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BACKGROUND: Gastric cancer is one of the most common malignant tumours of the gastrointestinal tract, which has a significant negative impact on human health. AIMS: CCL chemokines play important roles in a variety of tumor microenvironments; nevertheless, gastric cancer has surprisingly limited associations with CCL chemokines. METHODS: In our study, we comprehensively utilized bioinformatics analysis tools and databases such as cBioPortal, UALCAN, GEPIA, GeneMANIA, STRING, and TRRUST to clarify the clinical significance and biology function of CCL chemokines in gastric cancer. RESULTS: The mRNA expression levels of CCL1/3/4/5/7/8/14/15/18/20/21/22/26 were up-regulated, while the mRNA expression levels of CCL2/11/13/16/17/19/23/24/25/28 were down-regulated. The chemokine significantly associated with the pathological stage of gastric cancer is CCL2/11/19/21. In gastric cancer, the expression level of CCL chemokines was not associated with disease-free survival, but low expression of CCL14 was significantly associated with longer overall survival. Therein, associated with the regulation of CCL chemokines are only 10 transcription factors (RELA, NFKB1, STAT6, IRF3, REL, SPI1, STAT1, STAT3, JUN and SP1). The major biological process and functional enrichment of CCL chemokines are to induce cell-directed migration. CONCLUSION: These results may indicate that CCL chemokines may be immunotherapeutic targets and promising prognostic biomarkers for gastric cancer.
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Dihydromyricetin (DHM), which has various biological functions, possesses therapeutic potential for ulcerative colitis (UC). Neutrophil extracellular traps (NETs) and their components play a crucial role in several pathological processes in UC. However, whether DHM alleviates UC by regulating NETs remains unclear. Mice with dextran sulfate sodium (DSS)-induced acute colitis were treated with DHM at different concentrations, and the severity of colitis was evaluated by assessing body weight, colon length, histological scores, cytokine production, and epithelial barrier integrity. To quantify and visualize NETs, the expression of cell free-DNA (cf-DNA) in serum and Cit-H3 in colonic tissue was analyzed via western blotting and immunofluorescence analysis. HL-60 cells and mouse bone marrow-derived neutrophils (BMDNs) were used to evaluate the effects of DHM on NETs in vitro. NETs were treated with DHM at varying concentrations or DNase I and used to repair the intestinal epithelial barrier in a Caco-2/HIEC-6 cell monolayer model. Furthermore, the genes targeted by DHM through neutrophils for alleviating UC were identified by screening online databases, and the results of network pharmacological analysis were verified via western blotting and quantitative real-time polymerase chain reaction. DHM alleviated DSS-induced colitis in mice by reversing weight loss, increased DAI score, colon length shortening, enhanced spleen index, colonic pathological damage, cytokine production, and epithelial barrier loss in a dose-dependent manner. In addition, it inhibited the formation of NETs both in vivo and in vitro. Based on the results of network pharmacological analysis, DHM may target HIF-1α and VEGFA through neutrophils to alleviate UC. Treatment with PMA increased the expression of HIF-1α and VEGFA in D-HL-60 cells and BMDNs, whereas treatment with DHM or DNase I reversed this effect. Treatment with DMOG, an inhibitor of HIF prolyl hydroxylase (HIF-PH), counteracted the suppressive effects of DHM on NETs formation in D-HL-60 cells and BMDNs. Accordingly, it partially counteracted the protective effects of DHM on the intestinal epithelial barrier in Caco-2 and HIEC-6 cells. These results indicated that DHM alleviated DSS-induced UC by regulating NETs formation via the HIF-1α/VEGFA signaling pathway, suggesting that DHM is a promising therapeutic candidate for UC.
