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G2/M inhibitors as pharmacotherapeutic opportunities for glioblastoma:the old,the new,and the future

Cancer Biology & Medicine 2018年第4期15卷 354-374页

作者： Angel Mauricio Castro-Gamero Julia Alejandra Pezuk Maria Sol Brassesco luiz Gonzaga Tone Human Genetics Laboratory Institute of Natural SciencesFederal University of Alfenas(UNIFAL-MG)Alfenas 37130-001Brazil Biotechnology and Innovation in Health Program and Pharmacy Program Anhanguera University Sao Paulo(UNIANSP)Sao Paulo 05145-200Brazil Department of Biology Faculty of PhilosophySciences and Letters at Ribeirao PretoUniversity of Sao PauloRibeirao Preto 14040-901Brazil Department of Pediatrics Department of Genetics Ribeirao Preto School of MedicineUniversity of Sao PauloRibeirao Preto 14049-900Brazil

Glioblastoma(GBM) is one of the deadliest tumors and has a median survival of 3 months if left untreated. Despite advances in rationally targeted pharmacological approaches, the clinical care of GBM remains palliative in intent. Since the majority of altered signaling cascades involved in cancer establishment and progression eventually affect cell cycle progression, an alternative approach for cancer therapy is to develop innovative compounds that block the activity of crucial molecules needed by tumor cells to complete cell division. In this context, we review promising ongoing and future strategies for GBM therapeutics aimed towards G2/M inhibition such as anti-microtubule agents and targeted therapy against G2/M regulators like cyclin-dependent kinases,Aurora inhibitors, PLK1, BUB, 1, and BUBR1, and survivin. Moreover, we also include investigational agents in the preclinical and early clinical settings. Although several drugs were shown to be gliotoxic, most of them have not yet entered therapeutic trials. The use of either single exposure or a combination with novel compounds may lead to treatment alternatives for GBM patients in the near future.

关键词： Chemotherapy PLK1 AURK survivin BUB BUR1

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Collaborative Efforts and Strategies for Cholera Outbreak Control in Garissa County, Kenya: Implementation of Water Quality Monitoring Interventions

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Journal of Water Resource and Protection 2024年第2期16卷 123-139页

作者： Michael Habtu Mark Nanyingi Ali A. Hassan Abdiwahid M. Noor Joel Mutyandia Muli Alan Mwika Julius Wekesa Ahmed Fidhow Diba Dulacha Landry Kabego Ishata Nannie Conteh andre Arsene Bita Fouda Sonia Chene Aden H. Ibrahim Ahmed Nadhir Omar Martins C. Livinus Abdourahmane Diallo World Health Organization Nairobi Kenya Department of Health Garissa County Government Garissa Kenya Water Resources Authority Garissa Kenya World Health Organization Regional Office for Africa Brazzaville Congo Regional Agency for Health Dijon France

A multi-faceted Case Area Targeted Intervention (CATI) approach emphasizing the integration of Water, Sanitation and Hygiene (WASH) interventions and Oral Cholera Vaccine (OCV) campaign was employed to respond to the outbreak of cholera in Garissa County. Drinking water sources in areas heavily impacted by cholera were systematically mapped and tested for microbiological quality. The quality assessment was carried out in April 2023 during an ongoing cholera outbreak in the county. A total of 109 samples were collected and tested for thermotolerant coliforms and other in situ parameters. The finding revealed that more than 87% of the samples did not meet the World Health Organization (WHO) standard for thermotolerant coliforms;and 30% had turbidity values above the recommended threshold values. None of the 109 samples had any traceable residual chlorine. Following these findings, the county government implemented the targeted interventions which resulted in a positive impact in the fight against cholera. The WHO supported key interventions which included capacity building in water quality monitoring and prepositioning of critical WASH commodities to the cholera affected areas.

关键词： Cholera Drinking Water Household Water Treatment Kenya

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The transient receptor potential melastatin 2:a new therapeutical target for Parkinson's disease?

