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1.
Cell Rep ; 37(6): 109983, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34758309

RESUMO

Swallowing is an essential step of eating and drinking. However, how the quality of a food bolus is sensed by pharyngeal neurons is largely unknown. Here we find that mechanical receptors along the Drosophila pharynx are required for control of meal size, especially for food of high viscosity. The mechanical force exerted by the bolus passing across the pharynx is detected by neurons expressing the mechanotransduction channel NOMPC (no mechanoreceptor potential C) and is relayed, together with gustatory information, to IN1 neurons in the subesophageal zone (SEZ) of the brain. IN1 (ingestion neurons) neurons act directly upstream of a group of peptidergic neurons that encode satiety. Prolonged activation of IN1 neurons suppresses feeding. IN1 neurons receive inhibition from DSOG1 (descending subesophageal neurons) neurons, a group of GABAergic neurons that non-selectively suppress feeding. Our results reveal the function of pharyngeal mechanoreceptors and their downstream neural circuits in the control of food ingestion.

2.
BMC Med ; 19(1): 247, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34649530

RESUMO

BACKGROUND: We and others have confirmed activation of macrophages plays a critical role in liver injury and fibrogenesis during HBV infection. And we have also proved HBeAg can obviously induce the production of macrophage inflammatory cytokines compared with HBsAg and HBcAg. However, the receptor and functional domain of HBeAg in macrophage activation and its effects and mechanisms on hepatic fibrosis remain elusive. METHODS: The potentially direct binding receptors of HBeAg were screened and verified by Co-IP assay. Meanwhile, the function domain and accessible peptides of HBeAg for macrophage activation were analyzed by prediction of surface accessible peptide, construction, and synthesis of truncated fragments. Furthermore, effects and mechanisms of the activation of hepatic stellate cells induced by HBeAg-treated macrophages were investigated by Transwell, CCK-8, Gel contraction assay, Phospho Explorer antibody microarray, and Luminex assay. Finally, the effect of HBeAg in hepatic inflammation and fibrosis was evaluated in both human and murine tissues by immunohistochemistry, immunofluorescence, ELISA, and detection of liver enzymes. RESULTS: Herein, we verified TLR-2 was the direct binding receptor of HBeAg. Meanwhile, C-terminal peptide (122-143 aa.) of core domain in HBeAg was critical for macrophage activation. But arginine-rich domain of HBcAg hided this function, although HBcAg and HBeAg shared the same core domain. Furthermore, HBeAg promoted the proliferation, motility, and contraction of hepatic stellate cells (HSCs) in a macrophage-dependent manner, but not alone. PI3K-AKT-mTOR and p38 MAPK signaling pathway were responsible for motility phenotype of HSCs, while the Smad-dependent TGF-ß signaling pathway for proliferation and contraction of them. Additionally, multiple chemokines and cytokines, such as CCL2, CCL5, CXCL10, and TNF-α, might be key mediators of HSC activation. Consistently, HBeAg induced transient inflammation response and promoted early fibrogenesis via TLR-2 in mice. Finally, clinical investigations suggested that the level of HBeAg is associated with inflammation and fibrosis degrees in patients infected with HBV. CONCLUSIONS: HBeAg activated macrophages via the TLR-2/NF-κB signal pathway and further exacerbated hepatic fibrosis by facilitating motility, proliferation, and contraction of HSCs with the help of macrophages.


Assuntos
Antígenos E da Hepatite B , Receptor 2 Toll-Like , Animais , Humanos , Cirrose Hepática , Macrófagos , Camundongos , Fosfatidilinositol 3-Quinases
3.
Eur J Med Chem ; 226: 113823, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536671

