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Metadherin-driven promotion of cancer stem cell phenotypes and its effect on immunity in hepatocellular carcinoma

World Journal of Gastroenterology 2024年第20期30卷 2624-2628页

作者： Nevena Todorović Amedeo Amedei Department of experimental and clinical Medicine University of FlorenceFlorence 50134Italy Clinic for Infectious and Tropical Diseases University Clinical Centre of SerbiaBelgrade 11000Serbia

In this editorial we provide commentary on the article published by Wang et al,featured in the recent issue of the World Journal of Gastroenterology in *** focus on the metadherin(MTDH),also known as astrocyte elevated gene-1 or lysine rich CEACAM1,and its effects on cancer stem cells(CSCs)and immunity in hepatocellular carcinoma(HCC).HCC is the most common primary liver cancer and one of the leading causes of cancer-related deaths *** HCC cases develop in the context of liver *** the pivotal mechanisms of carcinogenesis are gene mutations,dysregulation of diverse signaling pathways,epigenetic alterations,hepatitis B virus-induced hepatocarcinogenesis,chronic inflammation,impact of tumor microenvironment,oxidative *** the years,extensive research has been conducted on the MTDH role in various tumor pathologies,such as lung,breast,ovarian,gastric,hepatocellular,colorectal,renal carcinoma,neuroblastoma,melanoma,and ***,its involvement in tumor development processes including transformation,apoptosis evasion,angiogenesis,invasion,and metastasis via multiple signaling *** has been demonstrated that knockdown or knockout of MTDH disrupt tumor development and *** addition,numerous reports have been carried out regarding the MTDH influence on HCC,demonstrating its role as a predictor of poor prognosis,aggressive tumor phenotypes prone to metastasis and recurrence,and exhibiting significant potential for therapy ***,more studies finely investigated the influence of MTDH on *** CSCs are a small subpopulation of tumor cells that sharing traits with normal stem cells like self-renewal and differentiation abilities,alongside a high plasticity that alters their *** their presumed role in tumor initiation,they can drive also disease relapse,metastasis,and resistance to chemo and radiotherapy.

关键词： Hepatocellular carcinoma Metadherin Astrocyte elevated gene-1 Lysine rich

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Quick and easy assessment of sarcopenia in cirrhosis: Can ultrasound be the solution?

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World Journal of Gastroenterology 2024年第17期30卷 2287-2293页

作者： Francesca Campani Tancredi Vincenzo Li Cavoli Umberto Arena Fabio Marra Erica Nicola Lynch Claudia Campani Department of Health Science University Hospital CareggiUniversity of FlorenceFlorence 50134Italy Internal Medicine and Liver Unit University Hospital CareggiUniversity of FlorenceFlorence 50134Italy Department of experimental and clinical Medicine University of FlorenceFlorence 50134Italy Gastroenterology Research Unit Department of Experimental and Clinical Biomedical Sciences“Mario Serio”University of FlorenceFlorence 50134Italy Department of Medical Biotechnologies University of SienaSiena 53100Italy

Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver *** nega-tively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma(HCC).For these reasons,identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient *** of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia,but exposure to radiation and high costs limit its application in this setting,especially for repeated *** believe that ultrasound,a cheap and harmless technique also used for HCC screening in cirrhotic patients,could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.

关键词： Sarcopenia Ultrasound Cirrhosis Hepatocellular carcinoma Computed tomography

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Diophantine equations and Fermat's last theorem for multivariate(skew-)polynomials

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Applied Mathematics(A Journal of Chinese Universities) 2024年第1期39卷 159-173页

作者： PAN Jie JIA Yu-ming LI Fang School of Mathematical sciences Zhejiang UniversityHangzhou 310058China Henan experimental High School Zhengzhou 450003China

Fermat’s Last Theorem is a famous theorem in number theory which is diﬃcult to ***,it is known that the version of polynomials with one variable of Fermat’s Last Theorem over C can be proved very *** aim of this paper is to study the similar problems about Fermat’s Last Theorem for multivariate(skew)-polynomials with any characteristic.

