Vitamin D plays a protective role in osteoarthritis by regulating AMPK/mTOR signalling pathway to activate chondrocyte autophagy.

OBJECTIVES: The deletion of chondrocyte autophagy seems to play a key role in the pathogenesis of osteoarthritis (OA). Patients with OA often have vitamin D (VD) deficiency, and VD supplementation can improve pain and alleviate the progression of joint structures in patients. In this study, we aimed to investigate whether VD could enhance autophagy by activating the adenosine monophosphate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signalling pathway and protect against OA. METHODS: In this study, the levels of target proteins and genes were examined by western blot and qRT-PCR. Apoptotic cells were detected using TUNEL staining. Characteristics of autophagy were observed by LysoTracker red staining, mRFP-GFP-LC3 adenovirus transfection, and transmission electron microscopy. siRNA-mediated AMPK and mTOR knockdown were used to investigate the role of the AMPK/ mTOR signalling pathway in VD-induced autophagy. Haematoxylin and eosin and safranin-O/fast green staining were used detect cartilage alterations. RESULTS: We suggested that VD significantly reduced chondrocyte death and alleviated extracellular matrix degradation. Further studies showed that VD promoted the expression of the autophagy-related protein LC3II through the AMPK/mTOR signalling pathway in chondrocytes, activated lysosome activity, promoted the formation of autophagy-associated lysosomes, which played a crucial role in the degradation of intracellular organelles and maintained homeostasis. The anti-apoptotic effect of VD on chondrocytes was associated with the activation of autophagy. The group of AMPK-normal and mTOR-knockdown in the presence of VD inhibited chondrocyte apoptosis by promoting autophagy. CONCLUSIONS: This study highlights that VD can activate chondrocyte autophagy through the AMPK/mTOR signalling pathway.

Diagnostic Significance of DCE-MRI-Related Quantitative Parameters for Nasal Cavity and Sinus Tumors.

Objective: Our aim was to explore the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-related quantitative parameters for benign and malignant nasal cavity and sinus tumors. Methods: A total of 78 patients with nasal sinus tumors admitted to People's Hospital of Qingdao Chengyang District in China were enrolled in our study, Of the patients, 41 were diagnosed as having benign tumors and 37 as having malignant tumors by pathological diagnosis. All patients received DCE-MRI scans before surgery to derive time-intensity curves (TICs) and related quantitative parameters (flux rate constant [Kep], transfer constant [Ktrans], extravascular volume fraction [Ve]). The diagnostic surgical pathology results were used as the gold standard to analyze the diagnostic effect of TIC and related quantitative parameters of DCE-MRI, and the receiver operating characteristic (ROC) curves were plotted to determine the values of each parameter in predicting nasal sinus tumors. Results: The percentage of class I in the benign group was significantly higher than in the malignant group (P < .05); the percentage of class III in the benign group was significantly lower than in the malignant group (P < .05); the percentage of class II in the 2 groups was comparable (P > .05). Kep, Ktrans and Ve in the benign group were 0.338±0.124, 0.061±0.035 and 0.532±0.138, respectively; Kep, Ktrans and Ve in the malignant group were 0.785±0.211, 0.441±0.125 and 0.327±0.048, respectively. The levels of Kep and Ktrans were significantly lower in the benign group than in the malignant group (all P < .05); the levels of Ve were significantly higher in the benign group than in the malignant group (P < .05). The optimal Kep cut-off value for predicting malignant nasal sinus tumors was 0.510 min-1, with a sensitivity of 81.4% and specificity of 89.5%; the optimal Ktrans cut-off value for predicting malignant nasal sinus tumors was 0.206 min-1, with a sensitivity of 84.3% and specificity of 89.7%; the optimal Ve cut-off value for predicting malignant nasal sinus tumors was 0.384 min-1, with a sensitivity of 71.8% and specificity of 82.4%. Conclusion: DCE-MRI-related quantitative parameters are ideal for the diagnosis of benign and malignant nasal sinus tumors. This modality provides more data for the identification of the nature of the tumor, and thus merits clinical promotion and application.

Evaluation of adalimumab biosimilar candidate (HS016) in Chinese patients with active ankylosing spondylitis based on a health survey: sub-analysis of a phase 3 study.