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Colite Ulcerativa , Armadilhas Extracelulares , Flavonóis , Subunidade alfa do Fator 1 Induzível por Hipóxia , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Células CACO-2 , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Flavonóis/farmacologia , Células HL-60 , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Fibrosis, a complex pathological process characterized by excessive deposition of extracellular matrix components, leads to tissue scarring and dysfunction. Emerging evidence suggests that neutrophil extracellular traps (NETs), composed of DNA, histones, and antimicrobial proteins, significantly contribute to fibrotic diseases pathogenesis. This review summarizes the process of NETs production, molecular mechanisms, and related diseases, and outlines the cellular and molecular mechanisms associated with fibrosis. Subsequently, this review comprehensively summarizes the current understanding of the intricate interplay between NETs and fibrosis across various organs, including the lung, liver, kidney, skin, and heart. The mechanisms by which NETs contribute to fibrogenesis, including their ability to promote inflammation, induce epithelial-mesenchymal transition (EMT), activate fibroblasts, deposit extracellular matrix (ECM) components, and trigger TLR4 signaling were explored. This review aimed to provide insights into the complex relationship between NETs and fibrosis via a comprehensive analysis of existing reports, offering novel perspectives for future research and therapeutic interventions.
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Armadilhas Extracelulares , Fibrose , Imunidade Inata , Humanos , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Animais , Transição Epitelial-Mesenquimal/imunologia , Matriz Extracelular/metabolismo , Matriz Extracelular/imunologia , Neutrófilos/imunologia , Transdução de SinaisRESUMO
Background: Colon cancer (CC) stem cells can self-renew as well as expand, thereby promoting tumor progression and conferring resistance to chemotherapeutic agents. The acetyltransferase NAT10 mediates N4-acetylcytidine (ac4C) modification, which in turn drives tumorigenesis, metastasis, stemness properties maintenance, and cell fate decisions. Nonetheless, the specific involvement of ac4C modification mediated by NAT10 in regulating stemness and chemosensitivity in CC remains undetermined. Methods: The levels of NAT10 in normal colon and chemoresistant CC tissues were determined utilizing quantitative real-time polymerase chain reaction alongside immunohistochemistry. Assessing cancer cell stemness and chemosensitivity was conducted by various methods including spheroid and colony formation, western blotting, and flow cytometry. RNA-Seq was used to identify target genes, and RNA immunoprecipitation analysis was used to explore the potential mechanisms. Results: We observed NAT10 overexpression and increased ac4C modification levels in chemoresistant CC tissues. The in vivo and in vitro analysis findings suggested that NAT10 promoted CC cell stemness while suppressing their chemosensitivity. Conversely, Remodelin, a NAT10-specific inhibitor, enhanced CC cell chemosensitivity. Mechanistically, NAT10 increased the level of NANOGP8 ac4C modification and promoted NANOGP8 mRNA stability. Conclusions: NAT10 promotes the maintenance of stemness and chemoresistance in CC cells by augmenting the mRNA stability of NANOGP8. The inhibition of NAT10 via Remodelin improves chemotherapeutic efficacy and impedes CC progression.
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Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.
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Infecções por Helicobacter , Helicobacter pylori , MicroRNAs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Helicobacter pylori/genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/complicações , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
Helicobacter pylori (H. pylori) is a pathogenic microorganism that colonizes the human gastric mucosa and can lead to various gastric disorders, including gastritis, gastric ulcers, and gastric cancer. However, the increasing prevalence of antibiotic resistance in H. pylori has prompted the search for alternative treatment options. Photodynamic therapy has emerged as a potential alternative therapy, thus offering the advantage of avoiding some of the side effects associated with antibiotics and effectively targeting drug-resistant strains. In the postantibiotic era, photodynamic therapy (PDT) has shown promise as a novel treatment for H. pylori infection. This review focused on elucidating the mechanism of photodynamic therapy in the treatment of H. pylori. Additionally, we present an overview of the current research on photodynamic therapy by examining both standalone photodynamic therapy and combination therapies for H. pylori infection treatment. Furthermore, the safety profile of photodynamic therapy was also evaluated. Finally, we discuss the challenges and prospects associated with this innovative technology, with an aim to provide new insights and methodologies for the treatment of H. pylori infection.
