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Is the combination of immunotherapy with conventional chemotherapy the key to increase the efficacy of colorectal cancer treatment?

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World Journal of Gastrointestinal Oncology 2023年第2期15卷 251-267页

作者： Jonadab E Olguin Monica G Mendoza-Rodriguez C Angel Sanchez-barrera Luis I Terrazas Laboratorio Nacional en Salud Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-degenerativasFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla 54090Estado de MexicoMexico Unidad de Biomedicina Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla 54090Estado de MexicoMexico

Colorectal cancer(CRC) is among the most prevalent and deadly neoplasms worldwide. According to GLOBOCAN predictions, its incidence will increase from 1.15 million CRC cases in 2020 to 1.92 million cases in 2040. Therefore, a better understanding of the mechanisms involved in CRC development is necessary to improve strategies focused on reducing the incidence, prevalence,and mortality of this oncological pathology. Surgery, chemotherapy, and radiotherapy are the main strategies for treating CRC. The conventional chemotherapeutic agent utilized throughout the last four decades is 5-fluorouracil, notwithstanding its low efficiency as a single therapy. In contrast, combining 5-fluorouracil therapy with leucovorin and oxaliplatin or irinotecan increases its efficiency. However, these treatments have limited and temporary solutions and aggressive side effects. Additionally, most patients treated with these regimens develop drug resistance, which leads to disease progression. The immune response is considered a hallmark of cancer;thus, the use of new strategies and methodologies involving immune molecules, cells, and transcription factors has been suggested for CRC patients diagnosed in stages Ⅲ and Ⅳ. Despite the critical advances in immunotherapy, the development and impact of immune checkpoint inhibitors on CRC is still under investigation because less than 25% of CRC patients display an increased 5-year survival. The causes of CRC are diverse and include modifiable environmental factors(smoking, diet, obesity, and alcoholism), individual genetic mutations, and inflammation-associated bowel diseases. Due to these diverse causes, the solutions likely cannot be generalized. Interestingly, new strategies, such as single-cell multiomics, proteomics, genomics, flow cytometry, and massive sequencing for tumor microenvironment analysis, are beginning to clarify the way forward. Thus,the individual mechanisms involved in developing the CRC microenvironment, their causes, and t

关键词： Colorectal cancer Immunotherapy checkpoint inhibitors Chemotherapy Immunotherapy Immune response

Establishing geothermometric constraints on the local geothermal gradients:Case study of the Eastern Cordillera Basin,Colombia

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Geodesy and Geodynamics 2018年第4期9卷 271-280页

作者： Carlos A.barrera Carlos A.Vargas Jorge E.Cortes Universidad Nacional de Colombia Carrera 45 No 26-85 Bogota Colombia Petromarkers Inc. 16850 Saturn Ln Houston TX 77058 United States

Geochemical analyses were performed on 170 coal bed-trapped groundwater samples from 97 underground mines located in the Eastern Cordillera Basin, Colombia. The waters analyzed in this paper are from exploited coal beds, located up to 0.73 km deep, which emerge along with the local fault *** hydrochemical facies were classified based on the concentration of major ions by inferring the equilibrium state and rock water source. The main hydrochemical facies presented in the groundwater study are SO_4-Ca-Mg, HCO_3-Ca, HCO_3-Ca-Mg, and SO_4-HCO_3 mixed waters. We used geothermometric equations to estimate the most probable temperature under in-situ conditions and the propagation of errors theory to test the results. The geothermal gradient in the study area is close to 30℃/km, which is consistent with measurements from oil wells within the study area. Principal Component Analysis was used to explain factors affecting formation water composition and hydrogeochemical evolution of aquifers.

