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2.
Sci Rep ; 14(1): 11237, 2024 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755283

RESUMEN

Osteoarthritis (OA) is the most prevalent form of arthritis, characterized by a complex pathogenesis. One of the key factors contributing to its development is the apoptosis of chondrocytes triggered by oxidative stress. Involvement of peroxisome proliferator-activated receptor gamma (PPARγ) has been reported in the regulation of oxidative stress. However, there remains unclear mechanisms that through which PPARγ influences the pathogenesis of OA. The present study aims to delve into the role of PPARγ in chondrocytes apoptosis induced by oxidative stress in the context of OA. Primary human chondrocytes, both relatively normal and OA, were isolated and cultured for the following study. Various assessments were performed, including measurements of cell proliferation, viability and cytotoxicity. Additionally, we examined cell apoptosis, levels of reactive oxygen species (ROS), nitric oxide (NO), mitochondrial membrane potential (MMP) and cytochrome C release. We also evaluated the expression of related genes and proteins, such as collagen type II (Col2a1), aggrecan, inducible nitric oxide synthase (iNOS), caspase-9, caspase-3 and PPARγ. Compared with relatively normal cartilage, the expression of PPARγ in OA cartilage was down-regulated. The proliferation of OA chondrocytes decreased, accompanied by an increase in the apoptosis rate. Down-regulation of PPARγ expression in OA chondrocytes coincided with an up-regulation of iNOS expression, leading to increased secretion of NO, endogenous ROS production, and decrease of MMP levels. Furthermore, we observed the release of cytochrome C, elevated caspase-9 and caspase-3 activities, and reduction of the components of extracellular matrix (ECM) Col2a1 and aggrecan. Accordingly, utilization of GW1929 (PPARγ Agonists) or Z-DEVD-FMK (caspase-3 inhibitor) can protect chondrocytes from mitochondrial-related apoptosis and alleviate the progression of OA. During the progression of OA, excessive oxidative stress in chondrocytes leads to apoptosis and ECM degradation. Activation of PPARγ can postpone OA by down-regulating caspase-3-dependent mitochondrial apoptosis pathway.


Asunto(s)
Apoptosis , Caspasa 3 , Condrocitos , Mitocondrias , Osteoartritis , PPAR gamma , Especies Reactivas de Oxígeno , Humanos , Condrocitos/metabolismo , Condrocitos/patología , PPAR gamma/metabolismo , Caspasa 3/metabolismo , Osteoartritis/metabolismo , Osteoartritis/patología , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo , Potencial de la Membrana Mitocondrial , Proliferación Celular , Óxido Nítrico/metabolismo , Células Cultivadas , Persona de Mediana Edad , Anciano , Femenino , Masculino
3.
Adv Sci (Weinh) ; : e2400594, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38689503

RESUMEN

Proteolysis targeting chimeras (PROTACs) have emerged as a promising strategy for drug discovery and exploring protein functions, offering a revolutionary therapeutic modality. Currently, the predominant approach to PROTACs discovery mainly relies on an empirical design-synthesis-evaluation process involving numerous cycles of labor-intensive synthesis-purification and bioassay data collection. Therefore, the development of innovative methods to expedite PROTAC synthesis and exploration of chemical space remains highly desired. Here, a direct-to-biology strategy is reported to streamline the synthesis of PROTAC libraries on plates, enabling the seamless transfer of reaction products to cell-based bioassays without the need for additional purification. By integrating amide coupling and light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) photoclick chemistry into a plate-based synthetic process, this strategy produces PROTAC libraries with high efficiency and structural diversity. Moreover, by employing this platform for PROTACs screening, we smoothly found potent PROTACs effectively inhibit triple-negative breast cancer (TNBC) cell growth and induce rapid, selective targeted degradation of cyclin-dependent kinase 9 (CDK9). The study introduces a versatile platform for assembling PROTACs on plates, followed by direct biological evaluation. This approach provides a promising opportunity for high-throughput synthesis of PROTAC libraries, thereby enhancing the efficiency of exploring chemical space and accelerating the discovery of PROTACs.

