[Discussion on the history of Pinelliae Rhizoma Praeparatum(Fa banxia) Processing].

Before the Song Dynasty, the main processing method of Pinelliae Rhizoma was soup washing. The "new method" in Taiping Huimin Heji JuFang is a processing method that concocted with Ginger,white alum and starter-making.The "Fa Banxia" in the Yuan Dynasty's Yuyuan Yaofang comes from the Taiping Huimin Heji JuFang, and the Fa Wen Banxia, Fa Bai Banxia, and Fa Hong Banxia are the processing methods of patent medicine with a variety of other herbs.Fa Banxia appeared in the Ming Dynasty, and its auxiliary materials were ginger and white alum, and medical formulary began to include formulas containing Fa Banxia. Bencao Gangmu abbreviates the Yuan Dynasty's Fabai Banxia as "Fa Banxia", and is elaborated under the item attached "prescription" item instead of the "treatment". In the literature of Materia Medica, it is recorded that the preparation of auxiliary materials in Fa Banxia increased, including lime, licorice, soap horn, and simple nitro.After Daoguang in the Qing Dynasty, the Fa Banxia in famous medical cases was more used, and at that time, Fa Banxia was Xian Banxia. There are two recipes for Xian Banxia: one is made with seven processes, and the other is soaked in alum licorice water. During the Republican period, Zhang Cigong also pointed out that Fa Banxia was sliced Xian Banxia after rinsing and boiling, while the preparation method of Xian Banxia was Banxia made of ginger and white alum.Ye Juquan pointed out that the so-called "fa" is neither an ancient method nor a new method, questioning the process of repeated immersion in Banxia. After 1949, the questioning of Fa Banxia continued unceasing.Influenced by this, the 1960 edition Beijing Traditional Chinese Medicine Slice Cutting Experience included the method of soaking alum, licorice ,lime water, and was included in the 1963 edition of the Pharmacopoeia of the People's Republic of China.The 1985 version reduced the soaking time and eliminated the soaking process of alum based on the 1963 version, and this method is still used today.

Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

Phyllosticta rizhaoensis sp. nov. causing leaf blight of Ophiopogon japonicus in China.

Ophiopogon japonicus (Asparagaceae) is a perennial grass species which can be cultivated as an ornamental and medicinal plant. From April 2021 to September 2022, a serious leaf blight disease of O. japonicus was discovered in Rizhao City, Shandong Province, China. The initial disease symptoms were small yellow spots, finally developing as tip blight, often associated with many small, black, semi-immersed pycnidial conidiomata formed in lesions. To obtain isolates of the causal agent for this disease, samples were randomly collected from O. japonicus diseased leaves in Rizhao City. In total 97 Phyllosticta isolates were obtained from samples, and studied using morphological features and multi-locus phylogenetic analyses of a combined dataset using the internal transcribed spacers (ITS), the 28S large subunit of ribosomal RNA (LSU), and partial translation elongation factor 1-alpha (tef), actin (act) and glyceraldehyde-3-phosphate dehydrogenase (gapdh) loci. Phylogenetically, these Phyllosticta isolates formed a clade in the P. concentrica species complex, and clustered with P. pilospora and P. spinarum. Morphologically, isolates in this clade differed from P. pilospora and P. spinarum by the size of conidiogenous cells and conidia, and the absence of an apical conidial appendage. As a result, these isolates were described as a novel species Phyllosticta rizhaoensis. Pathogenicity was confirmed using Koch's postulates, which showed that P. rizhaoensis could induce leaf blight symptoms on O. japonicus in China. Citation: Wang C-B, Wang T-T, Ma C-Y, Xue H, Li Y, Piao C-G, Jiang N (2023). Phyllosticta rizhaoensis sp. nov. causing leaf blight of Ophiopogon japonicus in China. Fungal Systematics and Evolution 11: 43-50. doi: 10.3114/fuse.2023.11.03.

Dietary supplementation with Bacillus subtilis DSM 32315 alters the intestinal microbiota and metabolites in weaned piglets.

