Severe Venous Calcifications in Phlebosclerotic Colitis and Significantly Decreased Expression in Betaine.

Phlebosclerotic colitis (PC) is a rare type of chronic ischemic colitis. Its etiology is still unknown, and PC is also known as idiopathic mesenteric phlebosclerosis colitis. Currently, many studies have reported that long-term use of Chinese herbal medicine and drinking history are related to its pathogenesis. In the early stage of the lesion, due to insufficient understanding of PC, it is difficult to distinguish it from inflammatory bowel disease and other nonneoplastic intestinal diseases. We reported a case of severe diffuse total colon calcification with multiple misdiagnosis, summarizing and analyzing the clinical pathological characteristics to increase clinical and pathological physicians' understanding of the disease and reduce misdiagnosis. Moreover, for the first time, we conducted metabolomics sequencing on fresh intestinal specimens of PC, in order to explore the possible mechanism of severe calcification in the patient. We found that betaine was significantly decreased in the intestinal specimens of the patient, which is an amino acid that has been shown to improve vascular risk factors, and may be one of the mechanisms underlying severe calcification in the patient.

A new equation for estimating low-density lipoprotein cholesterol concentration based on machine learning.

Low-density lipoprotein cholesterol (LDL-C) is a crucial marker of cardiovascular system damage. In the Chinese population, the estimation of LDL-C concentration by Friedewald, Martin-Hopkins or Sampson equations is not accurate. The aim of this study was to develop a group of new equations for calculating LDL-C concentration using machine learning techniques and to evaluate their efficacy. A total of 182,901 patient samples were collected with standard lipid panel measurements. These samples were collated and randomly divided into a training set and a test set. In the training set, a new equation was constructed using polynomial ridge-regression and compared to the Friedewald, Martin/Hopkins and extended Martin/Hopkins, or Sampson equations in the test set. Subsequently, an additional set of 17,285 patient samples were collected to evaluate the performance of the new equation in clinical practice. The new equation, a ternary cubic equation, was accurate and easy to use, with a goodness-of-fit R2 of 0.9815 and an uncertainty MSE of 37.4250 on the testing set. The difference between the calculated value by the new equation and the measured value of LDL-C was small (0.0424 ±â€…5.1161 vs Friedewald equation: -13.3647 ±â€…17.9198, vs Martin/Hopkins and extended Martin/Hopkins equation: -6.4737 ±â€…8.1036, vs Sampson equation: -8.9252 ±â€…12.6522, P < .001). It could accurately calculate LDL-C concentration even at high triglyceride and low LDL-C. Furthermore, the new equation could also precisely calculate LDL-C concentration in actual clinical use (R2 = 0.9780, MSE = 24.8482). The new equation developed in this study can accurately calculate LDL-C concentration within the full concentration range of triglyceride and LDL-C, and can serve as a supplement to the direct determination of LDL-C concentration for the prevention, treatment, evaluation, and monitoring of atherosclerotic diseases, compared to the Friedewald, Martin/Hopkins and extended Martin/Hopkins, or Sampson equations.

Schisandrin A alleviates renal fibrosis by inhibiting PKCß and oxidative stress.

BACKGROUND: Renal fibrosis is a common pathway that drives the advancement of numerous kidney maladies towards end-stage kidney disease (ESKD). Suppressing renal fibrosis holds paramount clinical importance in forestalling or retarding the transition of chronic kidney diseases (CKD) to renal failure. Schisandrin A (Sch A) possesses renoprotective effect in acute kidney injury (AKI), but its effects on renal fibrosis and underlying mechanism(s) have not been studied. STUDY DESIGN: Serum biochemical analysis, histological staining, and expression levels of related proteins were used to assess the effect of PKCß knockdown on renal fibrosis progression. Untargeted metabolomics was used to assess the effect of PKCß knockdown on serum metabolites. Unilateral Ureteral Obstruction (UUO) model and TGF-ß induced HK-2 cells and NIH-3T3 cells were used to evaluate the effect of Schisandrin A (Sch A) on renal fibrosis. PKCß overexpressed NIH-3T3 cells were used to verify the possible mechanism of Sch A. RESULTS: PKCß was upregulated in the UUO model. Knockdown of PKCß mitigated the progression of renal fibrosis by ameliorating perturbations in serum metabolites and curbing oxidative stress. Sch A alleviated renal fibrosis by downregulating the expression of PKCß in kidney. Treatment with Sch A significantly attenuated the upregulated proteins levels of FN, COL-I, PKCß, Vimentin and α-SMA in UUO mice. Moreover, Sch A exhibited a beneficial impact on markers associated with oxidative stress, including MDA, SOD, and GSH-Px. Overexpression of PKCß was found to counteract the renoprotective efficacy of Sch A in vitro. CONCLUSION: Sch A alleviates renal fibrosis by inhibiting PKCß and attenuating oxidative stress.

