The Antifungal Mechanism of Isoxanthohumol from Humulus lupulus Linn.

Humulus lupulus Linn. is a traditional medicinal and edible plant with several biological properties. The aims of this work were: (1) to evaluate the in vitro antifungal activity of H. lupulus ethanolic extract; (2) to study the in vitro and in vivo antifungal activity of isoxanthohumol, an isoprene flavonoid from H. lupulus, against Botrytis cinerea; and (3) to explore the antifungal mechanism of isoxanthohumol on B. cinerea. The present data revealed that the ethanolic extract of H. lupulus exhibited moderate antifungal activity against the five tested phytopathogenic fungi in vitro, and isoxanthohumol showed highly significant antifungal activity against B. cinerea, with an EC50 value of 4.32 µg/mL. Meanwhile, it exhibited moderate to excellent protective and curative efficacies in vivo. The results of morphologic observation, RNA-seq, and physiological indicators revealed that the antifungal mechanism of isoxanthohumol is mainly related to metabolism; it affected the carbohydrate metabolic process, destroyed the tricarboxylic acid (TCA) cycle, and hindered the generation of ATP by inhibiting respiration. Further studies indicated that isoxanthohumol caused membrane lipid peroxidation, thus accelerating the death of B. cinerea. This study demonstrates that isoxanthohumol can be used as a potential botanical fungicide for the management of phytopathogenic fungi.

HUS1 checkpoint clamp component (HUS1) is a potential tumor suppressor in primary hepatocellular carcinoma.

The HUS1 checkpoint clamp component (HUS1), which is a member of an evolutionarily conserved, genotoxin-activated checkpoint complex (Rad9-Rad1-Hus1 [9-1-1] complex), is involved in cell cycle arrest and DNA repair in response to DNA damage. We conducted this study to investigate the biological significances of HUS1 expression in hepatocellular carcinoma (HCC) development. The mRNA and protein expression levels of HUS1 were determined using Real-time PCR and Western blot, respectively. One hundered and twenty four paraffin sections from HCC tissues were analyzed by immunohistochemistry to assess the association between HUS1 expression and clinicopathological characteristics of patients. The Kaplan-Meier method was performed to calculate the OS and RFS curves. Cell proliferation and colony formation assays, cell migration and invasion assays and cell cycle assays were used to determine the suppressor role of HUS1 in vitro. A mouse model was used to determine the effect of HUS1 on tumorigenesis. The expression of HUS1 was significantly decreased in HCC cell lines and tissues, and low HUS1 expression was associated with poor prognosis of HCC patients. Upregulation of HUS1 expression inhibited the cell proliferation, colony formation, migration, and invasion, as well as arrested cell cycle at G0/G1 in HCC cells in vitro. Moreover, sufficient HUS1 expression inhibited the tumor growth in nude mice. Our study revealed for the first time that HUS1 is a potential tumor suppressor that might produce an antitumor effect in human HCC. Furthermore, HUS1 may serve as a prognostic indicator and could be used for therapeutic application in HCC patients.

Inhibition of invasion by N-trans-feruloyloctopamine via AKT, p38MAPK and EMT related signals in hepatocellular carcinoma cells.

N-trans-feruloyloctopamine (FO) isolated from Garlic skin was identified as the primary antioxidant constituents, however, the effect of which on HCC invasion is still unclear. Herein, the FO was synthesized and its antitumor activities were evaluated in HCC cell lines. Cellular functional analyses have revealed that the reformed FO owns strong abilities of inhibiting cell proliferation and invasion in HCC cells. Molecular data have further showed that FO could significantly decrease the phosphorylation levels of Akt and p38 MAPK. In addition, the expression of Slug was inhibited and the level of E-cadherin increased. Molecular docking analysis indicates that the H-bond and hydrophobic interactions were critical for FO and E-cadherin binding, but FO did not seem to act directly on phosphorylated Akt and p38 MAPK. We have thus concluded that reformed FO inhibits cell invasion might be directly through EMT related signals (E-cadherin) and indirectly through PI3K/Akt, p38 MAPK signaling pathways. FO might be a promising drug in HCC treatment and prognosis.