RESUMO

Schistosomiasis is a neglected disease of poverty that is caused by infection with blood fluke species contained within the genus Schistosoma. For the last 40 years, control of schistosomiasis in endemic regions has predominantly been facilitated by administration of a single drug, praziquantel. Due to limitations in this mono-chemotherapeutic approach for sustaining schistosomiasis control into the future, alternative anti-schistosomal compounds are increasingly being sought by the drug discovery community. Herein, we describe a multi-pronged, integrated strategy that led to the identification and further exploration of the quinoxaline core as a promising anti-schistosomal scaffold. Firstly, phenotypic screening of commercially available small molecules resulted in the identification of a moderately active hit compound against Schistosoma mansoni (1, EC50 = 4.59 µM on schistosomula). Secondary exploration of the chemical space around compound 1 led to the identification of a quinoxaline-core containing, non-genotoxic lead (compound 22). Compound 22 demonstrated substantially improved activities on both intra-mammalian (EC50 = 0.44 µM, 0.20 µM and 84.7 nM, on schistosomula, juvenile and adult worms, respectively) and intra-molluscan (sporocyst) S. mansoni lifecycle stages. Further medicinal chemistry optimisation of compound 22, resulting in the generation of 20 additional analogues, improved our understanding of the structure-activity relationship and resulted in considerable improvements in both anti-schistosome potency and selectivity (e.g. compound 30; EC50 = 2.59 nM on adult worms; selectivity index compared to the HepG2 cell line = 348). Some derivatives of compound 22 (e.g. 31 and 33) also demonstrated significant activity against the two other medically important species, Schistosoma haematobium and Schistosoma japonicum. Further optimisation of this class of anti-schistosomal is ongoing and could lead to the development of an urgently needed alternative to praziquantel for assisting in schistosomiasis elimination strategies.

4.
Cancer Cell Int ; 21(1): 494, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530821

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC), with a rapidly increasing incidence, is the most prevalent malignant cancer of the thyroid. However, its pathogenesis is unclear and its specific clinical indicators have not yet been identified. There is increasing evidence that microRNAs (miRNAs) play important roles in tumor occurrence and progression. Specifically, miR-613 participates in the regulation of tumor development in various cancers; however, its effects and mechanisms of action in PTC are still unclear. Therefore, in this study, we investigated the expression and function of miR-613 in PTC. METHODS: qRT-PCR was used to determine miR-613 expression in 107 pairs of PTC and adjacent-normal tissues as well as in PTC cell lines and to detect TAGLN2 mRNA expression in PTC tissues and adjacent normal tissues. Western blot analysis was performed to identify TAGLN2 and epithelial-mesenchymal transition (EMT) biomarkers. The effects of miR-613 on PTC progression were evaluated by performing MTS, wound-healing, and Transwell assays in vitro. Luciferase reporter assays were also performed to validate the target of miR-613. RESULTS: In PTC, miR-613 was significantly downregulated and its low expression level was associated with cervical lymph node metastasis. However, its overexpression significantly suppressed PTC cell proliferation, migration, and invasion and inhibited EMT. TAGLN2 was identified as a target of miR-613, which also significantly inhibited the expression of TAGLN2. Further, the restoration of TAGLN2 expression attenuated the inhibitory effects of miR-613 on PTC cell proliferation and metastasis. CONCLUSION: Our findings demonstrated that miR-613 can suppress the progression of PTC cells by targeting TAGLN2, indicating that miR-613 plays the role of a tumor suppressor in PTC. Overall, these results suggest that the upregulation of miR-613 is a promising therapeutic strategy for PTC.

5.
Infect Drug Resist ; 14: 3099-3108, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408453

RESUMO

Purpose: Carbapenem resistance due to the overuse of carbapenems has become a public health problem worldwide, particularly in low- and middle-income countries (LMICs). However, there are few policies guiding carbapenem prescription, and their effectiveness is still unclear. A regulation targeting carbapenem prescription was implemented in March 2017 in China. This study aimed to assess the effects of the regulation for providing evidence on the prudent use of carbapenems. Patients and Methods: This was an interventional, retrospective study started in January 2017. The intervention covered establishing performance appraisal indicators, special authorisation, strict prescribing restrictions, and dedicated supervision, particularly in the intensive care unit (ICU). Data on adult inpatients who received at least one carbapenems were extracted from January 2016 to December 2018. Segmented regression analysis was performed to evaluate the effect of the regulation. Results: A total of 2005 inpatients received carbapenems. Segmented regression models showed an immediate decline in the intensity of antibiotic consumption (IAC) of carbapenems (coefficient = -9.65, p < 0.001), particularly imipenem (coefficient = -6.82, p = 0.002), and the antibiotic consumption of carbapenems (coefficient = -133.60, p = 0.003) in the ICU. And there is a decreasing trend in the IAC of meropenem (coefficient = -0.03, p = 0.008) in all departments. Furthermore, the IAC of carbapenems and imipenem (coefficient = -0.36, p = 0.035; coefficient = -0.49, p = 0.025, respectively), and the average length of stay (ALoS) (coefficient = -0.73, p < 0.001) showed downward trends in the ICU. Conclusion: The intervention effectively reduced the IAC of carbapenems and imipenem, carbapenem consumption and the ALoS in the ICU, and the IAC of meropenem in all departments. The effects of the intervention were significant in the ICU, which indicated an urgent need for stronger regulations focusing on critical departments in the future.

