Objective To investigate the mechanism of high-glucose-induced injury to human peritoneal mesothelial cells(HPMC). Methods (1)The cultured HPMCs were exposed to culture medium containing different concentrations of glucose(1. 5% , 2. 5% , 4. 25% )for 48 hours and 4. 25% mannitol and normal culture medium were as control. Then apoptosis was observed by flow cytometry and caspase-3 activity was measured by ApoAlert?CPP33/Caspase-3 Assay kits. (2) The cultured HPMCs were exposed to 4.25% glucose culture medium containing different concentrations of caspases inhibitor, Z-VAD. fmk (25, 50, 100 ?mol/L) for 48 hours and 4. 25% glucose culture medium containing DMSO was as control. Then apoptosis was observed by flow cytometry and caspase-3 activity was measured by ApoAlert?CPP33/ Caspase-3 Assay kits as well. Results (1) Glucose increased caspase-3 activity in a concentration-dependent manner. Compared to control, caspase-3 activity was significantly higher in 4. 25% glucose group and 2. 5% glucose group, but not significantly different in 1. 5% glucose group and 4. 25% mannitol group. (2) Apoptotic rate of HPMC was significantly lower in Z-VAD. fmk group than that in control. Z-VAD. fmk decreased the number of apoptotic cells in a concentration-dependent manner. Also, caspase-3 activity of HPMC was significantly lower in Z-VAD. fmk group than that in control. Conclutions (1) High-glucose can induce apoptosis and caspase-3 activation of HPMC in a dose-dependent manner. (2) Z-VAD. fmk inhibits high glucose-induced apoptosis of HPMC in a dose-dependent manner. (3)High glucose induces apoptosis of human peritoneal mesothelial cells by caspase-3 activation.

AIM: To investigate effect of atrial natriuretic peptide (ANP) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rat. METHODS: Mean arterial blood pressure (MAP) was recorded with model 6280 physiology intelligentialize grapher, nitric oxide (NO) and endothelin (ET) concentrations in plasma were measured after lipopolysaccharide (LPS) or following LPS ,ANP was injected into vein in rats. After experiment,lung water as well as pulmonary histopathological changes was measured and observed, respectively. RESULTS: Administration of LPS elicited a persistence decrease in MAP (8.1 kPa?2.6 kPa,at 4 h,P0.05); The histopathological of lung displayed markedly improved. CONCLUSION: ANP attenuates ALI induced by LPS in the rat. The effect of ANP may be via decreasing secretion of ET,NO and regulation arterial blood pressure. [

Objective To investigate the correlation between BRAF V600E mutation and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) therapeutic effects in metastatic colorectal cancer.
Methods Studies were included into meta-analysis to investigate the association between BRAF V600E mutation and clinical outcome in metastatic colorectal cancer patients treated with anti-EGFR MoAbs.
Results A total of 7 studies were included in this meta-analysis. The 7 studies included 1352 patients in total, sample sizes ranged from 67 to 493. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were collected from included studies and were used to assess the strength of the relation. In patients with wild-type KRAS, the pooled odds ratio for ORR of mutant BRAF over wild-type BRAF was 0.27 (95%CI=0.10-0.70). BRAF mutation predicted a deterioration in PFS and OS in wild-type KRAS patients treated with anti-EGFR MoAbs (hazard ratio=2.78, 95% CI=1.62-4.76;hazard ratio=2.54, 95%CI=1.93-3.32).
Conclusion BRAF V600E mutation is related to lack of response and worse survival in wild-type KRAS metastatic colorectal cancer patients treated with anti-EGFR MoAbs.

To prepare ginseng saponin Compound K with ultrasound-assisted total zymolytic ginseng saponins. The conversion rate was taken as the index to detect the pre-treatment factors such as ultrasonic power and ultrasonic time, as well as the impact of enzymatic factors, such as pH value, temperature, concentration of substrate, dosage of enzyme and reaction time, on the conversion rate. The response surface method was used to optimize the preparation conditions. The enzymolytic products were identified with MS, 1H-NMR and 13C-NMR. The results showed that the optimum conditions of the ultrasound-assisted enzymolysis were 250 W for ultrasonic power, 15 min for ultrasonic time, 5.5 for enzymolytic pH, 50 degrees C for enzymolytic temperature, 36 h for enzymolytic time, 4:5 for enzymolytic dosage: substrate and 1.0 g x L(-1) for concentration of substrate. The relative molecular mass of reaction products was 622.4. Therefore, the nuclear magnetic map verified that the reaction product was rare ginseng saponin Compound K. Under the above conditions, based on the total zymolytic ginseng saponins, the conversion rate of rare ginseng saponin Compound K was 6.91% in proportion to the total of ginsenosides. The process features gentle reaction conditions, high conversion rate and simple and reliable process, which is suitable for industrial production.
Chemistry, Pharmaceutical ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Enzymes ; chemistry ; Panax ; chemistry ; Plant Roots ; chemistry ; Saponins ; chemistry ; isolation & purification ; Ultrasonics ; methods

