OBJECTIVETo establish the HPLC chromatographic fingerprint of Kumu injection and to simultaneously determine the contents of three beta-carboline alkaloids, comprehensively evaluating the immanent quality of Kumu injection.

METHODThe chromatographic analysis was performed on a Phenomenex Gemini C18 ( 4.6 mm x 250 mm, 5 microm) column with the gradient elution solvent system composed of methanol and 30 mmol x L(-1) aqueous ammonium acetate (adjusted with glacial acetic acid to pH 4.5). Similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (2004 A) was used in data analysis.

RESULTSixteen co-possessing peaks were selected as the fingerprints of Kumu injection, and 7 peaks were identified by chemical reference substances. There were good similarities between the standard fingerprint chromatogram and each fingerprint chromatogram from the eleven samples for their similarity coefficients were not less than 0.9. Three kinds of beta-carboline alkaloids were separated well. The correlation coefficients were 0.999 9. The linear ranges of three components were 0.020 0-0.300 0, 0.102 0-1.530 0, 0.015 2-0. 228 0 microg, respectively, and the average recoveries ranged were from 99.5% to 102%.

CONCLUSIONThe method of fingerprint combined with quantitative analysis is sensitive, selective, and provide scientific basis for quality control of Kumu Injection.

Alkaloids ; analysis ; Carbolines ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; Injections ; Pharmaceutical Solutions ; Picrasma ; chemistry ; Plants, Medicinal ; chemistry ; Quality Control ; Reproducibility of Results ; Sensitivity and Specificity

AIM: Recombinant human adenovirus-p53 injection (rAd-p53) is the first marketed gene therapeutic drug worldwide. This study aimed to evaluate the safety and primary efficacy of rAd-p53 administrated on advanced solid tumors. METHODS: 24 patients with advanced solid tumor treated with rAd-p53 were reviewed, including 5 cases of renal carcinoma, 4 of nasopharyngeal carcinoma, 4 of colorectal carcinoma, 2 of melanoma, 1 of non-small-celllung cancer, 1 of esophageal carcinoma, 1 of gastric cardia carcinoma, 1 of thymic carcinoma, 1 of duodenal carcinoma, 1 of thyroid carcinoma, 1 of pancreatic carcinoma, 1 of endometrial carcinoma and 1 of rhabdomyosarcoma. RAd-p53 was weekly administrated at the dose of 1?10~ 12 VP, and 4 times of administration was defined as one cycle. Administration approach included intratumoral injection,intrabronchial drop in, intraperitoneal injection, intra-arterial infusion and intravenous drip. Combined therapy was given with chemotherapy in 18 cases, radiotherapy in 2, concomitant chemotherapy and radiotherapy in 1, abdominal thermotherapy and orally gefitinib in 1, cytokine immunotherapy in 1 and without combination therapy in 1. RESULTS: 23 cases underwent 35 cycles of therapy except for 1 case discontinued because of early progression. Among the 21 evaluable cases 5 PR, 5 SD and 11 PD were observed. Overall response rate was 23.8%(5/21) and disease control rate was 47.6%(10/21). Grade I-II injection site pain, chill, fever and myalgia were the most frequent side effects. Grade III fever developed in 2 cases and grade III-IV myelosuppression in 4 cases combined with chemotherapy. Furthermore, severe ostealgia occurred in 2 cases and transient hypotension in 1. CONCLUSION: RAd-p53 is tolerable in patients with advanced solid tumor. A further randomized clinical trial is necessary to confirm the antitumor activity of rAd-p53 combined with conventional strategies.

Microglia (MG) are resident immune cells in the central nervous system (CNS) and the first defense line of CNS damage. The maintenance of MG function requires abundant energy, and lipid can serve as an energy source for the brain when glucose utilization is limited, and lipid can also function as signaling molecule. Alzheimer's disease (AD) is the most common neurodegenerative disease, and MG lipid metabolism plays an important role in the development of this disease. Drugs targeting lipid metabolism provide a new direction for AD treatment. This review starts with the specific mechanism of lipid metabolism in MG, and briefly introduces the effect of lipid metabolism on MG function and its role in AD.

Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.

Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.