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Inflammasome activation under high cholesterol load triggers a protective microglial phenotype while promoting neuronal pyroptosis

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Translational Neurodegeneration 2023年第1期12卷 722-744页

作者： Cristina de Dios Xenia Abadin Vicente Roca-Agujetas marina jimenez-martinez Albert Morales Ramon Trullas Montserrat Mari Anna Colell Department of Cell Death and Proliferation Institut d’Investigacions Biomèdiques de BarcelonaConsejo Superior de Investigaciones Científicas(CSIC)Institut d’Investigacions Biomèdiques August Pi I Sunyer(IDIBAPS)BarcelonaSpain Centro de Investigación Biomédica en Red Sobre Enferme-dades Neurodegenerativas(CIBERNED) MadridSpain Department of Biomedicine Faculty of MedicineUniversitat de BarcelonaBarcelonaSpain Present Address:Department of Biochemistry and Molecular Biology Faculty of PharmacyUniversidad de Sevilla.Instituto de Biomedicina de Sevilla(IBiS)-Hospital Universitario Virgen del Rocío/CSICSevilleSpain Present Address:Department of Clinical Immunology and Rheumatology Amsterdam UMCAmsterdamNetherlands

Background Persistent inflammatory response in the brain can lead to tissue damage and *** Alzheimer’s disease(AD),there is an aberrant activation of inflammasomes,molecular platforms that drive inflammation through caspase-1-mediated proteolytic cleavage of proinflammatory cytokines and gasdermin D(GSDMD),the executor of ***,the mechanisms underlying the sustained activation of inflammasomes in AD are largely *** have previously shown that high brain cholesterol levels promote amyloid-β(Aβ)accumulation and oxidative ***,we investigate whether these cholesterol-mediated changes may regulate the inflam-masome *** SIM-A9 microglia and SH-SY5Y neuroblastoma cells were cholesterol-enriched using a water-soluble cholesterol *** exposure to lipopolysaccharide(LPS)plus muramyl dipeptide or Aβ,activation of the inflammasome pathway was analyzed by immunofluorescence,ELISA and immunoblotting ***-labeled Aβwas employed to monitor changes in microglia *** medium was used to study how microglia-neuron interrelationship modulates the inflammasome-mediated *** In activated microglia,cholesterol enrichment promoted the release of encapsulated IL-1βaccompanied by a switch to a more neuroprotective phenotype,with increased phagocytic capacity and release of neurotrophic *** contrast,in SH-SY5Y cells,high cholesterol levels stimulated inflammasome assembly triggered by both bacterial toxins and Aβpeptides,resulting in GSDMD-mediated ***(GSH)ethyl ester treatment,which recovered the cholesterol-mediated depletion of mitochondrial GSH levels,significantly reduced the Aβ-induced oxidative stress in the neuronal cells,resulting in lower inflammasome activation and cell ***,using conditioned media,we showed that neuronal pyroptosis affects the function of the cholesterol-enriched microglia,lowering its phagocytic activity and,the

关键词： Neuroinflammation Mitochondrial oxidative stress Phagocytosis Alzheimer’s disease DAM signature NLRP3

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Fungi Associated with Sand and Plants from Marine Coastlines: Potential Relevance for Human Health

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Advances in Microbiology 2024年第6期14卷 303-316页

作者： marina Carrasco-Acosta Pilar Garcia-jimenez Department of Biology Universidad de Las Palmas de Gran Canaria Campus de Tafira Las Palmas Spain

The fungal community associated with beach sand and plants located along marine coasts are an under-studied area of research despite its potential relevance to human health. In this study, we isolated and identified the cultivable mycobiota associated with sand and plants collected along the coast of Gran Canaria (Spain) using culture-dependent and -independent methods. Clinically relevant species belonging to Cryptococcus spp. and related genera such as Naganishia and Papilotrema were isolated and identified from shoreline plants. Moreover, Candida tropicalis was isolated from beach sand, and Aspergillus fumigatus and Aspergillus terreus strains were associated with both types of samples (i.e., plants and beach sand). We conclude that beach sand and shoreline plants are potential reservoirs of fungi of high clinical interest. We recommend including beach sand and plants from the environment when assessing the quality of marine coastal systems. Our results open a framework for studying the natural marine environment and its role in the epidemiology of infectious diseases in order to more accurately manage public health.

关键词： Sand Beach Shoreline Plants Reservoir of Pathogenic Fungi Cryptococcus spp. Aspergillus spp.

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Colorectal cancer and dormant metastases:Put to sleep or destroy?

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2304-2317页

作者： marina A Senchukova Department of Oncology Orenburg State Medical UniversityOrenburg 460000Russia

After reading the review by An et al“Biological factors driving colorectal cancer metastasis”,which covers the problem of the metastasis of colorectal cancer(CRC),I had a desire to discuss with readers one of the exciting problems associated with dormant *** deaths from CRCs are caused by metastases,which can be detected both at diagnosis of the primary tumor and several years or even decades after *** is because tumor cells that enter the bloodstream can be destroyed by the immune system,cause metastatic growth,or remain dormant for a long *** tumor cells may not manifest themselves throughout a person’s life or,after some time and under appropriate conditions,may give rise to the growth of *** this editorial,we will discuss the most important features of dormant metastases and the mechanisms of premetastatic niche formation,as well as factors that contribute to the activation of dormant metastases in *** will pay special attention to the possible mechanisms involved in the formation of circulating tumor cell complexes and the choice of therapeutic strategies that promote the dormancy or destruction of tumor cells in CRCs.

