Diaporpyrone E, an undescribed α-pyrone from the endophytic fungus Diaporthe sp. CB10100.

An undescribed α-pyrone diaporpyrone E (1), and three known nucleotides, 5'-O-acetyl uridine (2), 5'-O-acetyl thymidine (3), and adenine (4), were identified from Diaporthe sp. CB10100, an endophytic fungus isolated from the medicinal plant Sinomenium acutum. The structure of 1 was determined by extensive analysis of its HRMS, 1D and 2D NMR spectroscopic data, as well as electronic circular dichroism calculations and comparison. The in vitro cytotoxic and antibacterial assays of 1 revealed that it has a 30.2% inhibitory effect on HepG2 cells at 50 µM, while no antibacterial activities against Staphylococcus aureus and Klebsiella pneumoniae at 64 µg/mL.

Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction.

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.

Syn-2, 3-diols and anti-inflammatory indole derivatives from Streptomyces sp. CB09001.

Two new natural diols, (2S, 3S, 4S)-4-methyl-1-phenylhexane-2,3-diol (1) and (2S, 3S)-4-methyl-1-phenylpentane-2,3-diol (2), together with five known compounds, xenocyloins B-D (3-5), lumichrome (6) and thymidine (7) were isolated from Streptomyces sp. CB09001. The absolute configurations of 1 and 2 were established by crystallographic structure analysis. The anti-inflammatory effects of 1-7 were also investigated in RAW246.7 murine macrophage cells stimulated by lipopolysaccharide. The indole derivative xenocyloin B (3) significantly inhibited inducible nitric oxide synthase expression in RAW264.7 cells and could be a potential anti-inflammatory drug lead.

Molecular mechanisms of apoptosis in hepatocellular carcinoma cells induced by ethanol extracts of Solanum lyratum Thumb through the mitochondrial pathway.

AIM: To explore the induction effects and mechanism of Solanum lyratum Thumb (ST) on human hepatocellular carcinoma SMMC-7721 cells through the mitochondrial pathway. METHODS: The experiments were conducted on three groups: an experimental group (with ST ethanol extracts' concentration being 2.5, 5 and 10 mg/L), a negative control group (with only nutrient solution, 0 mg/L ST ethanol extracts), and a positive control group (2.5 mg/L DDP). The inhibition rate of cell proliferation was checked by using the methyl thiazolyl tetrazolium method, and cell apoptosis was tested by TUNEL method. Furthermore, RT-PCR was used to examine mRNA expression of Fas, FasL, caspase-8, caspase-3, p53 and Bcl-2 genes. RESULTS: Compared with the negative control group, the inhibition and apoptosis rates of the experimental group with different concentrations of ST extracts on human hepatocellular carcinoma SMMC-7721 cells significantly increased (P < 0.05). Besides, the mRNA expression of FasL and Bcl-2 significantly decreased (P < 0.05) while the mRNA expression of Fas, caspase-8, caspase-3 and p53 increased significantly. When compared with the positive control group, the experimental groups with 5 mg/L ST ethanol extracts showed effects similar to the positive control group. CONCLUSION: ST ethanol extracts induced the apoptosis of hepatocellular carcinoma SMMC-7721 cells through up-regulated Fas, caspase-8, caspse-3 and p53, and down-regulated FasL and Bcl-2 in the mitochondrial pathway.

Novel augmentation by bufalin of protein kinase C-induced cyclooxygenase-2 and IL-8 production in human breast cancer cells.

Cyclooxygenase-2 (COX-2) and IL-8 are two inflammatory mediators induced by protein kinase C (PKC) via various stimuli. Both contribute significantly to cancer progression. Bufalin, a major active component of the traditional Chinese medicine Chan Su, is known to induce apoptosis in various cancer cells. This study clarifies the role and mechanism of bufalin action during PKC regulation of COX-2/IL-8 expression and investigates the associated impact on breast cancer. Using MB-231 breast cancer cells, bufalin augments PKC induction of COX-2/IL-8 at both the protein and mRNA levels, and the production of prostaglandin E2 (PGE2) and IL-8. The MAPK and NF-κB pathways are involved in both the PKC-mediated and bufalin-promoted PKC regulation of COX-2/IL-8 production. Bufalin increases PKC-induced MAPKs phosphorylation and NF-κB nuclear translocation. PGE2 stimulates the proliferation/migration of breast cancer cells. Furthermore, PKC-induced matrix metalloproteinase 3 expression is enhanced by bufalin. Bufalin significantly enhances breast cancer xenograft growth, which is accompanied by an elevation in COX-2/IL-8 expression. In conclusion, bufalin seems to promote the inflammatory response in vitro and in vivo, and this occurs, at least in part, by targeting the MAPK and NF-κB pathways, which then enhances the growth of breast cancer cells.