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Neural Regeneration Research 2023年第8期18卷 1652-1656页

作者： Ana Flávia F.Ferreira luiz Roberto G.Britto Department of Physiology and Biophysics Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil

The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating mechanism is dependent on reactive oxygen species. In pathological conditions, transient receptor potential melastatin 2 is overactivated, leading to a Ca~(2+) influx that alters cell homeostasis and promotes cell death. The role of transient receptor potential melastatin 2 in neurodegenerative diseases, including Alzheimer's disease and ischemia, has already been described and reviewed. However, data on transient receptor potential melastatin 2 involvement in Parkinson's disease pathology has emerged only in recent years and the issue lacks review studies that focus specifically on this topic. The present review aims to elucidate the role of the transient receptor potential melastatin 2 channel in Parkinson's disease by reviewing, summarizing, and discussing the in vitro, in vivo, and human studies published until August 2022. Here we describe fourteen studies that evaluated the transient receptor potential melastatin 2 channel in Parkinson's disease. The Parkinson's disease model used, transient receptor potential melastatin 2 antagonist and genetic approaches, and the main outcomes reported were discussed. The studies described transient receptor potential melastatin 2 activation and enhanced expression in different Parkinson's disease models. They also evidenced protective and restorative effects when using transient receptor potential melastatin 2 antagonists, knockout, or silencing. This review provides a literature overview and suggests where there is a need for more research. As a perspective point, this review shows evidence that supports transient receptor potential melastatin 2 as a pharmacological target for Parkinson's disease in the future.

关键词： 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine(MPTP) 1-methyl-4-phenylpyridinium(MPP+) 6-hydroxydopamine AG490 clotrimazole flufenamic acid N-(p-amylcinnamoyl)anthranilic acid Parkinson's disease poly-ADPR polymerase type 1(PARP1) rotenone paraquat transient receptor potential melastatin 2(TRPM2)

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Post-infectious irritable bowel syndrome:Mechanistic insights into chronic disturbances following enteric infection

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World Journal of Gastroenterology 2014年第14期20卷 3976-3985页

作者： Jennifer K Beatty Amol Bhargava andre G Buret Department of Biological Sciences University of Calgary

Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)*** 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious *** appearance of new IBS symptoms following an infectious event is defined as ***,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare ***,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in *** pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful ***,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and *** review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.

关键词： Post-infectious irritable bowel syndrome Infectious diarrhea Enteric pathogen Inflammatory disorders Immune alterations

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Medical,ethical,and legal aspects of hematopoietic stem cell transplantation for Crohn’s disease in Brazil

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World Journal of Stem Cells 2020年第10期12卷 1113-1123页

作者： Milton Artur Ruiz Roberto luiz Kaiser Junior Lilian Piron-Ruiz Priscila Samara Saran Lilian Castiglioni luiz Gustavo de Quadros Tainara Souza Pinho Richard K Burt Department of Bone Marrow Transplant Beneficência Portuguesa HospitalSão Josédo Rio Preto 15090470Brazil Department of Proctology Beneficencia Portuguesa HospitalSão Josédo Rio Preto 15090470Brazil Department of Bone Marrow Transplantation Beneficência Portuguesa HospitalSão Josédo Rio Preto 15090470Brazil Genetics and Molecular Biology FAMERP-Faculdade de Medicina de São Josédo Rio PretoSão Josédo Rio Preto 15090470 Brazil Department of Endoscopy Beneficência Portuguesa HospitalABC Medical SchoolSão Bernardo 15015110Brazil Department of Medicine Northwestern University Feinberg School of MedicineChicagoIL 60611United States

Crohn's disease(CD)is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal *** etiology of CD is unknown;however,genetic,epigenetic,environmental,and lifestyle factors could play an essential role in the onset and establishment of the *** results from immune dysregulation due to loss of the healthy symbiotic relationship between host and intestinal flora and or its *** affects both sexes equally with a male to female ratio of 1.0,and its onset can occur at any age,but the diagnosis is most commonly observed in the range of 20 to 40 years of *** diminishes quality of life,interferes with social activities,traumatizes due to the stigma of incontinence,fistulae,strictures,and colostomies,and in severe cases,affects survival when compared to the general *** fluctuate between periods of remission and activity in which complications such as fistulas,strictures,and the need for bowel resection,surgery,and colostomy implantation make up the most severe aspects of the *** can be progressive and the complications recurrent despite treatment with anti-inflammatory drugs,corticosteroids,immunosuppressants,and biological ***,over time many patients become refractory without treatment alternatives,and in this scenario,hematopoietic stem cell transplantation(HSCT)has emerged as a potential treatment *** rationale for the use of HSCT for CD is anchored in animal studies and human clinical trials where HSCT could reset a patient's immune system by eliminating disease-causing effector cells and upon immune recovery increase regulatory and suppressive immune *** HSCT using a non-myeloablative regimen of cyclophosphamide and anti-thymocyte globulin without CD34+selection has been to date the most common transplant conditioning regimen *** this review we will address the current situation regarding CD treatment with HSCT and emphasize the medical,ethical,and legal aspect