Effect of the tyrosinase inhibitor (S)-N-trans-feruloyloctopamine from garlic skin on tyrosinase gene expression and melanine accumulation in melanoma cells.

In our searching for novel tyrosinase inhibitors from natural sources, (S)-N-trans-feruloyloctopamine isolated from garlic skin was found to be a potential mushroom tyrosinase inhibitor. Here, we examined the effects of the potential tyrosinase inhibitor in B16F10 cells on intracellular melanin contents, cytotoxicity, and the signaling mechanism involved in the expression of tyrosinase. The results showed the inhibitor displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin contents in a dose-dependent manner in the α-MSH-stimulated B16F10 cells. Real-time PCR and Western blot analysis showed that it inhibits melanogenesis signaling by down-regulates mRNA and protein expression levels of tyrosinase, which leads to a lower melanin contents. These results suggested that (S)-N-trans-feruloyloctopamine was an ideal tyrosinase inhibitor, and could be used in food and medical industry.

Protective effects of the bioactive natural product N-trans-Caffeoyldopamine on hepatotoxicity induced by isoniazid and rifampicin.

In our searching for novel antioxidants from natural sources, N-trans-Caffeoyldopamine which was from natural product was found to be a potential compound for its remarkable antioxidant activity. Isoniazid (INH) and Rifampicin (RFP) is widely used for the treatment of Tuberculosis (TB) as the first line drugs, have been known to be potentially hepatotoxic and may lead to drug-induced liver injury. Oxidative stress has been regarded as the major mechanism of the hepatotoxicity. Therefore, in this study, the possible protective effects of N-trans-Caffeoyldopamine was investigated in the hepatotoxicity caused by INH and RFP in rats. Results showed that serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and hepatic malondialdehyde (MDA) content were reduced dramatically, and hepatic superoxide dismutase (SOD) activity and glutathione (GSH) content were restored remarkably by N-trans-Caffeoyldopamine co-administration, as compared to the INH-RFP treated rats (p<0.01). Moreover, the histopathological damage of liver and the number of apoptotic hepatocytes were also significantly ameliorated by the treatment. It is therefore suggested that N-trans-Caffeoyldopamine can provide a definite protective effect against acute hepatic injury caused by INH and RFP in rats, which may mainly be associated with its antioxidative effect. Mechanisms studies indicated that it inhibited the lipid peroxidation through the cytochrome P450 2E1 (CYP2E1) downregulation.

Antimicrobial activity of natural and semi-synthetic carbazole alkaloids.

Since the first natural carbazole alkaloid, murrayanine, was isolated from Mwraya Spreng, carbazole alkaloid derivatives have been widely concerned for their anti-tumor, anti-viral and anti-bacterial activities. In recent decades, a growing body of data suggest that carbazole alkaloids and their derivatives have different biological activities. This is the first comprehensive description of the antifungal and antibacterial activities of carbazole alkaloids in the past decade (2012-2022), including natural and partially synthesized carbazole alkaloids in the past decade. Finally, the challenges and problems faced by this kind of alkaloids are summarized. This paper will be helpful for further exploration of this kind of alkaloids.

Efficacy of pterostilbene suppression on Aspergillus flavus growth, aflatoxin B1 biosynthesis and potential mechanisms.

Aspergillus flavus, a widespread saprotrophic filamentous fungus, could colonize agricultural crops with aflatoxin contamination, which endangers food security and the agricultural economy. A safe, effective and environmentally friendly fungicide is urgently needed. Pterostilbene, a natural phytoalexin originated from Pterocarpus indicus Willd., Vaccinium spp. and Vitis vinifera L., has been reported to possess excellent antimicrobial activity. More importantly, it is quite safe and healthy. In our screening tests of plant polyphenols for the inhibition of A. flavus, we found that pterostilbene evidently inhibited mycelial growth of Aspergillus flavus (EC50 = 15.94 µg/mL) and the inhibitory effect was better than that of natamycin (EC50 = 22.01 µg/mL), which is a natural product widely used in food preservation. Therefore, we provided insights into the efficacy of pterostilbene suppression on A. flavus growth, aflatoxin B1 biosynthesis and its potential mechanisms against A. flavus in the present study. Here, pterostilbene at concentrations of 250 and 500 µg/mL could effectively inhibit the infection of A. flavus on peanuts. And the biosynthesis of the secondary metabolite aflatoxin B1 was also inhibited. The antifungal effects of pterostilbene are exerted by inducing a large amount of intracellular reactive oxygen species production to bring the cells into a state of oxidative stress, damaging cellular biomolecules such as DNA, proteins and lipids and destroying the integrity of the cell membrane. Taken together, our study strongly supported the fact that pterostilbene could be considered a safe and effective antifungal agent against A. flavus infection.

