Jinmaitong alleviates diabetic neuropathic pain by inhibiting JAK2/STAT3 signaling in microglia of diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinmaitong (JMT) is a prescription of Traditional Chinese Medicine that is composed of 12 crude drugs. It has been used in the treatment of diabetic neuropathic pain (DNP) for more than 30 years. AIM OF STUDY: Microglia are thought to play an important role in neuropathic pain. This study aimed to evaluate the protective effect of JMT against DNP and to investigate the underlying mechanisms in which the microglia and JAK2/STAT3 signaling pathway were mainly involved. MATERIALS AND METHODS: The chemical composition of JMT was analyzed using liquid chromatography tandem mass spectrometry. The diabetes model was constructed using 11 to 12-week-old male Zucker diabetic fatty (ZDF) rat (fa/fa). The model rats were divided into 5 groups and were given JMT at three dosages (11.6, 23.2, and 46.4 g/kg, respectively, calculated as the crude drug materials), JAK inhibitor AG490 (positive drug, 10 µg/day), and placebo (deionized water), respectively, for eight weeks (n = 6). Meanwhile, Zucker lean controls (fa/+) were given a placebo (n = 6). Body weight was tested weekly and blood glucose was monitored every 2 weeks. The mechanical allodynia and heat hyperalgesia were assessed using mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests. After treatment, the microglia activation marker Iba-1, CD11B, CD68, neuroinflammatory mediators, and mediators of the JAK2/STAT3 signaling pathway were compared between different groups. The mRNA and protein levels of target genes were assessed by quantitative real-time PCR and Western Blot, respectively. RESULTS: We found that JMT significantly inhibited the overactivation of microglia in spinal cords, and suppressed neuroinflammation of DNP model rats, thereby ameliorating neurological dysfunction and injuries. Furthermore, these effects of JMT could be attributed to the inhibition of the JAK2/STAT3 signaling pathway. CONCLUSIONS: Our findings suggested that JMT effectively ameliorated DNP by modulating microglia activation via inhibition of the JAK2/STAT3 signaling pathway. The present study provided a basis for further research on the therapeutic strategies of DNP.

Correction: Mechanistic investigation of B12-independent glycerol dehydratase and its activating enzyme GD-AE.

Correction for 'Mechanistic investigation of B12-independent glycerol dehydratase and its activating enzyme GD-AE' by Yaoyang Li et al., Chem. Commun., 2022, DOI: 10.1039/d1cc06991h.

Mechanistic investigation of B12-independent glycerol dehydratase and its activating enzyme GD-AE.

B12-Independent glycerol dehydratase (GD) is a glycyl radical enzyme in the biotransformation of glycerol to 1,3-propanediol. GD requires the activating enzyme GD-AE to initiate the radical reaction. GD-AE belongs to the radical S-adenosyl-L-methionine (SAM) enzyme superfamily. However, a previous study showed that GD-AE cleaves SAM unconventionally to generate 5'-deoxy-5'-methylthioadenosine. Herein, we show that GD-AE actually cleaves SAM to form 5'-deoxyadenosine, similar to other radical SAM enzymes. Furthermore, with the synthesized glycerol analogue 2-deoxy-2-fluoroglycerol, we demonstrate that B12-independent GD catalyzes the glycerol dehydration reaction by direct elimination of the C-2 hydroxyl group of a ketyl radical rather than 1,2-OH migration.

Total time of operation is a risk factor of stroke-associated pneumonia in acute ischemic stroke patients with intra-arterial treatment.

BACKGROUND AND PURPOSE: Stroke-associated pneumonia (SAP) is associated with poor functional outcome in patients with acute ischemic stroke (AIS). The objective of this study was to identify predictors of SAP in patients underwent intra-arterial treatment (IAT). METHODS: Consecutive patients with AIS within 6 h from the symptom onset underwent IAT were enrolled. Independent predictors of in-hospital SAP after AIS were obtained using multivariable logistic regression. Kaplan-Meier survival curves were calculated and compared by the log-rank test. RESULTS: Of 165 patients with AIS in the study period, 102 (61.8%) underwent IAT. Twenty-two (21.6%; 95% confidence interval [CI], 14.7-29.4) experienced SAP. Patients with SAP were older (69.2 vs 62.9 years, respectively; P = 0.011), more severely affected (National Institutes of Health Stroke Scale score, 18 vs 9, respectively; P = 0.004), more likely to underwent symptom of dysphagia (86.4% vs 15%, respectively; P < 0.001), lower Glasgow Coma Scale score (9 vs 13, respectively; P < 0.001), and longer operation time (149.5 vs 123, respectively; P < 0.001) than those without SAP. Only symptom of dysphagia (adjust odds ratio [OR], 12.051; 95% CI, 3.457-50.610; P < 0.001) and total time of operation (adjust OR, 1.040; 95% CI, 1.009-1.071; P < 0.001) were identified as independent predictors of SAP. Patients with SAP had stable or improved deficits after AIS with IAT (P < 0.001). CONCLUSIONS: Besides dysphagia, total time of operation is a risk factor of SAP in patients with AIS with IAT.