AIM: The study was conducted to investigate the effects of dietary Bacillus subtilis (BS) DSM 32315 on the intestinal microbiota composition and metabolites of weaned pigs. METHODS AND RESULTS: Sixty-four piglets were allocated to two groups (control and BS), each group including eight replicates with four piglets. Dietary BS DSM 32315 increased (P < 0·05) the abundances of jejunal Leucobacter and Cupriavidus, ileal Thermus, Coprococcus and Bifidobacterium, as well as colonic Succiniclasticum; and increased the concentrations of ileal straight-chain fatty acids, colonic propionate, branched-chain fatty acids (BCFAs), and tyramine, but decreased (P < .05) the colonic indole concentration. The ileal and colonic microbial community structure tended to cluster into two groups. LEfSe analysis identified five microbial biomarkers in jejunum and eight biomarkers in ileum in the BS group, and three biomarkers in colon in the control group. The ileal Bifidobacterium abundance was positively correlated (P < 0·05) with isovalerate concentration, while the colonic Actinobacteria and Lactobacillus abundances were negatively correlated (P < 0·05) with indole concentration. CONCLUSION: These findings suggest that dietary supplementation with BS DSM 32315 could alter the diversity, composition, and metabolites of intestinal microbiota in weaned piglets. SIGNIFICANCE AND IMPACT OF THE STUDY: Weaned piglets are often accompanied with impaired gastrointestinal tract and intestinal disorder affecting their growth. This study demonstrated that dietary BS DSM 32315 presented a beneficial role in gut health via regulating intestinal microbiota composition and metabolites.

ELECTROACUPUNCTURE IMPROVES INSULIN SENSITIVITY IN HIGH-FAT DIET-INDUCED INSULIN RESISTANT RATS BY ACTIVATING SIRT1 AND GLUT4 IN QUADRICEPS FEMORIS.

OBJECTIVES: To assess the effects of electroacupuncture (EA) at the Zusanli (ST36), Guanyuan (CV4), Zhongwan (CV12), and Fenglong (ST40) acupoints on sirtuin 1 (SIRT1) and glucose transporter type 4 (GLUT4) expression in high-fat diet (HFD)-induced insulin-resistant (IR) rats. METHODS: Wistar rats were divided into normal control (NC), HFD, and HFD+EA groups. NC rats were fed a standard chow diet and did not receive EA. After being fed an HFD for eight weeks, rats in the HFD+EA group received EA at 2 Hz five times a week for eight weeks. Rats in the HFD group did not receive EA. RESULTS: In HFD-induced IR rats, EA inhibited body weight increase and water intake, which were observed in HFD rats. EA had no effect on fasting blood glucose and postprandial blood sugar levels. Intraperitoneal insulin tolerance testing revealed that EA enhanced insulin sensitivity in HFD-induced IR rats. Compared with NC rats, SIRT1 and GLUT4 were downregulated in the quadriceps femoris of HFD-fed rats but were increased after eight weeks of EA stimulation. CONCLUSIONS: EA enhanced HFD-induced insulin resistance by activating SIRT1 and GLUT4 in the quadriceps femoris. These results provide powerful evidence supporting the beneficial effects of EA on HFD-induced insulin resistance.

Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron.

OBJECTIVE: Methamphetamine (MA) abuse induces neurotoxicity and causes neuronal cell apoptosis. Gastrodin is a traditional Chinese herbal medicine used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. The present study investigated the neuroprotective effects of gastrodin against MA-induced neurotoxicity in neuronal cells and its potential protective mechanism. METHODS: The primary cortex neuronal culture was divided into four groups (control group, MA group, MA + gastrodin group, and MA + gastrodin + small interfering RNA group). The neurotoxicity of MA was assessed by detecting apoptotic cells by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay and cell viability by cell counting kit 8 (CCK-8) method, the Tuj1-positive cells and the average axonal length were detected by immunofluorescence, and the expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding (CREB), and brain-derived neurotrophic factor (BDNF) proteins were detected by Western blot. RESULTS: The results of CCK-8 assay showed that 0.5 mM MA was an optimal concentration that induced neurotoxicity (p < 0.01). Pretreatment with 25 mg/L gastrodin exerted maximum protective effects on neuronal cells. The expression levels of cAMP, PKA, phosphorylated PKA, CREB, phosphorylated CREB, and BDNF proteins were decreased in the MA group, and pretreatment with gastrodin upregulated the expression levels of these proteins (p < 0.01). The expressions of PKA and CREB proteins showed no significant changes in the control group, MA group, and gastrodin group. Compared the MA + gastrodin + small interfering RNA group with MA + gastrodin group, the Tuj1-positive cells and the average axonal length were decreased significantly, while the number of apoptotic cells was increased (p < 0.05). CONCLUSION: Gastrodin has neuroprotective effects against MA-induced neurotoxicity, which exerts neuroprotective effects via regulation of cAMP/PKA/CREB signaling pathway and upregulates the expression of BDNF.