Phenolic compounds from cultivated Glycyrrhiza uralensis and their PD-1/PD-L1 inhibitory activities.

One new compound (1) and fifteen known phenolic compounds (2-16) were isolated and identified from the roots and rhizomes of Glycyrrhiza uralensis, including ten flavonoids, four coumarins, and two benzofurans compounds. Their structures were identified by NMR and MS analysis. Most of these compounds showed weak PD-1/PD-L1 inhibitory activities with the inhibition ratios from 30 to 65% at 100 uM. To our knowledge, it is the first time that their PD-1/PD-L1 inhibition activities were reported.

Transcranial Sonography of the Substantia Nigra for the Differential Diagnosis of Parkinson's Disease and Other Movement Disorders: A Meta-Analysis.

This meta-analysis aimed to evaluate the accuracy of hyperechogenicity of the substantia nigra (SN) for the differential diagnosis of Parkinson's disease (PD) and other movement disorders. We systematically searched the PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases for relevant studies published between January 2015 and May 2020. Eligible articles comparing the echogenicity of the SN between patients with PD and those with other movement disorders were screened, and two independent reviewers extracted data according to the inclusion and exclusion criteria. Statistical analyses were conducted using STATA (version 15.0) (Stata Corporation, College Station, TX, USA), Review Manager 5.3 (Cochrane Collaboration), and Meta-DiSc1.4 to assess the pooled diagnostic value of transcranial sonography (TCS) for PD. Nine studies with a total of 1046 participants, including 669 patients with PD, were included in the final meta-analysis. Our meta-analysis demonstrated that hyperechogenicity of the SN had a pooled sensitivity and specificity of 0.85 (0.82, 0.87) and 0.71 (0.66, 0.75), respectively, for distinguishing idiopathic Parkinson's disease from other movement disorders. Furthermore, the area under the curve of the summary receiver operating characteristic was 0.94. Transcranial sonography of the SN is a valuable tool for the differential diagnosis of PD and other movement disorders.

[Evaluation of 93 cases of mandibular first molar root bifurcation lesions treated with autologous dentin Granules combined with platelet-rich fibrin membrane].

PURPOSE: To investigate the efficacy of autologous dentin particles combined with platelet-rich fibrin membrane (PRF) in the treatment of root bifurcation lesions of mandibular first molar. METHODS: Ninety-three patients (93 teeth) with mandibular first molar root bifurcation lesions were selected from our department from February 2016 to October 2017. They were randomly divided into 2 groups. Forty-six patients with 46 teeth in the experimental group underwent autologous dentin particles combined with platelet-rich fibrin membrane, while patents in the control group (47 patients with 47 teeth) were treated with Bio-Oss implanted in the bone defect area covered with collagen membrane. The patients were revisted at 1, 3, 6 and 12 months after operation. The success rate of the operation group, the depth of periodontal pocket (PD), the loss of attachment (AL), the depth of penetration of the root bifurcation (HPD), and the bone density of the root bifurcation area before and after treatment. The data were recorded and compared with SPSS25.0 software package. RESULTS: The success rate was 97.83%(45/46) in the experimental group, 85.11%(40/47) in the control group, the difference between the two groups was significant(P<0.05). After treatment, PD, AL and HPD decreased significantly (P<0.05), and MGVs increased gradually. There was no significant difference in MGVs before treatment and 1 month after treatment in the experimental group (P>0.05). MGVs at other time points were significantly higher than those of the control group (P<0.05). PD, AL and HPD of the experimental group were lower significantly than the control group at each time point after treatment (P<0.05), and MGVs value was significantly higher than the control group (P<0.05). There was no significant difference in the incidence of complications(4.35% vs 6.38%, χ2=0.189, P>0.05). CONCLUSIONS: Autologous dentin particles combined with platelet-rich fibrin membrane is effective for the treatment of root bifurcation lesions of mandibular first molar, which is worthy of wide application.