[Combination of acupressure and magnetic sticker improved the quality of life in patients with advanced gastroenteric tumor: a clinical observation].

OBJECTIVE: To explore the clinical effect of combination of acupressure and magnetic sticker on the quality of life (QOL) including appetite, defecation, and sleep in patients with advanced gastroenteric tumor. METHODS: Totally 147 patients with advanced gastroenteric tumor were assigned to 4 groups according to different treatment methods, i.e., the supportive treatment group (A, 20 cases), the acupressure treatment group (B, 41 cases), the magnetic sticker treatment group (C, 40 cases), and a combination of acupressure and magnetic sticker treatment group (D, 46 cases). They were respectively treated with different methods, supportive treatment for group A, acupressure for group B, magnetic sticker for group C, and a combination of acupressure and magnetic sticker for group D. The scores of food intake, defecation frequency, sleep time, Karnofsky, and QOL were compared before treatment and at day 14 after treatment. RESULTS: After treatment, the scores of food intake, defecation frequency, and sleep time were obviously improved in B, C and D groups (P < 0.01). There was statistical difference between group D and group A (P < 0.01). In addition, in comparison with A group, both Karnofsky score and QOL score increased in B, C and D groups (P < 0.01). CONCLUSION: The assisted therapy of the combination of acupressure and magnetic sticker could ameliorate QOL such as the digestive functions and sleep in patients with advanced gastroenteric tumor.

Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, ameliorates adriamycin-induced renal inflammation and glomerular injury via inhibiting p38MAPK signaling pathway activity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of inflammatory diseases in China. Huangkui capsule (HKC), an extract from AM, has been proved clinically effective in improving renal inflammation and glomerular injury in chronic kidney disease (CKD). However, the dose-effects and the mechanisms involved in vivo are still unclear. AIM OF THE STUDY: This study was performed to examine the dose-effects of HKC on renal inflammation and glomerular lesion in adriamycin-induced nephropathy (ADRN), then to clarify the mechanisms in vivo of HKC by investigating its actions on modulating the activation of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. MATERIALS AND METHODS: The rats with chronic ADRN, created by the unilateral nephrectomy and twice adriamycin injections (ADR, 4 mg/kg and 2mg/kg) within 4 weeks, were divided into four groups, a Sham group, a Vehicle group, a high-dose HKC group, and a low-dose HKC group, and that, sacrificed at the end of the 4th week after the administration. The rat's general status, renal morphological appearance, proteinuria, blood biochemical parameters, glomerular morphological changes, podocyte shape, and macrophage (ED1(+) and ED3(+) cells) infiltration in glomeruli were examined, respectively. The protein expressions of inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-2, as well as p38MAPK signaling molecules such as transforming growth factor (TGF)-ß1, p38MAPK, and phosphorylated-p38MAPK (p-p38MAPK), were also evaluated individually. RESULTS: HKC at high dose of 2g/kg/d not only significantly ameliorated the rat's general status, renal morphological appearance, proteinuria, albumin, and glomerulosclerosis, but also obviously reduced the infiltrated ED1(+) and ED3(+) macrophages in glomeruli and TNF-α protein expression in the kidney, in addition to these, evidently down-regulated TGF-ß1 and p-p38MAPK protein expressions in ADRN rats, but had no influence on podocyte shape and renal function. CONCLUSION: HKC could dose-dependently ameliorate renal inflammation and glomerular injury in ADRN rats, by way of reducing the infiltration and the activation of macrophages in glomeruli, and TNF-α protein expression in the kidney, as well as inhibiting p38MAPK signaling pathway activity via the down-regulation of p-p38MAPK and TGF-ß1 protein expressions in vivo.