6.
PLoS Genet ; 17(8): e1009724, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34398892

RESUMO

Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. Interestingly, we found that one of the two known SK receptors, CCKLR-17D3, is expressed by some of Gr64f-expressing neurons in the proboscis and proleg tarsi. Thus, we have identified SK as a neuropeptide signal in a neuronal circuitry that responds to food intake, and regulates feeding behavior by diminishing gustatory receptor gene expression and activity of sweet sensing GRNs. Our findings demonstrate one nutritional state-dependent pathway that modulates sweet perception and thereby feeding behavior, but our experiments cannot exclude further parallel pathways. Importantly, we show that the underlying mechanisms are conserved in the two distantly related insect species.

7.
Eur Radiol ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215941

RESUMO

OBJECTIVES: The amount and distribution of intratumoural collagen fibre vary among different thymic tumours, which can be clearly detected with T2- and diffusion-weighted MR images. To explore the incidences of collagen fibre patterns (CFPs) among thymomas, thymic carcinomas and lymphomas on imaging, and to evaluate the efficacy and reproducibility of CFPs in differential diagnosis of thymic tumours. MATERIALS AND METHODS: Three hundred and ninety-eight patients with pathologically diagnosed thymoma, thymic carcinoma and lymphoma who underwent T2- and diffusion-weighted MR imaging were retrospectively enrolled. CFPs were classified into four categories: septum sign, patchy pattern, mixed pattern and no septum sign. The incidences of CFPs were compared among different thymic tumours, and the efficacy and reproducibility in differentiating the defined tumour types were analysed. RESULTS: There were significant differences in CFPs among thymomas, thymic squamous cell carcinomas (TSCCs), other thymic carcinomas and neuroendocrine tumours (OTC&NTs) and thymic lymphomas. Septum signs were found in 209 (86%) thymomas, which differed between thymomas and any other thymic neoplasms (all p < 0.005). The patchy, mixed patterns and no septum sign were mainly seen in TSCCs (80.3%), OTC&NTs (78.9%) and thymic lymphomas (56.9%), respectively. The consistency of different CFP evaluation between two readers was either good or excellent. CFPs achieved high efficacy in identifying the thymic tumours. CONCLUSION: The CFPs based on T2- and diffusion-weighted MR imaging were of great value in the differential diagnosis of thymic tumours. KEY POINTS: • Significant differences are found in intratumoural collagen fibre patterns among thymomas, thymic squamous cell carcinomas, other thymic carcinomas and neuroendocrine tumours and thymic lymphomas. • The septum sign, patchy pattern, mixed pattern and no septum sign are mainly seen in thymomas (86%), thymic squamous cell carcinomas (80.3%), other thymic carcinomas and neuroendocrine tumours (79%) and thymic lymphomas (57%), respectively. • The collagen fibre patterns have high efficacy and reproducibility in differentiating thymomas, thymic squamous cell carcinomas and thymic lymphomas.

8.
Front Oncol ; 11: 640375, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307124

RESUMO

Objective: To explore the usefulness of texture signatures based on multiparametric magnetic resonance imaging (MRI) in predicting the subtypes of growth hormone (GH) pituitary adenoma (PA). Methods: Forty-nine patients with GH-secreting PA confirmed by the pathological analysis were included in this retrospective study. Texture parameters based on T1-, T2-, and contrast-enhanced T1-weighted images (T1C) were extracted and compared for differences between densely granulated (DG) and sparsely granulated (SG) somatotroph adenoma by using two segmentation methods [region of interest 1 (ROI1), excluding the cystic/necrotic portion, and ROI2, containing the whole tumor]. Receiver operating characteristic (ROC) curve analysis was performed to determine the differentiating efficacy. Results: Among 49 included patients, 24 were DG and 25 were SG adenomas. Nine optimal texture features with significant differences between two groups were obtained from ROI1. Based on the ROC analyses, T1WI signatures from ROI1 achieved the highest diagnostic efficacy with an AUC of 0.918, the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.7, 72.0, 100.0, 100.0, and 77.4%, respectively, for differentiating DG from SG. Comparing with the T1WI signature, the T1C signature obtained relatively high efficacy with an AUC of 0.893. When combining the texture features of T1WI and T1C, the radiomics signature also had a good performance in differentiating the two groups with an AUC of 0.908. In addition, the performance got in all the signatures from ROI2 was lower than those in the corresponding signature from ROI1. Conclusion: Texture signatures based on MR images may be useful biomarkers to differentiate subtypes of GH-secreting PA patients.