Xuebijing enhances neuroprotective effects of ulinastatin on transient cerebral ischemia via Nrf2-are signal pathways in the hippocampus.

Prior studies have demonstrated that ulinastatin (UTI) plays a beneficial role in regulating cerebral ischemic injury evoked by cardiac arrest (CA). It is noteworthy to find interventions that can enhance effects of this drug and thereby increase its clinical application. Xuebijing (XBJ) is comprised of extracts from Chinese herbs and has been widely used in China as an anti-endotoxicity drug for the treatment of sepsis and ischemic disorders associated with multiple organ dysfunction syndrome. Thus, in this study we examined the effects of a combination of UTI and XBJ to improve neural injury in the process of neurological functions after transient cerebral ischemia. Our results show that CA impaired Nrf2- antioxidant response element (Nrf2-ARE) and superoxide dismutase (SOD) in the hippocampus CA1 region. This process further amplified products of oxidative stress, namely 8-isoprostaglandin F2α (8-iso PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). A lower dose of UTI failed to restore Nrf2-ARE and attenuate 8-iso PGF2α and 8-OHdG SOD following CA; however, systemic administration of XBJ amplified the effects of this dose of UTI on antioxidative signal pathway of the hippocampus. Overall, the results of this study have implications for the enhanced neuroprotective role played by a combination of XBJ and UTI in improving neural injury observed in transient cerebral ischemia; and Nrf2-ARE signal is a part of key mechanisms that are involved in neuroprotective effects of XBJ and UTI.

Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study.

Background: Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. Materials and Methods: This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. Results: No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). Conclusion: Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.

Comparative effect of antipsychotics on risk of self-harm among patients with schizophrenia.

OBJECTIVE: To investigate the association of different antipsychotic treatments with hospitalization due to self-harm among patients with schizophrenia. METHOD: This retrospective cohort study was based on Taiwan's universal health insurance database. Patients aged 15-45 years with a newly diagnosed schizophrenic disorder in 2001-2012 were included. The study outcome was the first hospitalization due to self-harm or undetermined injury after the diagnosis of schizophrenic disorders. The exposure status of antipsychotics was modeled as a time-dependent variable. The analyses were stratified by antipsychotic dosage based on defined daily dose (DDD). RESULTS: Among 70 380 patients with a follow-up of 500 355 person-years, 2272 self-harm hospitalization episodes were identified. Compared with none or former use, current use of several second-generation antipsychotics with a dose of one DDD or above, including amisulpride, aripiprazole, clozapine, risperidone, and sulpiride, was associated with decreased risk of self-harm hospitalization, with clozapine showing the strongest effect (adjusted rate ratio = 0.26, 95% confidence interval 0.15-0.47). CONCLUSION: The protective effect on self-harm may vary across different antipsychotics. Further studies are needed to replicate the findings.

Effect of Mg/Ca molar ratios on characteristics of anaerobic-anoxic denitrifying dephosphatation.

In this study, the effect of three Mg/Ca molar ratios (5.0, 3.8 and 1.7) on denitrifying phosphate removal performance, biomass morphology, and Extracellular Polymeric Substances (EPS) were examined. Results showed that when the influent Mg/Ca molar ratio was 3.8, the anaerobic-anoxic EBPR performed complete phosphate removal. The microbial bacterial population was a mixed culture comprised of 81±3% DPAO and 13±2% denitrifying glycogen accumulating organisms (DGAO). A higher influent Mg/Ca molar ratio (5.0) had a distinct impact on phosphate removal, biomass morphology, and EPS. This probably induced the deterioration of the anaerobic-anoxic Enhanced Biological Phosphorus Removal (EBPR). The results of this study may inform the proper operation of an anaerobic-anoxic EBPR, and contribute to its application in the real world.