[ClinicaAnalysis of osteosclerotic protein expression and bacterial distribution in periodontitis patients at different stages].

PURPOSE: To investigate the osteosclerin level and bacterial distribution in periodontitis patients at different stages, and to analyze the correlation between osteosclerin and the parameters of conventional periodontal examination. METHODS: Patients with periodontitis admitted to Guangzhou Huadu Maternal and Child Health Hospital from March 2017 to June 2019 were selected and divided into stage Ⅱ group (n=27), stage Ⅲ group (n=42) and stage Ⅳ group (n=22) according to the severity of periodontitis; meanwhile, 30 healthy individuals underwent physical examination in our hospital during the same period were selected as control group. Gingival crevicular fluid and plaque at buccal and lingual sites were collected for bacterial culture. The expression of osteosclerotin in gingival crevicular fluid was detected by enzyme-linked immunosorbent assay. The data were processed by SPSS 23.0 software package. Spearman correlation analysis was used to analyze the correlation between BI grade and osteosclerin, and correlation between PD, CAL and osteosclerin was determined by Pearson analysis. RESULTS: The mean PD and mean CAL of patients in stage Ⅱ group before and after treatment were significantly smaller than those in stage Ⅲ and Ⅳ group (P<0.05). The mean CAL of stage Ⅳ group before treatment was significantly greater than that of stage Ⅲ group (P<0.05). After treatment, the mean PD and mean CAL of three groups were all significantly smaller than those before treatment (P<0.05). The mean PD in stage Ⅲ group was significantly lower than that in stage Ⅳ group after treatment (P<0.05). Before treatment, the proportion of BI grade 2 in stage Ⅱ group was significantly higher than that in stage Ⅲ and Ⅳ group (85.19%, 19.05%, 18.18%, P<0.05). Before treatment, the proportion of BI grade 3 in stage Ⅲ group was significantly higher than that in stage Ⅱ group (64.29%, 14.81%, P<0.05). Before the treatment, the expression of osteosclerosis protein in stage Ⅱ group was significantly lower than that in stage Ⅲ and Ⅳ group (P<0.05). The levels of osteosclerin expression of three groups after treatment were all significantly lower than those before treatment (P<0.05). The expression of osteosclerosis protein in stage Ⅱ group was significantly lower than that in stage Ⅲ and Ⅳ group after treatment (P<0.05). PD, CAL and BI of patients with different stages of periodontitis were positively correlated with osclerosin in gingival crevicular fluid before and after treatment (P<0.05). The number of bacteria detected in stage Ⅳ group was significantly higher than that in stage Ⅲ group and stage Ⅱ group. The main bacteria in each group were anaerobic bacteria. The dominant bacteria were Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetes, Fusobacterium nucleatum, and Prevotella melaninogenicus. CONCLUSIONS: The expression level of osteosclerosin is closely related to PD, CAL and BI grades in patients with periodontitis, and bacterial colonization levels in gingival crevicular fluid and dental plaque in patients with periodontitis at different stages are different. Detection of osclerosin level and identification of periodontal microorganism culture have high clinical value in clinical diagnosis of periodontitis severity and can provide reference for selection of subsequent treatment plan.

Combined gastroscopic and choledochoscopic transabdominal nasobiliary drainage.

