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Determinants of survival outcomes among esophageal cancer patients at a national referral hospital in Kenya

Chronic Diseases and Translational Medicine 2023年第1期9卷 20-28页

作者： Amsalu Degu Peter N.Karimi Sylvia A.Opanga David G.Nyamu Department of Pharmaceutics and pharmacy Practice School of Pharmacy and Health SciencesUnited States International University–AfricaNairobiKenya Department of pharmacy Faculty of Health SciencesUniversity of NairobiNairobiKenya

Introduction:The overall 5-year survival rate for esophageal cancer patients in low-and middle-income countries was reported to be low,despite the availability of advanced treatments.Thus,this study aimed to assess determinants of survival outcomes among esophageal cancer patients in Kenya.Methods:A retrospective cohort study was employed among 299 adult esophageal cancer patients.The data were collected using a data abstraction tool consisting of patients’clinical characteristics and survival outcome measuring parameters.Statistical Package for the Social Sciences(SPSS)statistical software(version 20.0,IBM.USA)was used to analyze the data.The Kaplan–Meier and Cox regression analyses were used to determine the survival outcome and determinants of mortality,respectively.Results:The mortality rate was 43.1%,and 11.1%of patients demonstrated distant metastases in the follow-up period.Despite treatment,20.1%had progressed disease,and 13.0%did not respond to treatment.Radiotherapy(AHR:3.3,95%CI:1.4−7.8,p=0.007),chemotherapy(AHR:3.9,95%CI:1.2−6.1,p=0.020),and chemoradiation(AHR:5.6,95%CI:1.6−10.2,p=0.006)were the significant determinants of survival in advanced stage(III and and IV)patients.Conclusions:There was a high mortality rate,disease progression,and nonresponse of esophageal cancer patients.Hence,it is essential to improve the survival of patients through early detection and timely initiation of the available treatment options.

关键词： determinants esophageal cancer mortality survival outcomes

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Influence of hydroxypropyl methylcellulose,methylcellulose, gelatin, poloxamer 407 and poloxamer 188 on the formation and stability of soybean oil-in-water emulsions

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Asian Journal of Pharmaceutical Sciences 2017年第6期12卷 521-531页

作者： Miao Zhang Baixue Yang Wei Liu Sanming Li School of Pharmacy Shenyang Pharmaceutical University

Macromolecules of polysaccharides, proteins and poloxamers have a hydrophobic portion and a hydrophilic one that can be used as emulsifiers. Parts of these emulsifiers are safe pharmaceutical excipients, which can replace the irritant low molecular weight surfactants to formulate emulsions for the pharmaceutical field. This project focused on preparing O/W emulsions stabilized with polymers for pharmaceuticals such as polysaccharides, proteins and poloxamers, including hydroxypropyl methylcellulose (HPMC), methylcellulose (MC),gelatin, poloxamer 407 (F127) and poloxamer 188 (F68). Emulsion physical stability was assessed by centrifugation, autoclaving sterilization and droplet size measurements. The stabilization mechanisms of emulsions were determined by interfacial tension and rheological measurements. Results stated that the efficacy of these polymers for pharmaceuticals stabilized emulsions was sorted in the order: F127 > F68 > HPMC > MC > Gelatin.

关键词： Polymers for pharmaceuticals Emulsions Physical stability Stabilization mechanism

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Albumin-bound kynurenic acid is an appropriate endogenous biomarker for assessment of the renal tubular OATs-MRP4 channel

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Journal of Pharmaceutical Analysis 2023年第10期13卷 1205-1220页

作者： Yanrong Ma Fenglin Ran Mingyan Xin Xueyan Gou Xinyi Wang Xinan Wu The First school of Clinical Medicine Lanzhou UniversityLanzhou730000China School of Pharmacy Lanzhou UniversityLanzhou730000China

Renal tubular secretion mediated by organic anion transporters(OATs)and the multidrug resistanceassociated protein 4(MRP4)is an important means of drug and toxin excretion.Unfortunately,there are no biomarkers to evaluate their function.The aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 channel.Twenty-six uremic toxins were selected as candidate compounds,of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-,OAT3-,and MRP4-overexpressing cell lines.OAT1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in vitro.Serum kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3(rOAT1/3)inhibitor and in rOAT1/3 double knockout(rOAT1/3^(-/-))rats,and the renal concentrations were markedly elevated by the rat MRP4(rMRP4)inhibitor.Kynurenic acid was not filtered at the glomerulus(99%of albumin binding),and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity(Km)(496.7 mM and 382.2 mM for OAT1 and OAT3,respectively)and renal clearance half-life(t1/2)in vivo(3.7±0.7 h).There is a strong correlation in area under the plasma drug concentration-time curve(AUC0et)between cefmetazole and kynurenic acid,but not with creatinine,after inhibition of rOATs.In addition,the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury process.These results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.