关键词： Geothermometers Hydrochemistry Coal bed Formation waters Eastern Cordillera Basin

Racial differences in prevalence and severity of non-alcoholic fatty liver disease

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World Journal of Hepatology 2021年第7期13卷 763-773页

作者： Maurizio Bonacini Farah Kassamali Swathi Kari Nieves Lopez barrera Mohamed Kohla Department of Gastroenterology and Hepatology California Pacific Medical CenterCalifornia Pacific Medical CenterSan FranciscoCA 94115United States Department of Gastroenterology and Hepatology California Pacific Medical CenterSan FranciscoCA 94115United States Department of Internal Medicine St.Mary's medical CenterSan FranciscoCA 94117United States Quest Clinical Research San FranciscoCA 94115United States Department of Hepatology National Liver InstituteMenoufiya UniversityShibin Al Kom 32511MenoufiyaEgypt

The aim of this review is to assess the evidence regarding racial differences in the prevalence and severity of nonalcoholic fatty liver disease(NAFLD).We reviewed the published literature that reported prevalence,severity,and genetic associations of NAFLD in different ethnic *** metabolic syndrome(MetS)has been associated with NAFLD,but each component of the MetS is present in various races in different percentages and their effect on NAFLD appears to be *** elevated triglyceride(TG)level seems to have the strongest association with *** latter is more prevalent in Hispanic patients;Blacks have lower TG levels and a lower NAFLD prevalence,compared to Caucasians or *** severity of liver fibrosis is lower in some,but not all biopsy-based studies of Black *** study has evaluated the severity of liver disease controlling for the individual components of MetS,especially *** racial differences in the prevalence of selected genetic polymorphisms,particularly PNPLA-3 and MBOAT7 have been documented,together with their effects on the prevalence of liver steatosis and *** on overall and liver mortality have found no significant differences according to race/ethnicity,with the possible exception of one paper reporting lower cirrhosis mortality in Black *** conclude that NAFLD is more prevalent in Hispanics and less in *** is supported by differences in key genetic polymorphisms associated with hepatic fat ***,there is presently insufficient evidence to firmly conclude that race,per se,plays a role in the development of liver fibrosis and its *** studies,appropriately controlled for diet,exercise,and individual MetS parameters are needed.

关键词： Race Ethnicity Nonalcoholic fatty liver disease Fatty liver disease Metabolic syndrome

Impaired immune reaction and increased lactate and C-reactive protein for early prediction of severe morbidity and pancreatic fistula after pancreatoduodenectomy

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Hepatobiliary & Pancreatic Diseases International 2020年第1期19卷 58-67页

作者： Mario Rodriguez-Lopez Francisco J.Tejero-Pintor Martin Bailon-Cuadrado Asterio barrera-Rebollo Baltasar Perez-Saborido David Pacheco-Sanchez General and Digestive Surgery Department Rio-Hortega University Hospital

Background: Prediction of complications after pancreatoduodenectomy (PD) remains of interest. Blood parameters and biomarkers during rst and second postoperative days (POD1, POD2) may be early indi- cators of complications. Methods: This case-control study included 50 patients. Baseline, POD1 and POD2 values of leukocytes, neutrophils, lymphocytes, platelets, hemoglobin, C-reactive protein (CRP), procalcitonin and arterial lactate were compared between individuals presenting Clavien ≥ III morbidity, pancreatic stula (PF) or clinically relevant PF (CRPF) and those without these morbidities. Common variables reaching signi cance were further analyzed in order to calculate a predictive score. Results: Severe morbidity, PF and CRPF rates were 28.0%, 26.0% and 14.0%, respectively. Patients with severe morbidity had lower leukocytes on POD2 (P=0.04). Patients with PF presented higher CRP on POD2 (P=0.001), higher lactate on POD1 (P=0.007) and POD2 (P=0.008), and lower lymphocytes on POD1 (P=0.007) and POD2 (P=0.008). Patients with CRPF had lower leukocytes and neutrophils on POD1 (P =0.048, P =0.038), lower lymphocytes on POD1 (P =0.001) and POD2 (P =0.003), and higher CRP on POD2 (P =0.001). Baseline parameters and procalcitonin obtained no statistical associations. Score was de ned according to lymphocytes on POD1 < 650/μL and CRP on POD2 ≥ 250 mg/L allocating patients in 3 risk categories. PF and CRPF rates were statistically higher as risk category increased (P<0.001). Receiver operating characteristic curves and Hosmer Lemeshow tests showed a good accuracy. Conclusions: Impaired immunological reaction during early postoperative period (lower leukocytes and, particularly, lymphocytes) in response to surgical aggression would favor complications after PD. Likewise, acidosis (higher arterial lactate) could behave as risk factor of PF. An elevated CRP on POD2 is also an early biomarker of PF. Our novel score based on postoperative lymphocyte count and CRP seems reliable

