Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
1.
Cell ; 187(15): 3936-3952.e19, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936359

RESUMO

Duplication is a foundation of molecular evolution and a driver of genomic and complex diseases. Here, we develop a genome editing tool named Amplification Editing (AE) that enables programmable DNA duplication with precision at chromosomal scale. AE can duplicate human genomes ranging from 20 bp to 100 Mb, a size comparable to human chromosomes. AE exhibits activity across various cell types, encompassing diploid, haploid, and primary cells. AE exhibited up to 73.0% efficiency for 1 Mb and 3.4% for 100 Mb duplications, respectively. Whole-genome sequencing and deep sequencing of the junctions of edited sequences confirm the precision of duplication. AE can create chromosomal microduplications within disease-relevant regions in embryonic stem cells, indicating its potential for generating cellular and animal models. AE is a precise and efficient tool for chromosomal engineering and DNA duplication, broadening the landscape of precision genome editing from an individual genetic locus to the chromosomal scale.


Assuntos
Duplicação Gênica , Edição de Genes , Genoma Humano , Humanos , Edição de Genes/métodos , Sistemas CRISPR-Cas/genética , DNA/genética , Animais , Células-Tronco Embrionárias/metabolismo , Cromossomos Humanos/genética
2.
Mol Cell ; 82(21): 4160-4175.e6, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36272409

RESUMO

CRISPR-Cas9-mediated genome editing depends on PAM recognition to initiate DNA unwinding. PAM mutations can abolish Cas9 binding and prohibit editing. Here, we identified a Cas9 from the thermophile Alicyclobacillus tengchongensis for which the PAM interaction can be robustly regulated by DNA topology. AtCas9 has a relaxed PAM of N4CNNN and N4RNNA (R = A/G) and is able to bind but not cleave targets with mutated PAMs. When PAM-mutated DNA was in underwound topology, AtCas9 exhibited enhanced binding affinity and high cleavage activity. Mechanistically, AtCas9 has a unique loop motif, which docked into the DNA major groove, and this interaction can be regulated by DNA topology. More importantly, AtCas9 showed near-PAMless editing of supercoiled plasmid in E. coli. In mammalian cells, AtCas9 exhibited broad PAM preference to edit plasmid with up to 72% efficiency and effective base editing at four endogenous loci, representing a potentially powerful tool for near-PAMless editing.


Assuntos
Sistemas CRISPR-Cas , Escherichia coli , Animais , Escherichia coli/genética , Escherichia coli/metabolismo , Edição de Genes , DNA/genética , Plasmídeos , Mamíferos/metabolismo
3.
Biochem Biophys Res Commun ; 701: 149612, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38316091

RESUMO

Intestinal ischaemia‒reperfusion (I/R) injury is a surgical emergency. This condition is associated with a high mortality rate. At present, there are limited number of efficient therapeutic measures for this injury, and the prognosis is poor. Therefore, the pathophysiological mechanisms of intestinal I/R injury must be elucidated to develop a rapid and specific diagnostic and treatment protocol. Numerous studies have indicated the involvement of endoplasmic reticulum (ER) stress in the development of intestinal I/R injury. Specifically, the levels of unfolded and misfolded proteins in the ER lumen are increased due to unfolded protein response. However, persistent ER stress promotes apoptosis of intestinal mucosal epithelial cells through three signalling pathways in the ER, impairing intestinal mucosal barrier function and leading to the dysfunction of intestinal tissues and distant organ compartments. This review summarises the mechanisms of ER stress in intestinal I/R injury, diagnostic indicators, and related treatment strategies with the objective of providing novel insights into future therapies for this condition.


Assuntos
Estresse do Retículo Endoplasmático , Traumatismo por Reperfusão , Humanos , Resposta a Proteínas não Dobradas , Intestinos , Apoptose
4.
Sensors (Basel) ; 24(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38931689

RESUMO

Traffic flow prediction can provide important reference data for managers to maintain traffic order, and can also be based on personal travel plans for optimal route selection. On account of the development of sensors and data collection technology, large-scale road network historical data can be effectively used, but their high non-linearity makes it meaningful to establish effective prediction models. In this regard, this paper proposes a dual-stream cross AGFormer-GPT network with prompt engineering for traffic flow prediction, which integrates traffic occupancy and speed as two prompts into traffic flow in the form of cross-attention, and uniquely mines spatial correlation and temporal correlation information through the dual-stream cross structure, effectively combining the advantages of the adaptive graph neural network and large language model to improve prediction accuracy. The experimental results on two PeMS road network data sets have verified that the model has improved by about 1.2% in traffic prediction accuracy under different road networks.

