1.Therapeutic efficacy of Xiao’er Guangpu Zhixie Oral Liquid against bacterial diarrhea
Jiarui CAO ; Qianyue CAO ; Ruoyang CHI ; Yizhu CHEN ; Yuge JIANG ; Yayun ZHANG ; Xiaoqing ZHAO ; Lingman MA
Journal of China Pharmaceutical University 2026;57(4):505-515
Xiao’er Guangpu Zhixie Oral Liquid (XeGp) is clinically used to treat pediatric diarrhea attributed to dampness encumbering the spleen, but its efficacy against bacterial diarrhea has not been fully established. In this study, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of XeGp against Salmonella Typhimurium SL1344 were determined using a microplate assay and a viable plate count method. A mouse model of bacterial diarrhea was also established to evaluate its antidiarrheal effects. The results showed that the MIC and MBC of XeGp against SL1344 corresponded to 1:20 and 1:10 dilutions, respectively. In an SL1344-induced mouse model of diarrhea, XeGp alleviated diarrhea symptoms, reduced the diarrhea index, attenuated diarrhea-associated body weight loss, and ameliorated intestinal histopathological damage caused by bacterial infection. These effects may be associated with reduced expression of TLR4 and phosphorylated NF-κB (p-NF-κB) in colonic tissues, increased expression of the tight junction proteins ZO-1 and occludin in intestinal tissues, and elevated secretory immunoglobulin A (sIgA) levels in the small intestinal mucosa. In addition, XeGp treatment had no significant effect on intestinal microbial diversity and partially restored the reductions in the total numbers of Lactobacillus and Bifidobacteriumcaused by Salmonella infection. When administered in combination with cefixime granules, XeGp enhanced, to some extent, the effects of cefixime granules in alleviating diarrhea, intestinal inflammation, and tissue injury caused by infection. It also partially ameliorated the intestinal microbiota dysbiosis induced by continuous cefixime treatment. In conclusion, XeGp has certain therapeutic effects on bacterial diarrhea caused by S. Typhimurium, providing a scientific basis for its clinical application.
2.Identification of the related substances of antimicrobial peptide Cbf-14 gel by LC-MS
Yitong HUO ; Kehui XU ; Yuting LU ; Lingman MA ; Changlin ZHOU ; Taijun HANG ; Min SONG
Journal of China Pharmaceutical University 2022;53(5):591-598
Cbf-14 is a novel antimicrobial peptide composed of 14 amino acids.An optimized reversed phase high-performance liquid chromatographic method with electrospray-ionization quadrupole time-of-flight mass spectrometer (LC-ESI-QTOF/MS) method was developed for separation, identification and characterization of structurally related peptide impurities in Cbf-14 gel.Chromatographic separation was carried out on an Agilent ZORBAX SB-Phenyl column (150 mm × 4.6 mm, 3.5 μm), with acetonitrile-20 mmol/L ammonium formate buffer (adjusted to pH 3.0 with formic acid) as eluent using gradient elution.Under the established conditions, Cbf-14 and its structurally related peptide impurities were well separated; and a total of 24 impurities were detected and identified, of which 5 were impurities in the preparation manufacturing process and 19 were stressed products.Based on high resolution mass spectrometry analysis, the origins and formation mechanisms of these impurities were located.The obtained results are useful for the establishment of the manufacturing process, storage condition and quality control of Cbf-14 gel.
3.Autophagy and cancer treatment: four functional forms of autophagy and their therapeutic applications.
Zhaoshi BAI ; Yaling PENG ; Xinyue YE ; Zhixian LIU ; Yupeng LI ; Lingman MA
Journal of Zhejiang University. Science. B 2022;23(2):89-101
Cancer is the leading cause of death worldwide. Drugs play a pivotal role in cancer treatment, but the complex biological processes of cancer cells seriously limit the efficacy of various anticancer drugs. Autophagy, a self-degradative system that maintains cellular homeostasis, universally operates under normal and stress conditions in cancer cells. The roles of autophagy in cancer treatment are still controversial because both stimulation and inhibition of autophagy have been reported to enhance the effects of anticancer drugs. Thus, the important question arises as to whether we should try to strengthen or suppress autophagy during cancer therapy. Currently, autophagy can be divided into four main forms according to its different functions during cancer treatment: cytoprotective (cell survival), cytotoxic (cell death), cytostatic (growth arrest), and nonprotective (no contribution to cell death or survival). In addition, various cell death modes, such as apoptosis, necrosis, ferroptosis, senescence, and mitotic catastrophe, all contribute to the anticancer effects of drugs. The interaction between autophagy and these cell death modes is complex and can lead to anticancer drugs having different or even completely opposite effects on treatment. Therefore, it is important to understand the underlying contexts in which autophagy inhibition or activation will be beneficial or detrimental. That is, appropriate therapeutic strategies should be adopted in light of the different functions of autophagy. This review provides an overview of recent insights into the evolving relationship between autophagy and cancer treatment.
Antineoplastic Agents/therapeutic use*
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Apoptosis
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Autophagy/physiology*
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Humans
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Necrosis/drug therapy*
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Neoplasms/therapy*
4.Effective antimicrobial activity of Cbf-14-2 against penicillin-resistant bacteria in vitro and in vivo
Mengxiao WANG ; Lingman MA ; Hanhan LIU ; Meiling JIANG ; Jie DOU ; Changlin ZHOU
Journal of China Pharmaceutical University 2017;48(4):496-502
The antibacterial activity and mechanism of the antimicrobial peptide mutant Cbf-14-2 against NDM-1 carrying recombinant bacteria (E.coli BL21 (DE3)-NDM-1) was investigated in this study.The minimum inhibitory concentration (MIC),minimum bactericidal concentration (MBC) and killing curves (KCs) in vitro were determined by the broth microdilution method.Mice septicemia model was established by interaperitotoneal injection of E.coli BL21 (DE3)-NDM-1 to evaluate the antibacterial activity of this peptide in vivo.Results showed that Cbf-14-2 exhibited a potent antibacterial activity with MIC of 16 μg/mL and killed almost all recombinant bacteria within 120 min.Meanwhile,it significantly improved the survival rate of infected mice up to 70% with the decreasing of bacterial load in mice lung,liver,spleen and kidney.This powerful clearance ability of Cbf-14-2 against bacteria mainly related to its enhanced membrane penetration ability through neutralizing the negative charges and disrupting the integrity of the bacterial cell membrane.Therefore,Cbf-14-2 is expected to be a potential antimicrobial agent for the treatment of infection induced by multi-drug resistant bacteria,especially for the NDM-1carrying bacteria.

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