Common bile duct (CBD) stones are a frequent problem in Chinese populations, and their incidence is particularly high in certain areas (Wang et al., 2013). In recent years, laparoscopic common bile duct exploration (LCBDE) and endoscopic retrograde cholangiopancreatography (ERCP) have been the main surgical procedures for CBD stones, although each has different advantages and disadvantages in the treatment of choledocholithiasis (Loor et al., 2017; Zhou et al., 2017). For patients with large stones, a dilated CBD, especially concurrent gallstones, LCBDE is the preferred and most economical minimally invasive procedure (Koc et al., 2013). However, a T-tube is often placed during LCBDE to prevent postoperative bile leakage; this is associated with problems such as bile loss, electrolyte disturbance, and decreased gastric intake (Martin et al., 1998). In addition, the T-tube usually must remain in place for more than a month, during which time the patient's quality of life is seriously compromised. Many skilled surgeons currently perform primary closure of the CBD following LCBDE, which effectively speeds up rehabilitation (Hua et al., 2015). However, even in sophisticated medical centers, the incidence of postoperative bile leakage still reaches ≥10% (Liu et al., 2017). Especially for a beginner, bile leakage remains a key problem (Kemp Bohan et al., 2017). Therefore, a safe and effective minimally invasive surgical approach to preventing bile leakage during primary closure of the CBD after LCBDE is still urgently needed.

Realgar transforming solution-induced differentiation of NB4 cell by the degradation of PML/RARα partially through the ubiquitin-proteasome pathway.

PML/retinoic acid receptor alpha (RARα), as a hallmark of acute promyeloid leukemia (APL), is directly related to the outcome of clinical APL remedy. It is reported that arsenicals can effectively degrade PML/RARα, such as arsenic trioxide and realgar. However, the high toxicity or insolubility have hampered their clinical applications. Realgar transforming solution (RTS) was produced from realgar by bioleaching process in our lab. Previous studies demonstrated that RTS had a significant anti-cancer ability on chronic myeloid leukemia through oncoprotein degradation. The capacity of RTS on treating APL is what is focused on in this study. The results showed that RTS had a noticeable sensitivity in NB4 cell, and RTS remarkably down-regulated PML/RARα expression and induced cell differentiation. Further, RTS could accumulate PML/RARα into the nuclear bodies and then execute degradation, which could be reversed by proteasome inhibitor MG132. The results also exhibited that the reduction of RTS-induced PML/RARα expression accompanied by the elevation of ubiquitin and SUMO-1 protein expression. Finally, PML and SUMO-1 had been demonstrated to be co-localized after RTS treatment by immunofluorescence co-localization assay and immunoprecipitation assay. In conclusion, these results suggested that RTS-induced cell differentiation may attribute to the PML/RARα degradation partially through the ubiquitin-proteasome pathway.

Clinical Effect of Adjuvant Cytokine-Induced Killer Cells Immunotherapy in Patients with Stage II-IVB Nasopharyngeal Carcinoma after Chemoradiotherapy: A propensity score analysis.

As an adjuvant immunotherapy, cytokine-induced killer cells (CIKs) infusion has been demonstrated to exert potent effectiveness in several types of cancer patients who received curative treatment. However, controversy exists regarding whether nasopharyngeal carcinoma (NPC) patients can benefit from additional treatment after radical radiotherapy or chemoradiotherapy to improve their distant control and survival. In this retrospective study, we aimed to evaluate the efficacy of adjuvant CIK cells therapy in NPC patients with stage II-IVB after curative treatment. From January 1, 2005 to December 31, 2012, 85 pairs of NPC patients matching by propensity score matching (PSM) method to balance prognostic factors were included in this study: 85 cases underwent radical treatment, 85 cases received radical treatment and sequential CIKs infusion. We found that disease-free survival (DFS) and overall survival (OS) were significantly better in the CIK group than that in the control group (P = 0.009, P < 0.001, respectively). Adjuvant CIK cells immunotherapy was showed to be an independent prognostic factor for survival of the patients in further multivariate analysis. In subgroup analyses, the DFS and OS of patients with T3/4, III and IV A-B TNM (tumor-node-metastasis) stages were significantly enhanced in CIK group compared to control group. Nevertheless, both NPC patients with high and low EBV DNA benefited from adjuvant CIK cells immunotherapy. In conclusion, CIKs infusion is an effective adjuvant immunotherapy for enhancing the prognosis of NPC patients who have received the standard treatment, particularly for those with more aggressive tumor (T3/4) or advanced TNM stage.

Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer.

BACKGROUND: Tumor-derived exosomes were considered to be potential candidates for tumor vaccines because they are abundant in immune-regulating proteins, whereas tumor exosomal miRNAs may induce immune tolerance, thereby having an opposite immune function. OBJECTIVE: This study was designed to separate exosomal protein and depleted exosomal microRNAs (miRNAs), increasing the immune activity of exosomes for activating dendritic cell/cytokine-induced killer cells (DC/CIKs) against pancreatic cancer (PC). METHODS: PC-derived exosomes (PEs) were extracted from cultured PANC-1 cell supernatants and then ruptured; this was followed by ultrafiltered exosome lysates (UELs). DCs were stimulated with lipopolysaccharide (LPS), PE, and UEL, followed by co-culture with CIKs. The anti-tumor effects of DC/CIKs against PC were evaluated by proliferation and killing rates, tumor necrosis factor-α (TNF-α) and perforin secretion. Exosomal miRNAs were depleted after lysis and ultrafiltration, while 128 proteins were retained, including several immune-activating proteins. RESULTS: UEL-stimulated DC/CIKs showed a higher killing rate than LPS- and PE-stimulated DC/CIKs. CONCLUSIONS: miRNA-depleted exosome proteins may be promising agonists for specifically activating DC/CIKs against PC.

Two cinnamoyloctopamine antioxidants from garlic skin attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis.

Hepatic oxidative stress plays a key role in the development of non-alcoholic steatohepatitis (NASH), therefore, treatment approaches that address the antioxidant is helpful in the therapy of patients with NASH. N-trans-coumaroyloctopamine (1) and N-trans-feruloyloctopamine (2) were identified as the primary antioxidant constituents of garlic skin with high antioxidant activities. The aim of this study was to elucidate the protective effect and mechanism of the antioxidants on NASH in rats. The results provide morphological and molecular biological evidences for the protective role of the antioxidant 2 in ameliorating oxidative stress and hepatic apoptosis in experimental NASH for the first time. Mechanism study indicated that the antioxidant 2 significantly reduced the expression of COX-2 mRNA and protein by western blot, RT-PCR and immunohistochemical techniques.

A large inflammatory myofibroblastic tumor involving both stomach and spleen: A case report and review of the literature.

Inflammatory myofibroblastic tumor (IMT) is a rare, benign neoplasm that most commonly occurs in pediatric patients; it has been described as a pseudosarcomatous proliferation of spindled myofibroblasts mixed with lymphoplasmacytic cells. IMT has been reported in a number of locations throughout the body; however, cases occurring in the gastrointestinal tract are rare and to date, no case involving both the stomach and spleen has been reported. The current study presents a case of an extremely large IMT invading both the stomach and spleen in a 50-year-old female, presenting with a three-month history of left-sided abdominal distension without abdominal pain, fever or vomiting. As the tumor had invaded the stomach and spleen, it was completely excised and concomitantly, the entire stomach and spleen were removed. Histological examination of the biopsy revealed fascicles of spindle cells in a mixed inflammatory background, with inflammatory cells that were immunopositive for vimentin, smooth muscle actin, and negative for anaplastic lymphoma kinase and CD30, confirming the diagnosis of IMT. Four months following local excision of the mass, accompanied by a total gastrectomy and splenectomy, no abdominal distension, abdominal pain, fever or vomiting were observed and no IMT recurrence was identified.

Anti-tumor effects and apoptosis induction by Realgar bioleaching solution in Sarcoma-180 cells in vitro and transplanted tumors in mice in vivo.

