An integrated network pharmacology approach reveals that Darutigenol reduces inflammation and cartilage degradation in a mouse collagen-induced arthritis model by inhibiting the JAK-STAT3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Darutigenol (DL) is a natural active product derived from the Chinese herbal medicine Sigesbeckia glabrescens (Makino) Makino. It is administered as a traditional Chinese medicine (TCM) to dispel rheumatism, benefit the joints, and detoxify. However, its potential mechanism in the treatment of rheumatoid arthritis (RA) remains unknown. AIMS OF THE STUDY: The objectives of this research were to determine the effects and elucidate the modes of action of DL on RA-related joint inflammation. MATERIALS AND METHODS: Network pharmacology and molecular docking were used to screen and validate candidate DL targets for RA treatment, respectively. A DBA/1 mouse rheumatoid arthritis model was induced with bovine type II collagen. Intragastric DL administration was followed by the calculation of the clinical arthritis index. A section of the ankle joint was excised and stained and the pathological changes in it were observed. Enzyme-linked immunosorbent assays (ELISA) and western blotting (WB) were used to clarify the mechanisms of DL in RA treatment. RESULTS: DL effectively attenuated the inflammation, mitigated the articular cartilage degradation, and bone erosion, and alleviated the inflammatory joints associated with RA. Network pharmacology screened six key targets of DL while molecular docking revealed that it docked well with its protein targets. The DL treatment group presented with significantly less ankle joint redness and swelling, a lower arthritis index scores and serum and bone marrow supernatant IL-6 levels, more complete ankle joint surfaces, and less synovial inflammation, cartilage degradation, and bone erosion than the collagen-induced arthritis (CIA) group. The DL treatment also substantially downregulated the Janus kinase (JAK)1, JAK3, matrix metalloproteinase (MMP)2, MMP9, and phospho-signal transducer and activator of transcription (p-STAT)3 proteins in the joints. CONCLUSIONS: To the best of our knowledge, the present work was the first to demonstrate that DL has significant anti-inflammatory efficacy and reduces cartilage degradation and bone erosion. It also demonstrated that the anti-RA effect of DL may be explained by its ability to inhibit joint inflammation and reduce articular cartilage degradation through the interleukin (IL)-6/JAK1,3/STAT3 axis and downregulate MMP2 and MMP9. Hence, DL might play a therapeutic role in a mouse RA model.

Progress in diagnosis and treatment of ovarian metastases in rectal cancer / 中华胃肠外科杂志

Rectal cancer is the most common tumor of digestive tract. For female patients, ovarian metastasis ranks the second place in intraperitoneal organ metastasis. Its symptoms are occult, easily missed and insensitive to systemic treatment, so the prognosis is poor. Surgery is the treatment of choice for patients with rectal ovarian metastases, whether R0 resection is possible or not, and reducing tumor load is associated with better prognosis. With the continuous development of hyperthermic intraperitoneal chemotherapy (HIPEC), tumor reduction can reach the cellular level, which can significantly improve survival. Prophylactic ovariectomy remains a controversial issue in patients at high risk of ovarian metastasis. In this review, we summarize the diagnosis, treatment and prevention strategies of rectal cancer ovarian metastases, hoping to provide some reference for clinical practice.

Overview on Traditional Chinese Medicine syndrome differentiation and treatment of Coronavirus Disease 2019 (COVID-19) / 国际中医中药杂志

This paper reviews the Traditional Chinese Medicine (TCM) diagnosis and treatments for Coronavirus Disease 2019 (COVID-19) and the theories of different experts in TCM. The pathogenesis of COVID-19 involves dampness, toxin, heat, cold, blood stasis and deficiency. Dampness and poison were the core pathological factors. The treatment is based on the situation of patients in different regions and different stages of the disease, and focuses on dampness and toxin, with the purpose of eliminating evil and consolidating the foundation. Oral TCM prescriptions such as Qingfei-Paidu Decoction, Qingfei-Touxie-Fuzheng Decoction, Lianhua-Qingwen capsule (granule) show good curative effect. TCM non drug therapies, such as acupuncture, moxibustion, acupoint application, ear acupuncture, traditional exercises, etc., are mostly aimed at light, ordinary and convalescent patients, which can improve symptoms. However, high-quality TCM research is still needed.

Peritoneal Metastases in Colorectal Cancer: Biology and Barriers.

BACKGROUND: Advances in the molecular biology of tumor metastasis have paralleled the evolution in the management of metastatic disease from colorectal cancer. In this review, we summarize the current understanding of the mechanism of colorectal cancer metastases, in particular that of peritoneal metastases, as well as clinical data on the treatment of this disease. METHODS: A review of relevant English literature using MEDLINE/PubMed on the biology of colorectal cancer metastases, determinants of oligometastasis, and use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of metastatic colorectal cancer is presented. RESULTS: Recognition of oligometastasis in the evolution of colorectal peritoneal metastases provides the theoretical framework for which cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy is considered. Clearly, a subset of patients benefit from peritoneal metastasectomy. CONCLUSION: Advances in cancer biology and clinical imaging promise to expand the role of cytoreductive surgery with or without intraperitoneal chemotherapy in the management of peritoneal metastases from colorectal cancer.

