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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research centre for molecular oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

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2D phosphides heterostructures on titanium microfiltration membrane for enhanced ampere-level current density overall seawater splitting

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Nano Research 2025年第1期18卷 249-259页

作者： Wenjing Dai Xin Wang Yulong Ma Sisi He Ming Chen Zhaohui Yin Shuheng Tian Maolin Wang Shixiang Yu Hang Zhang Yuanzhe Wang Hong Wang Jianxin Li Faming Gao Bowen Cheng Yun Wang Zhen Yin Ding Ma Tianjin Key Laboratory of Brine Chemical Engineering and Resource Eco-utilization College of Chemical Engineering and Materials ScienceTianjin University of Science and TechnologyTianjin 300457China State Key Laboratory of Biobased Fiber Manufacturing Technology Tianjin University of Science and TechnologyTianjin 300457China Haian Institute of High-Tech Research Nanjing UniversityHaian 226600China Beijing National Laboratory for molecular Sciences College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China State Key Laboratory of Separation Membranes and Membrane Processes Separation Membrane Science and Technology International Joint Research CentreTiangong UniversityTianjin 300387China centre for Catalysis and Clean Energy School of Environment and ScienceGold Coast CampusGriffith UniversitySouthportQueensland 4222Australia

The advancement of direct seawater electrolysis is a significant step towards sustainable hydrogen production,addressing the critical need for renewable energy sources and efficient resource ***,direct seawater electrolysis has to face several challenges posed by the corrosiveness of highly concentrated chloride and the competitive chlorine evolution reaction(ClER).To overcome these issues,we designed a novel NiP_(2)@CoP electrocatalyst on a porous titanium microfiltration(Ti MF)*** obtained bifunctional NiP_(2)@CoP catalyst outperforms the Pt/C and IrO_(2),as evidenced by its low overpotentials of 192 and 425 mV at a current density of 500 mA·cm^(-2) for hydrogen evolution reaction(HER)and oxygen evolution reaction(OER)in alkaline seawater(1 M KOH+0.5 M NaCl),***,only 231 and 569 mV overpotentials are required at the current density of 1500 mA·cm^(-2) towards HER and OER in alkaline seawater,*** importantly,no ClER was observed,demonstrating its excellent selectivity to *** selection of porous Ti MF membrane as an electrode substrate further enhances the performance by providing a robust structure that promotes the fast generation and release of gas *** promising outcomes obtained with NiP_(2)@CoP catalysts on Ti MF support,therefore,pave the way for the commercial viability of direct seawater electrolysis technologies at industrial-level current densities.

关键词： direct seawater electrolysis porous titanium microfiltration membrane phosphides heterostructures NiP_(2)@CoP electrocatalyst excellent selectivity to oxygen evolution reaction(OER)

Epstein-Barr virus is associated with gastric carcinoma: The question is what is the significance?

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World Journal of Gastroenterology 2008年第27期14卷 4347-4351页

作者： Hugo Sousa Ana L Pinto-Correia Rui Medeiros Mario Dinis-Ribeiro molecular oncology Group and molecular Virology Laboratory Portuguese Institute of Oncology of Porto Gastroenterology Department Portuguese Institute of Oncology of Porto

AIM: To examine the possible role of the Epstein- Barr Virus (EBV) in the development of gastric adenocarcinoma (GC). It is unclear whether EBV is involved in GC development or is a consequence of gastric inflammation secondary to immunosuppressive treatments. METHODS: A systematic review was carried out of all published observational studies on the temporal association between EBV and GC, with a view to determine a causal relationship. RESULTS: The present study showed that the worldwide crude prevalence of EBV in gastric adenocarcinoma was 8.29%. The prevalence varied from 7.08% for intestinal type and 9.82% for diffuse type of GC. It was observed that Western and Central Asian countries had a significantly higher frequency of EBV positive cases compared to South-Eastern countries. America had the highest EBV-GC prevalence whereas Europe had the lowest. CONCLUSION: The present review has demonstrated a high prevalence of EBV in gastric adenocarcinoma. However, studies designed to assess a temporal relationship and histological association using sensitive techniques should be carried out to establish the role of EBV in GC carcinogenesis.