关键词： Circulating tumor cells Colorectal cancer Disseminated tumor cells Dormant metastases Metastases Premetastatic niche

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Current Zoology 2024年第1期70卷 1-12页

作者： Lucia V.Sommaro Juan J.martinez marina B.Chiappero Andrea R.Steinmann Cristina N.Gardenal JoséW.Priotto Laboratorio de Ecologia Evolutiva y Biogeografia Instituto de Ecorregiones Andinas(INECoA)Universidad Nacional de Jujuy-Consejo Nacional de Investigaciones Cientificas y Tecnicas(CONICET)San Salvador de JujuyJujuyArgentina Instituto de Diversidad y Ecologia Animal(IDEA) Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET)and Universidad Nacionalde CordobaCordobaArgentina Catedra de Genética de Poblaciones y Evolucion Facultad de Ciencias ExactasFisicas y NaturalesUniversidad Nacional de CordobaCordobaArgentina Grupo de Investigaciones en Ecologia Poblacional y Comportamental(GIEPCO) Instituto de Ciencias de la TierraBiodiversidad y Ambiente(ICBiA)Universidad Nacional de Rio Cuarto-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET)Rio CuartoCordobaArgentina

The sex-biased dispersal and kinship dynamics are important factors shaping the spatial distribution of individuals and are key parameters affecting a variety of ecological and evolutionary ***,we studied the spatial distribution of related individuals within a population of corn mice Calomys musculinus in a seasonal cycle to infer dispersal *** sampling was carried out from spring 2005 to winter 2006 in field borders of intensively managed *** data from 346 individuals with 9 microsatellites showed spatial genetic structure was weak for males,but not for *** results indicate a complex spatial kinship dynamic of related females across all ***,contrary to our expectations,dispersal distances decrease with the increase of the population ***,male dispersal distances were greater when population abundance increased and thus the availability of active *** disperse greater distances to mate and sire offspring with distant females as a possible inbreeding avoidance *** study shows that *** is capable of much greater scattering distances than previously reported and that dispersal occurs fluidly and without barriers across the *** indirect benefit of dispersal on individual fitness could be related to relaxing the competition in the natal area and increasing the mating *** study highlights the value of combining genetic relatedness,fieldwork observations,and behavioral data to estimate dispersal at a fine geographical scale.

关键词： dispersal distances kinship dynamics microsatellite small mammals spatial autocorrelation

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Synthetic lethality by PARP inhibitors: new mechanism uncovered based on unresolved transcription-replication conflicts

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3163-3164页

作者： marina Kolesnichenko Claus Scheidereit Department of Hepatology and Gastroenterology Charite-Universitatsmedizin BerlinBerlinGermany Laboratory for Signal Transduction in Tumor Cells Max Delbruck Center for Molecular Medicine in the Helmholtz Association(MDC)BerlinGermany

In a landmark study recently published in Nature,Petropoulous et *** that synthetic lethality of poly(ADP-ribose)polymerase(PARP)inhibitors in cells with defective homologous recombination repair(HR)results predominantly from transcription replication conflicts(TRC)and not,as previously proposed,from PARP trapping on DNA(Fig.1).The article unveils a new mechanism behind synthetic lethality of PARP inhibitors with relevance for cancer therapy.

关键词： al. PARP mechanism

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The bumpy road of purinergic inhibitors to clinical application in immune-mediated diseases

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Neural Regeneration Research 2024年第6期19卷 1206-1211页

作者： Matihias T.Wyss Christine Heuer marina Herwerth Institute of Pharmacology and Toxicology University of Zurich Neuroscience Center Zurich (ZNZ) University of Zurich and ETH Zurich 3. Neurology Department University Hospital of Zurich

Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis. This is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2) with numerous subtypes. In the last few decades, there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions. Mainly, signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies. Thus, interference with P2 receptors may be a promising strategy for the modulation of immune responses. Although only a few clinical studies have been conducted in isolated entities with limited success, preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases. Despite the association of P2 receptors with several disorders from this field, the use of P2 receptor antagonists in clinical therapy is still very scarce. In this narrative review, we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes. We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events. Using suramin, a non-specific purinergic inhibitor, as an example, we further show that off-target effects could be responsible for observed effects in immunological settings, which may have interesting implications. Overall, we believe that it is worthwhile to further investigate this hitherto underexplored area.