5.
Molecules ; 28(16)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37630409

RESUMO

This study focuses on the fabrication of fiber membranes containing different concentrations of AgNO3 via the electrospinning technique. The AgNO3 present in the fibers is subsequently reduced to silver nanoparticles (Ag NPs) through UV irradiation. The resulting nanofiber film is characterized using scanning electron microscopy, X-ray diffraction, and evaluations of its anti-UV and anti-electromagnetic radiation properties. Experimental results demonstrate that increasing the AgNO3 content initially decreases and then increases the fiber diameter and fiber diameter deviation. Under UV light, the nanofibers fuse and bond, leading to an increase in the fiber diameter. AgNO3 is effectively reduced to Ag NPs after UV irradiation for more than 60 min, as confirmed by the characteristic diffraction peaks of Ag NPs in the XRD spectrum of the irradiated AgNO3/PVB fibers. The nanofiber film containing AgNO3 exhibits superior anti-UV performance compared to the film containing AgNO3-derived Ag NPs. The anti-electromagnetic radiation performances of the nanofiber films containing AgNO3 and AgNO3-derived Ag NPs are similar, but the nanofiber film containing AgNO3-derived Ag NPs exhibits higher performance at approximately 2.5 GHZ frequency. Additionally, at an AgNO3 concentration of less than 0.5 wt%, the anti-electromagnetic radiation performance is poor, and the shielding effect of the nanofiber film on medium- and low-frequency electromagnetic waves surpasses that on high-frequency waves. This study provides guidance for the preparation of polyvinyl butyral nanofibers, Ag NPs, and functional materials with anti-ultraviolet and anti-electromagnetic radiation properties.

6.
J Bioenerg Biomembr ; 53(6): 655-664, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34586578

RESUMO

Dexmedetomidine (Dex) can protect the intestine against ischemia/reperfusion (I/R)-induced injury. Sirtuin 1 (SIRT1) pathway, which could be activated by Dex, was reported to inhibit I/R injury. Pyroptosis plays an important role in intestinal diseases. We aimed to investigate whether Dex could attenuate pyroptosis of hypoxia/reoxygenation (H/R)-induced intestinal epithelial cells via activating SIRT1. The intestinal epithelial cell line IEC-6 with or without SIRT1 knockdown after H/R treatment was exposed to Dex, then cell viability, endoplasmic reticulum stress (ERS), apoptosis, pyroptosis, inflammatory cytokines production and SIRT1 expression were detected. Results showed that Dex treatment had no significant effect on IEC-6 cell viability but rescued the H/R-reduced cell viability. The expression of proteins involved in ERS including Grp78, Gadd153 and caspase 12 was enhanced upon H/R stimulation, but was reversely reduced by Dex. The cell apoptosis increased by H/R was also decreased by Dex. Additionally, Dex inhibited pyroptosis and inflammation, which were markedly promoted upon H/R stimulation. The expression of SIRT1, which was reduced after H/R treatment was also partially rescued by Dex. Finally, the above effects of Dex were all blocked by SIRT1 knockdown. In conclusion, Dex could inhibit H/R-induced intestinal epithelial cells ERS, apoptosis and pyroptosis via activating SIRT1 expression.