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Gastrite , Infecções por Helicobacter , Helicobacter pylori , Fotoquimioterapia , Humanos , Infecções por Helicobacter/tratamento farmacológico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Gastrite/tratamento farmacológicoRESUMO
BACKGROUND: Gastric cancer is one of the major public health problems worldwide. Circadian rhythm disturbances driven by circadian clock genes play a role in the development of cancer. However, whether circadian clock genes can serve as potential therapeutic targets and prognostic biomarkers for gastric cancer remains elusive. METHODS: In this study, we comprehensively analyzed the potential relationship between circadian clock genes and gastric cancer using online bioinformatics databases such as GEPIA, cBioPortal, STRING, GeneMANIA, Metascape, TIMER, TRRUST, and GEDS. RESULTS: Biological clock genes are expressed differently in human tumors. Compared with normal tissues, only PER1, CLOCK, and TIMELESS expression differences were statistically significant in gastric cancer (p < 0.05). PER1 (p = 0.0169) and CLOCK (p = 0.0414) were associated with gastric cancer pathological stage (p < 0.05). Gastric cancer patients with high expression of PER1 (p = 0.0028) and NR1D1 (p = 0.016) had longer overall survival, while those with high expression of PER1 (p = 0.042) and NR1D1 (p = 0.016) had longer disease-free survival. The main function of the biological clock gene is related to the circadian rhythms and melatonin metabolism and effects. CLOCK, NPAS2, and KAT2B were key transcription factors for circadian clock genes. In addition, we also found important correlations between circadian clock genes and various immune cells in the gastric cancer microenvironment. CONCLUSIONS: This study may establish a new gastric cancer prognostic indicator based on the biological clock gene and develop new drugs for the treatment of gastric cancer using biological clock gene targets.
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Biomarcadores Tumorais , Proteínas CLOCK , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Proteínas CLOCK/genética , Relógios Circadianos/genética , Proteínas Circadianas Period/genética , Regulação Neoplásica da Expressão Gênica , Biologia Computacional , Ritmo Circadiano/genética , Proteínas de Ciclo Celular , Peptídeos e Proteínas de Sinalização Intracelular , Membro 1 do Grupo D da Subfamília 1 de Receptores NuclearesRESUMO
We conducted this study to systematically review and assess the current clinical practice guidelines (CPGs) related to the diagnosis and treatment of Helicobacter pylori (H. pylori) infection. The aim was to evaluate the quality of these included CPGs and provide clinicians with a convenient and comprehensive reference for updating their own CPGs. We searched four databases to identify eligible CPGs focusing on H. pylori diagnosis and treatment recommendations. The results were presented using evidence mappings. Quality and clinical applicability were assessed comprehensively using AGREE-II and AGREE-REX. Statistical tests, specifically Bonferroni tests, were employed to compare the quality between evidence-based guidelines and consensus. A total of 30 eligible CPGs were included, comprising 17 consensuses and 13 guidelines. The quality showed no statistical significance between consensuses and guidelines, mainly within the moderate to low range. Notably, recommendations across CPGs exhibited inconsistency. Nevertheless, concerning diagnosis, the urea breath test emerged as the most frequently recommended method for testing H. pylori. Regarding treatment, bismuth quadruple therapy stood out as the predominantly recommended eradication strategy, with high-dose dual therapy being a newly recommended option. Our findings suggest the need for specific organizations to update their CPGs on H. pylori or refer to recently published CPGs. Specifically, CPGs for pediatric cases require improvement and updating, while a notable absence of CPGs for the elderly was observed. Furthermore, there is a pressing need to improve the overall quality of CPGs related to H. pylori. Regarding recommendations, additional evidence is essential to elucidate the relationship between H. pylori infection and other diseases and refine test indications. Clinicians are encouraged to consider bismuth quadruple or high-dose dual therapy, incorporating locally sensitive antibiotics, as empirical radical therapy. .
