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Science China Chemistry 2024年第1期67卷 368-373页

作者： Xing-Yu Wang Pei Xu Wen-Wen Liu Hao-Qiang Jiang Song-Lei Zhu Dong Guo Xu Zhu Jiangsu Key Laboratory of New Drug Research and clinical pharmacy School of PharmacyXuzhou Medical UniversityXuzhou 22100China

Unprecedented divergent synthesis of gem-difluorovinylacetic acid and glutaric acid derivatives fromα-CF_(3)alkenes with formate as the carbonyl source was *** reaction can undergo selective mono-or triple C-F bond cleavage by simply switching the photocatalyst and hydrogen atom transfer(HAT)catalyst under visible-light-induced conditions at room *** acts as both the C1 source and the reductant through the generation of CO_(2)^(·-)species,which underwent Giese radical addition to electron-deficient alkenes to trigger the consecutive C-F bond cleavage and carboxylation process.

关键词： C-F bond activation defluorocarboxylation carbon dioxide radical anion visible light

Herbal compounds as promising therapeutic agents in precision medicine strategies for cancer:A systematic review

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Journal of Integrative Medicine 2024年第2期22卷 137-162页

作者： Bizhar Ahmed Tayeb Ikhwan Yuda Kusuma Alaa A.M.Osman Renáta Minorics Institute of Pharmacodynamics and Biopharmacy Faculty of PharmacyUniversity of Szeged6720 SzegedHungary Institution of clinical pharmacy Faculty of PharmacyUniversity of Szeged6725 SzegedHungary Department of clinical pharmacy and pharmacy Practice Faculty of PharmacyUniversity of Gezira20 Wad MadaniSudan pharmacy Study Program Facuity of HealthUniversitas Harapan BangsaPurwokerto 53182Indonesia

Background:The field of personalized medicine has gained increasing attention in cancer care,with the aim of tailoring treatment strategies to individual patients for improved *** medicine,with its long-standing historical use and extensive bioactive compounds,offers a rich source of potential treatments for various diseases,including ***:To provide an overview of the current knowledge and evidence associated with incorporating herbal compounds into precision medicine strategies for cancer ***,to explore the general characteristics of the studies included in the analysis,focusing on their key features and *** strategy:A comprehensive literature search was conducted from multiple online databases,including Pub Med,Scopus,Web of Science,and *** search strategy was designed to identify studies related to personalized cancer medicine and herbal *** criteria:Publications pertaining to cancer research conducted through in vitro,in vivo,and clinical studies,employing natural products were included in this *** extraction and analysis:Two review authors independently applied inclusion and inclusion criteria,data extraction,and assessments of methodological *** quality assessment and biases of the studies were evaluated based on modified Jadad scales.A detailed quantitative summary of the included studies is presented,providing a comprehensive description of their key features and ***:A total of 121 studies were included in this review for *** of them were considered as comprehensive experimental investigations both in vitro and in *** majority(n=85)of the studies included in this review were conducted in vitro,with 44 of them specifically investigating the effects of herbal medicine on animal ***,7 articles with a combined sample size of 31,271 patients,examined the impact of herbal medicine in clinical ***:Personal

关键词： Cancer Herbal medicine Personalized medication Active phytochemicals Natural compound

Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats

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Chinese Journal of Natural Medicines 2024年第4期22卷 293-306页

作者： YAO Wenhui TAO Rongpin WANG Kai DING Xuansheng School of Basic Medicine and clinical pharmacy China Pharmaceutical UniversityNanjing211198China