Shenling Baizhu Decoction (SLBZD) may play a synergistic role of tirelizumab in the treatment of colorectal cancer by influencing the imbalance of colon flora and Tumor microenvironment.

Objective: To explore whether SLBZD can play a synergistic role in promoting the efficacy of PD-1 inhibitors in the treatment of colorectal cancer by influencing the intestinal microenvironment and Tumor microenvironment. Method: Shenling Baizhu Decoction (SLBZD) and tirelizumab (TLzmab) treated the colorectal mouse model. The tumor growth rate, tumor weight, and tumor growth inhibition rate were evaluated. Fecal microbiota was detected by 16S rDNA sequencing and immune cell was detected by the flow cytometry analysis. Result: Compared to tumor weight, there exist significant differences between each group among the three groups. Compared to tumor volume, there was no statistically significant difference in tumor size between the control group and the TLzmab group at 7 days. However, there was a statistical difference in tumor size among the three groups at 18 days. By analyzing the diversity of the Gut microbiota, the diversity decreased after TLzmab treatment with a statistically significant difference. Compared with the control group, the diversity of the TLzmab+SLBZD group increased. The proportion of lymphocytes in the blood was analyzed by flow cytometry. Compared with the control group, Myeloid-derived suppressor cells (MDSCs) decreased and T regulatory cells (Treg) increased significantly in the TLzmab group. Compared with the control group and TLzmab group, the TLzmab+SLBZD group showed a significant increase in M1 type macrophages, while the M2 type macrophages, MDSCs, and Treg showed a significant decrease. Conclusion: An imbalance of Gut microbiota and imbalance of tumor immune microenvironment will occur during TLzmab treatment, which will lead to poor therapeutic effect of TLzmab or drug resistance. SLBZD will increase the abundance of Gut microbiota, which will lead to the increase of M1 macrophages in the tumor immune microenvironment and the decrease of M2 macrophages and Treg cells, thus exerting the synergistic effect of TLzmab. This study provides a new way to explore the improvement of ICIs through traditional Chinese medicine.

Initiation and duration of folic acid supplementation in preventing congenital malformations.

BACKGROUND: Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. METHODS: A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. RESULTS: Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44-1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21-1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08-5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33-0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36-0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. CONCLUSIONS: The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. TRIAL REGISTRATION: Chictr.org.cn identifier: ChiCTR-SOC-17010976.

Maternal traditional Chinese medicine exposure and risk of congenital malformations: a multicenter prospective cohort study.

INTRODUCTION: The potential teratogenic risk of traditional Chinese medicine (TCM) is of widespread concern; however, related evidence is largely absent in humans. This study aimed to compare the prevalence of congenital malformations between pregnant women with and without TCM exposure. MATERIAL AND METHODS: This was a multicenter prospective cohort study of 17 713 women who participated in a survey on periconceptional TCM exposure. Primary outcome was congenital malformations diagnosed from a survey conducted on the day 42 after delivery. RESULTS: A total of 16 751 pregnant women with 273 congenital malformations were included in the analysis. Fetuses exposed to TCM had an increased risk of congenital malformations compared to those without exposure (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.09-4.02) after controlling for potential confounders. There were significant associations with congenital malformations in women with early pregnant exposure (OR 2.04, 95% CI 1.00-4.20) and for those who received ≥2 TCM formulas (OR 5.84, 95% CI 1.44-23.65). Pre-pregnancy TCM exposure was significantly associated with an increased risk of congenital heart defects (OR 12.69; 95% CI 3.01-53.51). CONCLUSIONS: Periconceptional TCM exposure is associated with an increased risk of congenital malformation. This effect was cumulative and sensitive to periconceptional age. Therefore, TCM deserves more attention and should be used cautiously for pregnant women and those trying to become pregnant.

