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1.
World J Hepatol ; 16(6): 932-950, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38948436

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published. AIM: To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time. METHODS: DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. In vitro experiment in Huh7 cell was carried out. RESULTS: LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, P = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, P = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro. CONCLUSION: LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.

2.
Brain Behav ; 14(6): e3551, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38849983

RESUMEN

INTRODUCTION: Observational studies have found that most patients with arthritis have depression. We aimed to determine the causal relationship between various types of arthritis and depression. METHODS: We conducted a two-sample bidirectional Mendelian randomized (MR) analysis to determine whether there was a significant causal relationship between depression and multiple types of arthritis. The data of our study were derived from the publicly released genome-wide association studies (GWASs) and the largest GWAS meta-analysis. MR analysis mainly used inverse-variance weighted method; supplementary methods included weighted median, weighted mode, and MR-Egger using MR pleiotropy residual sum and outlier to detect and correct for the presence of pleiotropy. RESULTS: After adjusting for heterogeneity and horizontal pleiotropy, we found that depression was associated with an increased risk of osteoarthritis (OA) (OR = 1.02, 95%CI: 1.01-1.02, p = 2.96 × E - 5). In the reverse analysis, OA was also found to increase the risk of depression (OR = 1.10, 95%CI: 1.04-1.15, p = .0002). Depression only increased the risk of knee OA (KOA) (OR = 1.25, 95%CI: 1.10-1.42, p = 6.46 × E - 4). Depression could potentially increase the risk of spondyloarthritis (OR = 1.52, 95%CI: 1.19-1.94, p ≤ 8.94 × E - 4). CONCLUSION: There is a bidirectional causal relationship of depression with OA. However, depression only augments the risk of developing KOA. Depression may increase the risk of spondyloarthritis and gout.


Asunto(s)
Depresión , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Osteoartritis , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Depresión/genética , Depresión/epidemiología , Osteoartritis/genética , Osteoartritis/epidemiología , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/epidemiología , Artritis/genética , Artritis/epidemiología , Artritis Reumatoide/genética , Artritis Reumatoide/epidemiología , Gota/genética , Gota/epidemiología , Factores de Riesgo , Espondiloartritis/genética
3.
World J Clin Cases ; 12(9): 1660-1668, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38576747

RESUMEN

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients. There is no consensus on how to treat S. typhimurium-triggered sHLH. CASE SUMMARY: A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S. typhimurium, human rhinovirus, and Mycoplasma pneumoniae infections. At the time of admission to our institution, the patient's T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6 (IL-6), 9.1 pg/mL for IL-10, and 246.7 pg/mL for interferon-gamma (IFN-γ), for which the ratio of IL-10 to IFN-γ was 0.04. In this study, the patient received meropenem, linezolid, and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy (10 mg/kg/d for 3 d) and antishock supportive treatment twice. After careful evaluation, this patient did not receive HLH chemotherapy and recovered well. CONCLUSION: S. Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ ≤ 1.33, an IL-10 concentration ≤ 10.0 pg/mL, and/or an IFN-γ concentration ≤ 225 pg/mL at admission. Early antimicrobial and supportive treatment was sufficient, and the HLH-94/2004 protocol was not necessary under these conditions.

5.
Front Cardiovasc Med ; 11: 1273666, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590695

RESUMEN

Background: The relationship between gut microbiota composition and coronary heart disease (CHD) has been recently reported in several observational studies. However, the causal effect of gut microbiota on coronary heart disease is uncharted. Objective: This study attempted to investigate the effect of gut microbiota on coronary heart disease by Mendelian randomization (MR) analysis. Methods: Through the two-sample MR method, single-nucleotide polymorphisms relevant to gut microbiota were selected as instrument variables to evaluate the causal association between gut microbiota and the risk of CHD. Results: According to the selection criteria of the inverse variance-weighted average method, Class Actinobacteria, Class Lentisphaeria, Family Clostridiales vadinBB60group, Genus Clostridium innocuum group, Genus Bifidobacterium, Genus Butyricicoccus, Genus Oxalobacter, Genus Turicibacter, and Order Victivallales, presented a suggestive association with coronary heart disease. Conclusion: This two-sample Mendelian randomization study found that gut microbiota was causally associated with coronary heart disease. Further randomized controlled trials are needed to clarify the protective effect of probiotics on coronary heart disease and their specific protective mechanisms.