Assuntos
Dexmedetomidina , Traumatismo por Reperfusão , Apoptose , Dexmedetomidina/farmacologia , Estresse do Retículo Endoplasmático , Células Epiteliais/metabolismo , Humanos , Hipóxia , Intestinos , Piroptose , Transdução de Sinais , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia
7.
Sensors (Basel) ; 19(7)2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974923

RESUMO

Serum bilirubin is an important biomarker for the diagnosis of various types of liver diseases and blood disorders. A polydopamine/gold nanoclusters composite film was fabricated for the fluorescent sensing of free bilirubin. Bovine serum albumin (BSA)-stabilized gold nanoclusters (AuNCs) were used as probes for biorecognition. The polydopamine film was utilized as an adhesion layer for immobilization of AuNCs. When the composite film was exposed to free bilirubin, due to the complex that was formed between BSA and free bilirubin, the fluorescence intensity of the composite film was gradually weakened as the bilirubin concentration increased. The fluorescence quenching ratio (F0/F) was linearly proportional to free bilirubin over the concentration range of 0.8~50 µmol/L with a limit of detection of 0.61 ± 0.12 µmol/L (S/N = 3). The response was quick, the film was recyclable, and common ingredients in human serum did not interfere with the detection of free bilirubin.


Assuntos
Bilirrubina/isolamento & purificação , Técnicas Biossensoriais , Nanopartículas Metálicas/química , Fluorescência , Ouro/química , Humanos , Indóis/química , Limite de Detecção , Polímeros/química , Soroalbumina Bovina/química , Espectrometria de Fluorescência
8.
Pestic Biochem Physiol ; 128: 22-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26969436

RESUMO

The survival, growth, activity of the biotransformation system phase II enzyme glutathione-S-transferase (GST) and the oxidative defense enzyme catalase (CAT) of earthworms exposed to the contaminated soils from a former DDT plant and reference soils were investigated, and compared with the corresponding indicators in simulated soil-earthworm system, unpolluted natural soils with spiked-in DDT series, to identify the toxic effects of DDT on earthworms and their cellular defense system in complex soil system. The results indicated that DDT level in the contaminated soils was significantly higher than that in the reference soils with similar level of other pollutants and soil characters. The mortality, growth inhibition rates, GST and CST activities of earthworms exposed to the contaminated soils were significantly higher than that in reference soils. The contribution of historical DDT in contaminated soils to earthworms was confirmed by the DDT spiked tests. DDT spiked in soils at rates of higher than 200 mg·kg(-1) was significantly toxic to both the survival and the growth of earthworms. DDT significantly stimulated GST and CAT activity in earthworms after 14 days. The CAT and GST activities were also stimulated by DDT exposure at rates of 100 mg·kg(-1) after chronic exposure (42 days). The results provide implications for validating the extrapolation from laboratory simulated soils criteria to contaminated soils and for making site risk assessments.


Assuntos
DDT/toxicidade , Oligoquetos/efeitos dos fármacos , Estresse Oxidativo , Poluentes do Solo/toxicidade , Animais , Oligoquetos/crescimento & desenvolvimento , Oligoquetos/metabolismo
9.
Int Immunopharmacol ; 138: 112463, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971110

RESUMO

Intestinal ischemia/reperfusion injury (IRI) poses a serious threat to human survival and quality of life with high mortality and morbidity rates. The current absence of effective treatments for intestinal IRI highlights the urgent need to identify new therapeutic targets. Ursolic acid (UA), a pentacyclic triterpene natural compound, has been shown to possess various pharmacological properties including intestinal protection. However, its potential protective efficacy on intestinal IRI remains elusive. This study aimed to investigate the effect of UA on intestinal IRI and explore the underlying mechanisms. To achieve this, we utilized network pharmacology to analyze the mechanism of UA in intestinal IRI and assessed UA's effects on intestinal IRI using a mouse model of superior mesenteric artery occlusion/reperfusion and an in vitro model of oxygen-glucose deprivation and reperfusion-induced IEC-6 cells. Our results demonstrated that UA improved necroptosis through the RIP1/RIP3/MLKL pathway, reduced necroinflammation via the HMGB1/TLR4/NF-κB pathway, attenuated morphological damage, and enhanced intestinal barrier function. Furthermore, UA pretreatment downregulated the phosphorylation level of signal transducer and activator of transcription 3 (STAT3). The effects of UA were attenuated by the STAT3 agonist Colivelin. In conclusion, our study suggests that UA can improve intestinal IRI by inhibiting necroptosis in enterocytes via the suppression of STAT3 activation. These results provide a theoretical basis for UA treatment of intestinal IRI and related clinical diseases.