Isolation, synthesis and bioactivity evaluation of isoquinoline alkaloids from Corydalis hendersonii Hemsl. against gastric cancer in vitro and in vivo.

Isoquinoline alkaloid displays significant anti-gastric cancer effects due to its unique structure, which is attracting more and more attention for the development of anti-gastric cancer drugs. In this study, we explore the active components against gastric cancer from the Tibetan Medicine Corydalis hendersonii Hemsl, which is rich in isoquinoline alkaloids. 14 compounds including 2 previously undescribed natural products were obtained. Interestingly, an new active compound displays potent anti-gastric cancer activity. After accomplishing the total syntheses of the active compound and its derivatives, the anti-gastric cancer activity of the active compound was further investigated. In vitro experiments revealed that the active compound significantly attenuated the proliferative capacity, caused G2/M phase arrest, inhibited the cell migration and invasion, and induced cell apoptosis. Mechanistically, the active compound could increase the Bax/Bcl-2 ratio, elevate cytochrome c in the cytosol, and activate caspase-9/3, along with inactivating the upstream PI3K/Akt/mTOR signaling pathway. In addition, the active compound could also cause gastric cancer cell death by inhibiting topoisomerase I activity. More importantly, the anti-gastric cancer activity of the active compound was confirmed in MGC-803 xenograft nude mice in vivo. This work not only promotes the exploitation of Corydalis hendersonii Hemsl., but also provides some experience for discovering new entities from natural sources.

Kakkonto Inhibits Cytokine Production Induced by Rhinovirus Infection in Primary Cultures of Human Nasal Epithelial Cells.

Rhinovirus (RV) is a primary etiologic agent of common cold that can subsequently acutely exacerbate bronchial asthma or chronic obstructive pulmonary disease. Kakkonto (Ge-gen-tang in Chinese), one of the most frequently prescribed traditional Japanese (Kampo) medicines, is used for treating common cold, shoulder stiffness, or inflammatory diseases of the upper body. Previous experimental studies have indicated that kakkonto exerts antiviral and anti-inflammatory effects on the influenza virus and the human respiratory syncytial virus. However, there is a lack of reports investigating the efficacy of kakkonto in RV infection. Hence, the aim of the current study was to investigate the effects of kakkonto on RV infection of human nasal epithelial (HNE) cells. HNE cells obtained via endoscopic sinus surgery were cultured and infected with RV14, with or without kakkonto treatment. The supernatants from the cells were collected, and the RV14 titer and cytokine levels were assessed. Reverse transcription-polymerase chain reaction was performed to determine the amount of viral RNA, while the level of nuclear factor kappa B (NF-κB) subunits in the nucleus was assessed by enzyme-linked immunosorbent assay. Although kakkonto treatment did not reduce RV14 titer or RNA levels, indicating that it did not inhibit RV14 proliferation, it was found to reduce the production of specific pro-inflammatory cytokines, including interleukin (IL)-8, tumor necrosis factor (TNF)-α, and monocyte chemotactic protein-1 (MCP-1). Unlike that observed with the kakkonto extract, none of the crude drugs contained in kakkonto reduced IL-8 level. Furthermore, though kakkonto treatment significantly reduced p50 levels, it did not impact the p65 subunit of NF-κB. These results indicated that kakkonto can inhibit inflammation caused by RV infection and may exert an immunomodulatory effect on HNE cells. This is the first report to elucidate the effects of kakkonto extract on RV infection in primary cultures of HNE cells, providing evidence that kakkonto may act as an effective therapy for RV infection and subsequent airway inflammation.

[Different stimulation methods on auricular points for primary dysmenorrhea: a randomized controlled trial].