4.
Materials (Basel) ; 17(10)2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38793331

RESUMEN

The development of sustainable flame retardants is gaining momentum due to their enhanced safety attributes and environmental compatibility. One effective strategy is to use waste materials as a primary source of chemical components, which can help mitigate environmental issues associated with traditional flame retardants. This paper reviews recent research in flame retardancy for waste flame retardants, categorizing them based on waste types like industrial, food, and plant waste. The paper focuses on recent advancements in this area, focusing on their impact on the thermal stability, flame retardancy, smoke suppression, and mechanical properties of polymeric materials. The study also provides a summary of functionalization methodologies used and key factors involved in modifying polymer systems. Finally, their major challenges and prospects for the future are identified.

5.
Front Genet ; 15: 1385339, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660673

RESUMEN

Introduction: Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism's pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets. Methods: Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed. Results: MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol's binding to IRF3, indicating a stable interaction. Conclusion: This study comprehensively elucidates inflammation, immune response, and metabolism's intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo's etiology, informing future research and drug development endeavors.

6.
J Anal Methods Chem ; 2024: 9952318, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38567381

RESUMEN

Rosuvastatin calcium is a widely used 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitor developed for the treatment of dyslipidemia. To establish a control strategy for the elemental impurities, a new digestion method combined with an inductively coupled plasma-mass spectrometer (ICP-MS) was developed and validated by our team to determine elements Cd, Pb, As, Hg, Co, V, and Ni in rosuvastatin calcium tablets, which digest the sample perfectly even in the presence of a large number of excipients, especially titanium dioxide. The measurement mode was collision cell mode with kinetic energy discrimination (KED). 209Bi+, 115In+, and 89Y+ were chosen as internal standard elements. The recoveries of the limit of quantitation (LOQ) ranged from 90.5% to 106.4%, concentrations of the abovementioned elements in LOQ were 0.25 µg·L-1, 0.25 µg·L-1, 0.75 µg·L-1, 1.5 µg·L-1, 2.5 µg·L-1, 5 µg·L-1, and 8 µg·L-1 , respectively, linear correlation coefficients were above 0.9997, the recoveries in accuracy item ranged from 91.8% to 103.6%, and relative standard deviations (RSDs) of recovery in precision were not more than 1.8%, reflecting a reliable method of high sensitivity, strong anti-interference capacity, and good precision, and that it was suitable for the determination of elemental impurities in drugs.

7.
Mol Genet Genomic Med ; 12(3): e2401, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38444278

RESUMEN

BACKGROUND: The MYH3-associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like pterygia and vertebrae fusion. CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B) is the only known autosomal recessiveMYH3-associated myosinopathy so far, with no more than two dozen cases being reported. MATERIALS AND METHODS: A boy with CPSKF1B was recruited and subjected to a comprehensive clinical and imaging evaluation. Genetic detection with whole-exome sequencing (WES) was performed on the patient and extended family members to identify the causative variation. A series of in silico and in vitro investigations were carried out to verify the pathogenicity of the two variants of the identified compound heterozygous variation. RESULTS: The patient exhibited moderate CPSKF1B symptoms including multiarticular contractures, webbed neck, and spondylocarpotarsal fusion. WES detected a compound heterozygous MYH3 variation consisting of two variants, namely NM_002470.4: c.3377A>G; p. (E1126G) and NM_002470.4: c.5161-2A>C. It was indicated that the NM_002470.4: c.3377A>G; p. (E1126G) variant mainly impaired the local hydrogen bond formation and impacted the TGF-B pathway, while the NM_002470.4: c.5161-2A>C variant could affect the normal splicing of pre-mRNA, resulting in the appearance of multiple abnormal transcripts. CONCLUSIONS: The findings of this study expanded the mutation spectrum of CPSKF1B, provided an important basis for the counseling of the affected family, and also laid a foundation for the functional study of MYH3 mutations.