Retrospective Cohort Study to Compare Anesthesia in Living Donor Liver Transplantation Recipients Who Received Single and Dual Liver Grafts.

OBJECTIVE: Dual graft living donor liver transplantation (LDLT) is an alternative way to overcome small-for-size syndrome in LDLT. Surgical technique and outcome of using dual grafts have been reported, but there are no reports regarding anesthetic management. The aim of the current study is to compare the anesthetic management of single graft and dual graft liver transplantation. METHODS AND PATIENTS: Anesthesia records of 24 single graft liver transplantation recipients (GI) and 6 dual graft recipients (GII) were reviewed, analyzed, and compared retrospectively. Patient characteristics and intraoperative data between groups were compared with Mann-Whitney t test and Fisher's exact test where appropriate. P value less than .05 was regarded as significant. RESULTS: Patient characteristics and most of the intraoperative data were similar between groups. Significant difference was noted in the total anesthesia time and the anhepatic time. Both times were significantly longer in GII compared to GI. CONCLUSION: Dual graft living donor liver transplantation is surely a technically more challenging and demanding procedure. Therefore the total anesthesia time is longer, especially the anhepatic phase, because there are more graft vessels to be reconstructed before reperfusion. Overall the anesthetic management in terms of blood transfusion, fluid administration, sodium bicarbonate, calcium supplement, and the number of patients requiring fractional diluted noradrenaline support for maintenance of acceptable hemodynamic were not much different between the 2 groups.

Quantification and antioxidant and anti-HCV activities of the constituents from the inflorescences of Scabiosa comosa and S. tschilliensis.

To investigate the bioactive constituents of the inflorescences of Scabiosa comosa and S. tschilliensis, which are used traditionally for liver diseases, we tested the antioxidant activity using 2,2'-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), ferric reducing antioxidant potential (FRAP), and DPPH-ultra high performance liquid chromatography-mass spectrometer (UPLC-MS) assay. In addition, cell-based anti-HCV activity of the major compounds were evaluated. The plant extracts showed strong antioxidant activity. For the first time, 3,4-dicaffeoylquinic acid (DCQA), 3,5-DCQA and 4,5-DCQA were identified from genus Scabiosa. A UPLC-MS method in multiple reaction monitoring (MRM) mode was established to quantify 18 constituents in the inflorescences of Scabiosa. The 3,5-DCQA, chlorogenic acid and some glycosides of luteolin or apigenin were found to be the most abundant constituents. Chlorogenic acid and 3,5-DCQA showed excellent radical scavenging activity and demonstrated anti-HCV activity. These findings provided scientific evidences for the clinic use of this herbal medicine for liver diseases.

Effect of supplementing pasteurized milk balancer products to heat-treated whole milk on the growth and health of dairy calves.