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Infecções por Helicobacter , Helicobacter pylori , Guias de Prática Clínica como Assunto , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Humanos , Testes Respiratórios , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Quimioterapia CombinadaAssuntos
Histonas , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Histonas/genética , Pré-Eclâmpsia/genética , Placenta , Hipóxia/genéticaRESUMO
As more is learned about lactate, it acts as both a product and a substrate and functions as a shuttle system between different cell populations to provide the energy for sustaining tumor growth and proliferation. Recent discoveries of protein lactylation modification mediated by lactate play an increasingly significant role in human health (e.g., neural and osteogenic differentiation and maturation) and diseases (e.g., tumors, fibrosis and inflammation, etc.). These views are critically significant and first described in detail in this review. Hence, here, we focused on a new target, protein lactylation, which may be a "double-edged sword" of human health and diseases. The main purpose of this review was to describe how protein lactylation acts in multiple physiological and pathological processes and their potential mechanisms through an in-depth summary of preclinical in vitro and in vivo studies. Our work aims to provide new ideas for treating different diseases and accelerate translation from bench to bedside.
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Ácido Láctico , Osteogênese , Humanos , Diferenciação Celular , Inflamação , Processamento de Proteína Pós-TraducionalRESUMO
Intestinal fibrosis is a common complication of inflammatory bowel disease and is characterized by tissue stiffening and luminal narrowing. Dihydromyricetin (DHM) can alleviate liver fibrosis and renal interstitial fibrosis by inducing autophagy. However, whether DHM can alleviate intestinal fibrosis remains unclear. This study is aimed at evaluating the role and mechanism of action of DHM in inflammatory bowel disease-associated intestinal fibrosis. Mice were administered dextran sulfate sodium (DSS) in drinking water to induce inflammatory bowel disease-associated intestinal fibrosis. HE staining, qPCR, and Western blotting were used to analyze colon inflammation. Masson's trichrome staining, qPCR, Western blotting, and immunofluorescence staining were used to evaluate the severity of fibrosis. Transmission electron microscopy and Western blotting were used to assess the activation of autophagosomes. The human colonic fibroblast line CCD-18Co was cultured in the presence of TGF-ß1 to develop a fibrotic phenotype. Immunofluorescence staining, Western blotting, and qPCR were used to assess the alteration of fibrosis markers and used to investigate whether DHM-induced autophagy was involved in the inactivation of CCD-18Co cells. Additionally, the role of the PI3K/AKT/mTOR pathway was investigated. DHM alleviated intestinal inflammation and inhibited the progression of intestinal fibrosis. Additionally, DHM induced the activation of autophagy, thereby alleviating intestinal fibrosis, and downregulated the PI3K/AKT/mTOR signaling pathway in vitro. Overall, this study demonstrated that DHM can inhibit the progression of intestinal fibrosis and activation of colonic fibroblasts by inducing autophagy through the PI3K/AKT/mTOR signaling pathway, thereby playing a preventive and therapeutic role in intestinal fibrosis.
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Lipid nanoparticles (LNPs) are one of the most efficient carriers for RNA packaging and delivery, and vaccines based on mRNA-LNPs have received substantial attention since the outbreak of the COVID-19 pandemic. LNPs based on 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) have been widely used in preclinical and clinical settings. A novel non-viral gene delivery system called LNP3 was previously developed, which was composed of DOTAP, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and cholesterol. One of the helper lipids in this carrier was DOPE, which belongs to phospholipids. Given that substituting DOPE with non-phospholipids as helper lipids can increase the delivery efficiency of some LNPs, this study aimed to examine whether non-phospholipids can be formulated with DOTAP as helper lipids. It was found that monoglycerides with C14:0, C16:0, C18:0, C18:1, and C18:2 mediated mRNA transfection, and the transfection efficiency varied between C18:0, C18:1, and C18:2. Furthermore, substituting of the glycerol with other moieties such as the cholesterol or the ethanolamine similarly mediated mRNA transfection. The introduction of cholesterol can further improve the transfection capacity of some DOTAP-based LNPs. One of the best-performing formulations, LNP3-MO, was used to mediate luciferase-mRNA expression in vivo, and the luminescence signal was found to be mainly enriched in the lung and spleen. In addition, the level of SARS-CoV-2 spike antibody in the serum increased after three doses of LNP3-MO mediated SARS-CoV-2 spike mRNA. Altogether, this study demonstrates that non-phospholipids are promising helper lipids that can be formulated with DOTAP to facilitate efficient delivery of mRNAs in vitro and in vivo with organ-specific targeting.