关键词： Epstein-Barr virus infection Gastric carcinoma Systematic review

Allitridi induces apoptosis by affecting Bcl-2 expression and caspase-3 activity in human gastric cancer cells

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Acta Pharmacologica Sinica 2004年第2期25卷 93-99页

作者： Hong LAN, You-yong Lü1 Beijing molecular oncology, Beijing Institute for Cancer Research, School of oncology, Peking University, Beijing 100034, China Beijing molecular oncology Beijing Institute for Cancer Research School of Oncology Peking University 北京 100034

AIM: To investigate the mechanism of allitridi-induced apoptosis in human gastric cancer cell line BGC823. METHODS: Growth inhibition by allitridi was analyzed using cell growth curve and MTT assay. Apoptotic cells were detected using staining with Hoechst 33342, and confirmed by flow cytometric analysis and DNA fragmen- tation analysis. The protein expression affected by allitridi was determined using Western blot. The activity of caspase-3 was measured using a fluorescence assay. RESULTS: Allitridi induced apoptosis, and then inhibited cells proliferation in human gastric cancer cell line BGC823. The protein level of Bcl-2 was decreased dramatically, while Bax and p53 were not significantly affected by allitridi. The expression and activity of caspase-3 started to increase after allitridi treatment for 72 h. CONCLUSION: Allitridi induced apoptosis through down-regulation of Bcl-2, and increased caspase-3 expression and its activity.

关键词： human gastric cancer cell line apoptosis diallyl trisulfide Bcl-2 CPP32 protein

Viro-immune therapy:A new strategy for treatment ofpancreatic cancer

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World Journal of Gastroenterology 2016年第2期22卷 748-763页

作者： Andrea Marie Ibrahim Yao-he Wang centre for molecular oncology Barts Cancer InstituteQueen Mary University of LondonEC1M6BQ LondonUnited Kingdom National centre for International Research in Cell and Gene Therapy Sino-British Research Centre for Molecular OncologyZhengzhou UniversityZhengzhou 450000Henan provinceChina

Pancreatic ductal adenocarcinoma(PDAC) is an almost uniformly lethal disease with less than 5% survival at five years. This is largely due to metastatic disease, which is already present in the majority of patients when diagnosed. Even when the primary cancer can be removed by radical surgery, local recurrence occurs within one year in 50%-80% of cases. Therefore, it is imperative to develop new approaches for the treatment of advanced cancer and the prevention of recurrence after surgery. Tumour-targeted oncolytic viruses(TOVs) have become an attractive therapeutic agent as TOVs can kill cancer cells through multiple mechanisms of action, especially via virus-induced engagement of the immune response specifically against tumour cells. To attack tumour cells effectively, tumour-specific T cells need to overcome negative regulatory signals that suppress their activation or that induce tolerance programmes such as anergy or exhaustion in the tumour microenvironment. In this regard, the recent breakthrough in immunotherapy achieved with immune checkpoint blockade agents, such as anti-cytotoxic T-lymphocyte-associate protein 4, programmed death 1(PD-1) or PD-L1 antibodies, has demonstrated the possibility of relieving immune suppression in PDAC. Therefore, the combination of oncolytic virotherapy and immune checkpoint blockade agents may synergistically function to enhance the antitumour response, lending the opportunity to be the future for treatment of pancreatic cancer.

关键词： anti-cytotoxic T-lymphocyte-associateprotein 4 Anti-programmed death receptor ligand 1 Anti-programmed death receptor 1 Immunotherapy Oncolytic viruses Pancreatic ductal adenocarcinoma Pancreatic cancer Immune checkpoint blockadeinhibitors cancer vaccine

Leptomeningeal metastases originated from esophagogastric junction/gastric cancer:A brief report of two cases

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World Journal of Gastrointestinal oncology 2018年第1期10卷 56-61页

作者： Panteleimon Kountourakis Demetris Papamichael Haris Haralambous Michael Michael Georgios Nakos Sylvia Lazaridou Eleni Fotiou Vassilios Vassiliou Demetrios Andreopoulos Department of Medical oncology BOC Oncology Centre Department of Radiology BOC Oncology Centre Department of Cytology General Hospital of Nicosia Department of Pathology General Hospital of Nicosia Department of Radiation oncology BOC Oncology Centre

Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed with esophagogastric junction and gastric cancer. Its prognosis is ominous and therapy outcomes are disappointing. Herein, we present two patients; one initially diagnosed with gastric cancer and leptomeningeal carcinomatosis but no other evidence of metastatic disease and the other one initially diagnosed with esophagogastric junction cancer, who recurred solitary with leptomeningeal seedings several years after the initial diagnosis and treatment. Furthermore, a thorough and short review of the literature is carried out.