Asunto(s)
Artrogriposis , Conjuntiva , Contractura , Pterigion , Humanos , Masculino , Artrogriposis/genética , Conjuntiva/anomalías , Contractura/genética , Familia
8.
ACS Appl Bio Mater ; 7(3): 1801-1809, 2024 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-38416780

RESUMEN

Bacterial nanocellulose (BNC) is an attractive green-synthesized biomaterial for biomedical applications and various other applications. However, effective engineering of BNC production has been limited by our poor knowledge of the related metabolic processes. In contrast to the traditional perception that genome critically determines biosynthesis behaviors, here we discover that the glucose metabolism could also drastically affect the BNC synthesis in Gluconacetobacter hansenii. The transcriptomic profiles of two model BNC-producing strains, G. hansenii ATCC 53582 and ATCC 23769, which have highly similar genomes but drastically different BNC yields, were compared. The results show that their BNC synthesis capacities were highly related to metabolic activities such as ATP synthesis, ion transport protein assembly, and carbohydrate metabolic processes, confirming an important role of metabolism-related transcriptomes in governing the BNC yield. Our findings provide insights into the microbial biosynthesis behaviors from a transcriptome perspective, potentially guiding cellular engineering for biomaterial synthesis.


Asunto(s)
Perfilación de la Expresión Génica , Transcriptoma , Transcriptoma/genética , Materiales Biocompatibles , Ingeniería Celular , Transporte Iónico
9.
Alcohol ; 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38387693

RESUMEN

OBJECTIVES: Alcohol consumption is not uncommon among people with HIV (PWH) and may exacerbate HIV-induced intestinal damage, and further lead to dysbiosis and increased intestinal permeability. This study aimed to determine the changes in the faecal microbiota and its association with alcohol consumption in HIV-infected patients. METHODS: A cross-sectional survey was conducted between November 2021 and May 2022, and 93 participants were recruited. To investigate the alterations of alcohol misuse on fecal microbiology in HIV-infected individuals, we performed 16s rDNA gene sequencing on fecal samples from the low to moderate drinking (n=21) and non-drinking (n=72) groups. RESULTS: Comparison between groups using alpha and beta diversity showed that the diversity of stool microbiota in the low to moderate drinkinge group did not differ from that of the non-drinking group (all P>0.05). The Linear discriminant Analysis effect size (LEfSe) algorithm was to determine the bacterial taxa associated with alcohol consumption, and the results showed altered fecal bacterial composition in HIV-infected patients who consumed alcohol, with Coprobacillus, Pseudobutyrivibrio and Peptostreptococcaceae enriched, and Pasteurellaceae and Xanthomonadaceae were depleted. In addition, by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional microbiome features were also found to be altered in the low to moderate drinking group, showing a reduction in metabolic pathways (P=0.036) and cardiovascular disease pathway (P=0.006). CONCLUSION: Low to moderate drinking will change the composition, metabolism and cardiovascular disease pathway of the gut microbiota of HIV-infected patients.

10.
Aging (Albany NY) ; 16(2): 1767-1780, 2024 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-38244583

RESUMEN

Approximately 10% of gastric cancers are associated with Epstein-Barr virus (EBV). Tremella fuciformis polysaccharides (TFPs) are characterized by antioxidative and anti-inflammatory effects in different diseases. However, whether TFP improves EBV-associated gastric cancer (EBVaGC) has never been explored. The effects of TFP on EBV-infected GC cell viability were determined using a CCK-8 assay and flow cytometry. Western blotting and RT-qPCR were performed to explore the expression of ferroptosis-related proteins. The CCK-8 assay showed that TFP decreased EBV-infected GC cell viability in a dose- and time-dependent manner. Flow cytometry assays indicated that TFP significantly induced EBV-infected GC cell death. TFP also reduced the migratory capacity of EBV-infected GC cells. Furthermore, treatment with TFP significantly increased the mRNA levels of PTGS2 and Chac1 in EBV-infected GC cells. Western blot assays indicated that TFP suppressed the expression of NRF2, HO-1, GPX4 and xCT in EBV-infected GC cells. More importantly, overexpression of NRF2 could obviously rescue TFP-induced downregulation of GPX4 and xCT in EBV-infected GC cells. In summary, we showed novel data that TFP induced ferroptosis in EBV-infected GC cells by inhibiting NRF2/HO-1 signaling. The current findings may shed light on the potential clinical application of TFP in the treatment of EBVaGC.