6.
Huan Jing Ke Xue ; 45(2): 792-801, 2024 Feb 08.
Artículo en Chino | MEDLINE | ID: mdl-38471918

RESUMEN

The northern plain of Henan in the lower reaches of the Yellow River is an area where the Yellow River is frequently diverted. The shallow groundwater quality in this area is poor, and many types of components have been found to be exceeding the limit value; however, the contribution of various environmental factors to water quality needs to be further quantified. In order to clarify the genesis of water quality of shallow groundwater in the study area, 330 groups of shallow groundwater samples were collected via a regional water quality survey. The evolution of shallow groundwater quality in the Yellow River diversion area of northern Henan was revealed using the principal component-absolute principal component score-multiple linear regression (PCA-APCS-MLR) model. The results showed that the components with a shallow groundwater excess rate greater than 10% in descending order were manganese, iron, total hardness, total dissolved solids, sodium, fluoride, arsenic, chloride ions, sulfate, and ammonium. In particular, the excess rate of manganese reached 76%. The four factors of dissolution enrichment, native origin of soil, redox conditions, and agricultural activities were identified as the main reasons for poor groundwater quality, which accounted for 71.24% of the cumulative interpretation rate of variance. In addition, the recharge from the surface water also influenced the groundwater quality. The effects of dissolution between the water and aquifer matrix and redox condition in the aquifer of the Yellow River dried-riverway like Xinxiang were significantly enhanced, resulting in the increasing concentration of iron, arsenic, total hardness, TDS, and other components in groundwater. Fluoride enrichment was caused by dissolution enrichment, the origin of the soil, and lateral replenishment of the Yellow River. Groundwater with high manganese concentration was widely affected by the soil matrix. Nitrate pollution of the groundwater was caused by the extensive use of chemical fertilizers in agricultural activities in individual areas.

7.
Molecules ; 29(6)2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38542887

RESUMEN

Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

8.
Front Pharmacol ; 15: 1363212, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476326

RESUMEN

Both continuous oxidative stress and poly (ADP-ribose) polymerase 1 (PARP-1) activation occur in neurodegenerative diseases such as Parkinson's disease. PARP-1 inhibition can reverse mitochondrial damage and has a neuroprotective effect. In a previous study, we synthesized melatonin derivative 6a (MD6a) and reported that it has excellent antioxidant activity and significantly reduces α-synuclein aggregation in Caenorhabditis elegans; however, the underlying mechanism is largely unknown. In the present study, we revealed that MD6a is a potential PARP-1 inhibitor, leading to mammalian targe of rapamycin/heat shock factor 1 signaling downregulation and reducing heat shock protein 4 and 6 expression, thus helping to maintain protein homeostasis and improve mitochondrial function. Together, these findings suggest that MD6a might be a viable candidate for the prevention and treatment of Parkinson's disease.