Two experiments were conducted to determine the growth and health effects of supplementing heat-treated whole milk with pasteurized milk balancer products in calf-feeding programs. All calves were removed from their dams at birth (d 0), fed 3.8L of heat-treated colostrum, and received assigned treatments from d 1 until weaning at d 56. Calves were weighed and skeletal measurements taken every 7 d from d 0 until 56. Average daily gain (ADG) and feed efficiency (FE) were calculated. In experiment 1, 80 Holstein heifer calves were used to investigate the effects of supplementing 2 levels of heat-treated whole milk with or without a pasteurized all-milk balancer. Four dietary treatments (n=20) were used. Calves receiving milk (M) and milk plus balancer (M+B) were fed 3.8L of milk divided into 2 equal feedings daily. Calves fed increased milk (IM) and increased milk plus balancer (IM+B) received 3.8L of milk divided into 2 equal feedings from d 1 to 14, 5.7L from d 15 to 42, and 2.85L fed once daily from d 43 to 56. Treatments M+B and IM+B included pasteurized all-milk balancer fed at a rate of 0.23kg per 3.8L of milk. In experiment 2, 72 Holstein heifer calves were used to investigate the effects of supplementing either a pasteurized all-milk balancer or a pasteurized protein-blend milk balancer. Three dietary treatments (n=24) were used. Calves were fed 3.8L of milk divided into 2 equal feedings from d 1 to 14 and 5.7L from d 15 to 56. Treatment IM did not include any supplements. Balancer was added to IM+B and increased milk plus protein-blend balancer (IM+PB). Balancer was supplemented at a rate of 0.23kg per 3.8L of milk. In experiment 1, calves fed IM+B had greater average body weight (BW) and average daily gain compared with calves given other treatments. Calves fed 5.7L of milk had greater FE than those fed 3.8L regardless of balancer added. In experiment 2, calves fed IM+B and IM+PB had greater BW when compared with calves given M. Calves fed IM+PB had comparable BW and FE to calves given IM+B. The enhanced calf-feeding programs evaluated in this study were successful in increasing growth in preweaned calves when supplementing milk balancer product to heat-treated whole milk. Health scores of fecal, respiratory, and attitude determined illness. Feces were looser for calves receiving IM+B and IM+PB, but attitude scores did not confirm an illness and so overall health was not different between treatments.

Recombinant human thyrotropin versus thyroid hormone withdrawal in radioiodine remnant ablation for differentiated thyroid cancer: a meta-analysis.

AIM: We aim to assess the effects of recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal (THW), and rhTSH-aided low doses (1.11 GBq and 1.85 GBq) versus high dose (3.7 GBq) of radioiodine in the residual ablation for differentiated thyroid cancer (DTC). METHODS: Studies were obtained from computerized searches of MEDLINE, EMBASE, the Cochrane Library (all until September 2012). Randomized controlled trials were included. RESULTS: Altogether 1325 patients with DTC participated in seven trials for residual ablation. Overall, studies had a low risk of bias. We found no statistically significant differences between rhTSH and THW treatment in terms of successful ablation rate (OR 0.87, 95% CI 0.56 to 1.37, P=0.56) but significant benefits in health-related quality of life (mean difference 3.59, 95% CI 2.81 to 4.37, P<0.00001), adverse events during and after ablation (OR 0.57, 95% CI 0.44 to 0.73, P<0.00001), radiation exposure to blood and bone marrow (mean difference -0.01, 95% CI -0.02 to -0.01, P<0.00001). In addition, no significant difference was found in the successful ablation rate between the low dose (1.11 GBq and 1.85 GBq) and high dose (3.7 GBq) of radioiodine aided by rhTSH (OR 0.85, 95% CI 0.49 to 1.47, P=0.56). There were no deaths and no serious adverse effects in DTC patients treated with either rhTSH or THW, maximum follow-up was 12 months. None of the included trials investigated secondary malignancies or economic outcomes. CONCLUSION: rhTSH is as effective as THW on radioiodine thyroid remnant ablation with significant benefits on health-related quality of life, adverse effects during and after ablation, decreased whole body radiation exposure. The lower radioiodine doses are as effective as high doses for remnant ablation under rhTSH stimulation.

Budd-Chiari syndrome secondary to toxic pyrrolizidine alkaloid exposure.

In this report, we describe a case of pyrrolizidine alkaloid-related Budd-Chiari syndrome in Hong Kong. A 10-month-old boy presented with ascites, right pleural effusion, and hepatomegaly after consumption of herbal drinks for 3 months. His clinical (including imaging) features were compatible with Budd-Chiari syndrome. Budd-Chiari syndrome is a rare disease entity in paediatric patients. In our case, extensive workup performed to look for the underlying cause of Budd-Chiari syndrome was unrevealing, except for toxic pyrrolizidine alkaloid exposure in his herbal drinks.

ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3ß in the signal network.

