Screening Traditional Foods for the Prevention of Enterotoxigenic Escherichia coli K88ac (F4ac) Attachment to IPEC-J2 Cells.

Enterotoxigenic Escherichia coli (ETEC) is the major diarrhoea-causing pathogen world-wide. Fimbria-receptor recognition is the primary step when attachment of ETEC to the intestine occurs. This study aims to evaluate the potential of some traditional foods, particularly those rich in ß-glucans, as analogues for fimbriae or receptors in reducing ETEC colonisation. The adhesion test (AT) demonstrated that aqueous extracts of highland barley (EHB), black rice (EBR) and little millet (ELT) at concentrations of 2% and 1% could attach to more ETEC K88ac (p < 0.001), as well as aqueous extracts of shiitake (EST) (p < 0.01). The competition test (CT) revealed that EHB and EST significantly prevented ETEC K88ac from adhering to intestinal epithelial cells (IPEC-J2) at 2% (p < 0.01) and 1% (p < 0.05). In the Exclusion Test (ET) and the displacement test (DT), the food samples were unable to impair ETEC colonisation in terms of blocking receptors or removing attached pathogens. These results demonstrate how some traditional foods such as highland barley and shiitake contain bioactive compounds that interfere with the attachment of ETEC to the intestinal epithelium, and their potential in the prevention and treatment of ETEC diarrhoea.

TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception.

Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1+/+, Trpv1-/-, and Trpv1T634A/T634A. Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT. We identified the S4-S5 linker region exposed to the vanilloid pocket of TRPV1 to be critical for hyperthermia associated with certain TRPV1 antagonists. PSFL2874, a TRPV1 antagonist we discovered, is effective against inflammatory pain but devoid of binding to the S4-S5 linker and inducing CBT changes. These findings implicate that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, opening avenues for the development of non-opioid analgesics without affecting CBT.

Efficacy and Safety of Tirofiban in Clinical Patients With Acute Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis and endovascular thrombectomy have been approved for acute ischemic stroke (AIS). However, only a minority of patients received these treatments in China. We aimed to evaluate the efficacy and safety of tirofiban in patients with AIS who were not undergoing early recanalization treatments. METHODS: Patients with mild-to-moderate stroke [National Institutes of Health Stroke Scale (NIHSS) score, 4-15] were enrolled in this study. Patients due to cardiogenic embolism were excluded. Eligible patients within 12 h from symptom onset were randomly assigned (1:1) to receive tirofiban (a loading dose of 0.4 µg/kg/min over 30 min and a maintenance dose of 0.1 µg/kg/min up to 48 h) followed by regular treatment or to receive regular treatment (aspirin at a dose of 100 mg per day for 90 days) (control). The primary outcome was the proportion of favorable functional outcomes at 90 days [defined as the modified Rankin Scale (mRS) score of 0-2]. The secondary outcomes included a shift in the distribution of the mRS scores at 90 days and the NIHSS score at 24 h and 7 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) within 7 days after tirofiban treatment. RESULTS: A total of 380 eligible patients were randomly assigned to the tirofiban group (n = 190) or the control group (n = 190). The proportion of favorable functional outcomes was higher in the tirofiban group (79.1%) than that in the control group (67.8%) at 90 days [odds ratio (OR), 1.80; 95% CI, 1.12-2.90; p = 0.0155]. An improvement was also observed in the overall distribution of the 90-day mRS scores (adjusted common OR, 2.31; 95% CI, 1.58-3.39; p < 0.0001). Additionally, the median NIHSS score was lower in the tirofiban group than in the control group at 7 days (3 vs. 5, p < 0.0001). Next, we observed that the occurrence of sICH did not differ between the two groups. CONCLUSION: Our trial supports that tirofiban was safe and effective and might be a remedial treatment for patients with AIS who did not receive recanalization treatments. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/, identifier: ChiCTR2000031297.