9.
Adv Clin Exp Med ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38353506

RESUMEN

BACKGROUND: Oral chronic graft-versus-host disease (cGVHD) impacts quality of life of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, its precise pathogenesis remains unknown, with potential associations with differential microRNA (miRNA) expression and the TGF-â/Smad signaling pathway. OBJECTIVES: This study aims to explore miRNA expression profiles in the peripheral blood of oral cGVHD patients, focusing on miRNA-769-5p and its relationship with Smad2. MATERIAL AND METHODS: Peripheral venous blood samples were collected for RNA extraction from 8 patients with oral cGVHD, 8 patients without cGVHD and 8 participants from the healthy control group. The miRNA library was constructed using the Illumina Hiseq 2500 platform. We focused on identifying miRNAs associated with the TGF-â/Smad signaling pathway and subsequently conducted validation experiments. The oral cGVHD and without cGVHD groups were each expanded to include 15 individuals. Peripheral blood samples were subjected to polymerase chain reaction (PCR) analysis to assess miRNA levels and to evaluate Smad2 mRNA levels in peripheral blood mononuclear cells (PBMC). Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to determine the Smad2 protein levels in peripheral blood. RESULTS: The most significantly differentially expressed miRNAs among the 3 groups were miRNA-505-5p and miRNA-769-5p. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated an enrichment of the target genes of miRNA-769-5p in the TGF-â signaling pathway. It was observed that miRNA-769-5p expression was higher in patients without oral cGVHD in comparison to those with oral cGVHD. Receiver operating characteristic (ROC) analysis demonstrated that miRNA-769-5p holds diagnostic value for oral cGVHD. As a target of miRNA-769-5p, Smad2 mRNA exhibited a negative correlation with it. Moreover, both Smad2 mRNA and protein levels were higher in patients with oral cGVHD as opposed to those without cGVHD. CONCLUSIONS: Differential expression of miRNAs, particularly the downregulation of miRNA-769-5p, may influence the development of oral cGVHD by diminishing its inhibitory effect on the TGF-â/Smad signaling pathway through its interaction with Smad2.

10.
Front Oncol ; 14: 1301649, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38357206

RESUMEN

Purpose: We investigated the value of magnetic resonance imaging (MRI) histogram features, a non-invasive method, in assessing the changes in chemoresistance of colorectal cancer xenografts in rats. Methods: A total of 50 tumor-bearing mice with colorectal cancer were randomly divided into two groups: control group and 5-fluorouracil (5-FU) group. The MRI histogram characteristics and the expression levels of p53 protein and MRP1 were obtained at 24 h, 48 h, 72 h, 120 h, and 168 h after treatment. Results: Sixty highly repeatable MRI histogram features were obtained. There were 16 MRI histogram parameters and MRP1 resistance protein differences between groups. At 24 h after treatment, the MRI histogram texture parameters of T2-weighted imaging (T2WI) images (10%, 90%, median, energy, and RootMeanSquared) and D images (10% and Range) were positively correlated with MRP1 (r = 0.925, p = 0.005). At 48 h after treatment, histogram texture parameters of apparent diffusion coefficient (ADC) images (Energy) were positively correlated with the presence of MRP1 resistance protein (r = 0.900, p = 0.037). There was no statistically significant difference between MRI histogram features and p53 protein expression level. Conclusions: MRI histogram texture parameters based on T2WI, D, and ADC maps can help to predict the change of 5-FU resistance in colorectal cancer in the early stage and provide important reference significance for clinical treatment.

11.
World J Surg Oncol ; 22(1): 3, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38166925

RESUMEN

OBJECTIVE: To compare the effects of laparoscopic hepatectomy (LH) on the short-term and long-term outcomes in hepatocellular carcinoma (HCC) patients with and without clinically significant portal hypertension (CSPH). METHODS: A systematic literature search of the PubMed, EMBASE, and Cochrane databases was performed for articles published from inception to March 1, 2023. Meta-analysis of surgical and oncological outcomes was performed using a random effects model. Data were summarized as mean difference and risk ratio with 95% confidence intervals. RESULTS: Five cohort studies with a total of 310 HCC patients were included (CSPH 143; Non-CSPH 167). In terms of surgical outcomes, estimated blood loss and the length of hospital stay were significantly lower in the Non-CSPH group than in the CSPH group. There were no significant differences between the two groups regarding other surgical outcomes, including the operative time, ratio of conversion to open surgery, and overall complication rate. In addition, there were also no significant differences between the two groups regarding the oncological outcomes, such as 1-, 3-, and 5-year overall survival. CONCLUSIONS: HCC patients with and without CSPH who underwent LH had comparable surgical and oncological outcomes. LH is a safe and effective treatment for HCC patients with CSPH under the premise of rational screening of patients.