9.
Front Immunol ; 12: 640083, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248934

RESUMO

Objectives: Systemic sclerosis (SSc) is an uncommon autoimmune disease that varies with ethnicity. Single nucleotide polymorphisms (SNPs) in the GTFSI, NFKB1, and TYK2 genes have been reported to be associated with SSc in other populations and in individuals with various autoimmune diseases. This study aimed to investigate the association between these SNPs and susceptibility to SSc in a Chinese Han population. Method: A case-control study was performed in 343 patients with SSc and 694 ethnically matched healthy controls. SNPs in GTF2I, NFKB1, and TYK2 were genotyped using a Sequenom MassArray iPLEX system. Association analyses were performed using PLINK v1.90 software. Result: Our study demonstrated that the GTF2I rs117026326 T allele and the GTF2I rs73366469 C allele were strongly associated with patients with SSc (P = 6.97E-10 and P = 1.33E-08, respectively). Patients carrying the GTF2I rs117026326 TT genotype and the GTF2I rs73366469 CC genotype had a strongly increased risk of SSc (P = 6.25E-09 and P = 1.67E-08, respectively), and those carrying the NFKB1 rs1599961 AA genotype had a suggestively significantly increased risk of SSc (P = 0.014). Moreover, rs117026326 and rs73366469 were associated with SSc in different genetic models (additive model, dominant model, and recessive model) (P < 0.05) whereas rs1599961 was associated with SSc in the dominant genetic model but not in the addictive and recessive models (P = 0.0026). TYK2 rs2304256 was not significantly associated with SSc in this study. Conclusion: GTF2I rs117026326 and rs73366469 SNPs were strongly associated with SSc in this Chinese Han population. NFKB1 rs1599961 showed a suggestive association with SSc, and no significant association was found between TYK2 rs2304256 and SSc in this Chinese Han population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença/genética , Subunidade p50 de NF-kappa B/genética , Polimorfismo de Nucleotídeo Único/imunologia , Escleroderma Sistêmico/genética , TYK2 Quinase/genética , Fatores de Transcrição TFII/genética , Doenças Autoimunes/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
10.
Front Immunol ; 12: 685126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326839

RESUMO

Advanced hepatocellular carcinoma (HCC) is a highly lethal disease, mainly due to the late stage at diagnosis and its rapid progression. Although patients with advanced HCC can choose targeted therapy or chemotherapy, overall, the treatment response rate is extremely low and the average survival time is one year more or less. But the application of immunotherapy have led to a paradigm shift in the treatment of HCC,such as TILs (tumor infiltrating lymphocytes),Checkpoint blockade (immune Checkpoint blockade), CAR-T(chimeric antigen receptor T cells) and TCR-T (engineered t-cell receptor T cells). And recent data indicate neoantigens generated when tumors mutate are the main target of tumor-specific TILs, and they are also the main antigens mediating tumor regression in TILs treatment. Moreover, numerous evidences have revealed that radiotherapy lead to massive release of tumor antigens, which may increase the effectiveness of immunotherapy. Based on the above theory, we used neoantigen reactive T cells combined with tomotherapy to treat a patient with advanced HCC (Clinical Trial Study Registration Number: NCT03199807), who reached a long time progress free survival.