关键词： Transporter Biomarker Kynurenic acid Renal tubular excretion

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Nanopreparations for mitochondria targeting drug delivery system: Current strategies and future prospective

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Asian Journal of Pharmaceutical Sciences 2017年第6期12卷 498-508页

作者： Zhenjie Wang Weiling Guo Xiao Kuang Shanshan Hou Hongzhuo Liu School of Pharmacy Shenyang Pharmaceutical University

Mitochondria are a novel and promising therapeutic target for diagnosis, treatment and prevention of a lot of human diseases such as cancer, metabolic diseases and neurodegenerative disease. Owing to the mitochondrial special bilayer structure and highly negative potential nature, therapeutic molecules have multiple difficulties in reaching mitochondria. To overcome multiple barriers for targeting mitochondria, the researchers developed various pharmaceutical preparations such as liposomes, polymeric nanoparticles and inorganic nanoparticles modified by mitochondriotropic moieties like dequalinium (DQA),triphenylphosphonium (TPP), mitochondrial penetrating peptides (MPPs) and mitochondrial protein import machinery that allow specific targeting.The targeted formulations exhibited enhanced pharmacological effect and better therapeutic effect than their untargeted counterpart both in vitro and in vivo. Nanocarriers may be used for bio-therapeutic delivery into specific mitochondria that possess a great potential treatment of mitochondria related diseases.

关键词： Mitochondria-targeting Liposomes DQAsomes Nanoparticles Cancer Diabetes

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Study on the dynamic variation of the secondary metabolites in Viscum coloratum using targeted metabolomics

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Chinese Journal of Natural Medicines 2023年第4期21卷 308-320页

作者： ZHANG Ruizhen DUAN Rong WANG Weiqing YU Zhiguo LI Yun ZHAO Yunli Department of Pharmaceutical Analysis School of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Department of pharmacy the Second Hospital of Dalian Medical UniversityDalian 116023China

Viscum coloratum(Kom.)Nakai is a well-known medicinal plant.However,the optimal harvest time for V.coloratum is unknown.Few studies were performed to analyze compound variation during storage and to improve post-harvest quality control.Our study aimed to comprehensively evaluate the quality of V.coloratum in different growth stages,and determine the dynamic variation of metabolites.Ultra-performance liquid chromatography tandem mass spectrometry was used to quantify 29 compounds in V.coloratum harvested in six growth periods,and the associated biosynthetic pathways were explored.The accumulation of different types of compounds were analyzed based on their synthesis pathways.Grey relational analysis was used to evaluate the quality of v.coloratum across different months.The compound variation during storage was analyzed by a high-temperature high-humidity accelerated test.The results showed that the quality of V.coloratum was the hightest in March,followed by November,and became the lowest in July.During storage,compounds in downstream steps of the biosynthesis pathway were first degraded to produce the upstream compounds and some low-molecular-weight organic acids,leading to an increase followed by a decrease in the content of some compounds,and resulted in a large gap during the degradation time course among different compounds.Due to the rapid rate and large degree of degradation,five compounds were tentatively designated as“early warning components”for quality control.This report provides reference for better understanding the biosynthesis and degradation of metabolites in V.coloratum and lays a theoretical foundation for rational application of V.coloratum and better quality control of V.coloratum during storage.

