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Glial response in the midcingulate cortex in Huntington’s disease

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Neural Regeneration Research 2025年第1期20卷 207-208页

作者： Thulani H.Palpagama Andrea Kwakowsky Center for Brain Research and department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： Huntington degeneration cortex

Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

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World Journal of Gastroenterology 2004年第8期10卷 1191-1197页

作者： SungYiHong MyunHeeLee WooJinHyung SungHoonNoh SeungHoChoi Kyung Sup Kim HyunCheolJung JaeKyungRoh department of Surgery Yonsei University College of MedicineSeoulKorea Institute of genetic Science Department of Biochemistry and Molecular BiologyYonsei University College of MedicineSeoulKorea Oncology Internal MedicineCancer Metastasis Research CenterYonsei University College of Medicine

AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating ***, a sustained and high protein delivery is required to achieve the desired therapeutic *** evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell *** test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were *** biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in *** over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically *** animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated *** with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated ***,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.

关键词： Adenoviridae Animals Antineoplastic Agents Antineoplastic Agents, Phytogenic Camptothecin Carcinoma, Hepatocellular Cell Line, Tumor Combined Modality Therapy DNA Topoisomerases inhibitors Drug Synergism Endostatins Endothelium, Vascular Enzyme Inhibitors Etoposide Gene Expression Gene Therapy Humans Liver Neoplasms Mice Research Support, Non-U.S. Gov't Sarcoma Survival Rate Umbilical Veins

Amelioration of Alzheimer's disease pathology and cognitive deficits by immunomodulatory agents in animal models of Alzheimer's disease

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Neural Regeneration Research 2019年第7期14卷 1158-1176页

作者： Bridget Martinez Philip V.Peplow department of Molecular & cellular Biology University of California department of medicine St.Georges University School of Medicine department of Physics and Engineering Los Alamos National Laboratory department of Anatomy University of Otago

The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the *** lead to progressive impairment of cognitive *** is evidence of innate immune activation in AD with ***-activated microglia(M1 state) secrete inflammatory and neurotoxic mediators,and peripheral immune cells are recruited to inflammation sites in the *** few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable *** of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical *** with immunomodulatory/anti-inflammatory agents early in the disease process,while not preventive,is able to inhibit the inflammatory consequences of both Aβ and tau *** studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of *** majority of the animal studies reviewed had used transgenic models of early-onset *** effort needs to be given to creat models of late-onset *** effects of a combinational therapy involving two or more of the tested pharmaceutical agents,or one of these agents given in conjunction with one of the cell-based therapies,in an aged animal model of AD would warrant investigation.

关键词： Alzheimer’s disease neuropathology cognitive deficits behavioral deficits immunomodulatory agents animal models amyloid deposits gliosis

Apoptotic cell death and its relationship to gastric carcinogenesis

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World Journal of Gastroenterology 2007年第23期13卷 3183-3188页

作者： Ferda Bir Nese Calli-Demirkan A Cevik Tufan Metin Akbulut N Lale Satiroglu-Tufan Pamukkale University School of Medicine Department of Pathology Denizli Turkey Pamukkale University School of Medicine Department of Histology and Embryology Denizli Turkey Pamukkale University School of Medicine Department of Medical Biology Center for Genetic Diagnosis Molecular Genetics Laboratory Denizli Turkey

AIM: To investigate the apoptotic process of cells with in the intestinal metaplasia areas co-localizing with chronic gastritis and gastric carcinomas and to analyze the involvement of proteins regulating apoptosis in the process of intestinal metaplasia related gastric carcinogenesis. METHODS: Forty-two gastric carcinoma and seventeen chronic gastritis cases were included in this study. All cases were examined for the existence of intestinal metaplasia. Ten cases randomly selected from each group were processed for TUNEL assay. TUNEL positive cells within the intestinal metaplasia areas, co-localizing either to gastric carcinoma or chronic gastritis, were counted and converted to apoptotic indices. In addition, p53, bcl-2 and bax expression patterns within these tissues were analyzed on the basis of immunohistochemistry. RESULTS: Twenty-eight of the cases were intestinal and 14 of the cases were diffuse type adenocarcinomas. 64% (27/42) of the gastric carcinoma cases had intestinal metaplasia. Intestinal metaplasia co-localized more with intestinal type carcinomas compared with diffuse type carcinomas [75% (21/28) vs 42% (6/14), respectively; P ≤0.05]. The mean apoptotic index in tumor cells was 0.70±0.08. The mean apoptotic index in intestinal metaplasias co-localizing to tumors was significantly higher than that of intestinal metaplasias co-localizing to chronic gastritis (0.70±0.03 vs 0.09±0.01, respectively; P≤0.05). p53 positivity was not observed in areas of intestinal metaplasia adjacent to tumors or chronic gastritis. Intestinal metaplasia areas adjacent to tumors showed lower cytoplasmic bcl-2 positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [55.5% (15/27) vs 70.5% (12/17), respectively]. On the other hand, intestinal metaplasia areas adjacent to tumors showed significantly higher cytoplasmic bax positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [44.4% (12/27) vs 11.7% (2/17), respectively; P ≤

