cobramine (CB-6) / Celtic Biotech - LARVOL DELTA

Hypothyroidism impairs skeletal muscle regeneration after injury by altering myogenic and nonmyogenic pathways. (PubMed, JCI Insight) - "We used scRNA-seq and the FUCCI (fluorescent ubiquitination-based cell cycle indicator) reporter mouse model to examine how hypothyroidism impacts repair processes after cardiotoxin-induced injury in mice...Integrative regulon and ligand-receptor analysis further demonstrated that triiodothyronine acted through dual modes: a direct transcriptional control of myogenic cell cycle and oxidative programs and an indirect paracrine remodeling mediated by FAP and immune signaling networks. This study identified what we believe to be novel effects of hypothyroidism on myogenic heterogeneity and impaired tissue repair, offering insights into muscle-wasting mechanisms relevant to hypothyroidism-associated myopathy and sarcopenia."

Journal • Endocrine Disorders • Myositis • Sarcopenia • Targeted Protein Degradation

Injury-specific muscle regeneration: a computational blueprint for cellular and cytokine drivers. (PubMed, J R Soc Interface) - "Common in vivo injury models include cardiotoxin (CTX), freeze-induced (FI) and eccentric contraction (EC) injuries...These findings reveal distinct regeneration trajectories across injury models that differ in both mode and severity, highlighting potential molecular and cellular mechanisms that warrant further investigation. Our validated model provides a computational framework for future systematic exploration of how injury severity and other initial conditions independently influence regeneration outcomes, which could inform tailored therapeutic strategies in preclinical studies."

Journal • Oncology • CCL2 • HGF • TGFB1 • TNFA • VEGFA

Assessing the Potential Cardiovascular Risk of Microdosing the Psychedelic LSD in Mice. (PubMed, ACS Pharmacol Transl Sci) - "We calculated that levels of 5-HT2B activation by low-dose LSD were substantial, but short-lived, compared to the cardiotoxin d-fenfluramine. Together, these data provide no evidence of ventricular or valvular remodeling associated with prolonged administration of low-dose LSD in mice."

Journal • Preclinical • Cardiovascular • Heart Failure

Time of day of skeletal muscle injury is a factor in short and long term regeneration outcomes. (PubMed, Am J Physiol Cell Physiol) - "C57BL/6NCrl mice (n = 80) received bilateral cardiotoxin (CTX) injury to the tibialis anterior (TA) during either the rest phase (ZT2-ZT4) or active phase (ZT14-ZT16), with tissues collected at 7- or 42- days post-injury (DPI)...While there were notable differences in myosin isoform expression, such trends were observed at both 7 and 42 DPI, suggesting a specific morphological effect of injury timing. These findings indicate that the circadian phase at which skeletal muscle injury occurs causes persistent influence on the size distribution of regenerating myofibers, independent of functional recovery, and highlights the need to consider time-of-day and contribution of post-injury activity as a biological variable in muscle regeneration research."

Journal

Mustn1 ablation in male mice results in fiber type and gene expression alterations during skeletal muscle regeneration. (PubMed, Physiol Rep) - "To investigate Mustn1's role in muscle regeneration, we used these KO mice in a cardiotoxin (CTX)-induced tibialis anterior injury model...Lastly, expression of myogenic genes also differed significantly between the two strains. These data suggest that Mustn1 is integral to skeletal muscle fiber composition and myogenic gene expression thereby facilitating muscle repair and regeneration."

Journal • Preclinical • PAX7

LXR activation in skeletal muscle cells enhances differentiation and promotes protein synthesis. (PubMed, Am J Physiol Endocrinol Metab) - "Furthermore, gas chromatography-mass spectrometry (GC-MS) analyses revealed elevated levels of oxysterols, specifically 4β-hydroxycholesterol and 25-hydroxycholesterol, in response to muscle injury induced by cardiotoxin (CTX) or barium chloride (BaCl₂)...Importantly, LXR activation attenuates lipopolysaccharide (LPS)-induced inflammatory responses in myocytes and concurrently enhances anabolic signaling through the Akt-mTOR axis, leading to increased protein synthesis. Collectively, these findings highlight the previously underappreciated role of cholesterol-derived metabolites in coordinating muscle regeneration, suggesting that LXR-mediated transcriptional programs simultaneously govern differentiation, inflammation, and biosynthetic capacity in regenerating skeletal muscle."