Asunto(s)
Carcinoma Hepatocelular , Hipertensión Portal , Laparoscopía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , Hepatectomía/efectos adversos , Resultado del Tratamiento , Hipertensión Portal/complicaciones , Hipertensión Portal/cirugía , Laparoscopía/efectos adversos , Tiempo de Internación , Estudios Retrospectivos
12.
Org Lett ; 26(3): 586-590, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38198745

RESUMEN

An acid-promoted cyclization of α-azidobenzyl ketones has been developed for the synthesis of 6-substituted quinoline derivatives. A variety of synthetically useful 6-OTf or -OMs quinoline derivatives were obtained in moderate to good yields. The reaction proceeds via C═N bond formation without organophosphine, providing convenient access to structurally interesting and synthetically important 6-substituted quinoline derivatives in moderate to good yields. A mechanistic perspective that is different from the traditional intramolecular Schmidt reaction has been proposed.

13.
Metab Brain Dis ; 39(1): 147-171, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37542622

RESUMEN

Schizophrenia is a devastating neuropsychiatric disorder affecting 1% of the world population and ranks as one of the disorders providing the most severe burden for society. Schizophrenia etiology remains obscure involving multi-risk factors, such as genetic, environmental, nutritional, and developmental factors. Complex interactions of genetic and environmental factors have been implicated in the etiology of schizophrenia. This review provides an overview of the historical origins, pathophysiological mechanisms, diagnosis, clinical symptoms and corresponding treatment of schizophrenia. In addition, as schizophrenia is a polygenic, genetic disorder caused by the combined action of multiple micro-effective genes, we further detail several approaches, such as candidate gene association study (CGAS) and genome-wide association study (GWAS), which are commonly used in schizophrenia genomics studies. A number of GWASs about schizophrenia have been performed with the hope to identify novel, consistent and influential risk genetic factors. Finally, some schizophrenia susceptibility genes have been identified and reported in recent years and their biological functions are also listed. This review may serve as a summary of past research on schizophrenia genomics and susceptibility genes (NRG1, DISC1, RELN, BDNF, MSI2), which may point the way to future schizophrenia genetics research. In addition, depending on the above discovery of susceptibility genes and their exact function, the development and application of antipsychotic drugs will be promoted in the future.


Asunto(s)
Esquizofrenia , Humanos , Esquizofrenia/genética , Esquizofrenia/diagnóstico , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Genómica , Proteínas de Unión al ARN/genética
14.
Int J Nurs Pract ; 30(1): e13155, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37056171

RESUMEN

AIMS: This study aims to examine the prevalence of anxiety symptoms and identify predictors of anxiety among pregnant women with gestational diabetes mellitus and their partners and explore the mediating role of marital satisfaction between maternal and paternal anxiety. DESIGN: A cross-sectional study was conducted in Guangzhou, China, from July 2021 to May 2022. METHODS: A total of 306 dyads of pregnant women with gestational diabetes mellitus and their partners completed the State-Trait Anxiety Inventory, Locke-Wallace Marital Adjustment Test and the socio-demographic and clinical data sheet. RESULTS: The prevalence of anxiety symptoms was 32.4% and 36.6% in pregnant women with gestational diabetes mellitus and their partners, respectively. The predictors of maternal anxiety were paternal anxiety, maternal marital satisfaction, maternal monthly salary, fasting glucose value and 1-h glucose value. By contrast, the predictors of paternal anxiety were maternal anxiety, paternal marital satisfaction and paternal monthly salary. Moreover, the relationship between maternal and paternal anxiety was mediated by marital satisfaction. CONCLUSIONS: The anxiety symptoms of pregnant women with gestational diabetes mellitus and their partners influence each other, and this relationship was mediated by marital satisfaction. Every couple should be screened for anxiety symptoms and treated as a team rather than focusing solely on the pregnant woman.