OBJECTIVE: The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires. METHODS: We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors. RESULTS: HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks. CONCLUSION: This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction. TRIAL REGISTRATION: http://www.chictr.org.cn/enindex.aspx , ChiCTR1900022520, retrospectively registered. Key points • HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S • The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S • There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab.

Alleviative Effect of Ruellia tuberosa L. on Insulin Resistance and Abnormal Lipid Accumulation in TNF-α-Treated FL83B Mouse Hepatocytes.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, and most patients with T2DM develop nonalcoholic fatty liver disease (NAFLD). Both diseases are closely linked to insulin resistance (IR). Our previous studies demonstrated that Ruellia tuberosa L. (RTL) extract significantly enhanced glucose uptake in the skeletal muscles and ameliorated hyperglycemia and IR in T2DM rats. We proposed that RTL might be via enhancing hepatic antioxidant capacity. However, the potent RTL bioactivity remains unidentified. In this study, we investigated the effects of RTL on glucose uptake, IR, and lipid accumulation in vitro to mimic the T2DM accompanied by the NAFLD paradigm. FL83B mouse hepatocytes were treated with tumor necrosis factor-α (TNF-α) to induce IR, coincubated with oleic acid (OA) to induce lipid accumulation, and then, treated with RTL fractions, fractionated with n-hexane or ethyl acetate (EA), from column chromatography, and analyzed by thin-layer chromatography. Our results showed that the ethyl acetate fraction (EAf2) from RTL significantly increased glucose uptake and suppressed lipid accumulation in TNF-α plus OA-treated FL83B cells. Western blot analysis showed that EAf2 from RTL ameliorated IR by upregulating the expression of insulin-signaling-related proteins, including protein kinase B, glucose transporter-2, and peroxisome proliferator-activated receptor alpha in TNF-α plus OA-treated FL83B cells. The results of this study suggest that EAf2 from RTL may improve hepatic glucose uptake and alleviate lipid accumulation by ameliorating and suppressing the hepatic insulin signaling and lipogenesis pathways, respectively, in hepatocytes.

Application of WALANT technique for repairing finger skin defect with a random skin flap.

BACKGROUND: Wide-awake local anesthesia no tourniquet (WALANT) technique has emerged among hand surgeons with other indications. Surgeries involving pedicled flap and revascularization are no longer used as contraindications. The present study aimed to evaluate the feasibility and merits of the WALANT technique in random skin flap surgery. METHODS: From May 2018 to March 2019, 12 patients with finger skin defects repaired with random skin flaps were reviewed. Abdominal skin flaps or thoracic skin flaps were used to cover the wound. Both the fingers and the donor sites were anesthetized by the WALANT technique. A 40-mL conventional volume consisted of a mixture of epinephrine and lidocaine. A volume of 5 mL was injected at the distal palmar for nerve block, the other 5 mL was injected around the wound for hemostasis, and the remaining was injected at the donor site of flaps for both analgesia and hemostasis. Baseline data with respect to sex, age, side, type of finger, donor sites, flap size, dosage of anesthetics, usage of finger tourniquet, intraoperative and postoperative pain, hemostasis effect, operation time, Disabilities of the Arm, Shoulder, and Hand Questionnaire (QuickDASH) score, and hospitalization expense, were collected. RESULTS: All patients tolerated the procedure, and none of them needed sedation. Single finger skin defect in 8 patients and double finger skin defect occurred in 4 patients; 5 patients were repaired by abdominal skin flaps, and 7 patients were repaired by thoracic skin flaps. The good surgical field visibility was 91.7%. All flaps survived adequately, without necrosis, pulling fingers out, and other complications. The average visual analog scale (VAS) score of the maximal pain was 1.1 in fingers vs. 2.1 in donor sites during the operation. On postoperative day one, the average VAS score of the maximal pain in fingers and donor sites was 1.3 and 1.1, respectively. The average hospitalization expense before reimbursement of the whole treatment was 11% less expensive compared to the traditional method. The average QuickDASH score was 9.1. CONCLUSIONS: Under wide-awake anesthesia, patients have the ability to control their injured upper extremities consciously, avoiding the complications due to pulling flap pedicles. With the merits of safety, painlessness, less bleeding, and effectivity, the WALANT technique in random skin flaps is feasible and a reliable alternative to deal with finger skin defect.

