Deciphering feedback regulation of prostaglandin F2α in blood stasis syndrome using nitrogen-doped porous transition metal carbides.

Blood stasis syndrome (BSS) has persistent health risks; however, its pathogenesis remains elusive. This obscurity may result in missed opportunities for early intervention, increased susceptibility to chronic diseases, and reduced accuracy and efficacy of treatments. Metabolomics, employing the matrix-assisted laser desorption/ionization (MALDI) strategy, presents distinct advantages in biomarker discovery and unraveling molecular mechanisms. Nonetheless, the challenge is to develop efficient matrices for high-sensitivity and high-throughput analysis of diverse potential biomarkers in complex biosamples. This work utilized nitrogen-doped porous transition metal carbides and nitrides (NP-MXene) as a MALDI matrix to delve into the molecular mechanisms underlying BSS pathogenesis. Structural optimization yielded heightened peak sensitivity (by 1.49-fold) and increased peak numbers (by 1.16-fold) in clinical biosamples. Validation with animal models and clinical serum biosamples revealed significant differences in metabolic fingerprints between BSS and control groups, achieving an overall diagnostic efficacy of 0.905 (95% CI, 0.76-0.979). Prostaglandin F2α was identified as a potential biomarker (diagnostics efficiency of 0.711, specificity = 0.7, sensitivity = 0.6), and pathway enrichment analysis disclosed disruptions in arachidonic acid metabolism in BSS. This innovative approach not only advances comprehension of BSS pathogenesis, but also provides valuable insights for personalized treatment and diagnostic precision.

Efficacy and safety of tripterygium glycosides for active moderate to severe Graves' ophthalmopathy: a randomised, observer-masked, single-centre trial.

BACKGROUND: Tripterygium glycosides (TG) has been used to treat a spectrum of inflammatory and autoimmune diseases. Our preliminary studies have shown that TG is effective in the treatment of active Graves' ophthalmopathy (GO). OBJECTIVE: We aimed to compare the efficacy and tolerability of TG with intravenous methylprednisolone (iv.MP) in patients with active moderate-to-severe GO. METHODS: This study was an observer-masked, single-centre, block-randomised trial. Patients with active moderate-to-severe GO were randomly assigned to receive iv.MP (500 mg once per week for 6 weeks followed by 250 mg per week for 6 weeks) or with TG (20 mg tablet three times per day for 24 weeks). The primary endpoints were the overall response rate and the patients' quality of life at 12 and 24 weeks. RESULTS: In this study, 161 patients were enrolled and randomised from 2015 to 2019. A total of 79 were randomly assigned to receive iv.MP and 82 to receive TG. A greater overall response rate was found in the TG group compared with the iv.MP group at week 24 (90.2% vs 68.4%, P = 0.000). Similarly, the patients' quality of life of the TG group showed a significantly higher response than the iv.MP group at week 24 (89.02% vs 72.15%, P = 0.001). The TG therapy showed a better CAS response than the iv.MP (91.5% vs 70.9% improved, P < 0.05), and up to 91.2% of patients were inactive. Also, the TG group showed a significantly higher improved rate of diplopia, proptosis, visual acuity, soft tissue involved and the decrease of eye muscle motility than the iv.MP group at week 24. Significantly more patients in the iv.MP group than the TG group experienced adverse events. CONCLUSION: Compared with iv.MP treatment, TG therapy is more effective and safer for patients with active moderate to severe GO.

Effect of Schisandra chinensis on interleukins, glucose metabolism, and pituitary-adrenal and gonadal axis in rats under strenuous swimming exercise.

OBJECTIVE: To investigate the effect of Chinese medicine (CM) Schisandra chinensis on interleukin (IL), glucose metabolism, and pituitary-adrenal and gonadal axis of rats after strenuous navigation and exercise. METHODS: A total of 45 Sprague-Dawley rats were randomized into the quiet control group, the stress group, and the CM group (15 in each group). The CM group received 2.5 g/kg of Schisandra chinensis twice per day for one week before modeling. Except the quiet controls, rats were trained using the Bedford mode for 10 days. On the 11th day, they performed 3 h of stressful experimental navigation and 3 h of strenuous treadmill exercise. The levels of serum testosterone (T), cortisol (CORT), luteinizing hormone (LH), IL-1, IL-2, and IL-6 were tested by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The adrenal cortex ultrastructure was observed using electron microscopy. RESULTS: Compared with the quiet control group, after navigation and strenuous exercise, blood glucose was increased, and T level was decreased in the stress group (both P<0.01). The blood glucose, CORT, IL-1 and IL-2 levels were significantly reduced in the CM group (P<0.05 or P<0.01) as compared with the stress group. Electron microscopy revealed that the rats in the CM group had a smaller decrease in adrenal intracellular lipid droplets and higher levels of apoptosis than those in the stress group. CONCLUSIONS: Schisandra chinensis can reduce serum CORT and blood glucose levels in stressed rats. It appears to protect the cell structure of the adrenal cortex, and offset the negative effects of psychological stress and strenuous exercise related to immune dysfunction. Schisandra chinensis plays a regulatory role in immune function, and can decrease the influence of stress in rats.