Journal • Inflammation

CD47 Promotes, While Exposure to Apoptotic Cells Destroys the Fusion Program of Differentiating Myoblasts. (PubMed, FASEB J) - "The same was observed in differentiating myoblasts in vivo following cardiotoxin-induced injury in mouse skeletal muscle...Overall, our data show that differentiating myoblasts upregulate CD47 to avoid accidental phagocytosis of live cells but mainly to promote myoblast fusion. Therefore, the activity of this signaling pathway contributes to the decision-making between the two processes that would compete with each other during myoblast differentiation."

Journal • SIRPA

SMAD2 ubiquitination through PY motif regulates skeletal muscle mass and fibrotic degeneration. (PubMed, Sci Rep) - "Fibrotic tissue remodeling triggered by cardiotoxin injection was exacerbated in Smad2dPY mice. Altogether, our study identified SMAD2 ubiquitination through PY motif as an important regulatory mechanism operating in skeletal muscle tissue to maintain the TGFβ signaling pathway at the desired level in homeostasis and tissue remodeling."

Journal • Fibrosis • Immunology • Targeted Protein Degradation • NEDD4 • SMAD2

Hypobaric Hypoxia Ameliorates Impaired Regeneration After Diabetic Skeletal Muscle Injury by Promoting HIF-1α Signaling. (PubMed, Int J Mol Sci) - "To clarify these processes, adult male mice were divided into five groups: diabetes mellitus control (DM), cardiotoxin-injured (CTX) diabetes assessed on days 7 and 14 (CTX7, CTX14), and hypobaric-hypoxia-treated diabetic injury assessed on days 7 and 14 (H+CTX7, H+CTX14)...These findings suggest that hypobaric hypoxia modulates HIF-1α signaling, which in turn induces the VEGF-Kdr-eNOS pathway and the angiopoietin-Tie2-VE-cadherin pathway. Together, these pathways coordinate vascular remodeling and myogenic regeneration, ultimately improving the structural and functional recovery of diabetic muscle."

Journal • Diabetes • Fibrosis • Immunology • Metabolic Disorders • ANGPT1 • CD31 • CDH5 • EMCN • HIF1A • KDR • Myogenin • NOS3 • PECAM1

WDR62 is required for proper proliferation and early differentiation of skeletal myoblasts. (PubMed, Commun Biol) - "Following cardiotoxin injury to the tibialis anterior muscle, WDR62 deficient mice show normal satellite cell activation, but display a higher percentage of immature myofibers at day 7 post injury, suggesting premature differentiation...In C2C12 mouse myoblasts, WDR62 loss leads to decreased myoblast proliferation due to increased centriole numbers and centriole cohesion, and a slight increase in myoblast fusion at day 3 differentiation, which supports premature differentiation. These data implicate WDR62 in maintaining centrosome integrity that is critical for myoblast proliferation and preventing premature differentiation during early stages of myogenesis."

Journal • WDR62

Impact of obesity and an obesogenic environment on cardiotoxin-induced damage and recovery of human myotubes. (PubMed, Exp Physiol) - "Expressed as recovery (3D-IP) post-CTX, Ob-GM lowered total nuclei and FI in myotubes without differences between LN and OB. In human myotubes, impaired formation and recovery following damage in obesity appear primarily due to the obesogenic environment rather than inherent, individual differences."

Journal • Genetic Disorders • Obesity • Oncology

What Do Single-Cell Models Already Know About Perturbations? (PubMed, Genes (Basel)) - " Gradient flows recover known transitions in Irf8 knockout microglia, cardiotoxin-treated muscle, and worm embryogenesis. In the pretrained Census model, gradients help identify pathways with stronger statistical support and higher type 2 diabetes relevance than an average expression baseline. Trained single-cell decoders already contain rich perturbation-relevant information that can be accessed by automatic differentiation, enabling in-silico perturbation simulations and principled ranking of genes along observed disease or treatment axes without bespoke architectures or perturbation labels."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • IRF8

Adenosine Triggers an ADK-Dependent Intracellular Signaling Pathway Interacts PFKFB3-Mediated Glycolytic Metabolism to Promote Newly Formed Myofibers Development. (PubMed, Int J Mol Sci) - "In this study, an intramuscular injection of cardiotoxin was used to induce a skeletal muscle injury model; satellite cells and C2C12 cells were employed...The results demonstrated that adenosine dynamically distributes between extracellular and intracellular through concentrative nucleoside transports or equilibrative nucleoside transporters, and it rapidly induces an ADK-dependent intracellular signaling pathway, which interacts with PFKFB3-mediated glycolytic metabolism to promote satellite cell activity, new myofiber formation, differentiation, and fusion, and eventually enhances skeletal muscle regeneration after injury stress. The remarkable endogenous regeneration capacity of skeletal muscle, which is regulated by adenosine-triggered intracellular signaling, presents a promising therapeutic strategy for treating muscle trauma and muscular dystrophies."

