbi.nlm.nih.gov/40490737/
https://x.com/Scorcher78/status/2052829461045731528
GLYPHOSATE
Ivermectin induces PAK1-mediated cytostatic autophagy in breast cancer
https://x.com/Scorcher78/status/2065166113994932687/photo/1
https://pmc.ncbi.nlm.nih.gov/articles/PMC5173258/
In breast cancer cells, ivermectin inhibits PAK1 expression, thereby shutting down AKT-mTOR signaling, a pathway that normally acts as a negative regulator of autophagy.
https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0326742>>24731007