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Nanopartículas , Propano , Humanos , RNA Mensageiro/genética , Pandemias , Lipossomos , Fosfolipídeos , ColesterolRESUMO
Nonalcoholic fatty liver disease (NAFLD) is one of the leading chronic liver diseases with increased morbidity and mortality rates for extrahepatic diseases (including cardiovascular disease, portal vein thrombosis, etc.). There is an increased risk of thrombosis in both the portal and systemic circulation in patients with NAFLD, independent of traditional liver cirrhosis. However, increased portal pressure, the most critical factor, is frequently observed in NAFLD patients, predisposing them to portal vein thrombosis (PVT). It has been reported that there is an 8.5% incidence of PVT among patients with non-cirrhotic NAFLD in a prospective cohort study. Based on the prothrombotic status of NAFLD itself, patients combined with cirrhosis may accelerate the development of PVT and lead to a poor prognosis. Moreover, PVT has been shown to complicate the procedure and adversely affect the outcome during liver transplantation surgery. NAFLD is in a prothrombotic state, and its underlying mechanisms have not been fully understood so far. Particularly noteworthy is that gastroenterologists currently overlook the higher risk of PVT in NAFLD. We investigate the pathogenesis of NAFLD complicated with PVT from the perspective of primary, secondary, and tertiary hemostasis, and also summarize relevant studies in humans. Some treatment options that may affect NAFLD and its PVT are also explored to improve patient-oriented outcomes.
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Hepatopatia Gordurosa não Alcoólica , Trombose , Trombose Venosa , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fatores de Risco , Veia Porta/patologia , Estudos Prospectivos , Trombose Venosa/complicações , Cirrose Hepática/complicaçõesRESUMO
BACKGROUND: Glycosylation involved in various biological function, aberrant glycosylation plays an important role in cancer development and progression. Glycosyltransferase 8 domain containing 1 (GLT8D1) and GLT8D2, as members of the glycosyltransferase family proteins, are associated with transferase activity. However, the association between GLT8D1/2 and gastric cancer (GC) remains unclear. We aimed to investigate the potential prognostic value and oncogenic role of GLT8D1/2 in GC. METHODS: The relationship between GLT8D1/2 and GC was evaluated through comprehensive bioinformatics approaches. A series of factors like gene expression patterns, Kaplan-Meier survival analyses, Cox regression analyses, prognostic nomogram, calibration curves, ROC curves, function enrichment analyses, tumor immunity association, genetic alterations, and DNA methylation were included. Data and statistical analyses were performed using R software (v3.6.3). RESULTS: Both GLT8D1 and GLT8D2 expression were significantly upregulated in GC tissues(n = 414) compared with normal tissues(n = 210), and high expression of GLT8D1/2 was remarkably correlated with poor prognosis for GC patients. Cox regression analyses implied that GLT8D1/2 could act as independent prognostic factors in GC. Furthermore, gene function analyses indicated that multiple signaling pathways involving tumor oncogenesis and development enriched, such as mTOR, cell cycle, MAPK, Notch, Hedgehog, FGF, and PI3K-Akt signaling pathways. Moreover, GLT8D1/2 was significantly associated with immune cell infiltration, immune checkpoint genes, and immune regulators TMB/MSI. CONCLUSION: GLT8D1/2 may serve as potential prognostic markers of poor prognosis in GC correlated with tumor immunity. The study provided an insight into identifying potential biomarkers and targets for prognosis, immunotherapy response, and therapy in GC.