Journal • Inflammation • Muscular Dystrophy • Myositis • PFKFB3

Catalysis of Native Chemical Ligation and Expressed Protein Ligation by Alkylselenols. (PubMed, JACS Au) - "The utility of SeESNA was proved through the synthesis of the cardiotoxin A5, a snake venom peptide that contains eight cysteines, without orthogonal cysteine protection. Importantly, it has enabled expressed protein ligation under folding conditions with extraordinary speed, as shown with the Sonic Hedgehog and SUMO2 proteins. Thus, SeESNa is envisaged to have broad applicability in synthetic and semisynthetic protein chemistry."

Journal

Potent and durable gene modulation in heart and muscle with chemically defined lipophilic siRNAs. (PubMed, Nucleic Acids Res) - "As a proof of concept, MSTN inhibition with siRNAs successfully combated muscle wasting in an inflammatory myopathy model (cardiotoxin). These findings pave the way for long-lasting gene modulation in heart and muscle, offering new therapeutic strategies for muscular diseases."

Journal • Myositis

TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling. (PubMed, Cell Death Dis) - "In cultured myofibre, MuSCs express TRPV2 and exhibit Ca2+ responses to the TRPV2 agonists 2-aminoethoxydiphenyl borate and probenecid, which are abolished upon TRPV2 deletion...Muscle-administered cardiotoxin promoted muscle regeneration and resulted in the appearance of numerous Pax7-positive MuSCs between myofibres...Additionally, MuSCs exhibit Ca2+ responses to hypo-osmotic stimuli, which are suppressed by TRPV2 inhibitors and TRPV2 deletion, suggesting that MuSCs exhibit TRPV2-dependent mechanical responses. These results establish TRPV2 as a critical regulator of MuSC-mediated muscle remodelling, an important finding that may lead to therapeutic strategies for muscle repair and adaptation."

Journal • IGF1 • PAX7 • TRPV2

Effects of subject motion and acquisition time on cone-beam CT-guided adaptive therapy for novel 6 second fast scanning protocols. (PubMed, Med Phys) - "CB-16.6 and CB-6 provided high-quality images for ART. Compared to FB-0.5, fast CBCT exhibited increased blurring and streaking but significantly less geometric distortion with increasing motion, leading to reduced dose delivery error in a simulated ART workflow. The complex 3D motion phantom study supported trends observed in the 1D translational phantom study. Faster CBCT (6 vs. 16.6 s) reduced blur, improving auto-contouring performance for both periodic and non-periodic motions, but the interplay between the motion period and 6 s image acquisition must be carefully managed."

Journal

Iron Deficiency Impairs Muscle Stem Cell Proliferation and Skeletal Muscle Regeneration via HIF-2α Stabilization. (PubMed, J Cachexia Sarcopenia Muscle) - "Iron deficiency impairs skeletal muscle regeneration by stabilizing HIF-2α in MuSC, inducing Rb1 RNA expression, and repressing E2F-dependent proliferation. Transient HIF-2α inhibition rescues MuSC proliferation and muscle repair under iron-deficient conditions, highlighting HIF-2α as a potential therapeutic target to counteract sarcopenia in aging and chronic diseases."

Journal • Eye Cancer • Hematological Disorders • Oncology • Retinal Disorders • Sarcopenia • Solid Tumor • EPAS1 • RB1

Indian cobra (Naja naja) venom-induced neutrophil extracellular trap (NET) formation: The role of cytotoxins and calcium flux. (PubMed, Br J Pharmacol) - "This study identified N. naja venom cytotoxins/cardiotoxins of the 3FTx family as key inducers of NETs. The NET-forming mechanism involves a cytosolic Ca2+ spike, resulting in cytoskeletal rearrangements, highlighting potential therapeutic targets for mitigating venom-induced pathologies."