Asunto(s)
Basidiomycota , Infecciones por Virus de Epstein-Barr , Ferroptosis , Neoplasias Gástricas , Humanos , Herpesvirus Humano 4/genética , Neoplasias Gástricas/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Sincalida/metabolismo
12.
RMD Open ; 9(4)2023 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-38035758

RESUMEN

OBJECTIVE: To investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA). METHODS: 143 nuclear magnetic resonance-based plasma metabolic biomarkers were measured among 93 800 participants in the UK Biobank. The Cox regression model was used to assess the associations between these metabolic biomarkers and RA risk, and genetic correlation and Mendelian randomisation analyses were performed to reveal their causal relationships. Subsequently, a metabolic risk score (MRS) comprised of the weighted sum of 17 clinically validated metabolic markers was constructed. A PRS was derived by assigning weights to genetic variants that exhibited significant associations with RA at a genome-wide level. RESULTS: A total of 620 incident RA cases were recorded during a median follow-up time of 8.2 years. We determined that 30 metabolic biomarkers were potentially associated with RA, while no further significant causal associations were found. Individuals in the top decile of MRS had an increased risk of RA (HR 3.52, 95% CI: 2.80 to 4.43) compared with those below the median of MRS. Further, significant gradient associations between MRS and RA risk were observed across genetic risk strata. Specifically, compared with the low genetic risk and favourable MRS group, the risk of incident RA in the high genetic risk and unfavourable MRS group has almost elevated by fivefold (HR 6.10, 95% CI: 4.06 to 9.14). CONCLUSION: Our findings suggested the metabolic profiles comprising multiple metabolic biomarkers contribute to capturing an elevated risk of RA, and the integration of genome-wide PRSs further improved risk stratification.


Asunto(s)
Artritis Reumatoide , Bancos de Muestras Biológicas , Humanos , Estudios de Cohortes , Factores de Riesgo , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/genética , Biomarcadores , Reino Unido/epidemiología
13.
14.
Polymers (Basel) ; 15(13)2023 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-37447467

RESUMEN

In last years, the requirements for materials and devices have increased exponentially. Greater competitiveness; cost and weight reduction for structural materials; greater power density for electronic devices; higher design versatility; materials customizing and tailoring; lower energy consumption during the manufacturing, transport, and use; among others, are some of the most common market demands. A higher operational efficiency together with long service life claimed. Particularly, high thermally conductive in epoxy resins is an important requirement for numerous applications, including energy and electrical and electronic industry. Over time, these materials have evolved from traditional single-function to multifunctional materials to satisfy the increasing demands of applications. Considering the complex application contexts, this review aims to provide insight into the present state of the art and future challenges of thermally conductive epoxy composites with various functionalities. Firstly, the basic theory of thermally conductive epoxy composites is summarized. Secondly, the review provides a comprehensive description of five types of multifunctional thermally conductive epoxy composites, including their fabrication methods and specific behavior. Furthermore, the key technical problems are proposed, and the major challenges to developing multifunctional thermally conductive epoxy composites are presented. Ultimately, the purpose of this review is to provide guidance and inspiration for the development of multifunctional thermally conductive epoxy composites to meet the increasing demands of the next generation of materials.

15.
Int J Biometeorol ; 67(10): 1543-1553, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37522974

RESUMEN

BACKGROUND: The disease burden attributable to chronic obstructive pulmonary disease (COPD) is significant worldwide. Some studies have linked exposure to air pollution to COPD, but there has been little research on this. METHODS: We aimed to assess the COPD-related disease burden attributable to air pollution from multiple epidemiological perspectives. This study conducted a three-stage analysis. Firstly, we reported on the burden of disease worldwide in 2019 by different subgroups including sex, age, region, and country. Secondly, we studied the trends in disease burden from 1990 to 2019. Finally, we explored the association of some national indicators with disease burden to look for risk factors. RESULTS: In 2019, the death number of COPD associated with air pollution accounted for 2.32% of the total global death, and the number of DALY accounted for 1.12% of the global DALY. From 1990 to 2019, the death number of COPD associated with air pollution increased peaked at 1.41 million in 1993, fluctuated, and then declined. We found the same temporal pattern of DALY. The corresponding age-standardized rates had been falling. At the same time, the burden of COPD associated with air pollution was also affected by some national indicators. CONCLUSIONS: This study indicated that air pollution-related COPD contributed to a significant global disease burden. We called for health policymakers to take action and interventions targeting vulnerable countries and susceptible populations.


Asunto(s)
Contaminación del Aire , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Años de Vida Ajustados por Calidad de Vida , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Contaminación del Aire/efectos adversos , Carga Global de Enfermedades , Costo de Enfermedad , Factores de Riesgo
16.
AIDS Res Ther ; 20(1): 45, 2023 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-37452359

RESUMEN

BACKGROUND: This study conducted a survey of men who have sex with men (MSM) in Maanshan City of Anhui Province to assess the risk behaviors related to human immunodeficiency virus (HIV) infection. METHODS: A cross-sectional survey was conducted from June 2016 to June 2019. The MSM were recruited by a peer-driven sampling method. A face-to-face interview with anonymous questionnaire was used for data collection. The information collected by the survey was summarized and epidemiology described the basic characteristics of MSM, and then the related factors were statistically analyzed. RESULTS: A total of 934 MSM were recruited with a average age was 30.5 (SD = 8.90) years old, including 816 (87.4%) HIV negative participants and 118 (12.6%) HIV positive ones. This study showed that freelancer (OR = 4.02, 95% CI: 1.96-8.23), scope of sexual partners distribution (OR = 1.78, 95% CI: 1.36-2.33), number of male sexual partners (OR = 2.11, 95% CI: 1.47-3.02), role of anal sex with men was receptive (OR = 2.54, 95% CI: 1.25-5.13) and versatile (OR = 2.34, 95% CI: 1.31-4.19) and non-steady sex partners (OR = 2.14, 95% CI: 1.56-2.93) were risk factors for HIV infection, while monthly income (OR = 0.68, 95% CI: 0.57-0.82), education level (OR = 0.79, 95% CI: 0.66-0.95), frequency of condom use (OR = 0.53, 95% CI: 0.35-0.81) and number of oral sex partners (OR = 0.35, 95% CI: 0.24-0.51) in the past 6 months were protective factors for HIV infection. CONCLUSION: Risk behaviors were common in MSM, and urgent need for targeted and comprehensive interventions to reduce risky sexual behaviour and to prevent HIV infection in MSM.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Masculino , Humanos , Adulto , Niño , Estudios Transversales , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Conducta Sexual , Factores de Riesgo , China/epidemiología
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(3): 889-895, 2023 Jun.
Artículo en Chino | MEDLINE | ID: mdl-37356956

RESUMEN

OBJECTIVE: To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). METHODS: From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve. RESULTS: Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001). CONCLUSION: Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.


Asunto(s)
Lupus Eritematoso Sistémico , Linfohistiocitosis Hemofagocítica , Humanos , Relevancia Clínica , Curva ROC , Sensibilidad y Especificidad
18.
Heliyon ; 9(6): e17272, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37360094

RESUMEN

Duodenal stump fistula is a rare but dangerous complication of gastric cancer surgery. Reinforcement of the duodenal stump was suggested as a useful method to prevent the occurrence of duodenal stump fistula. Although laparoscopic surgery has been established as a safe procedure for gastric cancer, it is acknowledged that the application of duodenal stump reinforcement is a demanding process in laparoscopic radical gastrectomy. This review aims to provide a concise description of the proposed reinforcement methods of duodenal stump after laparoscopic radical gastrectomy for gastric cancer by summarizing the relevant literature written in English. The thorough knowledge of these reinforcement techniques may help surgeons to find the most suitable reinforcement method of duodenal stump for patients.

19.
Br J Pharmacol ; 180(20): 2641-2660, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37248964

RESUMEN

BACKGROUND AND PURPOSE: Necroptosis plays an essential role in acute kidney injury and is mediated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed lineage kinase domain-like pseudokinase (MLKL). A novel RIPK3 inhibitor, compound 42 (Cpd-42) alleviates the systemic inflammatory response. The current study was designed to investigate whether Cpd-42 exhibits protective effects on acute kidney injury and reveal the underlying mechanisms. EXPERIMENTAL APPROACH: The effects of Cpd-42 were determined in vivo through cisplatin- and ischaemia/reperfusion (I/R)-induced acute kidney injury and in vitro through cisplatin- and hypoxia/re-oxygenation (H/R)-induced cell damage. Transmission electron microscopy and periodic acid-Schiff staining were used to identify renal pathology. Cellular thermal shift assay and RIPK3-knockout mouse renal tubule epithelial cells were used to explore the relationship between Cpd-42 and RIPK3. Molecular docking and site-directed mutagenesis were used to determine the binding site of RIPK3 with Cpd-42. KEY RESULTS: Cpd-42 reduced human proximal tubule epithelial cell line (HK-2) cell damage, necroptosis and inflammatory responses in vitro. Furthermore, in vivo, cisplatin- and I/R-induced acute kidney injury was alleviated by Cpd-42 treatment. Cpd-42 inhibited necroptosis by interacting with two key hydrogen bonds of RIPK3 at Thr94 and Ser146, which further blocked the phosphorylation of RIPK3 and mitigated acute kidney injury. CONCLUSION AND IMPLICATIONS: Acting as a novel RIPK3 inhibitor, Cpd-42 reduced kidney damage, inflammatory response and necroptosis in acute kidney injury by binding to sites Thr94 and Ser146 on RIPK3. Cpd-42 could be a promising treatment for acute kidney injury.


Asunto(s)
Lesión Renal Aguda , Cisplatino , Ratones , Animales , Humanos , Cisplatino/farmacología , Necroptosis , Simulación del Acoplamiento Molecular , Lesión Renal Aguda/metabolismo , Proteínas Quinasas/metabolismo , Ratones Noqueados , Apoptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores
20.
Int J Biol Macromol ; 243: 125050, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37257540

RESUMEN

The large-scale application of ecofriendly polymeric materials has become a key focus of scientific research with the trend toward sustainable development. Mechanical properties and fire safety are two critical considerations of biopolymers for large-scale applications. Polylactic acid (PLA) is a flammable, melt-drop carrying, and strong but brittle polymer. Hence, it is essential to achieve both flame retardancy and mechanical enhancement to improve safety and broaden its application. This study reviews the recent research on the flame retardant functionalization and mechanical reinforcement of PLA. It classifies PLA according to the type of the flame retardant strategy employed, such as surface-modified fibers, modified nano/micro fillers, small-molecule and macromolecular flame retardants, flame retardants with fibers or polymers, and chain extension or crosslinking with other flame retardants. The functionalization strategies and main parameters of the modified PLA systems are summarized and analyzed. This study summarizes the latest advances in the fields of flame retardancy and mechanical reinforcement of PLA.


Asunto(s)
Retardadores de Llama , Poliésteres , Polímeros , Desarrollo Sostenible
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