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Neoplasias Gástricas , Humanos , Biomarcadores Tumorais/genética , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Potassium-competitive acid blockers (P-CAB) are recommended for the treatment of Helicobacter pylori infections, but dual therapy of P-CAB with amoxicillin has been poorly studied. The current study compared the efficacy, adverse reactions, compliance, and effects on gut microbiota of 14-day vonoprazan-amoxicillin (VA) dual therapy with esomeprazole, bismuth potassium citrate, amoxicillin, and metronidazole (EBAM) quadruple therapy in treatment-naive patients with H. pylori. MATERIALS AND METHODS: This was a multicenter, open-label, randomized, and controlled, non-inferiority study. Patients (n = 194) enrolled from six centers were randomly divided into either the VA or EBAM group. H. pylori eradication was determined using 13 C urea breath tests (UBT) 4-6 weeks post-treatment. Fecal samples were collected, and gut microbial populations were analyzed by 16S rDNA and metagenomic sequencing technology. RESULTS: Eradication rates of H. pylori in the VA and EBAM groups were 88.7% and 91.8%, respectively, according to intention-to-treat (ITT) analysis; 95.6% and 96.7% with per-protocol (PP) analysis; and 94.5% and 96.7% with modified ITT (mITT) analysis (all p > 0.05). The incidence of adverse reactions in the VA group was significantly lower compared to the EBAM group, and compliance within both groups was good. There was no difference in α-diversity or microbial composition in the VA and EBAM groups at one-month post-treatment compared to baseline, except for a markedly reduced abundance of Bacteroides in the EBAM group. CONCLUSION: VA therapy achieved excellent eradication rates with low adverse reactions, good compliance, and little impact on gut microbiota. VA therapy should be recommended as a first-line treatment against H. pylori.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Antibacterianos , Quimioterapia Combinada , Bismuto/uso terapêutico , Resultado do Tratamento , Inibidores da Bomba de Prótons/uso terapêutico , Claritromicina/uso terapêuticoRESUMO
BACKGROUND: The prognostic significance of nutrition indicators in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. OBJECTIVES: This systematic review and meta-analysis aimed to assess the prognostic value of serum albumin (SA), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI) in patients with HFpEF. METHODS: Databases of PubMed, Embase, The Cochrane Library, and Web of Science were systematically searched for all studies published up to January 2022. The prognostic significance of SA, GNRI, and PNI for HFpEF was explored. Pooled hazard ratio (HR) and 95% confidence interval (CI) were estimated using the STATA 15.0 software. The Quality of Prognosis Studies tool was used to assess the quality of studies. RESULTS: Nine studies met the inclusion criteria, and 5603 adults with HFpEF were included in the meta-analysis. The analyses showed that a decreased SA or GNRI was significantly related to high all-cause mortality (HR: 1.98; 95% CI: 1.282-3.057; p = 0.002; and HR: 1.812;95% CI: 1.064-3.086; p = 0.029, respectively). Furthermore, a lower SA indicates a bad composite outcome of all-cause mortality and HF rehospitalization (HR: 1.768; 95% CI: 1.483-2.108; p = 0.000), and a lower GNRI was significantly associated with high cardiovascular mortality (HR: 1.922; 95% CI: 1.504-2.457;p = 0.000). However, a lower PNI did not correlate with all-cause mortality (HR: 1.176; 95% CI: 0.858-1.612, p=0.314). CONCLUSIONS: Our meta-analysis indicates that SA and GNRI may be useful indicators to predict the prognosis of patients with HFpEF.