Identification of Bioactive Components from Ruellia tuberosa L. on Improving Glucose Uptake in TNF-α-Induced Insulin-Resistant Mouse FL83B Hepatocytes.

Ruellia tuberosa L. (RTL) has been used as a folk medicine to cure diabetes in Asia. RTL was previously reported to alleviate hyperglycemia, insulin resistance (IR), abnormal hepatic detoxification, and liver steatosis. However, the potential bioactive compounds of RTL have still not been identified. The aim of this study was to investigate the bioactive compounds in RTL ethyl acetate (EA) fractions by using a glucose uptake assay in TNF-α-treated mouse FL83B hepatocytes to discover a mechanism by which to improve IR. The bioactive compounds were identified by the high-performance liquid chromatography (HPLC) assay. Using the Sephadex LH20 gel packing chromatography column, the EAF5 fraction was isolated from RTL and significantly increased glucose uptake in TNF-α-treated FL83B cells. Moreover, the MCI gel packing chromatography column separated EAF5 into five subfractions and had no significant cytotoxic effect in FL83B cells when treated at the concentration of 25 µg/ml. Among the subfractions, EAF5-5 markedly enhanced glucose uptake in TNF-α-treated FL83B cells. The possible bioactive compounds of the EAF5-5 fraction that were identified by the HPLC assay include syringic acid, p-coumaric acid, and cirsimaritin. The bioactive compound with the best effect of increasing glucose uptake was p-coumaric acid, but its effect alone was not as good as the combined effect of all three compounds of the EAF5-5 fraction. Thus, we speculate that the antidiabetic effect of RTL may be the result of multiple active ingredients.

Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19.

PURPOSE: Huashi Baidu formula (HSBDF) was developed to treat the patients with severe COVID-19 in China. The purpose of this study was to explore its active compounds and demonstrate its mechanisms against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through network pharmacology and molecular docking. METHODS: All the components of HSBDF were retrieved from the pharmacology database of TCM system. The genes corresponding to the targets were retrieved using UniProt and GeneCards database. The herb-compound-target network was constructed by Cytoscape. The target protein-protein interaction network was built using STRING database. The core targets of HSBDF were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HSBDF were docked with SARS-CoV-2 and angiotensin converting enzyme II (ACE2). RESULTS: Compound-target network mainly contained 178 compounds and 272 corresponding targets. Key targets contained MAPK3, MAPK8, TP53, CASP3, IL6, TNF, MAPK1, CCL2, PTGS2, etc. There were 522 GO items in GO enrichment analysis (p < .05) and 168 signaling pathways (p < .05) in KEGG, mainly including TNF signaling pathway, PI3K-Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, and HIF-1 signaling pathway. The results of molecular docking showed that baicalein and quercetin were the top two compounds of HSBDF, which had high affinity with ACE2. CONCLUSION: Baicalein and quercetin in HSBDF may regulate multiple signaling pathways through ACE2, which might play a therapeutic role on COVID-19.

Anti-cancer Effects of a Neutral Triterpene Fraction from Ganoderma lucidum and its Active Constituents on SW620 Human Colorectal Cancer Cells.

