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Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin Li Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei Wang Zhizhong Guan Xiaolan Qi Wei Hong Yan Xiao key laboratory of Endemic and Ethnic Diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou Center for Disease Control and prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation Center for prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

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Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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Oncology Research 2025年第1期33卷 67-81页

作者： XIANG LI WENKE JIN LIFENG WU HUAN WANG XIN XIE WEI HUANG BO LIU State key laboratory of Southwestern Chinese Medicine Resources School of Pharmacy and College of Medical TechnologyChengdu University of Traditional Chinese MedicineChengdu611137China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China

Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional *** is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of *** contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference ***:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic ***,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after *** formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate ***:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related *** network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified ***,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay ***,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 ***:This study not

关键词： Triple-negative breast cancer(TNBC) Autophagy Protein-protein interactions(PPI) Artificial intelligence(AI) Beclin 2 Ubiquilin 1

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Selective G6PDH inactivation for Helicobacter pylori eradication with transformed polysulfide

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Science China Life Sciences 2025年

作者： Xiaonan Wang Ning Zhou Xuejiao J.Gao Zijing Zhu Minmin Sun Qian Wang Haolin Cao Xuetong Wu Caiyu Zhou Qingkang Zheng Ye Yuan Yuan Liu Lei Chen Jing Jiang Pengcheng Bu Lizeng Gao CAS Engineering laboratory for Nanozyme Key Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences School of Life Sciences University of Chinese Academy of Sciences College of Chemistry and Chemical Engineering Jiangxi Normal University key laboratory of Epigenetic Regulation and intervention Institute of Biophysics Chinese Academy of Sciences Nanozyme laboratory in Zhongyuan School of Basic Medical Sciences Zhengzhou University Nanozyme laboratory in Zhongyuan Henan Academy of Innovations in Medical Science

Alternative treatment for the highly prevalent Helicobacter pylori infection is imperative due to rising antibiotic resistance. We unexpectedly discovered that the anti-H. pylori component in garlic is hydrogen polysulfide（H2S_n, n≥2）, not organic polysulfides. Studies on the mechanism of action（MoA） show that H2S_nspecifically inactivates H. pylori glucose-6-phosphate dehydrogenase（G6PDH） by interfering with electron transfer from glucose-6-phosphate（G6P） to nicotinamide adenine dinucleotide phosphate（NADP+）. However, low H2S_nyield makes garlic derivatives hard to be a reliable donor of H2S_nto treat H. pylori infection. To address this challenge, we established a polysulfide transformation process from garlic organosulfur compounds into Fe3S4that generates H2S_nwith a 25–58 times increase in *** chitosan encapsulation, we designed a gastric-adaptive H2S_nmicroreactor（GAPSR） that eradicates H. pylori with 250 times higher efficiency under gastric conditions. A single GAPSR achieves more rapid H. pylori eradication than combined antibiotics therapy without disturbing the gut microbiota. These findings indicate a distinct MoA transformation mediated by polysulfide as an alternative candidate to treat H. pylori infection.

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Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第1期13卷 11-19页

作者： Zhong SHI1,Rui BAI1,Zhi-xuan FU1,Yong-liang ZHU2,Rong-fu WANG3,Shu ZHENG1(1cancer institute(key laboratory of cancer prevention and intervention,China National Ministry of Education,key laboratory of Molecular Biology in Medical Sciences,Zhejiang Province,China),the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China)(2Department of Gastroenterology,the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China)(3Center for Cell and Gene Therapy,Department of Pathology and Immunology,Baylor College of Medicine,Houston,Texas 77030,USA) cancer institute Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Zhejiang Province China.