关键词： Viscum coloratum Harvesting period Storage Plant metabolomics Quality control

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Development of precision medicine approaches based on inter-individual variability of BCRP/ABCG2

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Acta Pharmaceutica Sinica B 2019年第4期9卷 659-674页

作者： Liming Chen Jose E.Manautou Theodore P.Rasmussen Xiao-bo Zhong Department of Pharmaceutical Sciences School of Pharmacy University of Connecticut

Precision medicine is a rapidly-developing modality of medicine in human healthcare.Based on each patient’s unique characteristics, more accurate dosages and drug selection can be made to achieve better therapeutic efficacy and less adverse reactions in precision medicine. A patient’s individual parameters that affect drug transporter action can be used to develop a precision medicine guidance, due to the fact that therapeutic efficacy and adverse reactions of drugs can both be affected by expression and function of drug transporters on the cell membrane surface. The purpose of this review is to summarize unique characteristics of human breast cancer resistant protein(BCRP) and the genetic variability in the BCRP encoded gene ABCG2 in the development of precision medicine. Inter-individual variability of BCRP/ABCG2 can impact choices and outcomes of drug treatment for several diseases, including cancer chemotherapy. Several factors have been implicated in expression and function of BCRP, including genetic, epigenetic, physiologic,pathologic, and environmental factors. Understanding the roles of these factors in controlling expression and function of BCRP is critical for the development of precision medicine based on BCRP-mediated drug transport.

关键词： BCRP Epigenetics Gene polymorphisms Physiologic factors Precision medicine

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From liver fibrosis to hepatocarcinogenesis: Role of excessive liver H_(2)O_(2) and targeting nanotherapeutics

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Bioactive Materials 2023年第5期23卷 187-205页

作者： Meiyu Shao Yifan Wang Hongyan Dong Lu Wang Xiaoqing Zhang Xin Han Xianan Sang Yini Bao Mengyun Peng Gang Cao School of Pharmacy Zhejiang Chinese Medical UniversityHangzhou310000PR China

Liver fibrosis and hepatocellular carcinoma(HCC)have been worldwide threats nowadays.Liver fibrosis is reversible in early stages but will develop precancerosis of HCC in cirrhotic stage.In pathological liver,excessive H_(2)O_(2) is generated and accumulated,which impacts the functionality of hepatocytes,Kupffer cells(KCs)and hepatic stellate cells(HSCs),leading to genesis of fibrosis and HCC.H_(2)O_(2) accumulation is associated with overproduction of superoxide anion(O_(2)^(·-))and abolished antioxidant enzyme systems.Plenty of therapeutics focused on H_(2)O_(2) have shown satisfactory effects against liver fibrosis or HCC in different ways.This review summarized the reasons of liver H_(2)O_(2) accumulation,and the role of H_(2)O_(2) in genesis of liver fibrosis and HCC.Additionally,nanotherapeutics targeting H_(2)O_(2) were summarized for further consideration of antifibrotic or antitumor therapy.

关键词： Liver fibrosis Hepatocarcinogenesis Nanotherapeutics H_(2)O_(2)accumulation Oxidative stress

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Intracellular distribution and internalization pathways of guanidinylated bioresponsive poly(amido amine)s in gene delivery

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Asian Journal of Pharmaceutical Sciences 2018年第4期13卷 360-372页

作者： Jinmina Zhang Chunxi Wang Mei Lu Haonan Xing Tianzhi Yang Cuifang Cai Xiaoyun Zhao Minjie Wei Jiankun Yu Pingtian Ding School of Pharmacy Shenyang Pharmaceutical University Department of Basic Pharmaceutical Sciences School of PharmacyHusson University Department of Microbiology and Cell Biology School of life Science and BiopharmaceuticsShenyang Pharmaceutical University Department of Pharmacology School of PharmacyChina Medical University Department of Ion Channel Pharmacology School of PharmacyChina Medical University

Guanidinylated bioresponsive poly(amido amine)s polymers, CAR-CBA and CHL-CBA, weresynthesized by Michael-type addition reaction between guanidine hydrochloride(CAR) orchlorhexidine(CHL) and N,N-cystaminebisacrylamide(CBA). Previous studies have shownthat both polymers had high transfection efficiencies as gene delivery carriers. In this study,we investigated the nucleolus localization abilities and cellular internalization pathways ofthese two polymers in gene delivery. Each polymer condensed plasmid DNA(p DNA) andformed nanoparticle complexes, and then their transfection studies were performed inMCF-7 cells. Both complexes were found enriched in nucleolus after cellular transfection,and their transfection efficiencies were significantly improved when transfection was per-formed on MCF-7 cells arrested at M phase. The transfection efficiency of CAR-CBA-pDNAwas inhibited by chlorpromazine, and cell endosomes were disrupted after being exposedto CAR-CBA-pDNA. In regards to CHL-CBA-pDNA, its transfection efficiency was not affected by three types of endocytosis inhibitors used in the study, and CHL-CBA-pDNA showed no effect on endosomes. Cellular lactate dehydrogenase release and membrane morphology were changed after cells were transfected by the two complexes. The results indicated that both CAR-CBA and CHL-CBA polymers demonstrated good nucleolus localization abilities. It was beneficial for transfection when cells were arrested at M phase. CAR-CBA-pDNA cellular internalization was involved with clathrin-mediated endocytosis pathway, and escaping from endosomal entrapment, while the cellular uptake of CHL-CBA-pDNA occurs via clathrin-and caveolae-independent mechanism.