关键词： Esophagogastric junction cancer Gastric cancer Leptomeningeal carcinomatosis Prognosis Investigation Therapy

Müllerian duct anomalies and their effect on the radiotherapeutic management of cervical cancer

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Chinese Journal of Cancer 2013年第8期32卷 434-440页

作者： Madhup Rastogi Swaroop Revannasiddaiah Pragyat Thakur Priyanka Thakur Manish Gupta Manoj K Gupta Rajeev K Seam Department of Radiotherapy & oncology Regional Cancer Centre Department of Radiation oncology HCG-Bangalore Institute of Oncology

Radiotherapy plays a major role in the treatment of cervical cancer. A successful radiotherapy program integrates both external beam and brachytherapy components. The principles of radiotherapy are strongly based on the anatomy of the organ and patterns of local and nodal spread. However, in patients with distorted anatomy, several practical issues arise in the delivery of optimal radiotherapy, especially with brachytherapy. Müllerian duct anomalies result in congenital malformations of the female genital tract. Though being very commonly studied for their deleterious effects on fertility and pregnancy, they have not been recognized for their potential to interfere with the delivery of radiotherapy among patients with cervical cancer. Here, we discuss the management of cervical cancer among patients with Müllerian duct anomalies and review the very sparse amount of published literature on this topic.

关键词：放射治疗宫颈癌管理异常管道先天畸形传播模式解剖结构

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Hepatitis C virus genotype 3a infection and hepatocellular carcinoma: Pakistan experience

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World Journal of Gastroenterology 2009年第40期15卷 5080-5085页

作者： Muhammad Idrees Shazia Rafi que Irshad-ur Rehman Haji Akbar Muhammad Zubair Yousaf Sadia Butt Zunaira Awan Sobia Manzoor Madiha Akram Mahwish Aftab Bushra Khubaib Sheikh Riazuddin Division of molecular Virology & molecular Diagnostics National Centre of Excellence in Molecular BiologyUniversity of the Punjab Lahore National centre of Excellence in molecular Biology University of the Punjab Lahore

AIM: To assess the association between chronic hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) in Pakistan, and the genotype distribution among these HCC ***: One hundred and sixty-one subjects with HCC were included in this study. Liver biopsy was performed on 145 of the patients; sixteen were excluded because they failed to fulfill the inclusion criteria. Qualitative polymerase chain reaction (PCR) was performed for hepatitis B virus and HCV. Samples positive for HCV RNA were genotyped using genotype-specif ic PCR and conf irmed by HCV 5' noncoding region sequencing analysis. RESULTS: Chronic HCV infection was identified a major risk factor (63.44% of tested HCC patients) forthe development of HCC. The time from HCV infection to appearance of cancer was 10-50 years. In the HCC patient population, broader distributions of genotypes were present with genotype 3a as the predominant genotype. Using the type-specific genotyping method, we found HCV genotype 3a in 40.96%, 3b in 15.66%, 1a in 9.63%, and 1b in 2.40% of HCC tissue samples. About 28% of cases were found with mixed genotypes. Two cases were unable to be genotyped because of low viral load. Sixty-six percent of treated patients with cirrhosis had an end of treatment response, but unfortunately they relapsed quickly when the treatment was discontin-ued, and HCC developed during a median 3.8 years. CONCLUSION: There was a strong association between chronic HCV infection and HCC in Pakistan, and between HCV genotype 3a and HCC.

关键词： Hepatocellular carcinoma Hepatitis C Genotyping Etiology Prevalence

Significance of a novel sucrose permeability test using serum in the diagnosis of early gastric cancer

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World Journal of Gastroenterology 2005年第44期11卷 6905-6909页

作者： Tadayuki Shishido Taketo Yamaguchi Takeo Odaka Masanori Seimiya Hiromitsu Saisho Fumio Nomura Department of Medicine and Clinical oncology Department of molecular Diagnosis

AIM： To investigate the usefulness of sucrose permeability test using serum in the diagnosis of gastric diseases, with special reference to early gastric cancer （EGC）. METHODS： A total of 63 subjects, including 11 patients with gastric ulcer, 20 patients with gastric cancer （13, early; 7, advanced） and 32 healthy controls, were studied. Blood and urine samples were collected repeatedly for 5 h before and after the sucrose loading. Sucrose levels were measured by a newly developed RESULTS： Serum sucrose levels started to increase 15 min after loading, and peaked at 60 min in the gastric disease groups. The levels for gastric ulcer, EGC and advanced gastric cancer （AGC） at 60 min were significantly higher than that in the healthy controls （26.9±2.4, 34.4±5.0, and 71.8±15.6 vs 7.9±0.7 mol/L, respectively, P〈0.01）. The cut-off level set at 15.4 mol/L （60 min） offered the best distinction between EGC patients and healthy controls; and the sensitivity and specificity were 92.3% and 93.8%, respectively, while those of the urine method were 76.9% and 93.8%, respectively. CONCLUSIONS： The gastric permeability test using serum is reliable for the detection of EGC, and this test can provide results much earlier than the conventional urine method. This test may offer a useful alternative to more invasive tests for EGC.

关键词： Sucrose test Gastric permeability Early gastric cancer Advanced gastric cancer Gastric ulcer