BACKGROUND: Ganoderma lucidum (Leyss. ex Fr.) Karst. (G. lucidum, GL) belongs to the family of Ganodermataceae (Basidiomycetes), and possesses activities including antitumor, antimicrobial, antiviral, and antiaging activities. Triterpenoids are typical chemical constituents in G. lucidum, and play an important role in the anti-cancer effects. According to the substituent group at the carbon 26 position, GL total triterpenes fraction can be divided into two types, Neutral Triterpene Fraction (NTF) and an Acidic Triterpene Fraction (ATF). The anti-cancer effects of total triterpenes fraction and total acidic triterpene fraction extracted from G. lucidum have been widely known in vivo and in vitro, whereas few have focused on total neutral triterpene fraction. OBJECTIVE: The aim of this study was to evaluate the anti-cancer effects of NTF extracted from G. lucidum in vitro and in vivo and explore its anti-cancer active constituents on SW620 human colorectal cancer cells. METHODS: NTF and ATF were extracted from the dry fruiting body of G. lucidum by impregnation method with 90% ethanol, and further isolated by using alkaline extraction and acid precipitation method. The total triterpenoid content of NTF and ATF was determined by using ultraviolet-visible spectrophotometry. The cytotoxic effects on human colon cancer cells SW480, SW620, SW1116, and mouse embryonic fibroblast cell line NIH3T3 were evaluated by using the MTT method. The anti-cancer activity of NTF in vivo was evaluated in Athymic nude mice against SW620 cells. An activity-guided separation and purification process were used to identify the anti-cancer active constituents of NTF by column and preparative high-performance liquid chromatography. Structures of the constituents were confirmed by 1H-NMR, 13C-NMR and MS. Protein expression was performed by Western blotting. RESULTS: The percentage of total triterpenoids was 46.7% and 57.6% in ATF and NTF, respectively. Both fractions could reduce the viability of SW480, SW620, and SW1116 cells in vitro, whereby NTF exhibited a stronger effect than ATF. NTF markedly inhibited the growth of SW620 cell xenografts in mice at doses (250, 500mg/kg) during the treatment. Furthermore, a new garnoderic alcohol, named as ethyl ganoderate A and eight known ganoderic alcohols were isolated and identified from NTF by a bioassay-guided separation process. All of these compounds possessed anti-cancer activities against SW620 cells in vitro. As a representative ganoderma alcohol, ganodermanondiol significantly reduced the viability of SW620 cells through the induction of apoptosis, which was associated with the upregulated the levels of cleaved-poly (ADP-ribose) polymerase (PARP), cleaved-caspase-3, and -9. In addition, ganodermanondiol showed low cytotoxic activity against normal NIH3T3 cells. CONCLUSION: NTF are potential anti-cancer agents against colon cancer and the active constituents may be ganoderic alcohols whose inhibitory mechanism of anti-cancer action may be related to the activation of a mitochondrial- dependent pathway.

Genome-wide DNA methylation changes in placenta tissues associated with small for gestational age newborns; cohort study in the Chinese population.

Aim: To investigate DNA methylation changes in placenta tissues associated with small for gestational age (SGA). Materials & methods: A prospective cohort study consisting of 1292 pregnant women from China (including 39 SGA with placenta tissues) was performed, microarray and pyrosequencing were conducted. Results: Total 2012 methylation variable positions stood out from all probes (p < 0.05; Δß > 0.2). In SGA cases, a CpG site within ANKRD20B showed lower methylation level (p = 0.032) than appropriate for gestational age in validation cohort. Five sites within FAM198A (p = 0.047, 0.050, 0.039, 0.026 and 0.043, respectively) had a reduced methylation in male newborns whose mother had preconception folic acid supplementation. Conclusion: DNA methylation changes in placenta tissues may be associated with SGA, maternal preconception folic acid supplementation status and also be fetal sex-specific.

Modeling nitrogen and phosphorus export with InVEST model in Bosten Lake basin of Northwest China.

Bosten Lake is an important region of Northwest China that has transformed from a freshwater lake to a saltwater lake since the 1970s. The water quality in the Bosten Lake basin is important for social and economic development, and nitrogen (N) and phosphorus (P) are the key indicators of water quality. The land use data, precipitation data and Digital Elevation Model (DEM) data with the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model were used to simulate the N and P exports of the Bosten Lake basin. The spatial and temporal dynamics of nitrogen and phosphorus exports, and the response of nitrogen and phosphorus exports to land use change and precipitation change were analyzed between 2000 and 2015. The results show that the amount of N and P exports increased during 2000-2015, and the N and P exports are mainly distributed around Bosten Lake. The N and P exports are greatly affected by cultivated land, built-up areas and grassland, while they are less affected by other land use types. The high precipitation areas with small exports of N and P are mainly distributed in mountain areas, while small precipitation areas with large exports of N and P are distributed in plains where the cultivated land and built-up areas are concentrated. The InVEST model can be used in Northwest China, and the statistical downscaling of reanalysis precipitation data can be used in the InVEST model to improve the simulation accuracy in the data scarce regions of Northwest China.