10.
Curr Med Chem ; 30(36): 4130-4148, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36537607

RESUMO

Intestinal ischemia-reperfusion injury is a relatively common clinical condition that seriously threatens the prognosis of patients; however, the exact mechanism of intestinal ischemia-reperfusion injury has not been clarified. Recent studies have found that noncoding RNAs, including but not limited to lncRNA, circRNA, and miRNA, play an important role in the pathogenesis of intestinal ischemia-reperfusion. The findings cited in this paper reveal the expression, function, and mechanism of noncoding RNAs during intestinal ischemia-reperfusion. The mechanistic roles of noncoding RNAs in the occurrence and development of intestinal ischemia-reperfusion are discussed, including cell proliferation, autophagy, oxidative stress, apoptosis, oxidative stress, iron death, and many other aspects. However, many unknown mechanisms of association between noncoding RNAs and intestinal ischemia-reperfusion remain to be investigated.


Assuntos
MicroRNAs , RNA Longo não Codificante , Traumatismo por Reperfusão , Humanos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Isquemia
11.
Am J Chin Med ; 51(6): 1501-1526, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37530507

RESUMO

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that include Crohn's disease (CD) and ulcerative colitis (UC). Today, IBD has no successful treatment. As a result, it is of paramount importance to develop novel therapeutic agents for IBD prevention and treatment. Astragalus membranaceus (AMS) is a traditional Chinese medicine found in the AMS root. Modern pharmacological studies indicate that AMS and its constituents exhibit multiple bioactivities, such as anti-inflammatory, anti-oxidant, immune regulatory, anticancer, hypolipidemic, hypoglycemic, hepatoprotective, expectorant, and diuretic effects. AMS and its active constituents, which have been reported to be effective in IBD treatment, are believed to be viable candidate drugs for IBD treatment. These underlying mechanisms are associated with anti-inflammation, anti-oxidation, immunomodulation, intestinal epithelial repair, gut microbiota homeostasis, and improved energy metabolism. In this review, we summarize the efficacy and underlying mechanisms involved in IBD treatment with AMS and its active constituents in preclinical studies.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Astragalus propinquus , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Antioxidantes
12.
Eur J Pharmacol ; 959: 176090, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37778612

RESUMO

BACKGROUND: Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received increasing attention due to increased morbidity and mortality. To date, there are no effective treatments. Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, has been demonstrated to be effective against intestinal IRI. In this systematic review and meta-analysis, we evaluated the efficacy and potential mechanisms of DEX as a treatment for intestinal IRI in animal models. METHODS: Five databases (PubMed, Embase, Web of Science, Cochrane Library, and Scopus) were searched until March 15, 2023. Using the SYRCLE risk bias tool, we assessed methodological quality. Statistical analysis was conducted using STATA 12 and R 4.2.2. We analyzed the related outcomes (mucosa damage-related indicators; inflammation-relevant markers, oxidative stress markers) relied on the fixed or random-effects models. RESULTS: There were 15 articles including 18 studies included, and 309 animals were involved in the studies. Compared to the model groups, DEX improved intestinal IRI. DEX decreased Chiu's score and serum diamine oxidase (DAO) level. DEX reduced the level of inflammation-relevant markers (interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α). DEX also improved oxidative stress (decreased malondialdehyde (MDA), increased superoxide dismutase (SOD)). CONCLUSIONS: DEX's effectiveness in ameliorating intestinal IRI has been demonstrated in animal models. Antioxidation, anti-inflammation, anti-apoptotic, anti-pyroptosis, anti-ferroptosis, enhancing mitophagy, reshaping the gut microbiota, and gut barrier protection are possible mechanisms. However, in light of the heterogeneity and methodological quality of these studies, further well-designed preclinical studies are warranted before clinical implication.