BACKGROUND: Realgar which contains arsenic components has been used in traditional Chinese medicine (TCM) as an anticancer drug. However, neither Realgar nor its formula are soluble in water. As a result, high dose of Realgar has to be administered to achieve an effective blood medicine concentration, and this is associated with adverse side effects. The objective of the present study was to increase the solubility of a formula using hydrometallurgy technology as well as investigating its effects on in vitro and in vivo cell proliferation and apoptosis in Sarcoma-180 cell line. MATERIALS AND METHODS: Antiproliferative activity of Realgar Bioleaching Solution (RBS) was evaluated by MTT assay. Further, effects of RBS on cell proliferation and apoptosis were studied using flow cytometry and transmission electron microscopy. Kunming mice were administered RBS in vivo, where arsenic specifically targeted solid tumors. RESULTS: The results indicated that RBS extract potently inhibited the tumor growth of Sarcoma-180 cell line in a dose-dependent manner. Flow cytometry and transmission electron microscopy further indicated that RBS significantly induced cell apoptosis through the inhibition of cell cycle pathway in a dose-dependent manner. Further, on RBS administration to mice, arsenic was specifically targeted to solid tumors CONCLUSIONS: RBS could substitute for traditional Realgar or its formula to work as a potent tool in cancer treatment.

Synthesis and biological evaluation of hydroxycinnamic acid hydrazide derivatives as inducer of caspase-3.

In order to generate compounds with superior antitumor activity and reduced toxicity, twelve new hydroxycinnamic acid hydrazide derivatives were synthesized and evaluated for their antiproliferative activities against two cancer cell lines (H1299 lung carcinoma cells and MCF-7 breast cancer cells), and compared to two normal counterparts (NL-20 lung epithelial cells and H184B5F5/M10 breast cells) by MTT method. The results demonstrated that some of these compounds possessed good antiproliferative activity against the two cancer cell lines. Among them, compound 2c was active against the growth of H1299 lung carcinoma cells with IC50 values of 1.50 µM, which was more active than the positive topotecan (IC50 = 4.18 µM). Simultaneously, it showed lower cytotoxic effects on normal NL-20 lung epithelial cells (IC50 > 10 µM). Mechanism studies indicated that it induced cell cycle arrest at G2/M phase followed by activation of caspase-3, and consequently caused the cell death. Further studies on the structure optimization are ongoing.

[Comparison of effects of Wujia Bugu decoction) and alendronate sodium on protection the bone loss of hindlimb unloaded rats].

OBJECTIVE: To compare the effects of Wujia Bugu decoction and Alendronate sodium on protecting bone and muscle loss of hindlimb unloaded rats lasting three weeks. METHODS: March to May, 2009, 40 male Wistar rats with age of 6-week, were randomized divided to four groups (10 rats in each group): hindlimb unloaded group treated with Chinese medicine (HUC), hindlimb unloaded group treated with alendronate sodium (HUA), control group (CON), as well as hindlimb unloaded group (HU). During the experiment, rats of HUC was given Wujia Bugu decoction (including the Ciwujia, Shudihuang, Huainiuxi, Muli, etc. with the concentration of 0.704 g/ml) 10 ml/kg weight once a day, HUA was given quantitative alendronate sodium slice dissolve suspension (0.9 mg/ml) once a week. CON and HU were given double-distilled water. The experiment lasted 4 weeks,from the second to the forth week, rats in HU, HUC, HUA were hindlimb unloaded. All rats were sacrificed at the fourth weekend, the content of Ca, P and the activation of ALP in serum, Bone mineral density (BMD) of humerus and femurs, Biomechanical property of tibia and humerus, as well as the weight index of biceps and sural muscles were measured. RESULTS: Compared with CON, serum Ca of HU was significantly increased (P < 0.05), BMD, mechanical properties, muscle index of hindlimb were significantly reduce (P < 0.01), the serum Ca of HUA significantly increased (P < 0.05). Serum ALP of HUC was significantly higher than other three groups (P < 0.01). Compared with HU, femoral BMD of HUC and HUA significantly increased, tibial maximum load, maximum deflection and elastic load had increased tendency; calf muscle atrophy of HUC and HUA was alleviate 50% and 12.5% respectively (P > 0.05), humeral BMD had no significant difference, while the maximum deflection (P < 0.01) and elastic deflection (P < 0.05) in humerus of HUA were significantly lower. CONCLUSION: Herbal prescription and alendronate sodium can effectively protect the bone and muscle loss of hindlimb unloaded rats, improve its mechanical structure. Herbal prescription has advantages of relieving mechanical properties change. The effects of Wujia Bugu decoction and alendronate sodium are similar in treating space weightlessness bone loss.