Icariin, a flavonoid glycoside, is extracted from Epimedium. This study aimed to investigate the vascular protective effects of icariin in type 1 diabetic rats by inhibiting high-mobility group box 1 (HMGB1)-related inflammation and exploring its potential mechanisms. The impact of icariin on vascular dysfunction was assessed in streptozotocin (STZ)-induced diabetic rats through vascular reactivity studies. Western blotting and immunofluorescence assays were performed to measure the expressions of target proteins. The release of HMGB1 and pro-inflammation cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that icariin administration enhanced acetylcholine-induced vasodilation in the aortas of diabetic rats. It also notably reduced the release of pro-inflammatory cytokines, including interleukin-8 (IL-8), IL-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) in diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). The results also unveiled that the pro-inflammatory cytokines in the culture medium of HUVECs could be increased by rHMGB1. The increased release of HMGB1 and upregulated expressions of HMGB1-related inflammatory factors, including advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), and phosphorylated p65 (p-p65) in diabetic rats and HG-induced HUVECs, were remarkably suppressed by icariin. Notably, HMGB1 translocation from the nucleus to the cytoplasm in HUVECs under HG was inhibited by icariin. Meanwhile, icariin could activate G protein-coupled estrogen receptor (GPER) and sirt1. To explore the role of GPER and Sirt1 in the inhibitory effect of icariin on HMGB1 release and HMGB-induced inflammation, GPER inhibitor and Sirt1 inhibitor were used in this study. These inhibitors diminished the effects of icariin on HMGB1 release and HMGB1-induced inflammation. Specifically, the GPER inhibitor also negated the activation of Sirt1 by icariin. These findings suggest t

关键词： Icariin Diabetes Inflammation Vascular endothelial dysfunction GPER HMGB1

Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration Research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical Research center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular *** r,the causal relationship between hypertension and cerebral small vessel disease remains *** has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular *** hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and *** is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of *** review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive *** also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

Investigation of the active ingredients and mechanism of Shuangling extract in dextran sulfate sodium salt induced ulcerative colitis mice based on network pharmacology and experimental verification

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Journal of Traditional Chinese Medicine 2024年第3期44卷 478-488页

作者： CHU Mengzhen WANG Yu LIN Zhijian Lyu Jintao ZHANG Xiaomeng ZHANG Bing Department of clinical Chinese pharmacy School of Chinese Materia MedicaBeijing University of Chinese Medicine

OBJECTIVE: To explore the pharmacodynamic effects and potential mechanisms of Shuangling extract against ulcerative colitis(UC). METHODS: The bioinformatics method was used to predict the active ingredients and action targets of Shuangling extract against UC in mice. And the biological experiments such as serum biochemical indexes and histopathological staining were used to verify the pharmacological effect and mechanism of Shuangling extract against UC in mice. RESULTS: The Shuangling extract reduced the levels of seruminterleukin-1β(IL-1β), tumor necrosis factor-α(TNF-N), interleukin-6(IL-6) and other inflammatory factors in UC mice and inhibited the inflammatory response. AKT Serine/threonine Kinase 1 and IL-6 may be the main targets of the anti-UC action of Shuangling extract, and the TNF signaling pathway, Forkhead box O signaling pathway and T-cell receptor signaling pathway may be the main signaling pathways. CONCLUSION: The Shuangling extract could inhibit the inflammatory response induced by UC and regulate intestinal immune function through multiple targets and multiple channels, which provided a new option and theoretical basis for anti-UC.

关键词： Shuangling extract colitis, ulcerative molecular docking simulation network pharmacology pharmacodynamic study

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Successful management of severe hypoglycemia induced by total parenteral nutrition in patients with hepatocellular injury: Three cases reports

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World Journal of clinical Cases 2024年第1期12卷 157-162页

作者： Ling-Zhi Fang Hui-Xin Jin Na Zhao Yu-Pei Wu Ying-Qin Shi Department of pharmacy Hebei Key Laboratory of Clinical PharmacyHebei General HospitalShijiazhuang 050051Hebei ProvinceChina