关键词： Pancreatoduodenectomy Morbidity Pancreatic fistula Biomarker Prediction Score

Antifungal activity against Fusarium oxysporum of quinolizidines isolated from three controlled-growth Genisteae plants:structure-activity relationship implications

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Natural Products and Bioprospecting 2023年第1期13卷 639-649页

作者： Willy Cely-Veloza Lydia Yamaguchi Diego Quiroga Massuo J.Kato Ericsson Coy-barrera Bioorganic Chemistry Laboratory Facultad de Ciencias Básicas y AplicadasUniversidad Militar Nueva Granada250247 CajicáColombia Institute of Chemistry University of São PauloSão Paulo 05508-000SPBrazil

The Genisteae tribe belongs to the Fabaceae *** wide occurrence of secondary metabolites,explicitly high-lighting the quinolizidine alkaloids(QAs),characterizes this *** the present study,twenty QAs(1-20),including lupanine(1-7),sparteine(8-10),lupanine(11),cytisine and tetrahydrocytisine(12-17),and matrine(18-20)-type QAs were extracted and isolated from leaves of three species(i.e.,Lupinus polyphyllus(’rusell’hybrid),Lupinus muta-bilis,and Genista monspessulana)belonging to the Genisteae *** plant sources were propagated under greenhouse *** isolated compounds were elucidated by analyzing their spectroscopical data(MS,NMR).The antifungal effect on the mycelial growth of Fusarium oxysporum(Fox)of each isolated QA was then evaluated through the amended medium *** best antifungal activity was found to be for compounds 8(IC_(50)=16.5μM),9(IC_(50)=7.2μM),12(IC_(50)=11.3μM),and 18(IC_(50)=12.3μM).The inhibitory data suggest that some QAs could effi-ciently inhibit Fox mycelium growth depending on particular structural requirements deduced from structure-activity relationship *** identified quinolizidine-related moieties can be involved in lead structures to develop further antifungal bioactives against Fox.

关键词： Fabaceae Genista Lupinus Fusarium oxysporum Quinolizidines Antifungals

Severe morbidity after pancreatectomy is accurately pre dicte d by preoperative pancreatic resection score(PREPARE): A prospective validation analysis from a medium-volume center

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 559-565页

作者： Mario Rodriguez-Lopez Francisco J. Tejero-Pintor Baltasar Perez-Saborido Asterio barrera-Rebollo Martin Bailon-Cuadrado David Pacheco-Sanchez General and Digestive Surgery Department Rio-Hortega University Hospital

Background: Major morbidity in pancreatic surgery remains high. Different scores for predicting complications have been described. Preoperative pancreatic resection(PREPARE) score is based on objective preoperative variables and offers good predictive accuracy for Clavien ≥ III complications. This study aimed to validate this score and analyze other preoperative variables in a prospective study performed in a medium-volume center. Methods: A total of 50 pancreatic resections were included. Preoperative variables were registered and PREPARE was calculated. The main outcome was severe morbidity(Clavien ≥ III) up to 30 days after discharge. The secondary outcomes were length of stay(LOS) and readmission. Statistical validation was performed to compare severe morbidity rate among the scores categories. Association with other preoperative variables(not included in PREPARE) was also tested. Results: Of the 50 pancreatic resections, the severe morbidity was 34.0%, with median LOS of 11 days. Readmission rate was 25.5%. Severe morbidity rates according to PREPARE categories were 18.5% in lowrisk group, 41.7% in intermediate-risk group, and 63.6% in high-risk group, respectively( P = 0.023). The accuracy was 72%(Hosmer–Lemeshow, P = 0.86). ROC curve was obtained both for PREPARE score expressed as incremental values and categorized as the three risk groups, showing an area under curve(AUC) of 0.736(95% CI: 0.586–0.887; P = 0.007) and 0.712(95% CI: 0.555–0.869; P = 0.015), respectively. PREPARE was significant in multivariate analysis. Median LOS was statistically higher as PREPARE category increases(9, 11 and 15 days in low-, intermediate-and high-risk groups, respectively; P = 0.009). Readmission was not associated with any variables. Conclusions: PREPARE behaves as an independent risk factor for severe morbidity after pancreatic surgery. Score validation shows good accuracy prediction. Increasing PREPARE category is also associated with longer LOS.