OBJECTIVE: To prove the therapeutic effect of auricular intradermal needling and auricular point sticking on primary dysmenorrhea (PD), and to explore its mechanism. METHODS: A total of 90 patients with PD were randomized into an auricular intradermal needling group, an auricular point sticking group and a placebo group, 30 cases in each one. Neishengzhiqi (TF2), Neifenmi (CO18), Shenmen (TF4), Shen (CO10), Jiaogan (AH6a), Gan (CO12) and Pizhixia (AT4) were selected in the 3 groups, intradermal needling and cowherb seed sticking were applied respectively in the auricular intradermal needling group and the auricular point sticking group, adhesive tape without needle was stuck in the placebo group. Pressing and kneading for 3 to 4 times were required each day, 3 to 4 min each time, and the intervention was started 5 d before menstruation, once every other day, 4 times each menstrual cycle were as one course, and totally 3 courses were required in the 3 groups. The follow-up was adopted at the next menstruation after treatment. The Cox menstrual symptom scale (CMSS) score, the visual analogue scale (VAS) score and the self-rating anxiety scale (SAS) score before treatment, 1,2,3 courses into treatment and at follow-up were compared, the serum levels of PGF2αand PGE2 before and after treatment were detected, and the clinical therapeutic effect was evaluated in the 3 groups. RESULTS: Compared before treatment, the scores of CMSS, VAS and SAS were decreased at each time point of treatment in the auricular intradermal needling group, 2, 3 courses into treatment and at follow-up in the auricular point sticking group and 3 courses into treatment in the placebo group (P<0.001, P<0.05). Compared with the auricular point sticking group, the CMSS scores at each time point of treatment and the VAS scores of 1, 2 courses and at follow-up were decreased in the auricular intradermal needling group (P<0.05). Compared with the placebo group, the CMSS scores were decreased at each time point of treatment in the auricular intradermal needling group and 3 courses into treatment and at follow-up in the auricular point sticking group (P<0.001, P<0.05); the VAS scores were decreased at each time point of treatment in the auricular intradermal needling group and the auricular point sticking group (P<0.001, P<0.05). After treatment, the serum levels of PGF2α were decreased (P<0.05) and the serum levels of PGE2 were increased (P<0.05) in the auricular intradermal needling group and the auricular point sticking group, and the serum levels of PGF2α were lower than the placebo group (P<0.05), the serum levels of PGE2 were higher than the placebo group (P<0.05) in the two groups. Compared with the auricular point sticking group, the serum level of PGF2 was decreased (P<0.05), the serum level of PGE2α was increased in the auricular intradermal needling group (P<0.05). The total effective rates were 93.3% (28/30) in the auricular intradermal needling group and 80.0% (24/30) in the auricular point sticking group, which were both superior to 63.3% (19/30) in the placebo group (P<0.05). CONCLUSION: Auricular intradermal needling and auricular point sticking can both improve the clinical symptom of primary dysmenorrhea, relieve the pain and anxiety, their mechanism may be related to regulating the serum levels of PGF2α and PGE2. The therapeutic effect of auricular intradermal needling is superior to auricular point sticking, and the placebo effect can be preliminarily excluded.

Higenamine alleviates allergic rhinitis by activating AKT1 and suppressing the EGFR/JAK2/c-JUN signaling.

BACKGROUND: Allergic rhinitis (AR) is an inflammatory, immunoglobulin E (IgE)-mediated disease characterized by the typical symptoms of sneezing, rhinorrhea, nasal itching, and congestion. Higenamine (HG) is a plant-based alkaloid, possesses a wide range of activities, including vascular and tracheal relaxation, antioxidative, antiapoptotic, anti-inflammatory, and immunomodulatory activities. So far, the effect and the underlying mechanism of HG on AR have not been studied. HYPOTHESIS/PURPOSE: The purpose of this study was to evaluate the effects of HG on AR and investigate its underlying mechanism. METHODS: The effects of HG on AR were evaluated in an ovalbumin-induced AR mouse model. Network pharmacology-based methods such as target prediction, protein-protein interaction (PPI) network analysis, pathway analysis, and molecular docking were used to identify the likely HG targets. Finally, we validated the mechanism of action of HG through its effects on these targets in human nasal epithelial cells (HNEpCs). RESULTS: Oral administration of 30, 60, and 120 mg/kg HG significantly alleviated rubbing and sneezing in AR mice and attenuated histopathological changes in the lung and nasal tissues. Additionally, HG reduced the levels of IgE, histamine, and IL-4 in the serum of AR mice, and regulated imbalance in Th1/Th2 cells. Using network pharmacology-based methods, we identified 29 HG targets related to AR. These targets are mainly involved in the PD-L1, relaxin, estrogen, HIF-1, Th1 and Th2 cell differentiation, T cell receptor, and the Th17 cell differentiation signaling pathways. Molecular docking showed that HG may well be suited to the receptor binding pockets of key target AKT1, EGFR, c-Jun, NOS2, and JAK2. In HNEpCs, HG inhibited the histamine-induced mRNA expression and secretion of interleukin (IL)-6, and IL-8, as well as the expression of MUC5AC and the phosphorylation of NF-κB. Moreover, HG affected the changes of AKT1, EGFR, c-Jun, iNOS, and JAK2 induced by histamine. CONCLUSION: Overall, our results suggest that HG may alleviate AR by activating AKT1 and suppressing the EGFR/JAK2/c-JUN signaling. HG, therefore, has great potential as a therapeutic agent for the treatment of AR.