BACKGROUND Glucose imbalance is common in total parenteral nutrition(TPN).Hypoglycemia seems to be less frequent than hyperglycemia,but it influences the clinical outcome to a greater ***,it should be effectively prevented and ***,there is no relevant report on how to treat hypoglycemia caused by TPN in patients with liver cell *** SUMMARY We present three patients with liver cell injury who developed severe hypo-glycemia during or after TPN *** causes of severe hypoglycemia and glucose-raising strategies were *** to the physiological charac-teristics of the hepatocellular injury,the ratio of nutrition components prescribed in TPN was appropriately adjusted for the three *** simultaneously reduced the dose of insulin and fat emulsion,and increased the dose of glucose in *** blood glucose level was restored to normal range and clinical symptoms were *** When hypoglycemia occurs during or after TPN in patients with hepatocellular injury,physicians need to simultaneously reduce insulin and fat emulsion,and increase glucose,and correct severe hypoglycemia in time to reduce its adverse consequences.

关键词： Total parenteral nutrition Hepatocellular injury Severe hypoglycemia Treatment Causes Case report

Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1677-1692页

作者： Dongsheng Bai Jiawei Zhao Runde Wang Jiaying Du Chen Zhou Chunyang Gu Yuxiang Wang Lulu Zhang Yue Zhao Na Lu State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Carcinogenesis and InterventionDepartment of PhysiologySchool of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China Department of clinical Pharmacology School of PharmacyNanjing Medical UniversityNanjing 211166China

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal *** identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is *** our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus *** enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory ***,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy ***,*** up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet *** espe-cially significant finding is that *** activates the AhR pathway,thereby promoting the expression of *** summary,our results strongly indicate that *** enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.

关键词： Chemotherapy Mucositis Eubacterium coprostanoligenes MUC2 AUF1

Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma

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Journal of Pharmaceutical Analysis 2024年第2期14卷 211-224页

作者： Jingjing Wang Qi Su Kun Chen Qing Wu Jiayan Ren Wenjuan Tang Yu Hu Zeren Zhu Cheng Cheng Kaihui Tu Huaizhen He Yanmin Zhang School of pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an710061China

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

关键词： Pyrimethamine BNIP3 SNARE Autophagosome-lysosome fusion Hepatocellular carcinoma Sorafenib

Current perspective on amyloid aggregation accelerating properties of the artificial butter flavoring,diacetyl

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Neural Regeneration Research 2024年第10期19卷 2113-2114页

作者： Ashish P.Vartak Swati S.More center for Drug Design College of PharmacyUniversity of MinnesotaMinneapolisMNUSA

The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that *** amyloid-β(Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer's disease(AD) and are considered one of the causative factors for neurodegeneration and cognitive *** affects critical connected structures within the brain that are responsible for memory,language,and social behavior.

关键词： amyloid Alzheimer Aβ

Translating bacteriophage-derived depolymerases into antibacterial therapeutics:Challenges and prospects

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Acta Pharmaceutica Sinica B 2024年第1期14卷 155-169页

作者： Honglan Wang Yannan Liu Changqing Bai Sharon Shui Yee Leung School of pharmacy the Chinese University of Hong KongHong Kong SARChina Emergency Medicine clinical Research center Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China Department of Respiratory Shenzhen University General HospitalShenzhen University Clinical Medical AcademyGuangdong 518055China

Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and *** depolymerases are enzymes responsible for degrading diverse bacterial surface *** are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance,making them an invaluable asset in the era of antibiotic *** depolymerases have been investigated preclinically,with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection ***,some formulation approaches have been developed for improved stability and activity of ***,depolymerase formulation is limited to liquid dosage form and remains in its infancy,posing a significant hurdle to their clinical translation,compounded by challenges in their applicability and *** development must address these obstacles for clinical ***,after unravelling the history,diversity,and therapeutic use of depolymerases,we summarized the preclinical efficacy and existing formulation findings of recombinant ***,the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.

关键词： Phage-derived polysaccharide depolymerases Bacteriophage proteins Bacterial capsules Polysaccharide capsules Antibiotic resistance Biofilms Antibacterial therapy Antimicrobial adjuvants Combination treatment