关键词： p53 Bax Bcl-2 TUNEL staining Intestinal metaplasia Apoptosis Gastric cancer

BRAF mutation in colorectal carcinomas with signet ring cell component

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Cancer Biology & medicine 2017年第3期14卷 287-292页

作者： Serap Yalcin Onder Onguru department of Molecular Biology and genetic Ahi Evran UniversityKirsehir 40100Turkey department of Pathology Gulhane School of MedicineHealth Sciences UniversityAnkara 06010Turkey

Objective:Signet ring cell carcinoma is a rare subtype of colorectal carcinoma(CRC)with an associated BRAFV600E *** investigated frequencies of BRAF mutation in 28 CRCs containing variable signet ring cell component and their relation with clinicopathologic ***:According to the presence of signet ring cell component,tumors were categorized into groups as follows:0%–9%,10%–24%,25%–49%,and>50%.Genomic DNA was isolated and analyzed for BRAF V600E gene mutation by polymerase chain reaction-restriction fragment length *** of 28 cases(39.3%)showed BRAFV600E mutation,which was also confirmed by Sanger *** elucidate the importance of existence of signet ring cell component at the molecular level,we separated cases into two groups with cut-off levels of 10%and 50%,which pertain to percentages of signet ring ***:Seven of 19 cases(36.8%)under the threshold of 50%and four of nine cases(44.4%)over this threshold value demonstrated BRAF *** of 7 cases(42.8%)featuring10%were BRAF ***:BRAF mutation must be closely associated with the presence of malignant signet ring cells regardless of their percentages.

关键词： BRAF mutations colon cancer signet ring cell

Heterologous expression of Lolium perenne antifreeze protein confers chilling tolerance in tomato

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Journal of Integrative Agriculture 2018年第5期17卷 1128-1136页

作者： Srinivasan Balamurugan Jayan Susan Ann Inchakalody P Varghese Shanmugaraj Bala Murugan Mani ChANDra Harish Sarma Rajeev Kumar Ramalingam Sathishkumar Plant genetic Engineering Laboratory Department of BiotechnologyBharathiar University

Antifreeze proteins（AFP） are produced by certain plants, animals, fungi and bacteria that enable them to survive upon extremely low temperature. Perennial rye grass, Lolium perenne, was reported to possess AFP which protects them from cold environments. In the present investigation, we isolated AFP gene from L. perenne and expressed it in tomato plants to elucidate its role upon chilling stress. The T1 transgenic tomato lines were selected and subjected to molecular, biochemical and physiological analyses. Stable integration and transcription of Lp AFP in transgenic tomato plants was confirmed by Southern blot hybridization and RT-PCR, respectively. Physiological analyses under chilling conditions showed that the chilling stress induced physiological damage in wild type（WT） plants, while the transgenic plants remained healthy. Total sugar content increased gradually in both WT and transgenic plants throughout the chilling treatment. Interestingly, transgenic plants exhibited remarkable alterations in terms of relative water content（RWC） and electrolyte leakage index（ELI） than those of WT. RWC increased significantly by 3-fold and the electrolyte leakage was reduced by 2.6-fold in transgenic plants comparing with WT. Overall, this report proved that Lp AFP gene confers chilling tolerance in transgenic tomato plants and it could be a potential candidate to extrapolate the chilling tolerance on other chilling-sensitive food crops.

关键词： Lolium perenne antifreeze protein chilling tolerance genetic transformation transgenic tomato

Overcoming Resistance to Drugs Targeting KRAS^(G12C) Mutation

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The Innovation 2020年第2期1卷 71-81页

作者： Delong Jiao Shengyu Yang department of cellular and Molecular Physiology Penn State College of MedicineHersheyPA 17033USA

Activating KRAS mutations are present in 25%of human *** oncogenic Ras was deemed“undruggable”in the past,recent efforts led to the development of pharmacological inhibitors targeting the KRAS^(G12C) mutant,which have shown promise in early clinical *** development of allele-specific K-Ras^(G12C) inhibitors marked a new chapter in targeting oncogenic KRAS mutant in ***,drug resistance against these new drugs will likely limit their efficacy in the ***-wide approaches have been used to interrogate the mechanisms of resistance to K-Ras^(G12C ) inhibitors,which would facilitate the development of therapeutics overcoming drug *** article reviews the latest progress in resistance to K-Ras^(G12C)-targeted therapies and aims to provide insight in future research targeting drug resistance in cancer.