FUNDAMENTO: O significado prognóstico dos indicadores nutricionais em pacientes com insuficiência cardíaca com fração de ejeção preservada (ICFEP) não é claro. OBJETIVO: Esta revisão sistemática e metanálise teve como objetivo avaliar o valor prognóstico da albumina sérica (AS), o índice de risco nutricional geriátrico (IRNG) e o índice nutricional prognóstico (INP) em pacientes com ICFEP. MÉTODO: Os bancos de dados PubMed, Embase, The Cochrane Library e Web of Science foram sistematicamente pesquisados para todos os estudos publicados até janeiro de 2022. O significado prognóstico de IRNG, GNRI e INP para ICFEP foi explorado. A taxa de risco agrupada (HR) e o intervalo de confiança (IC) de 95% foram estimados usando o software STATA 15.0. A Ferramenta de Estudos de Qualidade de Prognóstico foi usada para avaliar a qualidade dos estudos. RESULTADOS: Nove estudos preencheram os critérios de inclusão e 5.603 adultos com ICFEP foram incluídos na metanálise. As análises mostraram que uma diminuição de AS ou IRNG estava significativamente relacionada à alta mortalidade por todas as causas (HR: 1,98; 95% IC: 1,2823,057; p = 0,002; e HR: 1,812;95% IC: 1,0643,086; p = 0,029, respectivamente). Além disso, uma AS mais baixa indica um resultado composto ruim de mortalidade por todas as causas e reinternação por IC (HR: 1,768; IC 95%: 1,4832,108; p = 0,000), e um IRNG mais baixo foi significativamente associado a alta mortalidade cardiovascular (HR: 1,922; 95% IC: 1,5042,457; p = 0,000). No entanto, um INP mais baixo não se correlacionou com mortalidade por todas as causas (HR: 1,176; IC 95%: 0,8581,612, p=0,314). CONCLUSÕES: Nossa metanálise indica que AS e IRNG podem ser indicadores úteis para prever o prognóstico de pacientes com ICFEP.
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Insuficiência Cardíaca , Adulto , Humanos , Idoso , Prognóstico , Volume Sistólico , Estado Nutricional , Readmissão do PacienteRESUMO
The genus Babesia includes parasites that can induce human and animal babesiosis, which are common in tropical and subtropical regions of the world. The gut microbiota has not been examined in hamsters infected by Babesia duncani. Red blood cells infected with B. duncani were injected into hamsters through intraperitoneal route. To evaluate the changes in gut microbiota, DNAs were extracted from small intestinal contents, acquired from hamsters during disease development. Then, the V4 region of the 16S rRNA gene of bacteria was sequenced using the Illumina sequencing platform. Gut microbiota alternation and composition were assessed according to the sequencing data, which were clustered with >97.0% sequence similarity to create amplicon sequence variants (ASVs). Bacteroidetes and Firmicutes were made up of the major components of the gut microbiota in all samples. The abundance of Bacteroidetes elevated after B. duncani infection than the B. duncani-free group, while Firmicutes and Desulfobacterota declined. Alpha diversity analysis demonstrated that the shown ASVs were substantially decreased in the highest parasitemia group than B. duncani-free and lower parasitemia groups. Potential biomarkers were discovered by Linear discriminant analysis Effect Size (LEfSe) analysis, which demonstrated that several bacterial families (including Muribaculaceae, Desulfovibrionaceae, Oscillospiraceae, Helicobacteraceae, Clostridia UGG014, Desulfovibrionaceae, and Lachnospiraceae) were potential biomarkers in B. duncani-infected hamsters. This research demonstrated that B. duncani infectious can modify the gut microbiota of hamsters.
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Babesia , Microbioma Gastrointestinal , Animais , Cricetinae , Humanos , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Parasitemia , Bactérias/genética , Firmicutes/genética , Bacteroidetes/genética , BiomarcadoresRESUMO
Discoidin domain receptors (DDRs) are receptor tyrosine kinases on the membrane surface that bind to extracellular collagens, but they are rarely expressed in normal liver tissues. Recent studies have demonstrated that DDRs participate in and influence the processes underlying premalignant and malignant liver diseases. A brief overview of the potential roles of DDR1 and DDR2 in premalignant and malignant liver diseases is presented. DDR1 has proinflammatory and profibrotic benefits and promotes the invasion, migration and liver metastasis of tumour cells. However, DDR2 may play a pathogenic role in early-stage liver injury (prefibrotic stage) and a different role in chronic liver fibrosis and in metastatic liver cancer. These views are critically significant and first described in detail in this review. The main purpose of this review was to describe how DDRs act in premalignant and malignant liver diseases and their potential mechanisms through an in-depth summary of preclinical in vitro and in vivo studies. Our work aims to provide new ideas for cancer treatment and accelerate translation from bench to bedside.