Quercetin serves as the major component of Xiang-lian Pill to ameliorate ulcerative colitis via tipping the balance of STAT1/PPARγ and dictating the alternative activation of macrophage.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herbal formula, Xiang-lian Pill (XLP), is commonly prescribed for ulcerative colitis (UC) patients to relieve their clinical symptom. Nonetheless, the underlying cellular and molecular mechanisms of XLP's anti-UC effect remain incompletely understood. AIM OF THE STUDY: To evaluate the therapeutic effect and elucidate the possible working mechanisms of XLP in UC treatment. The major active component of XLP was also characterized. MATERIALS AND METHODS: Colitis was induced in C57BL/6 mice with 3% dextran sulfate sodium (DSS) dissolved in drinking water for 7 consecutive days. The UC mice were grouped and treated with XLP (3640 mg/kg) or vehicle orally during the procedure of DSS induction. Mouse body weight, disease activity index (DAI) score and colon length were recorded. Histopathological changes and inflammatory cell infiltration were evaluated by pathological staining and flow cytometric analysis (FACS). Network pharmacology, bioinformatic analysis, widely targeted and targeted metabolomics analysis were performed to screen the potential effective ingredients and key targets. Bone marrow derived macrophages (BMDMs), peripheral blood mononuclear cells (PBMCs), RAW264.7 and THP-1 cells were used to dissect the anti-inflammatory effect of XLP. RESULTS: Oral administration of XLP ameliorated DSS induced mouse colitis, as evidenced by reduced DAI and colonic inflammatory destruction. FACS results demonstrated that XLP treatment effectively restored immune tolerance in colon, inhibited the generation of monocyte derived macrophages and skewed macrophage polarization into M2 phenotype. Network pharmacology analysis suggested that innate effector modules related to macrophage activation comprise the major targets of XLP, and the counter-regulatory STAT1/PPARγ signaling possibly serves as the critical downstream pathway. Subsequent experiments unveiled an imbalance of STAT1/PPARγ signaling in monocytes derived from UC patients, and validated that XLP suppressed LPS/IFN-γ induced macrophage activation (STAT1 mediated) but facilitated IL-4 induced macrophage M2 polarization (PPARγ dependent). Meanwhile, our data showed that quercetin served as the major component of XLP to recapitulate the regulatory effect on macrophages. CONCLUSION: Our findings revealed that quercetin serves as the major component of XLP that regulates macrophage alternative activation via tipping the balance of STAT1/PPARγ, which provides a mechanistic explanation for the therapeutic effect of XLP in UC treatment.

Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/ß-catenin pathway in the myocardium of mice after myocardial infarction.

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/ß-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/ß-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.

The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

Tumor-associated mesenchymal stem cells promote hepatocellular carcinoma metastasis via a DNM3OS/KDM6B/TIAM1 axis.

Tumor-associated mesenchymal stem cells (MSCs) play a critical role in the growth and metastasis of hepatocellular carcinoma (HCC). However, the mechanism underlying the crosstalk between MSCs and HCC cells is not completely understood. Here, HCC cells were treated with or without conditioned medium of MSCs (CM-MSC), and examined for differential expression of long non-coding RNAs (lncRNAs). Knockdown and overexpression experiments were conducted to explore the function of the lncRNA DNM3OS in MSC-induced HCC growth and metastasis. CM-MSC treatment led to a concentration-dependent induction of DNM3OS in HCC cells. DNM3OS was significantly upregulated in HCC compared to adjacent liver tissues. High DNM3OS expression was associated with TNM stage, vascular invasion, and poor prognosis of HCC patients. Silencing of DNM3OS inhibited HCC cell proliferation and invasion in vitro and tumorigenesis and metastasis in vivo. Overexpression of DNM3OS enhanced HCC cell proliferation, invasion, and metastasis. Biochemically, DNM3OS was mainly localized in the nucleus and physically interacted with KDM6B. The association of DNM3OS with KDM6B induced the expression of TIAM1 through reduction of H3K27me3 at the TIAM1 promoter. TIAM1 overexpression restored the proliferation and invasion of DNM3OS-depleted HCC cells. Our data delineate a mechanism by which MSCs accelerate HCC growth and metastasis through a DNM3OS/KDM6B/TIAM1 axis.

[Spectroscopic characteristics of dissolved organic matter in water from typical area of Taihu Lake].

Fluorescence spectroscopy, UV spectroscopy, and multiple UV parameters were applied to determine and analyze the dissolved organic matter (DOM) in water of Taihu Lake, in order to find out the sources and influencing factors of DOM in water from typical areas of Taihu Lake. The results showed that the components of DOM in water from different lake areas displayed some regional characteristics. The contents of macro-molecules matters with complex structures and humic substances in water from sampling points T1 (locates in the inflow river) and T2 (represents Zhu Shan Bay Lake) were in majority. This indicated that these areas were subjected to multiple sources, including biological sources, land-based sources, and domestic sewage. In the meanwhile, the complexities of DOM from sampling points T3 (Meiliang Bay Lake), T4 (Gonghu Bay Lake), and T5 (center of Taihu Lake) were relatively low. And protein-like materials with simple structures were in majority in water from sampling point T6 (East Taihu Lake), which suggested that this area was less influenced by the external environment.

[Treatment results of stage IA Hodgkin lymphoma: a report of 97 cases].

BACKGROUND & OBJECTIVE: The treatment strategies of Hodgkin's lymphoma (HL) are different according to clinical stage and risk factors, yet the optimal treatment strategy remains unclear. This study was to analyze the treatment results and prognostic factors of stage IA HL. METHODS: According to prognosis, 97 patients with stage IA HL were divided into 3 groups: 7 (7.2%) in very favorable (VF) group, 72 (74.2%) in favorable (F) group, and 18 (18.6%) in unfavorable (UF) group. Short-term treatment outcome and long-term survival were analyzed. The prognosis was analyzed with Cox regression model. RESULTS: Median follow-up time was 65 months. After radiotherapy or radiochemotherapy, 90 patients (92.8%) achieved complete remission (CR). The 5-and 10-year overall survival (OS) rates were 87.7% and 76.3%; the 5-and 10-year disease-free survival (DFS) rates were 79.4% and 74.5%. The 5-and 10-year OS rates were 100% and 100% in VF group, 88.9% and 88.4% in F group, 78.1% and 39.1% in UF group (P=0.292). The 5-and 10-year DFS rates were 100% and 87.2% in VF group, 86.3% and 71.8% in F group, 73.6% and 34.5% in UF group (P=0.032). Cox analysis showed that pathologic type (P=0.056) and tumor relapse (P=0.011) influenced OS, and the response to primary treatment (P=0.024) influenced DFS. The relapse rate was 18.6%û there was no significant difference between the patients received radiotherapy alone and those received radiochemotherapy (Chi(2)=0.072, P=0.788). The occurrence rate of secondary malignancies was 5.2%, including 2 cases of non-Hodgkin's lymphoma. All the 12 patients who died had received radiotherapy alone. CONCLUSIONS: More than 90% of stage IA HL patients can achieve CR with radiotherapy alone or chemoradiotherapy. The long-term OS and DFS of the patients who received radiochemotherapy are better than those of the patients who received radiotherapy alone. The pathologic type, response to primary treatment and tumor relapse may be independent prognostic factors of stage IA HL.