Assuntos
Antígenos de Neoplasias/imunologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Linfócitos T/imunologia , Idoso , Carcinoma Hepatocelular/imunologia , Humanos , Imunoterapia , Neoplasias Hepáticas/imunologia , Masculino , Prognóstico
11.
Arch Insect Biochem Physiol ; 107(3): e21796, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34076304

RESUMO

MicroRNAs (miRNAs) are a type of small noncoding RNAs that regulate gene expression at the posttranscriptional level and can influence significant biological processes. Arma chinensis (Hemiptera: Pentatomidae) is a predaceous insect species that preys upon a wide variety of insect pests. It is important to explore and understand the molecular mechanisms involving miRNAs in regulating developmental and other gene expression for beneficial insects. However, examination of miRNAs associated with Hemiptera, especially predatory bugs, has been absent or scarce. This study represents the first comprehensive analysis of predatory bug A. chinensis encoded miRNAs through high throughput sequencing and predicts genes and biological processes regulated by the newly identified miRNAs through analyzing their differential expression in and across five nymphal instars. A total of 64 A. chinensis miRNAs, including 46 conserved miRNAs and 18 novel miRNAs, were identified by analysis of high throughput sequence reads mapped to the genome. A total of 2913 potential gene targets for these 64 miRNAs were predicted by comprehensive analyses utilizing miRanda, PITA, and RNAhybrid. Gene Ontology annotation of predicted target genes of A. chinensis suggested the key processes regulated by miRNAs involved biological processes, regulation of cellular processes, and transporter activity. Kyoto Encyclopedia of Genes and Genomes pathway predictions included the Toll and Imd signaling pathway, Valine, leucine and isoleucine degradation, Steroid biosynthesis, the AGE-RAGE signaling pathway in diabetic complications, and Alanine, aspartate and glutamate metabolism. This newly identified miRNAs through analyzing their differential expression, assessment of their predicted functions forms a foundation for further investigation of specific miRNAs.


Assuntos
Heterópteros/metabolismo , MicroRNAs/metabolismo , Animais , Perfilação da Expressão Gênica , Ninfa/metabolismo , Análise de Sequência de RNA
12.
Ecol Evol ; 11(11): 7018-7028, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34141272

RESUMO

Herbivory is a highly sophisticated feeding behavior that requires abilities of plant defense suppression, phytochemical detoxification, and plant macromolecule digestion. For plant-sucking insects, salivary glands (SGs) play important roles in herbivory by secreting and injecting proteins into plant tissues to facilitate feeding. Little is known on how insects evolved secretory SG proteins for such specialized functions. Here, we investigated the composition and evolution of secretory SG proteins in the brown marmorated stink bug (Halyomorpha halys) and identified a group of secretory SG phospholipase C (PLC) genes with highest sequence similarity to the bacterial homologs. Further analyses demonstrated that they were most closely related to PLCs of Xenorhabdus, a genus of Gammaproteobacteria living in symbiosis with insect-parasitizing nematodes. These suggested that H. halys might acquire these PLCs from Xenorhabdus through the mechanism of horizontal gene transfer (HGT), likely mediated by a nematode during its parasitizing an insect host. We also showed that the original HGT event was followed by gene duplication and expansion, leading to functional diversification of the bacterial-origin PLC genes in H. halys. Thus, this study suggested that an herbivore might enhance adaptation through gaining genes from an endosymbiont of its parasite in the tripartite parasitic and symbiotic interactions.

13.
Front Immunol ; 12: 654540, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093544

RESUMO

Dendritic cells (DCs) induce and regulate adaptive immunity through migrating and maturing in the kidney. In this procedure, they can adopt different phenotypes-rejection-associated DCs promote acute or chronic injury renal grafts while tolerogenic DCs suppress the overwhelmed inflammation preventing damage to renal functionality. All the subsets interact with effector T cells and regulatory T cells (Tregs) stimulated by the ischemia-reperfusion procedure, although the classification corresponding to different effects remains controversial. Thus, in this review, we discuss the origin, maturation, and pathological effects of DCs in the kidney. Then we summarize the roles of divergent DCs in renal transplantation: taking both positive and negative stages in ischemia-reperfusion injury (IRI), switching phenotypes to induce acute or chronic rejection, and orchestrating surface markers for allograft tolerance via alterations in metabolism. In conclusion, we prospect that multidimensional transcriptomic analysis will revolute researches on renal transplantation by addressing the elusive mononuclear phagocyte classification and providing a holistic view of DC ontogeny and subpopulations.