Polydatin Restores Endothelium-Dependent Relaxation in Rat Aorta Rings Impaired by High Glucose: A Novel Insight into the PPARß-NO Signaling Pathway.

Polydatin, a natural component from Polygonum Cuspidatum, has important therapeutic effects on metabolic syndrome. A novel therapeutic strategy using polydatin to improve vascular function has recently been proposed to treat diabetes-related cardiovascular complications. However, the biological role and molecular basis of polydatin's action on vascular endothelial cells (VECs)-mediated vasodilatation under diabetes-related hyperglycemia condition remain elusive. The present study aimed to assess the contribution of polydatin in restoring endothelium-dependent relaxation and to determine the details of its underlying mechanism. By measuring endothelium-dependent relaxation, we found that acetylcholine-induced vasodilation was impaired by elevated glucose (55 mmol/L); however, polydatin (1, 3, 10 µmol/L) could restore the relaxation in a dose-dependent manner. Polydatin could also improve the histological damage to endothelial cells in the thoracic aorta. Polydatin's effects were mediated via promoting the expression of endothelial NO synthase (eNOS), enhancing eNOS activity and decreasing the inducible NOS (iNOS) level, finally resulting in a beneficial increase in NO release, which probably, at least in part, through activation of the PPARß signaling pathway. The results provided a novel insight into polydatin action, via PPARß-NO signaling pathways, in restoring endothelial function in high glucose conditions. The results also indicated the potential utility of polydatin to treat diabetes related cardiovascular diseases.

Curcumin attenuates cardiomyocyte hypertrophy induced by high glucose and insulin via the PPARγ/Akt/NO signaling pathway.

AIM: To investigate the potential effect of curcumin on cardiomyocyte hypertrophy and a possible mechanism involving the PPARγ/Akt/NO signaling pathway in diabetes. METHODS: The cardiomyocyte hypertrophy induced by high glucose (25.5mmol/L) and insulin (0.1µmol/L) (HGI) and the antihypertrophic effect of curcumin were evaluated in primary culture by measuring the cell surface area, protein content and atrial natriuretic factor (ANF) mRNA expression. The mRNA and protein expressions were assayed by reverse transcription PCR and Western blotting, whereas the NO concentration and endothelial NO synthase (eNOS) activity were determined using nitrate reduction and ELISA methods, respectively. RESULTS: The cardiomyocyte hypertrophy induced by HGI was characterized by increasing ANF mRNA expression, total protein content, and cell surface area, with downregulated mRNA and protein expressions of both PPARγ and Akt, which paralleled the declining eNOS mRNA expression, eNOS content, and NO concentration. The effects of HGI were inhibited by curcumin (1, 3, 10µmol/L) in a concentration-dependent manner. GW9662 (10µmol/L), a selective PPARγ antagonist, could abolish the effects of curcumin. LY294002 (20µmol/L), an Akt blocker, and N(G)-nitro-l-arginine-methyl ester (100µmol/L), a NOS inhibitor, could also diminish the effects of curcumin. CONCLUSIONS: The results suggested that curcumin supplementation can improve HGI-induced cardiomyocytes hypertrophy in vitro through the activation of PPARγ/Akt/NO signaling pathway.

[Effect and mechanism of polydatin on diabetic myocardial hypertrophy in mice].

To observe the preventive effect of polydatin on diabetic myocardial hypertrophy in mice and discuss its and mechanism. The diabetic model was induced with low dose STZ (40 mg x kg(-1) x d(-1) x 5 d, ip) for five days in mice. The myocardial hypertrophy was determined by hypertrophy indexes (LVHI, left ventricular/right ventricle and septum), left ventricular/body weight (LV/BW), the histological examination and the mRNA expression of atrial natriuretic factor(ANF). The fast blood glucose(FBG), serum insulin and plasma hemoglobin A1c ( HbA1c) levels were detected, and then HOMA insulin resistance index ( HOMA. IR) was calculated. The mRNA and protein expressions were measured by qRT-PCR and western blotting, respectively. According to the results, the FBG of the model group exceeded 11.1 mmol x L(-1), with notable decrease in BW and significant increase in insulin, HbA1c and HOME. IR, suggesting the successful establishment and stability of the diabetic model. The increases in LVHI, LV/BW, cell surface and ANF mRNA indicated a myocardial hypertrophy in diabetic mice. Meanwhile, the model group showed decrease in mRNA and protein expressions of PPARß and significant increase in NF-κB p65, COX-2 and iNOS expressions. After the preventation with PD (50, 100 mg x kg(-1) x d(-1)), diabetic mice showed increase in BW, reduction in the levels of FBG, insulin and HbA1 c, relief in insulin resistance and significant recovery in hypertrophy indexes, indicating PD has the protective effect in diabetic myocardial hypertrophy. Meanwhile, PD up-regulated the expression of PPARß, inhibited the expressions of NF-κB p65, COX-2 and iNOS, demonstrating that PD's protective effect may be related to the activation of PPARß and the inhibition of NF-κB, COX-2 and iNOS signaling pathways.