Wogonin ameliorates ER stress-associated inflammatory response, apoptotic death and renal fibrosis in a unilateral ureteral obstruction mouse model.

Wogonin, a vital bioactive compound extracted from the medicinal plant, Scutellaria baicalensis, has been wildly used for its potential in mitigating the progression of chronic diseases. Chronic kidney disease (CKD) represents a significant global health challenge due to its high prevalence, morbidity and mortality rates, and associated complications. This study aimed to assess the potential of wogonin in attenuating renal fibrosis and to elucidate the underlying molecular mechanisms using a unilateral ureteral obstruction (UUO) mouse model as a CKD mimic. Male mice, 8 weeks old, underwent orally administrated of either 50 mg/kg/day of wogonin or positive control of 5 mg/kg/day candesartan following UUO surgery. NRK52E cells were exposed to tumor growth factors-beta (TGF-ß) to evaluate the anti-fibrotic effects of wogonin. The results demonstrated that wogonin treatment effectively attenuated TGF-ß-induced fibrosis markers in NRK-52E cells. Additionally, administration of wogonin significantly improved histopathological alterations and downregulated the expression of pro-fibrotic factors (Fibronectin, α-smooth muscle actin, Collagen IV, E-cadherin, and TGF-ß), oxidative stress markers (Catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), inflammatory molecules (Cyclooxygenase-2 and TNF-α), and the infiltration of neutrophils and macrophages in UUO mice. Furthermore, wogonin treatment mitigated endoplasmic reticulum (ER) stress-associated molecular markers (GRP78, GRP94, ATF4, CHOP, and the caspase cascade) and suppressed apoptosis. The findings indicate that wogonin treatment ameliorates key fibrotic aspects of CKD by attenuating ER stress-related apoptosis, inflammation, and oxidative stress, suggesting its potential as a future therapeutic target.

Delay of Surgery for Spinal Metastasis due to the COVID-19 Outbreak Affected Patient Outcomes.

OBJECTIVE: The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. METHODS: The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. RESULTS: A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). CONCLUSION: The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.