Objective:We aimed to perform a preliminary study of the association between induced pluripotent stem cell(iPS)-related genes and biological behavior of human colorectal cancer(CRC) cells,and the potential for developing anti-cancer drugs targeting these ***:We used real-time reverse transcriptase polymerase chain reaction(RT-PCR) to evaluate the transcript levels of iPS-related genes NANOG,OCT4,SOX2,C-MYC and KLF4 in CRC cell lines and cancer stem cells(CSCs)-enriched tumor *** was knockdowned in CRC cell line SW620 by lentiviral transduction.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assays,plate colony formation,and a mouse xenograft model were used to evaluate alterations in biological behavior in NANOG-knockdown SW620 ***,mock-knockdown and NANOG-knockdown cells were treated with 5-fluorouracil(5-FU) and survival rate was measured by MTT assay to evaluate drug ***:A significant difference in the transcript levels of iPS-related genes between tumor spheres and their parental bulky cells was *** knockdown suppressed proliferation,colony formation,and in vivo tumorigenicity but increased the sensitivity to 5-FU of SW620 cells.5-FU treatment greatly inhibited the expression of the major stemness-associated genes NANOG,OCT4,and ***:These results collectively suggest an overlap between iPS-related genes and CSCs in *** a certain gene NANOG may truncate the aggressiveness of CRC cells.

关键词： Induced pluripotent stem cell cancer stem cell Colorectal cancer NANOG 5-Fluorouracil

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State key laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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Rational design of lipid-activatable NIR-II probes for precisely imaging atherosclerotic plaque

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Science China Chemistry 2025年

作者： Xinyu Xu Yuan Ma Hui Cao Li Xu Haoming Chen Sulai Liu Wei Sun Guosheng Song Xiaobing Zhang State key laboratory for Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical EngineeringHunan University Department of Hepatobiliary Surgery/Central laboratory Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Department of Cardiology the First Affiliated Hospital of Nanjing Medical University key laboratory of Targeted intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical University Shenzhen Research institute of Hunan University

Atherosclerosis(AS) is a prevalent condition associated with cardiovascular and cerebrovascular diseases, featuring lipid-laden plaque; however, the insufficient resolution and low sensitivity of traditional medical imaging techniques limit their application in lipid imaging. Currently, the second near-infrared(NIR-II) fluorescence imaging offers promising sensitivity and convenience. However, existing probes have limitations in terms of signal-to-background ratio, penetration depth, and tissue scattering. Herein, we use a molecular regulatory strategy to design a lipid-activatable probe Rh-965 with high specificity and NIR-II emission for improved imaging potential in deep tissues. The potential of Rh-965 for imaging plaque lipids in mice with AS is demonstrated by localizing carotid artery plaques using NIR-II imaging. The development of more stable lipid-activated NIR-II probes can significantly enhance atherosclerosis diagnosis and facilitate in vivo imaging in deeper tissues.

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Consumption of garlic and risk of colorectal cancer:An updated meta-analysis of prospective studies

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World Journal of Gastroenterology 2014年第41期20卷 15413-15422页

作者： Ji-Yi Hu Yi-Wang Hu Jiao-Jiao Zhou Meng-Wen Zhang Dan Li Shu Zheng cancer institute Key Laboratory of Cancer Prevention and InterventionChina National Ministry of Educationthe Second Affiliated HospitalSchool of MedicineZhejiang University

AIM: To conduct an updated meta-analysis of prospective studies addressing the association between garlic consumption and colorectal cancer.

关键词： Colorectal cancer Garlic Garlic supplement cancer prevention Meta-analysis

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Application of exosomes as liquid biopsy in clinical diagnosis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1212-1225页

作者： Biting Zhou Kailun Xu Xi Zheng Ting Chen Jian Wang Yongmao Song Yingkuan Shao Shu Zheng cancer institute Key Laboratory of Cancer Prevention and InterventionMinistry of EducationThe Second Affiliated HospitalZhejiang University School of Medicine310009 HangzhouZhejiangChina Department of Colorectal Surgery and Oncology Key Laboratory of Cancer Prevention and InterventionMinistry of EducationThe Second Affiliated HospitalZhejiang University School of Medicine310009 HangzhouZhejiangChina

Liquid biopsy refers to the sampling and molecular analysis of the biofluids of circulating tumor cells,extracellular vesicles,nucleic acids,and so *** are small extracellular vesicles with sizes between 30–150 *** are secreted by multivesicular bodies through exocytosis in live cells and can participate in intercellular communication due to their contents,including nucleic acids,proteins,and ***,we investigate publication frequencies on exosomes over the past 10 years,and review recent clinical studies on liquid biopsy of exosomes in the fields of oncology,pregnancy disorders,cardiovascular diseases,and organ *** also describe the advantages of exosomes as an effective liquid biopsy tool and the progression of exosome extraction ***,we depict the commercial development of exosome research and discuss the future role of exosomes in liquid biopsy.