关键词： Fermat's last theorem polynomial ring skew polynomial ring

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High-throughput computational screening and in vitro evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione(C3),as a novel EGFR—HER2 dual inhibitor in gastric tumors

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Oncology Research 2024年第2期32卷 251-259页

作者： MESFER AL SHAHRANI REEM GAHTANI MOHAMMAD ABOHASSAN MOHAMMAD ALSHAHRANI YASSER ALRAEY AYED DERA MOHAMMAD RAJEH ASIRI PRASANNA RAJAGOPALAN Department of clinical Laboratory sciences College of Applied Medical SciencesKing Khalid UniversityAbhaSaudi Arabia

Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation,adhesion,angiogenesis,and *** therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic ***,dual inhibition strategies are recommended to increase potency and reduce *** this study,we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase ***-based High-throughput Virtual Screening(D-HTVS)was used to screen the whole ChemBridge small molecular library against EGFR and *** atomistic molecular dynamic simulation was conducted to understand the dynamics and stability of the protein-ligand ***/HER2 kinase enzymes,KATOIII,and Snu-5 cells were used for in vitro *** atomistic Molecular Dynamics simulations followed by solvent-based Gibbs binding free energy calculation of top molecules,identified compound C3(5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione)to have a good affinity for both EGFR and *** predicted compound,C3,was promising with better binding energy,good binding pose,and optimum interactions with the EGFR and HER2 residues.C3 inhibited EGFR and HER2 kinases with IC50 values of 37.24 and 45.83 nM,*** GI50 values of C3 to inhibit KATOIII and Snu-5 cells were 84.76 and 48.26 nM,*** on these findings,we conclude that the identified compound C3 showed a conceivable dual inhibitory activity on EGFR/HER2 kinase,and therefore can be considered as a plausible lead-like molecule for treating gastric cancers with minimal side effects,though testing in higher models with pharmacokinetic approach is required.

关键词： Dual inhibitor Drug discovery EGFR/HER2 kinase Gastric cancer High-throughput screening

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Liver transplantation and liver resection as alternative treatments for primary hepatobiliary and secondary liver tumors: Competitors or allies?

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 111-116页

作者： Jan Lerut Institute for experimental and clinical Research(IREC) Universitécatholique Louvain(UCL)Avenue Hippocrate 561200 Woluwe Saint PierreBrusselsBelgium

Although Starzl designed in the 1960’s liver transplantation(LT)to treat unresectable primary and also secondary liver tumors,transplantation still occupies a(too)small place in the respective therapeutic algorithms[1].Due to the lack of(any)selection criteria,the concept of transplantation became rapidly challenged because of the prohibitively high incidence of tumor recurrence[1–3].

关键词： liver tumors Liver

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Endotoxin-induced alterations of adipose tissue function:a pathway to bovine metabolic stress

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1391-1407页

作者： Miguel Chirivi G.Andres Contreras Department of Large Animal clinical sciences Michigan State UniversityEast LansingMIUSA

