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1.
Postgrad Med ; : 1-10, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35930266

RESUMO

OBJECTIVE: To investigate the predictive value of the arterial blood lactate to serum albumin ratio (LAR) on in-hospital mortality of patients with community-acquired pneumonia (CAP) admitted to the Intensive Care Unit (ICU). METHODS: Clinical datasets of 1720 CAP patients admitted to ICU from MIMIC-IV database were retrospectively analyzed. Patients were randomly assigned to the training cohort (n=1204) and the validation cohort (n=516) in a ratio of 7:3. X-tile software was used to find the optimal cut-off value for LAR. The receiver operating curve (ROC) analysis was conducted to compare the performance between LAR and other indicators. Univariate and multivariate Cox regression analyses were applied to select prognostic factors associated with in-hospital mortality. Based on the observed prognostic factors, a nomogram model was created in training cohort, and the validation cohort was utilized to further validate the nomogram. RESULTS: The optimal cut-off value for LAR in CAP patients admitted to ICU was 1.6 (the units of lactate and albumin were, respectively, 'mmol/L' and 'g/dL'). The ROC analysis showed that the discrimination abilities of LAR were superior to other indicators except Sequential Organ Failure Assessment score and Simplified acute physiology score (SAPSII), which had the same abilities. Age, mean arterial pressure, SpO2, heart rate, SAPSII score, neutrophil-to-lymphocyte ratio, and LAR were found to be independent predictors of poor overall survival in the training cohort by multivariate Cox regression analysis and were incorporated into the nomogram for in-hospital mortality as independent factors. The nomogram model, exhibiting medium discrimination, had a C-index of 0.746 (95% CI = 0.715-0.777) in the training cohort and 0.716 (95% CI = 0.667-0.765) in the validation cohort. CONCLUSION: LAR could predict in-hospital mortality of patients with CAP admitted to ICU independently as a readily accessible biomarker. The nomogram that included LAR with other independent factors performed well in predicting in-hospital mortality.

2.
Front Pediatr ; 10: 908362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935369

RESUMO

Background: Early stage diagnosis of neonatal sepsis (NS) remains a major roadblock due to non-specific symptoms and the absence of precise laboratory index tests. The full blood count is a relatively cheap, universal, and rapid diagnostic test. Method: This study assessed the diagnostic accuracies of immature-to-total neutrophil ratio (ITR), immature-to-mature neutrophil ratio (IMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) used in the diagnosis of NS. Included studies were retrieved by searching four major databases and relevant references, and reviewed based on the inclusion/exclusion criteria. Pooled sensitivities and specificities were calculated, I 2 was utilized to test for heterogeneity, and the source was investigated via meta-regression analysis. Results: Finally, 38 studies passed the eligibility criteria. A total of thirty-one studies (6,221 neonates) included data on the ITR, eight studies (1,230 neonates) included data on the IMR, seven studies (751 neonates) included data on the NLR, and two studies (283 neonates) included data on the PLR. The summary sensitivity estimates with 95% confidence interval (CI) for the ITR, IMR, NLR, and PLR tests were, respectively, 0.74 (95% CI: 0.66-0.80), 0.74 (95% CI: 0.54-0.88), 0.73 (95% CI: 0.68-0.78), and 0.81 (95% CI: 0.55-1.00). The summary specificity values for the ITR, IMR, NLR, and PLR tests were 0.83 (95% CI: 0.77-0.87), 0.89 (95% CI: 0.80-0.94), 0.69 (95% CI: 0.57-0.79), and 0.93 (95% CI: 0.81-1.00), respectively. The area under the summary receiver operating characteristic curves for the ITR, IMR, and NLR tests were 0.85 (95% CI: 0.82-0.88), 0.91 (95% CI: 0.88-0.93), and 0.75 (95% CI: 0.71-0.79). The PLR could not be evaluated because only two studies included pertinent data. Conclusion: The NLR test might not be sufficiently accurate in precisely diagnosing NS. The ITR and IMR tests alone can improve the accuracy of NS diagnosis, but the marked heterogeneity and the limited number of studies prevented us from reaching any definitive conclusions. Thus, further studies are warranted to validate these findings. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021247850].