关键词： autoimmune diseases neurological disorders purinergic system P2 receptor inhibitors suramin

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Colon and rectal cancer:An emergent public health problem

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World Journal of Gastroenterology 2024年第7期30卷 644-651页

作者： marina Pinheiro David Nascimento Moreira Michele Ghidini LAQV REQUIMTEDepartment of ChemistryFaculty of PharmacyUniversity of Porto4050-313 PortoPortugal Unidade de Saúde Pública Unidade Local de Saúde Barcelos/EsposendeBarcelinhos 4755-069BragaPortugal Medical Oncology Unit Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilan 20122Italy

Colorectal cancer ranks third globally,with a high mortality *** the United States,and different countries in Europe,organized population screenings exist and include people between 50 and 74 years of *** screenings have allowed an early diagnosis and consequently an improvement in health *** and rectal cancer(CRC)is a disease of particular interest due to the high global burden associated with it and the role attributed to prevention and early diagnosis in reducing morbidity and *** study is a review of CRC pathology and includes the most recent scientific evidence regarding this pathology,as well as a diagnosis of the epidemiological situation of ***,the recommendation from a public health perspective will be discussed in detail taking into account the context and the most current recommendations.

关键词： Colon and rectal neoplasia Colon and rectal tumor Mortality Morbidity

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Periodontitis:An often-neglected complication of diabetes

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World Journal of Diabetes 2024年第3期15卷 318-325页

作者： marina G Kudiyirickal Joseph M Pappachan Primary Care Dental Practice The Smile ClinicPreston PR16PZUnited Kingdom Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

The bidirectional association between type 2 diabetes mellitus(T2DM)and periodontitis is now well established,resulting in periodontal disease being considered as the 6th major complication of diabetes mellitus(DM)after cardiovascular disease,eye disease,neuropathy,nephropathy,and peripheral vascular *** can worsen the virulence and invasiveness of pathogenic oral microbial flora aggravating the local inflammation and infection in those with periodontal *** the other hand,the chemical and immunological mediators released into the circulation as part of periodontal inflammation worsen the systemic insulin resistance with worsening of *** if undiagnosed or left untreated can also result in eventual tooth loss.A study by Xu et al in the World Journal of Diabetes examined the predictive factors associated with periodontitis in Chinese patients with *** prevalence of periodontitis was found to be 75.7%in this *** on logistic regression analysis,the predictive factors for higher risk were low tooth brushing frequency[odds ratio(OR)=4.3],high triglycerides(TG;OR=3.31),high total cholesterol(TC;OR=2.87),higher glycated hemoglobin(HbA1c;OR=2.55),and higher age(OR=1.05)while higher education level was protective(OR=0.53).However,the most influential variables were HbA1c followed by age,TC,TG,low education level,brushing frequency,and sex on the random forest model(this model showed higher sensitivity for predicting the risk).A good understanding of the predictors for periodontitis in T2DM patients is important in prevention,early detection of susceptible patients,and intervention to improve periodontal health and enable long-term glycaemic control as observed by Xu et al.

关键词： Diabetes mellitus Periodontitis Predictive factors Cardiovascular disease Glycaemic control

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Immune signature of small bowel adenocarcinoma and the role of tumor microenvironment

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World Journal of Gastroenterology 2024年第8期30卷 794-798页

作者： Grigorios Christodoulidis marina Nektaria Kouliou Konstantinos Eleftherios Koumarelas Department of General Surgery University Hospital of LarissaLarissa 41110Greece

In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such *** detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor *** involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor *** are linked to genetic disorders and risk factors,including chronic inflammatory *** unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable *** cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic *** instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to *** presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI *** tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.

关键词： Programmed cell death 1 Programmed cell death-ligand 1 Programmed death ligand Small bowel adenocarcinoma Tumor infiltrating lymphocytes Tumor microenvironment Microsatellite instability

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Double role of depression in gastric cancer:As a causative factor and as consequence

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World Journal of Gastroenterology 2024年第10期30卷 1266-1269页

作者： Grigorios Christodoulidis Koumarelas Konstantinos-Eleftherios Kouliou marina-Nektaria Department of General Surgery University Hospital of LarissaLarissa 41110Greece

In this editorial we comment on the article“Hotspots and frontiers of the rela-tionship between gastric cancer and depression:A bibliometric study”.Gastric cancer(GC)is a common malignancy in the digestive system with increased mortality and morbidity rates *** treatments,such as gastrectomy,negatively impact patients'quality of life and beyond the physical strain,GC patients face psychological challenges,including anxiety and *** prevalence of depression can be as high as 57%,among gastrointestinal cancer *** to the advancements in treatment effectiveness and increased 5-year overall survival rates,attention has shifted to managing psychological ***,the significance of managing the depression doesn’t lie solely in the need for a better psychological *** leads to chronic stress acti-vating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis,leading release of catecholamines inducing tumor proliferation,migration,and metastasis,contributing to GC *** dysregulation of neurotrans-mitters and the involvement of various signaling pathways underscore the complex interplay between depression and *** strategies are required to address the psychological aspects of GC,including region-specific interventions and increased monitoring for *** the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex *** this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.

关键词： Gastric cancer Depression Anxiety Chronic stress Pathogenesis of gastric cancer

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