During the periparturient period, dairy cows exhibit negative energy balance due to limited appetite and increased energy requirements for lactogenesis. The delicate equilibrium between energy availability and expenditure puts cows in a state of metabolic stress characterized by excessive lipolysis in white adipose tissues(AT), increased production of reactive oxygen species, and immune cell dysfunction. Metabolic stress, especially in AT, increases the risk for metabolic and inflammatory diseases. Around parturition, cows are also susceptible to endotoxemia. Bacterial-derived toxins cause endotoxemia by promoting inflammatory processes and immune cell infiltration in different organs and systems while impacting metabolic function by altering lipolysis, mitochondrial activity, and insulin sensitivity. In dairy cows, endotoxins enter the bloodstream after overcoming the defense mechanisms of the epithelial barriers, particularly during common periparturient conditions such as mastitis, metritis, and pneumonia, or after abrupt changes in the gut microbiome. In the bovine AT, endotoxins induce a pro-inflammatory response and stimulate lipolysis in AT, leading to the release of free fatty acids into the bloodstream. When excessive and protracted, endotoxin-induced lipolysis can impair adipocyte's insulin signaling pathways and lipid synthesis. Endotoxin exposure can also induce oxidative stress in AT through the production of reactive oxygen species by inflammatory cells and other cellular components. This review provides insights into endotoxins' impact on AT function, highlighting the gaps in our knowledge of the mechanisms underlying AT dysfunction, its connection with periparturient cows' disease risk, and the need to develop effective interventions to prevent and treat endotoxemia-related inflammatory conditions in dairy cattle.

关键词： Adipose tissue dysfunction Endotoxin Inflammation Insulin resistance

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Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis

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Asian Journal of Andrology 2024年第2期26卷 144-154页

作者： Rossella Cannarella Carmelo Gusmano Claudia Leanza Vincenzo Garofalo Andrea Crafa Federica Barbagallo Rosita A Condorelli Sandro La Vignera Aldo E Calogero Department of clinical and experimental Medicine University of CataniaCatania 95123Italy Glickman Urological&Kidney Institute Cleveland Clinic FoundationClevelandOH44195USA

To evaluate the relationship between testosterone replacement therapy(TRT)and arterial and/or venous thrombosis in patients with pre-treatment total testosterone(TT)<12 nmol I^(-1),we performed a meta-analysis following the Population Intervention Comparison Outcome ***:men with TT<12 nmol I^(-1) or clear mention of hypogonadism in the inclusion criteria of patients;intervention:TRT;comparison:placebo or no therapy;outcomes:arterial thrombotic events(stroke,myocardial infarction[MI],upper limbs,and lower limbs),VTE(deep vein thrombosis[DVT],portal vein thrombosis,splenic thrombosis,and pulmonary embolism),and mortality.A total of 2423 abstracts were assessed for ***-four studies,including 14 randomized controlled trials(RCTs),were finally included,with a total of 4027 and 310288 hypotestosteronemic male patients,from RCTs and from observational studies,*** on RCT-derived data,TRT did not influence the risk of arterial thrombosis(odds ratio[OR]=1.27,95%confidence interval[CI]:0.47-3.43,P=0.64),stroke(OR=1.34,95%CI:0.09-18.97,P=0.83),MI(OR=0.51,95%CI:0.11-2.31,P=0.39),VTE(OR=1.42,95%CI:0.22-9.03,P=0.71),pulmonary embolism(OR=1.38,95%CI:0.27-7.04,P=0.70),and mortality(OR=0.70,95%CI:0.20-2.38,P=0.56).Meanwhile,when only observational studies are considered,a significant reduction in the risk of developing arterial thrombotic events,Ml,venous thromboembolism,and mortality was *** risk for DVT remains uncertain,due to the paucity of RCT-based *** in men with TT<12 nmol I^(-1) is safe from the risk of adverse cardiovascular *** studies specifically assessing the risk of DVT in men on TRT are needed.

关键词： hypogonadism testosterone testosterone replacement therapy thromboembolism thrombosis TRT

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A cup of coffee for a brain long life

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Neural Regeneration Research 2024年第1期19卷 158-159页

作者： Chiara Porro Antonia Cianciulli Maria Antonietta Panaro Department of clinical and experimental Medicine University of FoggiaFoggiaItaly(Porro C)Department of BiosciencesBiotechnologies and EnvironmentUniversity of BariBariItaly

Coffee is one of the world's favorite and most popular beverages,the third most popular beverage after water and *** many people,it is an indispensable habit before going to work and a socialization tool for the rest of the *** general,the average consum ption varies from 2 to6 cups per *** are the health implications?Given this consum ption,the benefits are actually greater than the *** is the conclusion of a careful study published in the New England Journal of Medicine(van Dam et al.,2020).