Assuntos
Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Transplante de Rim , Imunologia de Transplantes , Doença Aguda , Aloenxertos , Animais , Doença Crônica , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Tolerância Imunológica , Imunomodulação , Imunoterapia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo
14.
Mol Biol Evol ; 38(10): 4505-4519, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34175934

RESUMO

UV irradiation induces the formation of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts in DNA. These two types of lesions can be directly photorepaired by CPD photolyases and 6-4 photolyases, respectively. Recently, a new class of 6-4 photolyases named iron-sulfur bacterial cryptochromes and photolyases (FeS-BCPs) were found, which were considered as the ancestors of all photolyases and their homologs-cryptochromes. However, a controversy exists regarding 6-4 photoproducts only constituting ∼10-30% of the total UV-induced lesions that primordial organisms would hardly survive without a CPD repair enzyme. By extensive phylogenetic analyses, we identified a novel class of proteins, all from eubacteria. They have relatively high similarity to class I/III CPD photolyases, especially in the putative substrate-binding and FAD-binding regions. However, these proteins are shorter, and they lack the "N-terminal α/ß domain" of normal photolyases. Therefore, we named them short photolyase-like. Nevertheless, similar to FeS-BCPs, some of short photolyase-likes also contain four conserved cysteines, which may also coordinate an iron-sulfur cluster as FeS-BCPs. A member from Rhodococcus fascians was cloned and expressed. It was demonstrated that the protein contains a FAD cofactor and an iron-sulfur cluster, and has CPD repair activity. It was speculated that this novel class of photolyases may be the real ancestors of the cryptochrome/photolyase family.

15.
Front Immunol ; 12: 674343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122433

RESUMO

Background: Autoimmune diseases (ADs) are characterized by immune-mediated tissue damage, in which angiogenesis is a prominent pathogenic mechanism. Vascular endothelial growth factor (VEGF), an angiogenesis modulator, is significantly elevated in several ADs including rheumatoid arthritis (RA), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE). We determined whether circulating VEGF levels were associated with ADs based on pooled evidence. Methods: The analyses included 165 studies from the PubMed, EMBASE, Cochrane Library, and Web of Science databases and fulfilled the study criteria. Comparisons of circulating VEGF levels between patients with ADs and healthy controls were performed by determining pooled standard mean differences (SMDs) with 95% confidence intervals (CIs) in a random-effect model using STATA 16.0. Subgroup, sensitivity, and meta-regression analyses were performed to determine heterogeneity and to test robustness. Results: Compared with healthy subjects, circulating VEGF levels were significantly higher in patients with SLE (SMD 0.84, 95% CI 0.25-1.44, P = 0.0056), RA (SMD 1.48, 95% CI 0.82-2.15, P <0.0001), SSc (SMD 0.56, 95% CI 0.36-0.75, P <0.0001), Behcet's disease (SMD 1.65, 95% CI 0.88-2.41, P <0.0001), Kawasaki disease (SMD 2.41, 95% CI 0.10-4.72, P = 0.0406), ankylosing spondylitis (SMD 0.78, 95% CI 0.23-1.33, P = 0.0052), inflammatory bowel disease (SMD 0.57, 95% CI 0.43-0.71, P <0.0001), psoriasis (SMD 0.98, 95% CI 0.62-1.34, P <0.0001), and Graves' disease (SMD 0.69, 95% CI 0.20-1.19, P = 0.0056). Circulating VEGF levels correlated with disease activity and hematological parameters in ADs. Conclusion: Circulating VEGF levels were associated with ADs and could predict disease manifestations, severity and activity in patients with ADs. Systematic Review Registration: PROSPERO, identifier CRD42021227843.


Assuntos
Doenças Autoimunes/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Humanos
16.
Antibiotics (Basel) ; 10(5)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33925971

RESUMO

The general population has increasingly become the key contributor to irrational antibiotic use in China, which fuels the emergence of antibiotic resistance. This study aimed to estimate the prevalence of the general population's irrational use behaviors of antibiotics and identify the potential reasons behind them. A systematic review and meta-analysis were performed concerning four main behaviors relevant to easy access and irrational use of antibiotics and common misunderstandings among the population about antibiotics. Four databases were searched, and studies published before 28 February 2021 were retrieved. Medium and high-level quality studies were included. Random effects meta-analysis was performed to calculate the prevalence of the general population's irrational behaviors and misunderstandings relevant to antibiotic use. A total of 8468 studies were retrieved and 78 met the criteria and were included. The synthesis showed the public can easily obtain unnecessary antibiotics, with an estimated 37% (95% CI: 29-46) of the population demanding antibiotics from physicians and 47% (95% CI: 38-57) purchasing non-prescription antibiotics from pharmacies. This situation is severe in the western area of China. People also commonly inappropriately use antibiotics by not following antibiotic prescriptions (pooled estimate: 48%, 95% CI: 41-55) and preventatively use antibiotics for non-indicated diseases (pooled estimate: 35%, 95% CI: 29-42). Misunderstanding of antibiotic use was also popular among people, including incorrect antibiotic recognition, wrong antibiotic use indication, inappropriate usage, and ignorance of potential adverse outcomes. Over-and inappropriate use of antibiotics is evident in China and a multifaceted antibiotic strategy targeted at the general population is urgently required.