[Needle-embedding treatment for hemifacial spasm: research progress].

The articles regarding needle-embedding treatment for hemifacial spasm published before September 30, 2019 were searched from SinoMed, Wanfang, CNKI, VIP and PubMed database, and were analyzed and summarized from treatment methods, acupoint selection, stage differentiation and action mechanism. As a result, 45 Chinese articles were obtained. The needle-embedding treatment was divided into intradermal needling and acupoint thread-embedding; the top five acupoints were Sibai (ST 2), Taiyang (EX-HN 5), Dicang (ST 4), Jiache (ST 6) and spasm trigger points. The basic research of needle-embedding treatment for hemifacial spasm is weak, and the literature regarding stage differentiation is insufficient, which are in need of further study.

Electroacupuncture Promotes Neural Proliferation in Hippocampus of Perimenopausal Depression Rats via Wnt/ß-Catenin Signaling Pathway.

BACKGROUND AND OBJECTIVE: Perimenopausal depression is caused by the impaired function of the ovarium before menopause and with a series of symptoms. Electroacupuncture (EA) therapy has been demonstrated to improve clinically depression. However, the mechanism underlying its therapeutic activity remains unknown. This study aimed to investigat the effects of EA treatment on the hippocampal neural proliferation through Wnt signaling pathway. METHODS: Chronic unpredictable mild stress (CUMS) combined with bilateral ovariectomy (OVX) were used to establish a rat model of perimenopausal depression. The open field test (OFT) and sucrose preference test (SPT) were used to assess depression-like behaviors in rats. ELISAs were used to measure estrogen (E2), luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) levels in the serum. RT-PCR and Western blot assay were utilized for measuring the mRNA expressions and protein expressions of GSK-3ß/ß-catenin. RESULTS: Four-week EA treatment at three points including "Shenshu" (BL23), "Baihui" (GV20) and "Sanyinjiao" (SP6) simultaneously ameliorated depression-like behaviors in rats with CUMS and OVX, whereas rescued the decreased serum level of E2 and prevented the increased serum levels of GnRH and LH. EA treatment ameliorated CUMS and OVX-induced alterations of glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin mRNA levels, ß-catenin and phosphorylated ß-catenin (p-ß-catenin) protein levels. CONCLUSIONS: The results showed that EA treatment promoted hippocampal neural proliferation in perimenopausal depression rats via activating the Wnt/ß-catenin signaling pathway, indicating that EA may represent an efficacious therapy for perimenopausal depression.

Effect of circulation and micro-aeration on sludge characteristics and microbial community in an ABR for treating traditional Chinese medicine wastewater.

The effects of circulation reflux and micro-aeration on the performance of a modified anaerobic baffled reactor (ABR) for treatment of traditional Chinese medicine (TCM) wastewater were evaluated. The characteristics of anaerobic sludge and microbial community structure in the modified ABR were also investigated. The results indicated that with conditions of reflux ratio of 1, reflux ratio of 2, reflux ratio of 2 with micro-aeration, and reflux ratio of 3, the modified ABR achieved an average COD removal efficiency of 90%, 87.7%, 87.8%, and 88.4%, respectively. In addition, the NH3-N average removal efficiency was 45.1%, 50%, 55.9%, and 55.4%, respectively. The analysis of excitation-emission matrix (EEM) fluorescence spectra of soluble microbial products (SMP) and extracellular polymeric substances (EPS) showed that there were tyrosine-like, aromatic protein-like, and coenzyme F420 substances in the sludge. The EPS were analysed by the Fourier transform infrared spectroscopy (FTIR), which showed that aromatic compounds were partially degraded, while the protein and polysaccharide compounds increased in each compartment of the modified ABR. Interestingly, the microbial community of anaerobic sludge analysis results showed that Chloroflexi was the dominant in the first, third and fourth compartments. Meanwhile, Levilinea and Methanothrix were the dominant species in the first and third compartments at the genus level.

The combined effect of oleonuezhenide and wedelolactone on proliferation and osteoblastogenesis of bone marrow mesenchymal stem cells.

BACKGROUND: Regulation of the survival and differentiation of bone marrow mesenchymal stem cells is an essential consideration in the development of targeted drugs for treatment of osteoporosis. PURPOSE: The present study aimed to evaluate the combined effect of wedelolactone and oleonuezhenide, two compounds from Chinese formula Er-Zhi-Wan, on osteoblastogenesis and the underlying molecular mechanisms. METHODS: MTT assay was taken to evaluate cell proliferation. The alkaline phosphatase (ALP) activity assay was used to determine the activity of ALP. Alizarin red S (ARS) staining was taken to indicate the intensity of the calcium deposits. Quantitative real-time PCR and Western blot were performed to the levels of Runx2, Osteocalcin, and Osterix expression in mouse bone marrow mesenchymal stem cells (BMSCs). Ovariectomized mouse model and bone histomorphometric analysis were also used to research the effects of wedelolactone and oleonuezhenide on bone loss caused by ovariectomy. RESULTS: Wedelolactone combined with oleonuezhenide enhanced osteoblast differentiation and bone mineralization. Osteoblastogenesis-related marker genes including osteocalcin, Runx2, and osteorix were upregulated in the presence of wedelolactone and oleonuezhenide. At the molecular level, oleonuezhenide did not affect GSK-3ß phosphorylation induced by wedelolactone, but elevated casein kinase 2-alpha (CK2α) expression, resulting in ß-catenin and Runx2 nuclear translocation. In addition, 30 µM wedelolactone-induced cytotoxicity in bone marrow mesenchymal stem cells was relieved by 9 µM oleonuezhenide. These cells were protected by oleonuezhenide and maintained osteoblastic activity. Oleonuezhenide increased Wnt5a and CK2α expression. Wedelolactone-reduced extracellular signal-regulated kinase (ERK) phosphorylation was reversed by oleonuezhenide. In ovariectomized mice, administration of wedelolactone and oleonuezhenide prevented ovariectomy-induced bone loss by enhancing osteoblastic activity. CONCLUSION: These results suggested that oleonuezhenide enhanced the effects of wedelolactone on osteoblastogenesis. These two compounds could be developed as a combined therapeutic agent for osteoporosis.

Wedelolactone Enhances Osteoblastogenesis through ERK- and JNK-mediated BMP2 Expression and Smad/1/5/8 Phosphorylation.

Our previous study showed that wedelolactone, a compound isolated from Ecliptae herba, has the potential to enhance osteoblastogenesis. However, the molecular mechanisms by which wedelolactone promoted osteoblastogenesis from bone marrow mesenchymal stem cells (BMSCs) remain largely unknown. In this study, treatment with wedelolactone (2 µg/mL) for 3, 6, and 9 days resulted in an increase in phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal protein kinase (JNK), and p38. Phosphorylation of mitogen-activated protein kinases (MAPKs), ERK and JNK started to increase on day 3 of treatment, and p38 phosphorylation was increased by day 6 of treatment. Expression of bone morphogenetic protein (BMP2) mRNA and phosphorylation of Smad1/5/8 was enhanced after treatment of cells with wedelolactone for 6 and 9 days. The addition of the JNK inhibitor SP600125, ERK inhibitor PD98059, and p38 inhibitor SB203580 suppressed wedelolactone-induced alkaline-phosphatase activity, bone mineralization, and osteoblastogenesis-related marker genes including Runx2, Bglap, and Sp7. Increased expression of BMP2 mRNA and Smad1/5/8 phosphorylation was blocked by SP600125 and PD98059, but not by SB203580. These results suggested that wedelolactone enhanced osteoblastogenesis through induction of JNK- and ERK-mediated BMP2 expression and Smad1/5/8 phosphorylation.