Isaindigotone as an inhibitor of the lipopolysaccharide­induced inflammatory reaction of BV­2 cells and corresponding mechanisms.

Isaindigotone possesses extensive pharmacological activities, including anti­inflammatory effects. The present study investigated the role of isaindigotone in the inhibition of neuroinflammation. Mouse BV­2 cells were incubated with lipopolysaccharide (LPS; 1 mg/l) for 24 h in a microglial inflammatory model in vitro. The effects of isaindigotone on BV­2 cell proliferation were observed using the 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide method. Following co­incubation, an enzyme­linked immunosorbent assay and western blot analysis were used to analyze cellular levels of cytokines and associated protein expression, including the phosphorylation of nuclear factor (NF)­κB. The effects of isaindigotone concentration on LPS­mediated cell chemotaxis behavior were assessed using a chemotaxis assay. The results indicated that isaindigotone is non­toxic towards BV­2 cells. Compared with the LPS group, isaindigotone significantly reduced the secretion of tumor necrosis factor­α and interleukin­1ß in BV­2 cells and reduced the cell chemotaxis caused by LPS; it also reversed morphological changes in the BV­2 cells and inhibited the phosphorylation of NF­κB. The results of the present study suggest that isaindigotone can inhibit inflammatory reactions in LPS­induced BV­2 cells, and provides a theoretical basis and experimental evidence for examining the mechanism underlying the isaindigotone­induced inhibition of neuroinflammation.

Protein-rich extract of Musca domestica larvae alleviated metabolic disorder in STZ-induced type 2 diabetic rat model via hepatoprotective and pancreatic ß-cell protective activities.

The study was designed to explore the beneficial effect of Musca domestica larvae extract (MDLE) on a metabolic disorder using a diabetic rat model. Streptozotocin-induced diabetic rats were treated with or without MDLE. Blood glucose, insulin levels, lipid profiles, and oxidative stress markers were measured. The morphological changes in the pancreas and liver were determined, as well as insulin expression. The expression of glucose transporter 4 (GLUT4), phospho-adenosine monophosphate-activated protein kinase (p-AMPK)/total AMPK, superoxide dismutase 1 (SOD1), catalase (CAT), and peroxisome proliferator-activated receptor gamma (PPARγ) were detected. Compared with untreated diabetic rats, MDLEtreated rats had decreased urine volume, food intake, and water intake, along with significantly lower levels of blood glucose, malondialdehyde (MDA), plasma triglycerides, low-density lipoprotein (LDL), and total cholesterol. MDLEtreated rats also had higher levels of SOD activity, high-density lipoprotein (HDL), and insulin. MDLE treatment partially restored the ß-cell population, improved the liver necrosis and islet cell damage, reversed the decreased expression of GLUT4, phospho-AMPK, SOD1, and CAT in the liver, skeletal muscle and pancreatic tissue, and also increased the expression of PPARγ in the liver and adipose tissue in diabetic rats. In conclusion, the obtained results suggest that MDLE could possibly be used pharmacologically as an adjuvant for the treatment of diabetes.

Bufalin reverses acquired drug resistance by inhibiting stemness in colorectal cancer cells.

Drug resistance is an obstacle to chemotherapy in tumor patients. Recent studies have shown that the high stemness of cancer cells may be induced by chemotherapeutic drugs, which is correlated with drug resistance. In the present study, we investigated the effects of bufalin on the stemness of colorectal cancer. We found that cisplatin could induce high stemness through the tumorsphere formation assay in vitro and in vivo in the colorectal cancer cell lines HCT116 and LoVo. In addition, cisplatin-treated tumorsphere cells showed drug­resistant properties. These results suggested that acquired drug resistance induced by cisplatin in colorectal cancer cells occurred via high stemness. On assessing the effects of bufalin, a traditional Chinese medicine monomer, we found that it could reverse the high stemness and drug resistance induced by cisplatin in colorectal cancer. These findings suggest that bufalin plays an adjuvant role in colorectal cancer chemotherapy and may help reverse acquired drug resistance. These findings may aid in the development of new therapeutic strategies.