Xuezhikang attenuated the functional and morphological impairment of pancreatic islets in diabetic mice via the inhibition of oxidative stress.

Xuezhikang, purified from red yeast rice, is a traditional Chinese medicine with pleiotropic effects on the cardiovascular system. Oxidative stress plays a crucial role in the dysfunction of pancreas islet in diabetic condition and represents a promising therapeutical target for diabetes mellitus. Therefore, the purpose of this study was to explore the effects and possible mechanisms of xuezhikang on the microenvironment and insulin secretion by pancreatic islets in db/db diabetic mice. Our results showed that xuezhikang decreased the blood glucose level by improving glucose tolerance and insulin secretion in db/db mice. Xuezhikang protected islets from hyperglycemic injury as illustrated by the conserved ß-cell content and microenvironment. Furthermore, xuezhikang potently inhibited the expression of key factors in oxidative stress. In addition, administration of xuezhikang caused an upregulated expression of glucose-sensing apparatus. These observations provide evidence that the influence of xuezhikang on oxidative stress may at least partly account for its protective effects on the microenvironment and insulin secretion function of pancreatic islets in diabetes.

[Effect of rhein treatment on first-phase insulin secretory function in db/db mice].

OBJECTIVE: The aim of the present study is to investigate the effect of rhein treatment on the first-phase insulin secretory function in db/db mice. METHOD: Twenty 4-week-old male db/db mice were randomized to treatment with rhein (120 mg x kg(-1), n = 10) and placebo respectively (1% natrium cellulose solution, n = 10) by gavage for 8 weeks respectively. Ten age-matched non-diabetic male littermates db/m mice treated with placebo were studied as non-diabetic control. Body weight and fasting blood glucose level were measured before and after medication. The islets were isolated after 8 weeks' gavage. Islet perifusion system was set up, and all columns were perfused in parallel at a flow rate of 0.5 mL x min(-1) with KRB (2.8 mmol L(-1) glucose) at 37 degrees C. After 60-min static incubation with KRB (2.8 mmol x L(-1) glucose), the islets were stimulated in the continuous presence of a high concentration of 16.7 mmol x L(-1) glucose. Samples were collected every 20-second until 2-min, every 1-min until 5-min, thereafter every 5-min until 30-min. Samples were immediately stocked at -80 degrees C until further analysis. RESULT: Compared with the db/db control group, the fasting glucose concentration was significantly decreased in the rhein treatment group. The first-phase insulin secretory function was impaired significantly in db/db mice, while the first-phase insulin secretory peak was obvious in the rhein treatment mice. CONCLUSION: Rhein treatment significantly improved glucose tolerance, restored the first-phase insulin secretion and protected the islets function.

[Effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axis and carbohydrate metabolism in rats undergoing experimental chronic psychological stress, navigation and strenuous exercise].

OBJECTIVE: To investigate the effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axis and carbohydrate metabolism in male rats undergoing experimental chronic psychological stress, navigation and strenuous exercise. METHODS: Thirty-four SD rats were randomly allocated into a non-stress group (Group A), a stress control group (Group B) and a schisandra group (Group C). The latter two groups received 10 days of Benford's high-intensity training, followed by 3 hours of wearing floating with psychological stress and another 3 hours of running at the speed of 26.7 m/min. Then blood samples were immediately obtained for the measurement of the levels of testosterone (T), corticosterone (CORT), luteinizing hormone (LH) and blood glucose (Glu). Meanwhile the adrenal gland was excised and its cortex ultrastructure observed under the electron microscope. RESULTS: The Glu level was increased while the T level decreased significantly in Group B as compared with Group A. The CORT level remained unchanged in Group B. Both the Glu and CORT levels were significantly reduced in Group C in comparison with B. However, no significant differences were found in serum LH levels among the three groups. And electron microscopy revealed a reduction of lipid droplets and apoptosis of the adrenal cortex cells in Group B as compared with C. CONCLUSION: Schisandra can reduce the levels of CORT and Glu and protect the structure of the adrenal cortex.