3.
Front Mol Biosci ; 9: 849723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928223

RESUMO

The B7-CD28 gene family plays a crucial role in modulating immune functions and has served as potential targets for immunotherapeutic strategies. Therefore, we systematically analyzed B7-CD28 family gene expression profiles and constructed a B7-CD28 family-based prognostic signature to predict survival and immune host status in diffuse gliomas. The TCGA dataset was used as a training cohort, and three CGGA datasets (mRNAseq_325, mRNAseq_693 and mRNA-array) were employed as validation cohorts to intensify the findings that we have revealed in TCGA dataset. Ultimately, we developed a B7-CD28 family-based signature that consisted of CD276, CD274, PDCD1LG2 and CD80 using LASSO Cox analysis. This gene signature was validated to have significant prognostic value, and could be used as a biomarker to distinguish pathological grade and IDH mutation status in diffuse glioma. Additionally, we found that the gene signature was significantly related to intensity of immune response and immune cell population, as well as several other important immune checkpoint genes, holding a great potential to be a predictive immune marker for immunotherapy and tumor microenvironment. Finally, a B7-CD28 family-based nomogram was established to predict patient life expectancy contributing to facilitate personalizing therapy for tumor sufferers. In summary, this is the first mathematical model based on this gene family with the aim of providing novel insights into immunotherapy for diffuse glioma.

4.
Sci Rep ; 12(1): 13309, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922642

RESUMO

As a highly infectious epidemic in aquaculture, Pseudomonas plecoglossicida infection results in high mortality of teleosts and serious economic losses. Host-pathogen interactions shape the outcome of an infection, yet we still understand little about the molecular mechanism of these pathogen-mediated processes. Here, a P. plecoglossicida strain (NZBD9) and Epinephelus coioides were investigated as a model system to characterize pathogen-induced host metabolic remodeling over the course of infection. We present a non-targeted metabolomics profiling of E. coioides spleens from uninfected E. coioides and those infected with wild-type and clpV-RNA interference (RNAi) strains. The most significant changes of E. coioides upon infection were associated with amino acids, lysophospatidylcholines, and unsaturated fatty acids, involving disturbances in host nutritional utilization and immune responses. Dihydrosphingosine and fatty acid 16:2 were screened as potential biomarkers for assessing P. plecoglossicida infection. The silencing of the P. plecoglossicida clpV gene significantly recovered the lipid metabolism of infected E. coioides. This comprehensive metabolomics study provides novel insights into how P. plecoglossicida shape host metabolism to support their survival and replication and highlights the potential of the virulence gene clpV in the treatment of P. plecoglossicida infection in aquaculture.


Assuntos
Bass , Doenças dos Peixes , Infecções por Pseudomonas , Animais , Proteínas de Bactérias/metabolismo , Bass/genética , Doenças dos Peixes/genética , Pseudomonas/fisiologia , Infecções por Pseudomonas/genética
5.
Adv Funct Mater ; : 2204692, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35942272

RESUMO

SARS-CoV-2 variants are now still challenging all the approved vaccines, including mRNA vaccines. There is an urgent need to develop new generation mRNA vaccines with more powerful efficacy and better safety against SARS-CoV-2 variants. In this study, a new set of ionizable lipids named 4N4T are constructed and applied to form novel lipid nanoparticles called 4N4T-LNPs. Leading 4N4T-LNPs exhibit much higher mRNA translation efficiency than the approved SM-102-LNPs. To test the effectiveness of the novel delivery system, the DS mRNA encoding the full-length S protein of the SARS-CoV-2 variant is synthesized and loaded in 4N4T-LNPs. The obtained 4N4T-DS mRNA vaccines successfully trigger robust and durable humoral immune responses against SARS-CoV-2 and its variants including Delta and Omicron. Importantly, the novel vaccines have higher RBD-specific IgG titers and neutralizing antibody titers than SM-102-based DS mRNA vaccine. Besides, for the first time, the types of mRNA vaccine-induced neutralizing antibodies are found to be influenced by the chemical structure of ionizable lipids. 4N4T-DS mRNA vaccines also induce strong Th1-skewed T cell responses and have good safety. This work provides a novel vehicle for mRNA delivery that is more effective than the approved LNPs and shows its application in vaccines against SARS-CoV-2 variants.