Elimination of quiescent slow-cycling cells via reducing quiescence depth by natural compounds purified from Ganoderma lucidum.

The medical mushroom Ganoderma lucidum has long been used in traditional Chinese medicine and shown effective in the treatment of many diseases including cancer. Here we studied the cytotoxic effects of two natural compounds purified from Ganoderma lucidum, ergosterol peroxide and ganodermanondiol. We found that these two compounds exhibited cytotoxicity not only against fast proliferating cells, but on quiescent, slow-cycling cells. Using a fibroblast cell-quiescence model, we found that the cytotoxicity on quiescent cells was due to induced apoptosis, and was associated with a shallower quiescent state in compound-treated cells, resultant from the increased basal activity of an Rb-E2F bistable switch that controls quiescence exit. Accordingly, we showed that quiescent breast cancer cells (MCF7), compared to its non-transformed counterpart (MCF10A), were preferentially killed by ergosterol peroxide and ganodermanondiol treatment presumably due to their already less stable quiescent state. The cytotoxic effect of natural Ganoderma lucidum compounds against quiescent cells, preferentially on quiescent cancer cells vs. non-cancer cells, may help future antitumor development against the slow-cycling cancer cell subpopulations including cancer stem and progenitor cells.

Antitumor effects and mechanisms of Ganoderma extracts and spores oil.

Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self-prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ganoderma extracts and spores oil presented dose-dependent inhibitory effects on tumor cells. The half maximal inhibitory concentration (IC50) values of Ganoderma extracts on HL60, K562 and SGC-7901 cells for 24 h were 0.44, 0.39 and 0.90 mg/ml, respectively; for Ganoderma spores oil, the IC50 values were 1.13, 2.27 and 6.29 mg/ml, respectively. In the in vivo study, the inhibitory rates of Ganoderma extracts (4 g/kg/d, intragastrically) on S180 and H22 cells were 39.1 and 44.6%, respectively, and for Ganoderma spores oil (1.2 g/kg/d, intragastrically) the inhibitory rates were 30.9 and 44.9%, respectively. Ganoderma extracts and spores oil inhibited the activities of topoisomerase I and II. Ganoderma spores oil was shown block the cell cycle at the transition between the G1 and S phases and induce a marked decrease in cyclin D1 levels in K562 cells, with no significant change in cyclin E level. These results suggest that the Ganoderma extracts and spores oil possessed antitumor effects in the in vitro and in vivo studies. The antitumor mechanisms of the extracts and spores oil were associated with inhibitory effects on topoisomerase I and II activities, and for Ganoderma spores oil, the antitumor effects may also be associated with decreased cyclin D1 levels, thus inducing G1 arrest in the cell cycle.

Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects.

L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3.

Efficacy and safety of Xinfeng capsule in patients with rheumatoid arthritis: a multi-center parallel-group double-blind randomized controlled trial.

OBJECTIVE: To evaluate the efficacy. and safety of Xinfeng capsule in patients suffering rheumatoid arthritis (RA). METHODS: A multi-center parallel-group designed, double-blind, randomized, controlled trial was conducted. Totally 304 RA patients were assigned to two groups: one group was administered Xinfeng capsule (XFC) plus the placebo of leflunomide and the other given leflunomide (LEF) plus the placebo of XFC for twelve weeks. The clinical and laboratory parameters were compared at baseline and fourth, eighth, and twelfth weeks. RESULTS: After twelve-week treatment, patients in two groups all showed some trend of effectiveness when compared in terms of American Rheumatism Association (ACR) recommended 20%, 50%, 70% improvement criteria, but it was insignificant. The validity in ameliorate modified disease activity score (DAS28) and laboratory indexes as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) were also found no difference. The score of health assessment questionnaire (HAQ), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and quality of life questionnaire with rheumatoid arthritis (RAQOL) both lower than the first week and the changes showed no difference. However, the score of SDS dropped more in XFC group than in the other. A total of 147 adverse reaction cases were reported, which shows no difference between the two groups. The most common adverse reactions were hepatic impairment, anemia, leukocytopenia, epigastric discomfort and phalacrosis. CONCLUSION: XFC demonstrated better improvement in the scores of SDS and compared with those of LEF group.