关键词： biopsy diagnosis clinical

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Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2010年第9期11卷 647-653页

作者： Yan-qin HUANG Ying YUAN Wei-ting GE Han-guang HU Su-zhan ZHANG Shu ZHENG key laboratory of cancer prevention and intervention of Ministry of Education Key Laboratory of Molecular Biology in Medical Science of Zhejiang Province Cancer Institute the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

Objective:The purpose of this study was to determine the unique and universal features of microsatellite instability-high(MSI-H) colorectal cancer(CRC) and MSI-H gastric cancer(GC) in the Chinese ***:A new panel of mononucleotide MSI markers,BAT25,BAT26,NR21,NR24,and MONO-27,was used to define MSI status in 303 CRC and 288 GC *** features of both types of MSI-H tumors were *** analysis in the hMLH1 promoter region by methylation specific polymerase chain reaction(PCR) and mutation detection of hMSH2/hMLH1 genes by denaturing high-performance liquid chromatography(DHPLC) were carried out ***:MSI-H CRCs and MSI-H GCs account for 11.9% and 8.0% of unselected sporadic CRCs and GCs,***-H CRCs are strongly characterized by early onset,right-side location,low differentiation,mucinous tumor,less infiltration,less lymphatic metastasis,and more often familial ***-H GCs only showed site preference for the antrum and less lymphatic *** and epigenetic analyses were positive in 6/36 MSI-H CRCs and 0/23 MSI-H GCs with pathological mutation in major mismatch repair genes,and in 7/36 MSI-H CRCs and 18/23 MSI-H GCs with methylated hMLH1 promoter(P<0.01),***:Although there are many differences in the genetic basis and clinicopathological features between MSI-H CRC and MSI-H GC,when compared with their microsatellite stable(MSS) counterparts,site preference and lymphatic metastasis are features common to both types of MSI-H tumors.

关键词： Microsatellite instability Colorectal cancer Gastric cancer Mutation DNA methylation

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Surgical intervention for malignant bowel obstruction caused by gastrointestinal malignancies

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World Journal of Gastrointestinal Oncology 2020年第3期12卷 323-331页

作者： Peng-Ju Chen Lin Wang Yi-Fan Peng Nan Chen Ai-Wen Wu key laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Gastrointestinal Cancer Center Unit Ⅲ Peking University Cancer Hospital and Institute

BACKGROUND Malignant bowel obstruction(MBO)is a common event for end-stage gastrointestinal cancer *** studies had demonstrated manifestations and clinical management of MBO with mixed *** still lack reports of the surgical treatment of *** To analyze the short-term outcomes and prognosis of palliative surgery for MBO caused by gastrointestinal *** A retrospective chart review of 61 patients received palliative surgery between January 2016 to October 2018 was performed,of which 31 patients underwent massive debulking surgery(MDS)and 30 underwent ostomy/by-pass surgery(OBS).The 60-d symptom palliation rate,30-d morbidity and mortality,and overall survival rates were compared between the two *** The overall symptom palliation rate was 75.4%(46/61);patients in the MDS group had significantly higher symptom palliation rate than OBS group(90%vs 61.2%,P=0.016).Patients with colorectal cancer who were in the MDS group showed significantly higher symptom improvement rates compared to the OBS group(overall,76.4%;MDS,61.5%;OBS,92%;P=0.019).However,patients with gastric cancer did not show a significant difference in symptom palliation rate between the MDS and OBS groups(OBS,60%;MDS,80%;P=1.0).The median survival time in the MDS group was significantly longer than in the OBS group(10.9 mo vs 5.3 mo,P=0.05).CONCLUSION For patients with MBO caused by peritoneal metastatic colorectal cancer,MDS can improve symptom palliation rates and prolong survival,without increasing mortality and morbidity rates.

关键词： Gastrointestinal neoplasms Malignant bowel obstruction Metastasis Palliative surgery Prognosis Quality of life

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