关键词： Pancreatic surgery Morbidity Complications Preoperative pancreatic resection score Validation

Heterogeneous catalysts with programmable topologies generated by reticulation of organocatalysts into metal-organic frameworks:The case of squaramide

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Nano Research 2021年第2期14卷 458-465页

作者： Anna Broto-Ribas Claudia Vignatti Alicia Jimenez-Almarza Javier Luis-barrera Zahra Dolatkhah Felipe Gandara Inhar Imaz Ruben Mas-Balleste Jose Aleman Daniel Maspoch Catalan Institute of Nanoscience and Nanotechnology(ICN2) CSIC and The Barcelona Institute of Science and Technology08193 BarcelonaSpain Inorganic Chemistry Department Modulo 7Universidad Autonoma de Madrid28049 MadridSpain Organic Chemistry Department Modulo 1Universidad Autonoma de Madrid28049 MadridSpain Materials Science Factory Instituto de Ciencia de Materiales de Madrid(ICMM)Consejo Superior de Investigaciones Cientificas(CSIC)Calle Sor Juana Ines de la Cruz328049 MadridSpain Institute for Advanced Research in Chemical Sciences(IAdChem) Campus Universidad Autonoma de Madrid28049 MadridSpain Institucio Catalana de Recerca i Estudis Avangats(ICREA) 08100 BarcelonaSpain

A well-established strategy to synthesize heterogeneous,metal-organic framework(MOF)catalysts that exhibit nanoconfinement effects,and specific pores with highly-localized catalytic sites,is to use organic linkers containing organocatalytic ***,we report that by combining this linker approach with reticular chemistry,and exploiting three-dimensioanl(3D)MOF-structural data from the Cambridge Structural Database,we have designed four heterogeneous MOF-based catalysts for standard organic *** programmable MOFs are isoreticular versions of pcu IRMOF-16,feu UiO-68 and pillared-pcu SNU-8X,the three most common topologies of MOFs built from the organic linker p.p'-terphenyldicarboxylic acid(tpdc).To synthesize the four squaramide-based MOFs,we designed and synthesized a linker,4,4’-((3,4-dioxocyclobut-1-ene-1,2-diyl)bis(azanedyil))dibenzoic acid(Sq_tpdc),which is identical in directionality and length to tpdc but which contains organocatalytic squaramide *** were chosen because their immobilization into a framework enhances its reactivity and stability while avoiding any self-quenching ***,the four MOFs share the same organocatalytic squaramide moiety,but confine it within distinct pore *** then evaluated these MOFs as heterogeneous H-bonding catalysts in organic transformations:a Friedel-Crafts alkylation and an epoxide *** of them exhibited good performance in both reactions but all showed distinct catalytic profiles that reflect their structural differences.

关键词： reticular chemistry metal-organic frameworks H-bond catalysis squaramide Friedel-Cratts epoxide ring-opening

Gene transcription profiting of astheno-and normo-zoospermic sperm subpopulations

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Asian Journal of Andrology 2020年第6期22卷 608-615页

作者： Pedro Caballero-Campo Saul Lira-Albarran David barrera Elizabeth Borja-Cacho Hector S Godoy-Morales Claudia Rangel-Escareno Fernando Larrea Mayel Chirinos Department of Reproduction Biology National Institute of Medical Sciences and Nutrition Salvador ZubiranMexico City 14080Mexico Tambre Foundation Madrid 28002Spain Reproductive Medicine Unit Angeles del Ped regal HospitalMexico City 10700Mexico Computational Genomic and Integrative Biology Laboratory National Institute of Genomic MedicineMexico City 14610Mexico