Asunto(s)
Diabetes Gestacional , Mujeres Embarazadas , Masculino , Embarazo , Femenino , Humanos , Diabetes Gestacional/epidemiología , Estudios Transversales , Ansiedad/epidemiología , Glucosa , Satisfacción Personal
15.
Microbes Infect ; 26(1-2): 105244, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37914020

RESUMEN

OBJECTIVE: This study aimed to investigate the impact of Corydalis Saxicola Bunting Total Alkaloid (CSBTA) on Porphyromonas gingivalis internalization within macrophages and explore the potential role of Toll-Like Receptor 2 (TLR2) in this process. METHODS: We established a P. gingivalis internalization model in macrophages by treating P. gingivalis-infected macrophages (MOI=100:1) with 200 µg/mL metronidazole and 300 µg/mL gentamicin for 1 h. Subsequently, the model was exposed to CSBTA at concentrations of 0.02 g/L or 1 µg/mL Pam3CSK4. After a 6 h treatment, cell lysis was performed with sterile water to quantify bacterial colonies. The mRNA expressions of TLR2 and interleukin-8 (IL-8) in macrophages were analyzed using RT-qPCR, while their protein levels were assessed via Western blot and ELISA respectively. RESULTS: P. gingivalis could internalize into macrophages and enhance the expression of TLR2 and IL-8. Activation of TLR2 by Pam3CSK4 contributed to P. gingivalis survival within macrophages and increased TLR2 and IL-8 expression. Conversely, 0.02 g/L CSBTA effectively cleared intracellular P. gingivalis, achieving a 90 % clearance rate after 6 h. Moreover, it downregulated the expression of TLR2 and IL-8 induced by P. gingivalis. However, the inhibitory effect of CSBTA on the internalized P. gingivalis model was attenuated by Pam3CSK4. CONCLUSION: CSBTA exhibited the ability to reduce the presence of live intracellular P. gingivalis and lower IL-8 expression in macrophages, possibly by modulating TLR2 activity.


Asunto(s)
Alcaloides , Corydalis , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Porphyromonas gingivalis/metabolismo , Corydalis/metabolismo , Alcaloides/metabolismo , Alcaloides/farmacología , Macrófagos/microbiología
16.
Surg Endosc ; 38(1): 56-65, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38017157

RESUMEN

OBJECTIVE: How different surgical procedures, including the robotic-assisted liver resection (RLR) and laparoscopic liver resection (LLR), can affect the prognosis of patients with liver malignancies is unclear. Thus, in this study, we compared the effects of RLR and LLR on the surgical and oncological outcomes in patients with liver malignancies through propensity score-matched cohort studies. METHODS: The PubMed, Embase, and Cochrane databases were searched using Medical Subject Headings terms and keywords from inception until May 31, 2023. The quality of the included studies was assessed using the Newcastle-Ottawa quality assessment scale. The mean difference with 95% confidence interval (95% CI) was used for analysis of continuous variables; the risk ratio with 95% CI was used for dichotomous variables; and the hazard ratio with 95% CI was used for survival-related variables. Meta-analysis was performed using a random-effects model. RESULTS: Five high-quality cohort studies with 986 patients were included (370 and 616 cases for RLR and LLR, respectively). In terms of surgical outcomes, there were no significant differences in the operation time, conversion rate to open surgery, overall complication rate, major complication rate, and length of hospital stay between the RLR and LLR groups. In terms of oncological outcomes, there were no significant differences in the 5-year overall survival and disease-free survival between the two groups. CONCLUSION: Surgical and oncological outcomes are comparable between RLR and LLR on patients with liver malignancies. Therefore, the benefits of applying RLR in patients with liver malignancies need to be further explored.


Asunto(s)
Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Puntaje de Propensión , Hepatectomía/métodos , Laparoscopía/métodos , Tiempo de Internación , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía
17.
Org Lett ; 25(47): 8501-8505, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37975639

RESUMEN

An efficient synthesis of (+)-peniciketal B has been accomplished in 15 steps from the commercially available materials atraric acid, acryloyl chloride, and (+)-homoallylic alcohol. A convergent synthetic approach that is quite concise for constructing either "hemisphere" of (+)-peniciketal B with a common intermediate is employed that relies on a cascade intermolecular FeCl3-mediated "inner sphere" Michael-type reaction/double cyclization of an α,ß-unsaturated ketone and substituted phenol to build the benzo-fused 2,8-dioxabicyclo[3.3.1]nonane with excellent diastereoselectivity. The generality of the transformation was also demonstrated by the broad scope of substrates that would be potential candidates for natural product synthesis and medicinal chemistry. Benzannulated [6,6]spiroketal was installed by a late-stage acid-catalyzed spiroketalization.