HeLa cells treated with celastrol, a natural compound with inhibitive effect on proteasome, exhibited increase in apoptotic rate and characteristics of apoptosis. To clarify the signal network activated by celastrol to induce apoptosis, both the direct target proteins and undirect target proteins of celastrol were searched in the present study. Proteasome catalytic subunit ß1 was predicted by computational analysis to be a possible direct target of celastrol and confirmed by checking direct effect of celastrol on the activity of recombinant human proteasome subunit ß1 in vitro. Undirect target-related proteins of celastrol were searched using proteomic studies including two-dimensional electrophoresis (2-DE) analysis and iTRAQ-based LC-MS analysis. Possible target-related proteins of celastrol such as endoplasmic reticulum protein 29 (ERP29) and mitochondrial import receptor Tom22 (TOM22) were found by 2-DE analysis of total cellular protein expression profiles. Further study showed that celastrol induced ER stress and ER stress inhibitor could ameliorate cell death induced by celastrol. Celastrol induced translocation of Bax into the mitochondria, which might be related to the upregulation of BH-3-only proteins such as BIM and the increase in the expression level of TOM22. To further search possible target-related proteins of celastrol in ER and ER-related fractions, iTRAQ-based LC-MS method was use to analyze protein expression profiles of ER/microsomal vesicles-riched fraction of cells with or without celastrol treatment. Based on possible target-related proteins found in both 2-DE analysis and iTRAQ-based LC-MS analysis, protein-protein interaction (PPI) network was established using bioinformatic analysis. The important role of glycogen synthase kinase-3ß (GSK3ß) in the signal cascades of celastrol was suggested. Pretreatment of LiCL, an inhibitor of GSK3ß, could significantly ameliorate apoptosis induced by celastrol. On the basis of the results of the present study, possible signal network of celastrol activated by celastrol leading to apoptosis was predicted.

Separation of oil/water emulsion using nano-particle (TiO(2)/Al(2)O(3)) modified PVDF ultrafiltration membranes and evaluation of fouling mechanism.

In the present study, nano-sized TiO(2)/Al(2)O(3) modified polyvinylidene fluoride (PVDF) membranes (MM) were fabricated and then utilized for oil/water emulsion separation. The results showed that, compared with PVDF membrane (OM), the contact angle of MM decreased and hydrophilicity increased. The ultrafiltration (UF) of oil in water emulsions with transmembrane pressure (TMP) increasing results in a sharp fall in relative flux with time. The cake filtration models did not always predict the performance over the complete range of filtration times very well. In the initial 30 min, all the four cake models can simulate this UF process to a certain extent, and the suitability was: cake filtration > intermediate pore blocking > standard pore blocking > complete pore blocking models. However, they were no longer adapted well with UF time extent to 60 min, but only cake filtration (R(2) = 0.9535) maintained a high adaptability. Surface and cross-sectional morphology of the membrane was investigated by SEM to make an advanced certificate of this UF mechanism.

Ethnobotanical approach versus random approach in the search for new bioactive compounds: support of a hypothesis.

CONTEXT: Whether natural product drug discovery programs should rely on wild plants collected "randomly" from the natural environment, or whether they should also include plants collected on the basis of use in traditional medicine remains an open question. OBJECTIVE: This study analyzes whether plants with ethnomedical uses from Vietnam and Laos have a higher hit rate in bioassay testing than plants collected from a national park in Vietnam with the goal of maximizing taxonomic diversity ("random" collection). MATERIALS AND METHODS: All plants were extracted and subjected to bioassay in the same laboratories. Results of assays of plant collections and plant parts (samples) were scored as active or inactive based on whether any extracts had a positive result in a bioassay. Contingency tables were analyzed using χ(2) statistics. RESULTS: Random collections had a higher hit rate than ethnomedical collections, but for samples, ethnomedical plants were more likely to be active. Ethnomedical collections and samples had higher hit rates for tuberculosis, while samples, but not collections, had a higher hit rate for malaria. Little evidence was found to support an advantage for ethnomedical plants in HIV, chemoprevention and cancer bioassays. Plants whose ethnomedical uses directly correlated to a bioassay did not have a significantly higher hit rate than random plants. DISCUSSION: Plants with ethnomedical uses generally had a higher rate of activity in some drug discovery bioassays, but the assays did not directly confirm specific uses. CONCLUSIONS: Ethnomedical uses may contribute to a higher rate of activity in drug discovery screening.