Spermatozoa contain a repertoire of RNAs considered to be potential functional fertility *** this study,the gene expression of human sperm subpopulations with high(F1)and low(F2)motility from healthy normozoospermic(N)and asthenozoospermic(A)individuals was evaluated using RNA microarray followed by functional genomic analysis of differentially expressed *** from A-F1 versus N-F1,A-F2 versus N-F2,N-F1 versus N-F2,and A-F1 versus A-F2 comparisons showed a considerably larger set of downregulated genes in tests versus *** ontology(GO)analysis of A-F1 versus N-F1 identified 507 overrepresented biological processes(BPs),several of which are associated with sperm *** addition,gene set enrichment analysis of the same contrast showed 110 BPs,36 cellular comp on ents,and 31 molecular functions,several of which are involved in sperm motility.A leadi ng・edge analysis of selected GO terms resulted in several down regulated genes encoding to dyn eins and kin esins,both related to sperm ***,the predicted activation state of asthenozoospermia was increased,while fertility,cell movement of sperm,and gametogenesis were ***,several downregulated genes characteristic of the canonical pathway protein ubiquitination were involved in asthenozoospermia ***,GO analysis of A-F2 versus N-F2 did not identify overrepresented BPs,although the gene set enrichment analysis detected six enriched BPs,one cellular component,and two molecular ***,the results show differences in gene transcription between sperm subpopulations from asthenozoospermic and normozoospermic semen samples and allowed the identification of gene sets relevant to sperm physiology and reproduction.

关键词： asthenozoospermia male in fertility microarray sperm transcriptome

Selection of patients with hepatocellular carcinoma for livertransplantation:Past and future

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World Journal of Hepatology 2016年第1期8卷 58-68页

作者： Arturo Soriano Aranzazu Varona Rajesh Gianchandani Modesto Enrique Moneva Javier Arranz Antonio Gonzalez Manuel barrera Liver Transplantation Unit University Hospital Nuestra Señora de CandelariaSanta Cruz38010 Santa Cruz de TenerifeSpain

The aim of liver transplantation(LT) for hepatocellular carcinoma(HCC) is to ensure a rate of disease-free survival similar to that of patients transplanted due to benign disease. Therefore, we are forced to adopt strict criteria when selecting candidates for LT and prioritizing patients on the waiting list(WL), to have clarified indications for bridging therapy for groups at risk for progression or recurrence, and to establish certain limits for downstaging therapies. Although the Milan criteria(MC) remain the standard and most employed criteria for indication of HCC patients for LT by far, in the coming years, criteria will be consolidated that take into account not only data regarding the size/volume and number of tumors but also their biology. This criteria will mainly include the alpha fetoprotein(AFP) values and, in view of their wide variability, any of the published logarithmic models for the selection of candidates for LT. Bridging therapy is necessary for HCC patients on the WL who meet the MC and have the possibility of experiencing a delay for LT greater than 6 mo or any of the known risk factors for recurrence. It is difficult to define single AFP values that would indicate bridging therapy(200, 300 or 400 ng/m L); therefore, it is preferable to rely on the criteria of a French AFP model score > 2. Other single indications for bridging therapy include a tumor diameter greater than 3 cm, more than one tumor, and having an AFP slope greater than 15 ng/m L per month or > 50 ng/m L for three months during strict monitoring while on the WL. When considering the inclusion of patients on the WL who do not meet the MC, it is mandatory to determine their eligibility for downstaging therapy prior to inclusion. The upper limit for this therapy could be one lesion up to 8 cm, 2-3 lesions with a total tumor diameter up to 8 cm, or a total tumor volume of 115 cm^3. Lastly, liver allocation and the prioritization of patients with HCC onthe WL should take into account

关键词： Hepatocarcinoma Liver transplantation Alpha fetoprotein Patient selection Prioritization Waiting list Bridging therapy Allocation Downstaging