17.
Clin Appl Thromb Hemost ; 27: 10760296211010976, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33926262

RESUMO

The prognostic role of hypercoagulability in COVID-19 patients is ambiguous. D-dimer, may be regarded as a global marker of hemostasis activation in COVID-19. Our study was to assess the predictive value of D-dimer for the severity, mortality and incidence of venous thromboembolism (VTE) events in COVID-19 patients. PubMed, EMBASE, Cochrane Library and Web of Science databases were searched. The pooled diagnostic value (95% confidence interval [CI]) of D-dimer was evaluated with a bivariate mixed-effects binary regression modeling framework. Sensitivity analysis and meta regression were used to determine heterogeneity and test robustness. A Spearman rank correlation tested threshold effect caused by different cut offs and units in D-dimer reports. The pooled sensitivity of the prognostic performance of D-dimer for the severity, mortality and VTE in COVID-19 were 77% (95% CI: 73%-80%), 75% (95% CI: 65%-82%) and 90% (95% CI: 90%-90%) respectively, and the specificity were 71% (95% CI: 64%-77%), 83% (95% CI: 77%-87%) and 60% (95% CI: 60%-60%). D-dimer can predict severe and fatal cases of COVID-19 with moderate accuracy. It also shows high sensitivity but relatively low specificity for detecting COVID-19-related VTE events, indicating that it can be used to screen for patients with VTE.


Assuntos
Teste para COVID-19 , COVID-19 , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , SARS-CoV-2/metabolismo , Tromboembolia , COVID-19/sangue , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Valor Preditivo dos Testes , Taxa de Sobrevida , Tromboembolia/sangue , Tromboembolia/diagnóstico , Tromboembolia/etiologia , Tromboembolia/mortalidade
18.
Biomed Res Int ; 2021: 6635963, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928154

RESUMO

Background: Baveno VI criteria, based on liver stiffness (LS) measured by transient elastography and platelet counts (PLT), have been proposed to avoid unnecessary endoscopy screening for high-risk varices (HRVs). However, the cut-off value of LS measured by 2D-SWE and PLT to predict HRVs in compensated hepatitis B-related cirrhotic patients remains unknown. Aims: To prospectively analyze the cut-off of the combination of LS measured by 2D-SWE and PLT in predicting HRVs and the influence of antiviral therapies in its efficacy. Methods: Serum parameters, LS, and endoscopy results were obtained from 160 compensated hepatitis B-related cirrhotic patients. The accuracy of the combined algorithm was assessed in the whole cohort and subgroups with or without consecutive antiviral therapies in the past 6 months. Results: In the whole cohort, the optimal cut-off value of LS for HRVs was 14.5 kPa. Patients with a LS value < 14.5 kPa with a PLT value > 110 × 109/L can be excluded from HRVs (NPV = 0.99, endoscopy saved rates = 0.68). Conversely, a LS value of ≥14.5 kPa and a PLT value of ≤110 × 109/L indicated HRVs, with accurate rates of 82.35%, and 10.63% of patients can avoid additional endoscopy screening. Moreover, antiviral therapy had no significant effect on the accuracy and rates saved from further endoscopy screening, when comparing patients with or without antiviral therapies (all p values > 0.05). Conclusions: The combination of LS (14.5 kPa) measured by 2D-SWE and PLT (110 × 109/L) can predict HRVs accurately in compensated hepatitis B-related cirrhotic patients without significant interference of antiviral therapy histories.