With low molecular weight chitosan and poloxamer 188 as the joint carriers, ginsenoside Rg3 solid dispersions were prepared by using the solvent evaporation method for an in vitro dissolution test. Subsequently, differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X-ray diffraction (X-RD) were adopted for a phase analysis. The results showed that the 60 min in vitro cumulative dissolution rate of ginsenoside Rg3 solid dispersions prepared with low molecular weight chitosan and poloxamer 188 at the ratio of 2:1 exceeded 90%, and the drug was dispersed in carriers in an amorphous state. Therefore, ginsenoside Rg3 solid dispersions prepared with low molecular weight chitosan and poloxamer 188 could help significantly improve the drug dissolution, with a practical application value.
Chitosan ; chemistry ; Drug Compounding ; methods ; Ginsenosides ; chemistry ; Molecular Weight ; Poloxamer ; chemistry ; Solvents ; chemistry

AIM: In this study, we aimed to explore the alteration and pathophysiological significance of the L-arginine (L-Arg)/NOS/NO pathway in the adventitia of rats with sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP). Rat cardiac function was determined. NO generation, NOS activity and L-Arg transport were measured. The iNOS mRNA levels was determined by using RT-PCR. RESULTS: Cecal ligation and puncture induced severe sepsis with severe low glucose, high lacticemia and cardiac function inhibition. The iNOS activity was increased by 2.8-fold compared with controls (P

Biomacromolecule drugs have been increasingly used in clinical practice due to their distinct advantages, including precise targeting, small dose, high safety and activity. However, owing to their high molecular weight, strong hydrophilicity, and poor stability in the gastrointestinal tract, the oral bioavailability of the biomacromolecule drugs remains extremely poor. As a novel and innovative technology for active drug delivery, gastrointestinal microneedles hold immense potential in the oral delivery of biomacromolecule drugs because of their low-invasive nature and high permeation enhancement effects. This review primarily summarizes the actuating force, design strategies, fabrication techniques, and applications of gastrointestinal microneedles for the oral delivery of biomacromolecule drugs. Additionally, the challenges and further perspectives in the development this technology are presented, aiming to promote the subsequent research and clinical translation of gastrointestinal microneedles, and to provide a new efficient and safe strategy for oral delivery of biomacromolecule drugs.

The excipient processing is an essential part of traditional Chinese medicine processing, and understanding its scientific connotations is a critical scientific issue that urgently needs resolution. Building upon a foundation where the composition of traditional Chinese medicine substances is fundamentally clear, this paper applies the techniques and methods of chemoinformatics to the study of the excipient processing mechanism. Relevant information on traditional Chinese medicines processed with four kinds of excipients (wine, vinegar, salt and honey) was collected, including properties, taste, meridian tropism, chemical components, etc. Molecular descritors and skeletons corresponding to each chemical component were calculated using chemoinformatics to characterize the properties and structural features of the components. Characteristic components associated with the four excipients (wine, vinegar, salt and honey) were explored through multivariate statistical analysis and Murcko skeleton analysis. Further analysis, taking honey-processed Astragali Radix as an example, the focus was on the impact of the processing excipient honey on the solubility and permeability of its characteristic pharmacologically active components (isoflavones). It was discovered that the excipient honey can increase their solubility and permeability, emphasizing that the impact of processing excipients on the pharmacological classification properties is a key breakthrough in elucidating the mechanism of excipient processing. In summary, this study analyzed the characteristic components associated with the processing excipients "wine, vinegar, salt and honey" based on their composition characteristics, providing data support for the research on the mechanism of excipient processing from a biopharmaceutical perspective.

Objective To explore a proper dose of endothelial progenitor cells (EPCs)administration that can achieve optimal hematopoietic improving effectiveness in a murine allogeneic hernatopoietic stem cell transplantation (allo-HSCT) model.Methods Female Balb/c mice were lethally irradiated with 60Co source,and then were injected intravenously with 5 106 bone marrow cells from C57BL/6 mice (bone marrow transplantation group).In co-transfer experiments,5 × 104,1 ×105,5 × 105 or 1 × 106 donor EPCs (EPCs treated groups) were injected simultaneously with bone marrow cells.The recipients were monitored for survival,peripheral white blood cells,hematopoietic stem cells (HSCs) and bone marrow histology.Results Compared with bone marrow transplantation group,all EPCs treated groups had accelerated recovery of peripheral white blood cells (P＜0.05),platelets (P＜0.05) and HSCs (P＜0.05).When infused with less than 5 × 105 EPCs,these effective hernatopoietic improving phenomena showed a positive correlation with the administrated doses of EPCs.However,when infused with 1 × 106 EPCs,the mice showed lower survival rate (P＜0.05)and slower recovery of peripheral white blood cells (P＜0.05),platelets (P＜0.05) and HSCs (P＜0.05) than 5 × 105 EPCs treated grpup.Bone marrow histopathology analysis confirmed the above findings.Conclusion Co-transfer with donor EPCs can improve survival rate and hematopoietic reconstitution of recipient mice in allo-HSCT,and 5 × 105 EPCs should be a proper dose to achieve the best effectiveness.

Adult ; Carcinoma, Renal Cell ; secondary ; Female ; Humans ; Kidney Neoplasms ; pathology ; Magnetic Resonance Imaging ; Vaginal Neoplasms ; secondary