Search

Human intestinal bacteria are the primary producers of azo reductase, and the content of azo reductase is closely associated with various intestinal diseases, including ulcerative colitis (UC). The rapid detection of changes in azo reductase levels is crucial for diagnosing and promptly intervening in UC. In this study, a therapeutic agent, FAI, specifically targeting UC, was designed and synthesized. This agent was developed by linking the anti-inflammatory drug indomethacin to flavonols with antioxidant activity via an azo bond (off–on). Breakage of the azo bond breaks results in the release of both fluorophores and drugs, achieving targeted tracing and integrated treatment effects. In vivo and in vitro fluorescence imaging experiments were used to demonstrate the potential of FAI in the diagnosis of UC, together with synergistic therapeutic effects through the release of both fluorophores and anti-inflammatory agents. Therefore, this diagnostic agent shows promise as a potential tool for diagnosing and treating UC. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of dabigatran etexilate for Chinese patients with cerebral venous thrombosis (CVT) has not been well established. Methods: CHOICE-CVT was an exploratory, single-center, randomized, open-label study in the National Center for Neurological Disorders involving Chinese patients with CVT aged 18 to 80 years who were randomly assigned (1:1) to either dabigatran etexilate or warfarin. Oral anticoagulants were initiated after 10–15 days of LMWH. The primary efficacy and safety endpoints included the number of patients with recurrent CVT and/or deep venous thrombosis (DVT) and major clinical bleeding within 180 days. Secondary efficacy endpoints included venous recanalization and change in papilledema at day 180. Secondary safety outcomes comprised death, clinical nonmajor bleeding, and any bleeding. The study was registered with ClinicalTrials.gov under NCT03930940. Results: Between October 2017 and February 2023, a total of 89 patients were enrolled and randomly assigned to receive either dabigatran etexilate (n = 44) or warfarin (n = 45). At day 180, the dabigatran etexilate group showed a statistically nonsignificant but likely clinically significant number of patients with recurrent CVT and/or DVT (8 (18.2%; 95% CI, 6.3–30.0) vs 3 (6.7%; 95% CI, 0.0–14.2), p = 0.099, with a power (1-β) of 38.401%) compared with the warfarin group. The dabigatran etexilate group showed a comparable number of patients with clinical major bleeding (0 (0) vs 0 (0) p = 1.000), and clinical nonmajor bleeding (1 (2.3%; 95% CI, 0.0–6.9) vs 1 (2.2%; 95% CI, 0.0–6.7)) but demonstrated a lower risk of any bleeding (1 (2.3%; 95% CI, 0.0–6.9) vs 9 (20.0%; 95% CI, 7.8–32.2)) compared with the warfarin group. Most patients in both groups achieved venous recanalization according to the Modified Qureshi scale (27 (75%; 95% CI, 60.1–89.9) in the dabigatran etexilate group vs 34 (82.9%; 95% CI, 70.9–95.0) in the warfarin group) and exhibited improvement in papilledema as per the Frisén classification (35 (97.2%; 95% CI, 91.6–100.0) in the dabigatran etexilate group vs 37 (88.1%, 95% CI, 77.9–98.3) in the warfarin group). Conclusions: These findings regarding efficacy and safety support the consideration of dabigatran etexilate therapy as a viable treatment option for Chinese patients with CVT. [ABSTRACT FROM AUTHOR]

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi‐faceted senescence‐associated secretory phenotype (SASP). Induction of aHSCs senescence by inhibiting SASP may be a potential therapeutic model against hepatic fibrosis. To evaluate the role of atractylenolide III (ATR III) in the development of chemotherapeutic drug‐induced SASPs in hepatic stellate cells. Etoposide‐induced senescent HSC‐LX2 model was established and treated with ATR III at different concentrations (20, 30 and 40 μM). We found that ATR III dose‐dependently enhanced senescence in etoposide‐induced LX2 cells. ATR III dose‐dependently decreased the release and expression of SASP factors (interleukin [IL]‐1α, IL‐1β, IL6 and IL‐8) in senescent cells. ATR III regulated cyclic GMP‐AMP synthase (cGAS)/nuclear factor κ (NF‐κB) signalling to affect SASP expression in senescent cells. The addition of 2'3′ cGAMP counteracted the effect of ATR III. The release of SASP factors in the conditioned medium from senescent cells could affect cell migration, proliferation and contraction through paracrine manner. Our results indicated ATR III could still enter senescence and prevent the production of SASP and its paracrine effects in senescent cells, an effect that may be related to the possible inhibition of cGAS/NF‐κB signalling by ATR III. Our study proves that ATR III may be an effective potential drug against liver fibrosis by promoting aHSC senescence, which can provide a new choice for the future clinical treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: NLRP3 inflammasome-related inflammation might play an important role in the pathophysiology of severe CVT. The use of steroids as anti-inflammatory agents in improving severe CVT prognosis remains controversial., Methods: A total of 94 male Sprague-Dawley rats were used. We evaluated the dynamic and association between NLRP3 inflammasome in brain, blood, and CSF and severity in severe CVT rats and/or patients. We also explored the effect of steroids on NLRP3 activation, neurological injury, and CSF circulation disturbance after CVT in animals and/or patients., Results: In rats, compared with the sham group, NLRP3-related factors rose on day 1, peaked on day 2 (NLRP3, Sham: 0.79 ± 0.22; day 2: 1.25 ± 0.08, p < 0.01; pro-Caspase-1, Sham: 0.58 ± 0.13, day 2: 1.20 ± 0.44, p < 0.05; GSDMD, Sham: 0.94 ± 0.22, day 2: 1.72 ± 0.46, p < 0.05; pro-IL-1β, Sham: 0.74 ± 0.15, day 2: 1.35 ± 0.09, p < 0.01), decreased on day 7 in rats (n = 4 per group). Thrombus (Sham: 0.00 ± 0.00, day 2: 3.44 ± 0.70, p < 0.0001), infarct size (Sham: 0.00 ± 0.00, day 2: 11.99 ± 6.26, p < 0.01) and neurological deficits appeared similar trend. In 50 patients, serum NLRP3 and IL-6 levels correlated positively with NIHSS (r = 0.4273, p = 0.0020; r = 0.4938, p = 0.0029) and mRS (r = 0.5349, p = 0.0125; r = 0.6213, p = 0.026), while CSF IL-6 correlated positively with mRS on admission (r = 0.5349, p = 0.0125). Compared with baseline, NLRP3 (0.36 (0.36, 0.36) vs. 0.41 (0.37, 0.84), p < 0.0001) and IL-6 decreased (4.06 ± 1.48 vs. 12.03 ± 7.80, p < 0.05), accompanying by improvement of neurological deficits and CSF circulation (all p < 0.01) after steroids therapy in severe CVT patients at discharge and 3 months follow-up. No significant steroid-related adverse effects were observed., Conclusion: Short-term steroid therapy may improve prognosis of severe CVT by suppressing NLRP3 inflammasome-related inflammation., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Joint degeneration has become a commonplace problem in aging populations. The main clinical manifestations include joint pain, joint stiffness and joint swelling with functional disorder. Mega MSM is a nutritional supplement that may provide potential relief for joint problems associated with joint degeneration. The current experiment performed was a 12-week, randomized, double-blind, controlled study conducted on populations in China experiencing joint degeneration. The objective of the study was to determine whether the daily use of Mega MSM capsules could improve joint function, relieve symptoms of joint degeneration and improve the quality of life in aging populations. A total of 100 male and female participants over 50 years old who had at least one of the related symptoms of joint degeneration (joint pain, joint stiffness, joint swelling, difficulty walking, difficulty getting up from bed and difficulty going down stairs) were recruited and their symptoms of joint degeneration before and after the intervention were recorded. In this study, Mega MSM shows positive effects in improving joint function, relieving symptoms associated with joint degeneration and improving the quality of life in aging populations.