Assuntos
Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas/sangue , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Hepatite B/sangue , Hepatite B/complicações , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Resistência ao Cisalhamento , Algoritmos , Antivirais/farmacologia , Antivirais/uso terapêutico , Varizes Esofágicas e Gástricas/fisiopatologia , Feminino , Hepatite B/diagnóstico por imagem , Hepatite B/fisiopatologia , Humanos , Fígado/fisiopatologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Fatores de Risco
19.
Photodiagnosis Photodyn Ther ; 34: 102305, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33901688

RESUMO

Photodynamic therapy (PDT) is a promising modality against various cancers including squamous cell carcinoma (SCC) with which the induction of apoptosis is an effective mechanism. Here, we initially describe the preclinical activity of 5-ethylamino-9-diethylaminobenzo [a] phenoselenazinium(EtNBSe)-mediated PDT treatment in SCC. Results of our studies suggest that EtNBSe-PDT provokes a cellular state of endoplasmic reticulum (ER) stress triggering the PERK/ eIF2α signaling pathway and induces the appearance of apoptosis in A431 cells at the meantime. With ER stress inhibitor 4-PBA or eIF2α inhibitor ISRIB, suppressing the EtNBSe-PDT induced ER stress substantially promotes apoptosis of A431 cells. Furthermore, we demonstrate that ATF4, whose expression is ER-stress-inducible and elevated in response to the PERK/eIF2α signaling pathway activation, contributes to cytoprotection against EtNBSe-PDT induced apoptosis. In a mouse model bearing A431 cells, EtNBSe shows intense phototoxicity and when associated with decreased ER stress, EtNBSe-PDT ameliorates tumor growth. Taken together, our study reveals an antagonistic activity of ER stress against EtNBSe-PDT treatment via inhibiting apoptosis in A431 cells. With further development, these results provide a proof-of-concept that downregulation of ER stress response has a therapeutic potential to improve EtNBSe-PDT sensitivity in SCC patients via the promotion of induced apoptosis.


Assuntos
Fotoquimioterapia , Fator 4 Ativador da Transcrição/farmacologia , Animais , Apoptose , Humanos , Camundongos , Compostos Organosselênicos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , eIF-2 Quinase/farmacologia
20.
Int J Rheum Dis ; 24(5): 633-646, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33713557

RESUMO

AIM: To evaluate the diagnostic value of anti-citrullinated α-enolase peptide 1 (anti-CEP 1) antibody in patients with rheumatoid arthritis (RA) by conducting a systematic review and meta-analysis. METHODS: The PubMed, Web of Science, Embase, Scopus, and Cochrane Library databases were searched for relevant studies published until September 23, 2020. A bivariate mixed-effects model was used to calculate the diagnostic indices from primary data of eligible studies. We performed meta-regression and subgroup analysis to explore the sources of heterogeneity. RESULTS: Twenty-four articles, with a total of 17 380 patients with RA and 7505 control participants, met the criteria for inclusion in the meta-analysis. The pooled sensitivity, specificity, and positive and negative likelihood ratios for the anti-CEP 1 antibody were 44% (95% CI: 38%-51%), 97% (95% CI: 96%-98%), and 14.81 (95% CI: 10.66-20.57) and 0.57 (95% CI: 0.52-0.64), respectively. The pooled positive and negative predictive values were 0.96 (95% CI: 0.95-0.97) and 0.53 (95% CI: 0.43-0.63), respectively. The area under the summary receiver operating characteristic curve was 0.86. Meta-regression indicated that the anti-CEP 1 antibody detection method may be a source of heterogeneity. The subgroup analysis of the group in which the anti-CEP 1 antibody was detected by using a commercial enzyme-linked immunosorbent assay (ELISA) kit had a sensitivity of 59% (95% CI: 50%-68%) and a specificity of 93% (95% CI: 85%-97%). CONCLUSIONS: The anti-CEP 1 antibody had moderate RA diagnostic value with relatively low sensitivity and high specificity. An ELISA may increase the RA diagnostic sensitivity.


Assuntos
Anticorpos Anti-Proteína Citrulinada/imunologia , Anticorpos/imunologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fosfopiruvato Hidratase/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Anticorpos/análise , Artrite Reumatoide/genética , Ensaio de Imunoadsorção Enzimática , Predisposição Genética para Doença , Humanos , Peptídeos Cíclicos/genética , Peptídeos Cíclicos/imunologia , Sensibilidade e Especificidade
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