The inhibitory effect of Aconiti Sinomontani Radix extracts on the proliferation and migration of human synovial fibroblast cell line SW982.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconiti Sinomontani Radix is frequently used in the treatment of Bi syndrome in traditional Chinese medicine. Several reports indicate that Aconiti Sinomontani Radix has therapeutic effects for rheumatoid arthritis (RA). However, the cellular mode of action is still unclear. To investigate the effect of alkaloid extracts of Aconiti Sinomontani Radix on proliferation and migration of human synovial sarcoma SW982 cells as well as the molecular mechanism underlying. MATERIALS AND METHODS: SW982 cells were examined for proliferation by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method. Wound scratch assays were performed to assess the migrated rate of SW982 cells. Quantitative real-time PCR was used to measure the mRNA expression levels of Wnt5a, Runx2, MMP3, and Bmp2. Western blotting was used to measure the phosphorylated levels of JNK and NF-κB as well as the expression of MMP3. RESULTS: The alkaloid extract from Aconiti Sinomontani Radix (MQA) and MQB, which removed lappaconitine from MQA significantly inhibited the proliferation of SW982 in a dose-dependent manner. The proliferation inhibitory effect of MQB was more potent. Incubation with 10µg/ml MQB for 12, 24, and 36h inhibited the migration of SW982 cells by 83%, 58%, and 42%, respectively. Treatment with different concentrations of MQB for 24h inhibited mRNA expression of Wnt5a, Runx2, and MMP3, but Bmp2 mRNA expression was elevated by MQB. Further, MQB inhibited phosphorylation of JNK and NF-κB p65 as well as MMP3 expression by Western blotting analysis. CONCLUSION: The results showed that MQB inhibited proliferation and migration of SW982 cells possibly through suppressing Wnt5a-mediated JNK and NF-κB pathways. These results indicated that MQB might be an active extract of Aconiti Sinomontani Radix for targeting fibroblast-like synoviocytes (FLS) and be potential for RA therapy.

[Research progress of Guanxin Danshen formula and its effective components in treating coronary artery heart disease].

Coronary artery heart disease (CHD) is one of the common cardiovascular diseases in clinical. The morbidity and mortality of CHD recently continue increasing in our country, which has aroused wide attention. Many studies confirm that traditional Chinese medicine has better therapeutic effect on CHD. Guanxin Danshen formula, widely used in the treatment of CHD, consists of Salviae Miltiorrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and volatile oil from Dalbergiae Odoriferae Lignum, and has the efficacy in promoting blood circulation to resolve stasis, regulating the circulation of Qi and alleviating pain. This review summarized the pharmacologic effects and mechanism of Guanxin Danshen formula and its effective components in the treatment of CHD to provide reference for its fundamental research and clinical application.

[Research progress in epigenetic regulation of myocardial ischemia/ reperfusion injury by traditional Chinese medicine].

Epigenetic is a hotspot of post-genomic era research, and epigenetic modification is a mechanism in the study of cardiovascular disease. Myocardial ischemia-reperfusion injury (MIRI) is one of the problems in the cardiovascular disease, and many experimental interventions are reported in the protection of the ischemic myocardium in experimental animals. However, with the exception of early reperfusion, none has been translated into clinical practice. There is an advantage of traditional Chinese medicine (TCM) in the regulation of epigenetic modification, and pathogenesis of myocardial ischemia-reperfusion injury. This review article is prepared to cover the research progress in the treatment of myocardial ischemia-reperfusion injury by TCM with a focus on epigenetic regulation. The epigenetic regulation is documented in TCM theory through a systematic review of the protecting drugs in the MIRI development guidelines.

Comparison of Beneficial Effects of Acupuncture at PC6, LU7 & Non- acupuncture Points on Cardiac Cell Function in Myocardial Ischemia (MI) Rats by Testing Protein Expression of L-type Calcium Channel Protein and its Related Protein.