关键词： ONCOGENE KRAS INHIBITOR TARGETED THERAPY DRUG RESISTANCE

The varicocele： diagnostic dilemmas, therapeutic challenges and future perspectives

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Asian Journal of Andrology 2016年第2期18卷 276-281,J0007页

作者： Koji Chiba Ranjith Ramasamy Dolores J Lamb Larry I Lipshultz Center for Reproductive medicine Baylor College of Medicine Houston TX USA Scott department of Urology Baylor College of Medicine Houston TX USA department of Molecular and cellular Biology Baylor College of Medicine Houston TX USA.

A varicocele is defined as the abnormal dilation of the internal testicular vein and pampiniform venus plexus within the spermatic cord. If a semen analysis is not obtained from the adolescent male, in the absence of other symptoms, the main clinical indication used by many urologists to recommend repair is testicular atrophy. The varicocele may result in testicular damage in some males causing testicular atrophy with impaired sperm production and decreased Leydig cell function, while in other males the varicocele may seemingly cause no ill effects. In adult men, varicoceles are frequently present and surgically correctable, yet the measurable benefits of surgical repair are slight according to a Cochrane review. While occurring more commonly in infertile men than fertile men, only 20% of men with a documented varicocele will suffer from fertility problems. Most varicoceles found in adolescents are detected during a routine medical examination, and it is difficult to predict which adolescent presenting with a varicocele will ultimately show diminished testicular function in adolescence or adulthood. As in adults, the mainstay of treatment for varicocele in adolescents is surgical correction. However, unlike an adult varicocelectomy （the microsurgical approach is the most common）, treatment for an adolescent varicocele is more often laparoscopic. Nevertheless, the goals of treatment are the same in the adolescent and adult patients. Controversy remains as to which patients to treat, when to initiate the treatment, and what type of treatment is the best. This review will present the current understanding of the etiology, diagnosis and treatment of the adolescent varicocele.

关键词： adolescent adult management varicocele

Chronic bacterial prostatitis and irritable bowel syndrome： effectiveness of treatment with rifaximin followed by the probiotic VSL#3

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Asian Journal of Andrology 2014年第5期16卷 735-739,I0009页

作者： Enzo Vicari Sandro La Vignera Roberto Castiglione Rosita A Condorelli Lucia O Vicari Aldo E Calogero Section of Endocrinology Andrology and Internal Medicine Department of MedicaJ and Pediatric Sciences Master in Experimental and Clinical medicine and cellular Physiopathology University of Catania Catania Italy

This study was undertaken to evaluate the influence of treatment with rifaximin followed by the probiotic VSL#3 versus no treatment on the progression of chronic prostatitis toward chronic microbial prostate-vesiculitis （PV） or prostate-vesiculo-epididymitis （PVE）. A total of 106 selected infertile male patients with bacteriologically cured chronic bacterial prostatitis （CBP） and irritable bowel syndrome （IBS） were randomly prescribed rifaximin （200 mg, 2 tablets bid, for 7 days monthly for 12 months） and probiotic containing multiple strains VSL#3 （450 × 10^9 CFU per day） or no treatment. Ninety-five of them （89.6%） complied with the therapeutic plan and were included in this study. Group A = ＂6Tx/6-＂： treatment for the initial 6 and no treatment for the following 6 months （n = 26）; Group B = ＂12Tx＂： 12 months of treatment （n = 22）; Group C = ＂6-/6Tx＂： no treatment for the initial 6 months and treatment in the last 6 months （n = 23）; Group D = ＂12-＂： no treatment （n = 24）. The patients of Groups A = ＂6Tx/6-＂ and B = ＂12Tx＂ had the highest frequency of chronic prostatitis （88.5% and 86.4%, respectively）. In contrast, group ＂12-＂： patients had the lowest frequency of prostatitis （33.4%）. The progression of prostatitis into PV in groups ＂6Tx/6-＂（15.5%） and ＂6-/6Tx＂（13.6%） was lower than that found in the patients of group ＂12-＂（45.8%）. Finally, no patient of groups ＂6Tx/6-＂ and ＂6-/6Tx＂ had PVE, whereas it was diagnosed in 20.8% of group ＂12-＂ patients. Long-term treatment with rifaximin and the probiotic VSL#3 is effective in lowering the progression of prostatitis into more complicated forms of male accessory gland infections in infertile patients with bacteriologically cured CBP plus IBS.

关键词： chronic bacterial prostatitis irritable bowel syndrome probiotic VSL#3 prostate-vesiculitis prostate-vesiculo-epididymitis rifaximin