关键词： Guanidinylated poly(amido amine)s polymers Nucleolus localization Cell cycle status Internalization pathways

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Review on microbial metabolomics of probiotics and pathogens:Methodologies and applications

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BIOCELL 2023年第1期47卷 91-107页

作者： XIN MENG XUE LI LIANRONG YANG RUI YIN LEHUI QI QI GUO School of Pharmacy Heilongjiang University of Chinese MedicineHarbin150040China

In recent years,microbial metabolomics,a new field that has attracted wide attention,provides a map of metabolic pathways and clarifies the interaction mechanism between microorganisms and hosts.Many microorganisms are found in the human intestine,oral cavity,vagina,etc.Probiotics could maintain the good health of the host,while pathogens and an imbalance of bacterial flora lead to a series of diseases of the body and mind.Metabolomics is a science for qualitative and quantitative analysis of all metabolites in an organism or biological system,which could provide key information to understand the related metabolic pathways and associated changes.This approach analyzes the final products of cellular regulatory processes,the level of which can be regarded as the ultimate response of the biological system to genetic or environmental changes.Microbial metabolomics has been widely used in different research fields,such as microbial phenotypic classification,mutant screening,metabolic pathways,microbial metabolic engineering,fermentation engineering monitoring and optimization,microbial environmental pollution,and so on.However,there are only a few reviews on microbial metabolomics of probiotics and pathogens.This review summarizes the main methodologies,including sample preparation,identification of metabolites,data processing,and analysis.Recent applications in microbial metabolomics of probiotics and pathogens are also described.This paper first summarized the research progress and application of microbial metabolomics from two aspects:probiotics and pathogenic bacteria.Probiotics and pathogenic bacteria do not exist independently most of the time;hence,these were reviewed in the research field of coexistence of probiotics and pathogenic bacteria,which was subdivided into important microbial research fields closely related to human health,including the human gut,oral cavity,food,and nutrition-related microorganisms.Then,the main problems and trends associated with microbial metabolomics are discussed.

关键词： Probiotics Pathogens Microbial metabolomics Methodology Application

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Three Co(Ⅱ) Coordination Polymers Incorporated with a Bent Connector: Crystal Structures and Magnetic Properties

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Chinese Journal of Structural Chemistry 2019年第4期38卷 587-596页

作者：刘汉甫李海叶姚鹏飞舒春月黄富平 school of Chemistry and pharmacy Guangxi Normal University College of pharmacy Guilin Medical University

Based on the bent ligand 1 H-3-(3-pyridyl)-5-(4-pyridyl)-1,2,4-triazole(3,4?-Hbpt) with Co(Ⅱ) ions as well as a series of polycarboxylate co-ligands, three new coordination polymers were yielded, namely, {[Co(op)(3,4?-Hbpt)(H_2O)_3]?2 H_2O}n(1), [Co(cyc)(3,4′-Hbpt)(H_2O)]n(2) and [Co(pro)(3,4′-Hbpt)(H_2O)]n(3)(here, op = o-phthalic anion, cyc = 1,1-cyclobutanedicarboxylic anion, pro = propanedioic anion). In cooperation with the auxiliary polycarboxylate co-ligands, a variety of Co(Ⅱ) coordination networks, such as 1-D chain 1 and 2-D layer 2 and 3 have been assembled. The magnetic behaviors of compounds 1～3 were studied. All of them indicated the existence of interesting spin-canting behavior.

关键词： Co(Ⅱ) complexes bent connector spin canting behavior

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