Multi-glycoside of Tripterygium wilfordii Hook. f. reduces proteinuria through improving podocyte slit diaphragm dysfunction in anti-Thy1.1 glomerulonephritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) has been proved clinically effective in reducing proteinuria in chronic kidney disease in China. However, the mechanisms involved are still unclear. In this study we examined the effects of GTW at the different dosages on proteinuria and podocyte slit diaphragm (SD) dysfunction in anti-Thy1.1 glomerulonephritis (GN). MATERIALS AND METHODS: Rats with anti-Thy1.1 GN were divided into 2 groups, a GTW group and a vehicle group, and sacrificed at 30 min, on day 7, and on day 14 in Experiments 1, 2 and 3, respectively. The administration of GTW at the moderate and high doses was started 3 days before or at the same time of antibody injection till sacrifice. Proteinuria was determined in Experiments 1, 2, and 3. After sacrifice, the staining intensity of SD-associated key functional molecules including nephrin and podocin, podocyte structure, mesangial change, macrophage infiltration, and blood biochemical parameters were examined, respectively. Protein and mRNA expressions of nephrin and podocin in glomeruli were also investigated. Besides, liver histological characteristics were analyzed. RESULTS: In Experiment 1, GTW pretreatment at the medium dose (75 mg/kg body weight) caused no influence on the induction of anti-Thy1.1 GN and the basal nephrin expression. In Experiment 2, the high dosage (100mg/kg body weight) of GTW ameliorated proteinuria, the distribution of nephrin and podocin, mesangial proliferation, and the activated macrophage accumulation, as compared with vehicle group (P<0.05). Additionally, it increased mRNA and protein expressions of nephrin and podocin in glomeruli on day 7, but had no influence on podocyte structure. In Experiment 3, the medium dosage (75 mg/kg body weight) of GTW improved proteinuria, the partial matrix expansion, and the distribution of nephrin and podocin on day 14, as compared with anti-Thy1.1 GN rats (P<0.05). GTW at the high or moderate dose did not affect hepatic function on day 7 and on day 14. CONCLUSIONS: Podocyte SD dysfunction, such as the disordered distribution and down-regulation of nephrin and podocin expression, is critically involved in the pathogenesis of anti-Thy1.1 GN induced by mAb 1-22-3. The restoration of the distribution and expression of nephrin and podocin by GTW could be an important mechanism by which GTW ameliorates proteinuria and podocyte SD dysfunction.

An uncoupling screen for autonomous embryo mutants in Arabidopsis thaliana.

Simple de novo screens in Arabidopsis thaliana have previously identified mutants that affect endosperm development but viable-embryo mutants have not been identified. Our strategy to identify autonomous embryo development was to uncouple embryo and endosperm fertilisation. This involved a male-sterile mutant population being crossed with a distinct pollen parent--the pollen was needed to initiate endosperm development and because it was distinct, the maternal progeny could be selected from the hybrid population. This process was refined over three stages, resulting in a viable approach to screen for autonomous embryo mutants. From 8,000 screened plants, a mutation was isolated in which the integument cells extended from the ovule and proliferated into a second complete twinned ovule. Some embryos from the mutant were normal but others developed fused cotyledons. In addition, a proportion of the progeny lacked paternal genes.

Targeting TGF-beta in prostate cancer: therapeutic possibilities during tumor progression.

BACKGROUND: TGF-beta regulates prostate growth by inhibiting epithelial cell proliferation and inducing apoptosis through eliciting a dynamic signaling pathway. In metastatic prostate cancer, however, TGF-beta serves as a tumor promoter. TGF-beta engages Smad-dependent and Smad-independent mechanisms to exert its action. During prostate tumorigenesis, prostate cells exhibit loss or mutation of TGF-beta transmembrane receptors. Increased production of TGF-beta causes immunosuppression, extracellular matrix degradation, epithelia to mesenchymal transition and angiogenesis that promotes tumor cell invasion and metastasis. OBJECTIVE: The molecular basis for effective therapeutic targeting of TGF-beta must be directed towards the double-edge-sword nature of the cytokine: inhibiting the TGF-beta tumor promoter capabilities in advanced metastatic prostate cancer, although retaining the growth-inhibitory abilities exhibited in early stages of prostate tumorigenesis. RESULTS/CONCLUSION: The current understanding of the therapeutic possibilities of targeting TGF-beta signaling during prostate tumor progression is built on preclinical studies. Studies targeting TGF-beta signaling pathway for the treatment of several human malignancies include the use of neutralizing antibodies, antisense oligonucelotides and small molecule inhibitors of kinase activity of the receptor complex. This review focuses on exploiting the therapeutic potential of targeting TGF-beta signaling in the context of its contribution to prostate cancer initiation and progression to metastasis.

[Apoptosis-inducing effect of Scutellaria barbata extract on human lung cancer SPC-A-1 cells and the expression of apoptosis associated genes].

OBJECTIVE: To explore the apoptosis-inducing effect of Scutellaria barbata extract (SBE) and the expression of apoptosis associated genes survivin and caspase-3 on human lung cancer SPC-A-1 cells. METHODS: Lung cancer SPC-A-1 cells were treated with 2.5, 5 and 10 mg/L for 48 h,and the cells were treated with 2.5 mg/L DDP as positive control. The inhibitory rat was evaluated by MTT assay. Apoptotic rate was determined by TUNEL method. The expression of survivin and caspase-3 mRNA were detected by semi-quantitive RT-PCR. RESULTS: Compared with control group, the inhibitory rate was increased obviously (P < 0.001), the apoptotic rate was increased markedly (P < 0.01), the expression of caspase-3 mRNA was increased significantly (P < 0.05 or P < 0.01), while survivin mRNA was decreased markedly (P < 0.05 or P < 0.01) in SBE groups. CONCLUSION: SBE can induce apoptosis of SPCA-1 cells. The molecular mechanism may be related to up-regulating expression of caspase-3 and down-regulating expression of survivin genes.