关键词： favorite conclusion life

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Bioactivities,Mechanisms,Production,and Potential Application of Bile Acids in Preventing and Treating Infectious Diseases

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Engineering 2024年第7期38卷 13-26页

作者： Shuang Liu Shuo Yang Biljan Blazekovic Lu Li Jidan Zhang Yi Wang experimental Research Center China Academy of Chinese Medical SciencesBeijing 100700China Faculty of Pharmacy and Biochemistry University of ZagrebZagreb 10000Croatia

Infectious diseases are a global public health problem,with emerging and re-emerging infectious diseases on the rise ***,their prevention and treatment are still major *** acids are common metabolites in both hosts and microorganisms that play a significant role in controlling the metabolism of lipids,glucose,and *** acids have historically been utilized as first-line,valuable therapeutic agents for related metabolic and hepatobiliary ***,bile acids are the major active ingredients of cow bezoar and bear bile,which are commonly used traditional Chinese medicines(TCMs)with the therapeutic effects of clearing heat,detoxification,and relieving wind and *** recent years,the promising performance of bile acids against infectious diseases has attracted attention from the scientific *** paper reviews for the first time the biological activities,possible mechanisms,production routes,and potential applications of bile acids in the treatment and prevention of infectious *** with previous reviews,we comprehensively summarize existing studies on the use of bile acids against infectious diseases caused by pathogenic microorganisms that are leading causes of global morbidity and *** addition,to ensure a stable supply of bile acids at affordable prices,it is necessary to clarify the biosynthesis of bile acids in vivo,which will assist scientists in elucidating the accumulation of bile acids and discovering how to engineer various bile acids by means of chemosynthesis,biosynthesis,and chemoenzymatic ***,we explore the current challenges in the field and recommend a development strategy for bile-acid-based drugs and the sustainable production of bile *** presented studies suggest that bile acids are potential novel therapeutic agents for managing infectious diseases and can be artificially synthesized in a sustainable way.

关键词： Bile acids Infectious diseases Bioactivities Mechanisms Anti-infective agents

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Cardioprotective effects of glucagon-like peptide 1 receptor agonists in heart failure: Myth or truth?

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World Journal of Diabetes 2024年第5期15卷 818-822页

作者： Lorenzo Nesti Domenico Trico Department of clinical and experimental Medicine University of PisaPisa 56126Italy Laboratory of Metabolism Nutritionand AtherosclerosisUniversity of PisaPisa 56126Italy

Therapy with glucagon-like peptide 1(GLP1)receptor agonists has raised great interest for its beneficial cardiovascular effects in preventing atherosclerosis and heart failure-related ***,while evidence about atherosclerosis consistently suggests a cardioprotective potential with class effect,controversies remain on its impact on heart ***1 receptor agonists appear to prevent hospitalization for new-onset heart failure and reduce symptoms in heart failure with preserved ejection fraction(as demonstrated by the recent STEP-HFpEF Trial).Still,GLP1 agonism has resulted in neutral or even harmful effects in patients with established heart failure with reduced ejection fraction(the LIVE trial).GLP1 receptor agonists benefit the cardiovascular system indirectly through their marked metabolic effects(improved weight management,glycemic control,blood pressure,systemic and tissue inflammation),while direct effects on the heart have been ***,weight loss alone achieved through GLP1 receptor agonists has failed in improving left ventricular *** is a dual agonist of GLP1 and glucose-dependent insulinotropic polypeptide,representing an innovative treatment option in diabetes with a major impact on weight loss and promising cardiovascular *** this class of therapies is going to change the history of heart failure is an ongoing debate.

关键词： Atherosclerosis Cardiovascular system Glucagon-like peptide-1 Heart failure Tirzepatide Type 2 diabetes Ventricular function Left

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