Assuntos
Dexmedetomidina , Traumatismo por Reperfusão , Ratos , Animais , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Ratos Sprague-Dawley , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Traumatismo por Reperfusão/patologia , Inflamação/tratamento farmacológico , Isquemia/tratamento farmacológico
13.
Biosci Rep ; 43(8)2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37530723

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salidroside (SAL), a phenolic natural product present in Rhodiola rosea, are commonly used in the treatment of various ischemic-hypoxic diseases, including intestinal ischemia-reperfusion (IR) injury. However, their efficacy and potential mechanisms in the treatment of intestinal IR injury have not been investigated. OBJECTIVE: The objective of the present study is to investigate the pharmacological mechanism of action of SAL on intestinal IR injury using a network pharmacology approach combined with experimental validation. METHODS: In the present study, we used the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database and analysis platform and Comparative Toxicogenomics Database (CTD) to predict possible target genes of SAL, collected relevant target genes of intestinal IR injury from GeneCards and DisGenet websites, and collected summary data to screen common target genes. Then, the protein-protein interaction (PPI) target network was constructed and analyzed by STRING database and Cytoscape 3.8.2 with the above intersecting genes. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed and the component-target-pathway network was constructed, followed by the use of molecular docking and molecular dynamic simulation to verify the possible binding conformation between SAL and candidate targets to further explore the potential targets of SAL in the treatment of intestinal IR injury. Finally, an in vivo model of mouse superior mesenteric artery ligation was established to assess the anti-intestinal IR injury effect of SAL by assessing histopathological changes in mouse small intestine by HE staining, detecting inflammatory factor expression by ELISA kit, and detecting the expression of key protein targets by Western blotting. RESULTS: A total of 166 SAL target genes and 1740 disease-related targets were retrieved, and 88 overlapping proteins were obtained as potential therapeutic targets. The pathway enrichment analysis revealed that the pharmacological effects of SAL on intestinal IR injury were anti-hypoxic, anti-inflammatory and metabolic pathway related, and the molecular docking and molecular dynamic simulation results showed that the core bioactive components had good binding affinity for TXNIP and AMPK, and the immunoblotting results indicated that the expression levels of TXNIP and AMPK in the small intestinal tissues of mice in the drug-treated group compared with the model group were significantly changed. CONCLUSION: SAL may target AMPK and TXNIP domains to act as a therapeutic agent for intestinal IR. These findings comprehensively reveal the potential therapeutic targets for SAL against intestinal IR and provide theoretical basis for the clinical application of SAL in the treatment of intestinal IR.


Assuntos
Medicamentos de Ervas Chinesas , Traumatismo por Reperfusão , Animais , Camundongos , Farmacologia em Rede , Proteínas Quinases Ativadas por AMP , Simulação de Acoplamento Molecular , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
14.
Cell Insight ; 2(6): 100126, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38047138

RESUMO

CRISPR-Cas12a has been used for genome editing and molecular diagnosis. The well-studied Cas12a orthologs have a T-rich PAM and are usually categorized as non-thermally stable enzymes. Here, we identified a new Cas12a ortholog from Clostridium thermobutyricum, which survives at 60 °C. This Cas12a ortholog is named as CtCas12a and exhibits low sequence similarity to the known Cas12a family members. CtCas12a is active in a wide temperature range from 17 to 77 °C. Moreover, this ortholog has a relaxed PAM of YYV (Y=C or T, V = A or C or G). We optimized the conditions for trans-cleavage and enabled its detection of nucleic acids. CtCas12a executed genome editing in human cells and generated up to 26% indel formation in the EGFP locus. With the ability to be active at high temperatures as well as having a relaxed PAM sequence, CtCas12a holds potential to be further engineered for pathogen detection and editing a wide range of genomic sequences.