Efficient inhibition of growth of metastatic cancer cells after resection of primary colorectal cancer by soluble Flt-1.

Removal of primary tumors often leads to increases in growth of metastatic tumor cells. Thus, development of an efficient treatment to inhibit the growth of metastatic tumor cells after resection of primary tumors appears to be critical for cancer therapy. Here, we reported that administration of a Chinese medicine Shiquandabutao (SQDBT) after removal of the primary cancer significantly inhibited the growth of metastatic cancer cells in mouse liver. Further analyses showed that the effect of SQDBT resulted from one of its main component, Siwutang (SWT), rather than from another main component, Sijunzitang (SJZT). Moreover, we found that the soluble Flt-1 from SWT neutralized the increased placental growth factor (PLGF) secreted by the metastatic cancer cells after primary cancer resection and subsequently inhibited the cancer neovascularization to suppress the metastatic cancer growth. Thus, our study reveals an essential role of SQDBT in inhibiting the growth of metastatic cancer after removal of primary cancer and further highlights PLGF as a potential target for metastatic cancer treatment.

A Chinese herbal Formula, Chang-Wei-Qin, Synergistically Enhances Antitumor Effect of Oxaliplatin.

Chang-Wei-Qing (CWQ), a Chinese herbal formula, has long been employed clinically to treat cancers. In this study, we investigated the synergistic effect of CWQ with oxaliplatin (OXA) on the tumor growth inhibition of orthotopic transplanted colon cancer and explored the underlying mechanism. By generating the orthotopic transplanted nude mouse model of human colon carcinoma, we found that (1) CWQ enhanced OXA-mediated tumor suppression by 4.25-fold. (2) The body weights of nude mice in CWQ group and combination group were increased. (3) The survival time of tumor-bearing nude mice was dramatically improved in CWQ and CWQ/OXA group. (4) CWQ could restore OXA-mediated deregulation of copper transporter genes, hCTR1, ATP7A and ATP7B. (5) OXA-induced drug resistance index for OXA, 5-FU, HCPT and THP were 7.59, 4.28, 5.78 and 4.50 respectively, while the reversal index by combined CWQ treatment were 6.57, 2.61, 4.97 and 3.10, respectively. Our study demonstrates that the repeated intraperitoneal injection of OXA can induce multi-drug resistance of orthotopic transplanted nude mouse model of human colon carcinoma. The CWQ treatment can alleviate OXA-triggered side effects and reverse platinum drug resistance via up-regulation of hCTR1 expression and down-regulation of ATP7A and ATP7B levels.

Case-only designs for exploring the interaction between FCRL4 gene and suspected environmental factors in patients with ankylosing spondylitis.

The aim of this study was to explore the interaction between FCRL4 gene and environmental factors in patients with ankylosing spondylitis. Two hundred ninety-seven ankylosing spondylitis (AS) Han Chinese patients were selected who were diagnosed at the Department of Rheumatology, First Affiliated Hospital, Anhui Medical University, in accordance with the modified New York criteria. The single nucleotide polymorphism (SNP) was genotyped by multiplex SNaPshot technique. The interaction between FCRL4 gene and ten environmental factors in AS patients was assessed by using a case-only study. The interaction between FCRL4 gene (rs2777963) and environmental factors was analyzed by chi-square test and logistic models. p values, odds ratio, and 95 % confidence intervals (CIs) were used for estimating the effects of interaction. Odds ratio (OR) for the interaction of gene × environment (G × E) between drinking group and non-drinking group was 2.61 [95 % CI (1.30, 5.23), p=0.007], with statistical significance. Within the cooking oil group, there also may be an interaction of G × E between main animal oil and main plant oil [OR=10.55, 95 % CI (5.55, 20.04), p<0.001]. However, there was no interaction between FCRL4 gene and the other eight environmental factors in patients with AS. The observed significant gene-environment interaction suggests that drinking and cooking oil with FCRL4 gene has a significant interaction. Drinking and cooking oil may be risk exposure factors to take a combined action with predisposing genes in patients with AS. A larger sample case-control study is needed to illustrate the interaction mechanism in the further study.