关键词： Crohn disease Hematopoietic stem cell transplant Stem cell therapy Autologous transplant Ethics Treatment

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Differential expression of apoptosis related proteins and nitric oxide synthases in Epstein Barr associated gastric carcinomas

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World Journal of Gastroenterology 2006年第31期12卷 4959-4965页

作者： Maria D Begnami andre L Montagnini andre L Vettore Sueli Nonogaki Mariana Brait Alex Y Simoes-Sato andrea Q A Seixas Fernando A Soares Department of PathologyHospital do C(a|^)ncer A C Camargo S(a|~)o PauloSPBrazil Department of Abdominal SurgeryHospital do C(a|^)ncer A C Camargo S(a|~)o PauloSPBrazil Ludwig Institute for Cancer ResearchS(a|~)o Paulo SPBrazil

AIM： To determine the incidence of Epstein Barr virus associated gastric carcinoma （GC） in Brazil and compare the expressions of apoptosis related proteins and nitric oxide synthases between EBV positive and negative gastric carcinoma. METHODS： In situ hybridization of EBV-encoded small RNA-1 （EBER-1） and PCR was performed to identify the presence of EBV in GCs. Immunohistochemistry was used to identify expressions of bcl-2, bcl-xl, bak, bax, p53, NOS-1, NOS-2, and NOS-3 proteins in 25 EBV positive GCs and in 103 EBV negative GCS. RESULTS： 12% of the cases of GC （25/208） showed EBER-1 and EBNA-1 expression. The cases were preferentially of diffuse type with intense lymphoid infiltrate in the stroma. EBV associated GCs showed higher expression of bcl-2 protein and lower expression of bak protein than in EBV negative GCs. Indeed, expressions of NOS-1 and NOS-3 were frequently observed in EBV associated GCs. CONCLUSION： Our data suggest that EBV infection may protect tumor cells from apoptosis, giving them the capacity for permanent cell cycling and proliferation. In addition, EBV positive GCs show high expression of constitutive NOS that could influence tumor progression and aggressiveness.

关键词： Gastric carcinoma EBV Apoptosis p53 Nitric oxide synthases

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First Psocodean (Psocodea,Empheriidae) from the Cretaceous Amber of New Jersey

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Acta Geologica Sinica(English Edition) 2010年第4期84卷 762-767页

作者： Dany AZAR andre NEL Julian F.PETRULEVICIUS Lebanese University Faculty of Sciences IINatural Sciences DepartmentFanar-MatnLebanon Museum National d'Histoire Naturelle EntomologieUMR CNRS 7205ParisFrance Division Paleozoologia Invertebrados Museo de La Plata-UNLP-CONICETLa Plata 1900Argentina

Representatives of the extinct psocid family Empheriidae are known from Eocene Baltic amber, Lowermost Eocene French amber （Oise）, and Lower Cretaceous Spanish amber （Alava）. We report herein the first discovery of an empheriid psocid from the Cretaceous amber of New Jersey as Jerseyempheria grimaldii gen. et sp. nov. The fossil is figured and described. The new species is distinguished from related taxa. A discussion and checklist of Empheriidae are provided.

关键词： Psocodea Trogiomorpha Atropetae Empheriidae Turonian Cretaceous amber New Jersey USA

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A CK2-RNF4 interplay coordinates non-canonical SUMOylation and degradation of nuclear receptor FXR

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Journal of Molecular Cell Biology 2017年第3期9卷 195-208页

作者： Stephanie Bilodeau Veronique Caron Jonathan Gagnon Alexandre Kuftedjian andre Tremblay Research Center CHU Sainte-Justine Montreal Quebec H3T 1C5 Canada Department of Biochemistry and Molecular Medicine Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada Department of Obstetrics & Gynecology Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada

Farnesoid X receptor （FXR） is a ligand-activated nuclear receptor that plays a central role in regulating genes involved in bile acid homeostasis, and fat and glucose metabolism. Here, we demonstrate a post-translational interplay between FXR phosphoryl- ation, SUMOylation, and ubiquitination that directs the receptor into an activation-degradation pathway in hepatocytes. We iden- tify a non-canonical SUMOylation motif termed pSuM that conjugates SUM02 at Lys-325 of FXR under the direct control of casein kinase 2 （CK2）, which provides the required negative charge for Ubc9 and PIAS1 to perform SUMOylation, by phosphorylating Ser-327. Lys-325 SUMOylation is indispensable to the promotion of efficient ligand activation and transcriptional coactivation of FXR. Constitutive pSuM activation using a phospho-mimic Ser-327 mutant or catalytic CK2 expression strongly induces SUM02 conjugation, which directs FXR ubiquitination and proteasome-dependent degradation. We also determine that such SUMOylation-dependent ubiquitination of FXR is mediated by the E3 ubiquitin ligase RNF4, which is required to achieve maximal induction of FXR and optimal up- or downregulation of responsive genes involved in bile acid homeostasis and liver regeneration. Our findings identify a highly regulated atypical SUMO conjugation motif that serves to coordinate FXR transcriptional compe- tence, thereby expanding the intricate dynamics of the SUMOylation process used by incoming signals to govern metabolic gene regulation.

关键词： farnesoid receptor SUMOylation ubiquitination 26S proteasome bile acid

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The presence of primary sclerosing cholangitis in patients with ileal pouch anal-anastomosis is associated with an additional risk for vitamin D deficiency

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Gastroenterology Report 2016年第4期4卷 320-324,I0003页

作者： andre Fialho andrea Fialho Gursimran Kochhar Bo Shen Department of Internal Medicine Cleveland Clinic FoundationClevelandOHUSA Department of Gastroenterology and Hepatology Cleveland Clinic FoundationClevelandOHUSA

Objective:Vitamin D deficiency is common in patients with ileal pouch-anal anastomosis(IPAA)for ulcerative colitis(UC).Whether vitamin D levels are further lowered in patients with concomitant IPAA and primary sclerosing cholangitis(PSC)is not *** aim of this study was to evaluate the presence of PSC as a risk factor for vitamin D deficiency in patients with UC and ***:In this case control study,74 patients with concurrent IPAA and PSC were included in the study group,and 79 patients with IPAA,but without PSC,served as ***-four variables were *** analysis and multivariate analysis with stepwise logistic regression were ***:A total 153 eligible patients were included,with 74(48.4%)in the study group and 79(51.6%)in the control *** D level in the study group was 18.961.4 ng/dL compared with 30.361.7 ng/d in the control group(P=0.011).Vitamin D deficiency(≤20 ng/dL)was present in 65(42.5%)*** occurred in 49(75.4%)of the 65 patients with vitamin D *** the multivariate analysis,only the presence of PSC(odds ratio[OR]:7.56;95% confidence interval[CI]:2.39–24.08;P=0.001)and vitamin D supplementation(OR:2.58;95% CI:1.57–9.19;P=0.018)remained associated with vitamin D ***:The presence of PSC was found to be an independent risk factor for vitamin D deficiency in UC patients with *** patients should be routinely screened and closely monitored for vitamin D deficiency.

关键词： inflammatory bowel disease primary sclerosing cholangitis ileal pouch-anal anastomosis vitamin D deficiency

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The V(z) Inversion Technique for Evaluation of an Adhesively Bonded Structure

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Chinese Physics Letters 2015年第12期32卷 78-82页

作者：刘婧徐卫疆胡文祥 OURAK Mohame'd DUBOIS andre Institut d'Electronique de Microelectronique et de Nanotechnologie UMR CNRS 8520 Departement DOAE Universite de Valenciennes Valenciennes 59313 France Institute of Acoustics Tongji University Shanghai 200092 Laboratoire d'Automatique de Mdcanique et d'Informatique Industrielles et Humaines UMR CNRS 8201 Universite de Valenciennes Valenciennes 59313 France

Based on the fact that the evolution trace in incident angle and frequency of the resonance zeros of the reflec- tion coemcient function for a water charged layered medium is equivalent to its guided wave mode dispersion, the interracial adhesion of a three-layer aluminum-adhesive aluminum bonding structure is characterized nonde- structively by determining the interface shear stiffness kt associated with the interracial strength. The resonance reflection function is obtained experimentally by the V （z） inversion technique using an ultrasonic focused trans- ducer of wide-band and large angular aperture （up to ±45°）. The dispersion curves are numerically calculated, adjusting the parameter kt so that the difference between the dispersion curves and the angular-frequency tracing of the reflection zeros is minimum. The parameter kt at an interface of weakly adhered aluminum epoxy-resin is estimated to be 1014 N/m3.

关键词： The V

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