15.
Stem Cell Res Ther ; 13(1): 216, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35619154

RESUMO

BACKGROUND: Intestinal ischemia-reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI, leading to its high rates of morbidity and mortality. Thus far, this is poorly treated, and there is an urgent need for new more efficacious treatments. This study evaluated the beneficial effects of mesenchymal stem cells (MSCs) therapy on intestinal IRI using many animal experiments. METHODS: We conducted a comprehensive literature search from 4 databases: Pubmed, Embase, Cochrane library, and Web of science. Primary outcomes included the survival rate, Chiu's score, intestinal levels of IL-6, TNF-α and MDA, as well as serum levels of DAO, D-Lactate, and TNF-α. Statistical analysis was carried out using Review Manager 5.3. RESULTS: It included Eighteen eligible researches in the final analysis. We demonstrated that survival rates in animals following intestinal IRI were higher with MSCs treatment compared to vehicle treatment. Besides, MSCs treatment attenuated intestinal injury caused by IRI, characterized by lower Chiu's score (- 1.96, 95% CI - 2.72 to - 1.19, P < 0.00001), less intestinal inflammation (IL-6 (- 2.73, 95% CI - 4.19 to - 1.27, P = 0.0002), TNF-α (- 3.00, 95% CI - 4.74 to - 1.26, P = 0.0007)) and oxidative stress (MDA (- 2.18, 95% CI - 3.17 to - 1.19, P < 0.0001)), and decreased serum levels of DAO (- 1.39, 95% CI - 2.07 to - 0.72, P < 0.0001), D-Lactate (- 1.54, 95% CI - 2.18 to - 0.90, P < 0.00001) and TNF-α (- 2.42, 95% CI - 3.45 to - 1.40, P < 0.00001). The possible mechanism for MSCs to treat intestinal IRI might be through reducing inflammation, alleviating oxidative stress, as well as inhibiting the apoptosis and pyroptosis of the intestinal epithelial cells. CONCLUSIONS: Taken together, these studies revealed that MSCs as a promising new treatment for intestinal IRI, and the mechanism of which may be associated with inflammation, oxidative stress, apoptosis, and pyroptosis. However, further studies will be required to confirm these findings.


Assuntos
Células-Tronco Mesenquimais , Traumatismo por Reperfusão , Animais , Inflamação , Interleucina-6 , Lactatos , Células-Tronco Mesenquimais/patologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/terapia , Fator de Necrose Tumoral alfa
16.
Gut Pathog ; 14(1): 27, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35733158

RESUMO

Neutrophil extracellular traps (NETs) are extracellular reticular fibrillar structures composed of DNA, histones, granulins and cytoplasmic proteins that are delivered externally by neutrophils in response to stimulation with various types of microorganisms, cytokines and host molecules, etc. NET formation has been extensively demonstrated to trap, immobilize, inactivate and kill invading microorganisms and acts as a form of innate response against pathogenic invasion. However, NETs are a double-edged sword. In the event of imbalance between NET formation and clearance, excessive NETs not only directly inflict tissue lesions, but also recruit pro-inflammatory cells or proteins that promote the release of inflammatory factors and magnify the inflammatory response further, driving the progression of many human diseases. The deleterious effects of excessive release of NETs on gut diseases are particularly crucial as NETs are more likely to be disrupted by neutrophils infiltrating the intestinal epithelium during intestinal disorders, leading to intestinal injury, and in addition, NETs and their relevant molecules are capable of directly triggering the death of intestinal epithelial cells. Within this context, a large number of NETs have been reported in several intestinal diseases, including intestinal infections, inflammatory bowel disease, intestinal ischemia-reperfusion injury, sepsis, necrotizing enterocolitis, and colorectal cancer. Therefore, the formation of NET would have to be strictly monitored to prevent their mediated tissue damage. In this review, we summarize the latest knowledge on the formation mechanisms of NETs and their pathophysiological roles in a variety of intestinal diseases, with the aim of providing an essential directional guidance and theoretical basis for clinical interventions in the exploration of mechanisms underlying NETs and targeted therapies.

17.
Clin Transl Oncol ; 24(12): 2272-2284, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36008615

RESUMO

Lung cancer is one of the most common malignant tumors with growing morbidity and mortality worldwide. Several treatments are used to manage lung cancer, including surgery, radiotherapy and chemotherapy, as well as molecular-targeted therapy. However, the current measures are still far from satisfactory. Therefore, the current research should focus on exploring the molecular mechanism and then finding an effective treatment. Interestingly, we and others have embarked on a line of investigations focused on the mechanism of lung cancer. Specifically, lncRNA small nucleolar RNA host gene has been shown to be associated with biological characteristics and therapeutic resistance of lung cancer. In addition, small nucleolar RNA host genes may be used as diagnostic biomarker in the future. Herein, we will provide a brief review demonstrating the importance of small nucleolar RNA host genes in lung cancer, especially non-small cell lung cancer. Although lncRNA has shown a crucial role in tumor-related research, a large number of studies are needed to validate its clinical application in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , RNA Longo não Codificante , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno
18.
Polymers (Basel) ; 13(18)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34578090