The mechanism of why electro-acupuncture (EA) at PC6 improves the heart function was investigated by studying how the L-type cardiac voltage-dependent calcium channel in myocardial ischemia (MI) is regulated. Cava,., Cavo and Cava2-61 are main component proteins of L-type calcium channel; CaM and Calmodulin kinase II (CaMKII) are Ca2+ channel associated proteins. In this experiment, MI was induced by injection of isoproterenol (ISO) in rats and electrocardiograms (ECGs) were recorded before and after every injection, and protein expressions of Cava,c, Cavp, Cava2_61, CaM and CaMKII were higher [The protein expression increased 43.39%, 54.85%, 47.08%, 48.29% and 50.36% respectively] than the control rats significantly (p<0.05). After MI induction, the MI rats were divided into three groups, including PC6 (Neiguan-point), LU7 (Lieque-point) and Non-acupuncture-point group, which were acupunctured once a day for 7 days respectively. After EA at PC6, the protein expressions showed obvious decrease [EA at PC6: the protein expressions of Cava1c, CavP, Cava2-81, CaM and CaMKII decreased 26.36%, 27.58%, 25.21%, 27.21% and 26.61% respectively.] and they are all lower than MI rats significantly (p<0.05). After EA at LU7 and Non-acupuncture-point, the protein expressions showed no significant changes. The effect of EA at PC6 was significantly better than LU7 and Non- acupuncture-point (p<0.05). PC6 is an acupoint of the pericardium meridian, and the pericardium meridian, which corresponds to opioid system according to Li P's research, can affect the cardio-vascular function directly. LU7 is located on the lung meridian; it cannot affect the heart function directly although the lung is related to the heart in blood circulation function so PC6 showed the target treating effect of meridian specificity on regulating the L-type calcium channel in MI.

[Analgesic effect of electroacupuncture on gastric ulcer rats with liver-depression syndrome].

OBJECTIVE: To explore the analgesic effect and action mechanism of electroacupuncture (EA) on gastric ulcer rats with liver-depression syndrome. METHODS: Through open-field experimental method, 45 qualified SPF-grade male SD rats were selected and divided into a blank group, a model group and an EA group according to random number table method, 15 rats in each group. The model of gastric ulcer rats with liver-depression syndrome was established in the model group and the EA group by using chronic unpredictable stimulation combined with acetic acid burning method. Rats in the blank group did not receive intervention. Rats in the model group were treated with fixation and immobilization for 13 days. Rats in the EA group were treated with EA at "Liangqiu" (ST 34) and "Ganshu" (BL 18); EA voltage was 2 V; disperse-dense wave was selected with 4 Hz of disperse wave and 15 Hz of dense wave, and the intensity of EA was according to the slight vibration of local skin and; muscles; the needles were retained for 20 min, once a day for consecutive 6 days; there was an interval of 1 day' and the treatment was given for 2 weeks. The general condition, open-field experimental result and gastric ulcer index were observed; the western blotting method was applied to measure the expression of vanilloid receptor subtype 1 (VR1) in hypothalamus and gastric antral mucosal, and ELISA method was applied to test the expression of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in hippocampus. RESULTS: After model establishment, the general behavior condition in the model group was inferior to that in the blank group, which was obviously improved after EA. The range of motion in the model group was less than that in the blank group (P<0.01) while that in the EA group was higher than that in the model group (P<0.01). The ulcer inhibition rate was. 54.95%, and the ulcer index in the EA group was lower than that in the model group (P<0.01). Compared with; the blank group, the expression of VR1 in hypothalamus and gastric antral mucosal in the model group was increased (P<0.05); compared with the model group, the expression of VR1 in the EA group was reduced (P<0.05). Compared with the blank group, the expression of 5-HT an NE in hippocampus in the model group was significantly reduced (both P<0.01); compared with the model group, the expression of 5-HT and NE in the EA group was increased (both P<0.01). CONCLUSION: EA at "Liangqiu" (ST 34) and "Ganshu" (BL 18) has certain analgesic effect in gastric ulcer rats with liver-depression syndrome, which is likely to be related with lowering the contents of VR1 in hypothalamus and gastric antral mucosal and increasing the content of 5-HT and NE in hippocampus.