Journal

Mitochondria transplantation mitigates attenuation of muscle fiber regeneration by evoked contractions. (PubMed, Am J Physiol Cell Physiol) - "Cardiotoxin (CTX) was injected into the tibialis anterior (TA) muscle of one limb of C57BL/6 mice at 8-12 weeks of age to induce muscle injury...The percentage of collagen and other non-contractile tissue was elevated in CTX-injured and EC treated muscles; however, MT reduced fibrosis/non-contractile tissue deposition in regenerating muscles. Our results provide evidence that systemic mitochondria delivery can improve muscle repair and can attenuate contraction-suppressed muscle fiber regeneration during recovery after injury."

Journal • Fibrosis • Immunology • Transplantation

Cardioprotective potential of sulfated glycosaminoglycan from Amphioctopus marginatus against cardiotoxin-induced toxicity in human iPSC-derived cardiomyocytes. (PubMed, Int J Biol Macromol) - "Additionally, AMP-3 promoted a notable increase in 3D cardiosphere diameter (273 μm), comparable to the standard drug liraglutide (290 μm), and reduced intracellular [Ca2+] levels by 98.6 %, restoring calcium homeostasis. The structure-activity correlations revealed that higher uronic acid content (⁓23 %), sulfation (⁓10 %) and (1→3) β-glycosidic linkages with C-3 sulfation at β-GlcNAcp in AMP-3 contributed to its prospective cardioprotective effects, as further confirmed by ADME studies. These findings suggest that AMP-3 represents a promising bioactive lead with strong cardioprotective potential and offers a multifaceted therapeutic approach for improving cardiovascular health."

Journal • Cardiovascular

Clonal Hematopoiesis Associated with Trp53 and Dnmt3a Mutations Promotes Tissue Repair in Acute Cardiovascular Diseases (AHA 2025) - "Acute CVD models—including myocardial infarction (MI, via left anterior descending artery ligation), hind limb ischemia (HLI, via femoral artery ligation), and cardiotoxin (CTX)-induced muscle injury—were evaluated for functional and histological repair using echocardiography, histology, and fibrosis quantification... DNMT3A- and TP53-driven CH promotes cardiac repair following MI through macrophage-mediated angiogenesis and myocyte regeneration. These findings reveal a novel E2F–VEGF axis in mutant macrophages as a key driver of post-ischemic recovery and suggest that engineered macrophages bearing CH-associated mutations may offer a promising therapeutic strategy for ischemic heart and limb disease."

Cardiovascular • Fibrosis • Hematological Disorders • Immunology • Myocardial Infarction • DNMT3A • TP53

Tofogliflozin ameliorates cardiotoxin induced skeletal muscle injury and fibrosis in obesity. (PubMed, Sci Rep) - "Tofo activates fibro-adipogenic progenitors (FAPs) in skeletal muscle, leading to upregulated follistatin (Fst) expression and boosting the recovery process after acute injury. Mechanistically, Tofo prevented the obesity-induced decline in AMPK phosphorylation, rescued the impairment of lipid metabolism, and improved skeletal muscle function, which led to increased exercise tolerance, activation of FAPs, facilitation of skeletal muscle repair, and reduction of fibrosis."

Journal • Diabetes • Fibrosis • Genetic Disorders • Immunology • Inflammation • Metabolic Disorders • Obesity • AMPK • Myogenin • PAX7

The role of sestrin2 in skeletal muscle regeneration after injury. (PubMed, Korean J Physiol Pharmacol) - "Intriguingly, Sesn2-knockout mice developed normally under basal conditions but exhibited regenerative defects, characterized by prolonged inflammation, necrosis, and delayed muscle regeneration, following cardiotoxininduced injury. Transcriptomic analysis of Sesn2 transgenic mice further supported this conditional role, revealing that genes involved in mitochondrial function and myogenesis were preferentially upregulated under immobilized conditions compared to basal conditions. These findings underscore that the context-dependent role of Sesn2 is essential for effective muscle regeneration under injury, positioning it as a potential therapeutic target for degenerative muscle diseases."

Journal • Inflammation • Muscular Atrophy • SESN2

High-Dose Insulin for Calcium Channel-Blocker and Beta-Blocker Poisoning in Children: Referrals to the Minnesota Regional Poison Center, 2000-2024. (PubMed, Pediatr Crit Care Med) - "In our three-state poison center, over a 25-year period (2000-2024), HDI was predominantly used in adolescents with intentional BB/CCB overdoses. No adverse events required early discontinuation of HDI. Escalation to ECMO support was rare. More experience is needed to evaluate the safety and effectiveness of HDI in small children."

Journal • Cardiovascular • Pediatrics