RESUMO

To analyze the feasibility of electrospinning nanofiber yarn using a wrapping yarn forming device, electrospun nanofiber-wrapped yarns and multiscale yarns were prepared by self-made equipment. The relationship between the surface morphology and properties of yarn and its preparation process was studied. The process parameters were adjusted, and it was found that some nanofibers formed Z-twisted yarns, while others showed exposed cores. To analyze the forming mechanism of electrospun nanofiber-wrapped yarn, the concept of winding displacement difference in the twisted yarn core A was introduced. The formation of nanofiber-wrapped structural yarns was discussed using three values of A. The starting point of each twist was the same position when A = 0 with a constant corner angle ß. However, the oriented nanofiber broke or was pulled out from the gripping point when it was twisted, and it appeared disordered. The forming process of electrospun nanofiber-wrapped yarn displayed some unique phenomena, including the emission of directional nanofibers during collection, fiber non-continuity, and twist angle non-uniformity. The conclusions of this research have theoretical and practical value to guide the industrial preparation of nanofiber yarns and their wrapped yarns.

19.
Am J Chin Med ; 49(2): 413-435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622215

RESUMO

The intestinal tract plays an essential role in protecting tissues from the invasion of external harmful substances due to impaired barrier function. Furthermore, it participates in immunomodulation by intestinal microorganisms, which is important in health. When the intestinal tract is destroyed, it can lose its protective function, resulting in multiple systemic complications. In severe cases, it may lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Thus far, there are no curative therapies for intestinal mucosal barrier injury, other than a few drugs that can relieve symptoms. Thus, the development of novel curative agents for gastrointestinal diseases remains a challenge. Ursolic acid (UA) and its isomer, Oleanolic acid (OA), are pentacyclic triterpene acid compounds. Both their aglycone and glycoside forms have anti-oxidative, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, antidiabetic, cardio protective, hepatoprotective, and anti-neurodegenerative properties in living organisms. In recent years, several studies have shown that UA and OA can reduce the risk of intestinal pathological injury, alleviate intestinal dysfunction, and restore intestinal barrier function. The present study evaluated the beneficial effects of UA and OA on intestinal damage and diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC).


Assuntos
Gastroenteropatias/tratamento farmacológico , Ácido Oleanólico/farmacologia , Substâncias Protetoras/farmacologia , Triterpenos/farmacologia , Humanos , Estrutura Molecular , Ácido Oleanólico/química , Substâncias Protetoras/química , Triterpenos/química , Ácido Ursólico
20.
PeerJ ; 8: e10584, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33384904

RESUMO

BACKGROUND: The mushroom industry produces a large amount of spent mushroom substrate (SMS), which requires a large geographical footprint and causes pollution. METHODS: We sought to optimize the C:N ratio of the initial feedstock used in vermicomposting of SMS by adding pig manure additions. We applied five treatments to the initial feedstock (S0, S1, S2, S3, and S4) with different C:N ratio of approximately 35, 30, 25, 20, and 15, respectively. RESULTS: Our results showed that lignin and cellulose in SMS were degraded after 56 days vermicomposting, especially in S2 (77.05% and 45.29%, respectively) and S3 (65.05% and 48.37%, respectively) treatments. We observed the degradation of the fibrous structure in SMS using pig manure treatments after vermicomposting by microscope and scanning electron microscope. Cellulase and polyphenol oxidase (PPO) were enhanced in pig manure treatments during vermicomposting, especially in the S2 and S3 treatments. The biomass of earthworms in the S2 treatments was at its highest level among all treatments at 28 to 56 days. The high level of PPO activity in the S2 treatment may protect cellulase and earthworms against the aromatic toxicity that is a byproduct of lignin degradation, particularly at 28 to 56 days of vermicomposting. Conclusively, it indicated that the C/N ratio of 25 in the S2 treatment was the optimal for SMS vermicomposting with the addition of pig manure. Our results provide a positive application for the recycling of both SMS and pig manure.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA