Ziyuglycoside I Attenuates Deinagkistrodon acutus Venom–Induced Injury in Renal Tubular Epithelial Cells by Modulating PAR1–NLRP3–IL-1β Signaling

Posted by
  Ziyuglycoside I Attenuates Deinagkistrodon acutus Venom–Induced Injury in Renal Tubular Epithelial Cells by Modulating PAR1–NLRP3–IL-1β Signaling Abstract Introduction Sanguisorba officinalis L. ( Di Yu ) has traditionally been used for snakebite treatment. Ziyuglycoside I, a major bioactive constituent of Di Yu , exhibits anti-inflammatory activity, but its role in snake venom-associated renal injury remains unclear. This study aimed to investigate its potential protective effects against Deinagkistrodon acutus venom (DAV)-induced renal tubular epithelial cell injury in vitro. Methods HK-2 cells were exposed to DAV to establish an in vitro renal tubular epithelial injury model. Cellular metabolic activity and intracellular ATP levels were assessed using Cell Counting Kit-8 and CellTiter-Glo assays, respectively. DAV-induced molecular alterations were examined by transcriptomic sequencing, bioinformatic analysis, western blotting, and qRT-PCR. PAR1 knockdown and pharmacological...

Admission Point-of-Care D-Dimer for Identifying Haemostatic Envenomation After Snakebite: A Prospective Observational Study

Posted by

 


Admission Point-of-Care D-Dimer for Identifying Haemostatic Envenomation After Snakebite: A Prospective Observational Study

Abstract

Haemostatic envenomation (HE) — comprising venom-induced coagulopathy, thrombocytopenia, and systemic bleeding — is the principal determinant of snakebite morbidity in South Asia. Conventional coagulation tests lack sensitivity for early haemostatic activation; D-dimer has been proposed as a rapid triage biomarker, but data from Indian emergency settings are lacking. We conducted a prospective diagnostic accuracy study (JMMC&RI, Thrissur, Kerala; March–December 2022; n=96 consecutive snakebite patients). The primary aim was to evaluate the diagnostic accuracy of admission point of care D-dimer for identifying HE. Secondary aims were to compare its performance with standard coagulation tests and to evaluate it against the broader composite outcome — clinically significant envenomation (CSE). HE was defined as modified Lee–White clotting time (MLW) ≥15 min, failed 20-minute whole-blood clotting test (20WBCT), INR ≥1.4, fibrinogen <100 mg/dL, platelet count <100 ×109/L, or systemic haemotoxic bleeding. Comparators were MLW/20WBCT, prothrombin time, INR, aPTT, fibrinogen, and platelet count.
Thirty-three patients (34.4%) met HE criteria. At the Youden-optimal threshold of 620 ng/mL, D-dimer achieved sensitivity 87.9% (95% CI: 72.7–95.2%), specificity 79.0% (67.4–87.3%), PPV 69.0% (54.0–80.9%), NPV 92.5% (82.1–97.0%), LR+ 4.19, LR− 0.153, and accuracy 82.1% (73.2–88.5%). AUC was 0.874 (0.791–0.957) — highest among all comparators: MLW 0.763, WBCT 0.652, aPTT 0.544, fibrinogen 0.728, platelet count 0.681, INR 0.646, and PT 0.615. D-dimer ≥620 ng/mL was the strongest independent predictor of HE (OR 22.04; 95% CI: 6.13–79.25; p<0.001). Three of four patients with delayed coagulopathy had D-dimer ≥620 ng/mL at admission. Against the broader clinically significant envenomation (CSE) endpoint (n=52, 54.2%), AUC was 0.885 (0.816–0.954) at 139 ng/mL (sensitivity 88.2%, specificity 81.8%).
Admission D-dimer demonstrated higher discriminatory performance for HE than all standard coagulation comparators. Its NPV of 92.5% supports potential utility as a rapid rule-out biomarker. These findings are exploratory and require external validation before clinical implementation.
Mathew, D., Abraham, S. V., Paul, S., Rafi, A. M., Suseel, A., & Kassyap, C. (2026). Admission Point-of-Care D-Dimer for Identifying Haemostatic Envenomation After Snakebite: A Prospective Observational Study. Toxicon: X, 100266. https://doi.org/10.1016/j.toxcx.2026.100266