18.
Adv Sci (Weinh) ; 10(36): e2302494, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37985839

RESUMEN

Stromal antigen 2 (STAG2), a subunit of the cohesin complex, is recurrently mutated in various tumors. However, the role of STAG2 in DNA repair and its therapeutic implications are largely unknown. Here it is reported that knockout of STAG2 results in increased double-stranded breaks (DSBs) and chromosomal aberrations by reducing homologous recombination (HR) repair, and confers hypersensitivity to inhibitors of ataxia telangiectasia mutated (ATMi), Poly ADP Ribose Polymerase (PARPi), or the combination of both. Of note, the impaired HR by STAG2-deficiency is mainly attributed to the restored expression of KMT5A, which in turn methylates H4K20 (H4K20me0) to H4K20me1 and thereby decreases the recruitment of BRCA1-BARD1 to chromatin. Importantly, STAG2 expression correlates with poor prognosis of cancer patients. STAG2 is identified as an important regulator of HR and a potential therapeutic strategy for STAG2-mutant tumors is elucidated.


Asunto(s)
Neoplasias , Reparación del ADN por Recombinación , Humanos , Reparación del ADN por Recombinación/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Reparación del ADN/genética , Neoplasias/tratamiento farmacológico , Cohesinas , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo
19.
Org Lett ; 25(47): 8489-8494, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37966853

RESUMEN

A new electrophilic trifluoromethylselenolation reagent, N-trifluoromethylselenophthalimide (Phth-SeCF3), was developed. A strategy for the synthesis of 4-trifluoromethylselenolated isoxazoles through electrophilic trifluoromethylselenolation cyclization has been established by using Phth-SeCF3 as an electrophilic reagent. Moreover, this protocol has the features of broad substrate scope, good functional group tolerance, and high yields.

20.
Quant Imaging Med Surg ; 13(9): 5986-5995, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37711789

RESUMEN

Background: Iliac vein compression syndrome (IVCS) is an underlying cause of varicose vein (VV) recurrence after venous surgery. However, the management of recurrent varicose veins (RVVs) combined with IVCS has rarely been reported. This study aimed to investigate the outcomes of a one-stop procedure to correct outflow obstruction and superficial reflux for patients with RVVs and IVCS. Methods: A retrospective analysis was conducted of 102 consecutive patients diagnosed with RVVs. Computed tomography venography (CTV) was performed to confirm IVCS. The cases were divided into 2 groups: the IRVVs group, including patients with RVVs and IVCS (n=48), and the RVVs group, including patients with RVVs only (n=54). The characteristics, vein reflux, and clinical, etiological, anatomical, and pathophysiological (CEAP) distribution were investigated. Then, the IRVVs group patients who underwent endovenous laser ablation (EVLA) (n=39) were divided into a further 2 groups: the EVLA + S group (n=19), who received EVLA and stenting of iliac vein, and the EVLA group (n=20), who received EVLA treatment alone. The great/small saphenous vein (GSV/SSV) trunk occlusion, VV recurrence, visual analogue scale (VAS), and venous clinical severity score (VCSS) were investigated. Results: The prevalence rate of femoral vein reflux was 81.2% in IRVVs group and 50% in RVVs group (P<0.05). In the IRVVs group, 72.9% of patients manifested as CEAP clinical class >3, which was higher than that in RVVs group (48.1%) (P<0.05). The 12-month GSV/SSV occlusion rate in the EVLA + S and EVLA groups were 94.7% and 90.0%, respectively. Totals of 9 patients in EVLA + S group and 6 patients in EVLA group had active venous ulcers, and the ulcer healing time in EVLA + S group was significantly shorter (27.22±7.12 vs. 46.67±9.83 days, P<0.05). The reductions in the VAS and VCSS values between baseline, 1 month, and 12 months in the EVLA + S group were more obvious than those in EVLA group (P<0.05). Conclusions: The one-stop combination treatment of iliac venous stenting and EVLA in patients with RVVs and IVCS is safe and effective and provides prominent symptom relief, improved quality of life, and a more satisfactory ulcer healing than EVLA alone.

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