6.
Front Oncol ; 12: 944025, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912266

RESUMO

The hypoxic state of the tumor microenvironment leads to reprogramming lipid metabolism in tumor cells. Adipose triglyceride lipase, also known as patatin-like phospholipase= domain-containing protein 2 and Adipose triglyceride lipase (ATGL), as an essential lipid metabolism-regulating enzyme in cells, is regulated accordingly under hypoxia induction. However, studies revealed that ATGL exhibits both tumor-promoting and tumor-suppressing effects, which depend on the cancer cell type and the site of tumorigenesis. For example, elevated ATGL expression in breast cancer is accompanied by enhanced fatty acid oxidation (FAO), enhancing cancer cells' metastatic ability. In prostate cancer, on the other hand, tumor activity tends to be negatively correlated with ATGL expression. This review outlined the regulation of ATGL-mediated lipid metabolism pathways in tumor cells, emphasizing the Hypoxia-inducible factors 1 (HIF-1)/Hypoxia-inducible lipid droplet-associated (HIG-2)/ATGL axis, peroxisome proliferator-activated receptor (PPAR)/G0/G1 switch gene 2 (G0S2)/ATGL axis, and fat-specific protein 27 (FSP-27)/Early growth response protein 1 (EGR-1)/ATGL axis. In the light of recent research on different cancer types, the role of ATGL on tumorigenesis, tumor proliferation, and tumor metastasis was systemically reviewed.

7.
Peptides ; 155: 170842, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35872259

RESUMO

Pulmonary fibrosis, a severe condition that can progress to respiratory failure and death, is characterized by aberrant activation/proliferation of fibroblasts and excessive extracellular matrix (ECM) deposition and has limited therapeutic options. Identifying novel mediators of pulmonary fibrosis is currently needed to facilitate the development of more effective therapeutic strategies targeting pulmonary fibrosis. The present study was designed to investigate whether transforming growth factor-ß (TGF-ß) induced protein (TGFBI), an extracellular matrix protein, regulates pulmonary fibrosis in vitro and in vivo and the possible mechanism of actions. It was found that protein expressions of TGFBI were significantly upregulated and G-protein signaling modulator 2 (GPSM2) expression downregulated in fibrotic lung tissues from bleomycin (BLM)-induced rats and TGF-ß1-stimulated human lung IMR-90 fibroblasts. Either silencing TGFBI with specific siRNA or treatment with the TGF-ß signaling inhibitor SB431542 significantly inhibited TGF-ß1-induced fibrotic effects and dysregulation of GPSM2 and Snail expressions in IMR-90 fibroblasts. Moreover, GPSM2 overexpression also inhibited TGF-ß1-induced fibrotic effects and Snail upregulation in IMR-90 fibroblasts. Silencing Snail with specific siRNA attenuated TGF-ß1-induced fibrotic effects. Therefore, our findings suggest that the extracellular matrix protein TGFBI mediates pulmonary fibrosis through regulation of the GPSM2/Snail axis, which identifies TGFBI as a novel mediator of pulmonary fibrosis and may be a potential therapeutic target for the treatment of pulmonary fibrosis.


Assuntos
Fibrose Pulmonar , Animais , Proteínas da Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/farmacologia , Proteínas da Matriz Extracelular/uso terapêutico , Proteínas de Ligação ao GTP/metabolismo , Humanos , Pulmão/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/genética , RNA Interferente Pequeno/metabolismo , Ratos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta1/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-35886187

RESUMO

During the COVID-19 pandemic, lockdowns and isolation have limited the availability of face-to-face support services for victims of intimate partner violence (IPV). Despite the growing need for online help in supporting IPV victims, far less is known about the underlying mechanisms between IPV and online help-seeking. We studied the mediating role of emotion dysregulation (ED) and the moderating role of perceived anonymity (PA) on the internet to explain IPV victims' willingness of online help-seeking (WOHS). Through a PROCESS analysis of the questionnaire data (n = 510, 318 female, 192 male, Mage = 22.41 years), the results demonstrate that: (1) ED has been linked with the experience of IPV, and IPV significantly induces ED. (2) When IPV victims realize the symptoms of ED, they have a strong willingness to seek external intervention to support themselves. ED mediates the relationship between IPV and online help-seeking. (3) For youth growing up in the era of social networking sites (SNS), personal privacy protection is an important factor when seeking online help. The anonymity of the internet has a positive effect on victims who experience IPV and ED, and it increases WOHS. This study introduces a new perspective on the psychological mechanism behind IPV victims' help-seeking behaviors, and it suggests that the improvement of anonymity in online support can be an effective strategy for assisting IPV victims.


Assuntos
COVID-19 , Violência por Parceiro Íntimo , Adolescente , Adulto , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Emoções , Feminino , Humanos , Violência por Parceiro Íntimo/psicologia , Masculino , Pandemias , Adulto Jovem
9.
Front Psychol ; 13: 872464, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846618

RESUMO

Public opinion guidance plays a crucial role in the management of major public health incidents, and thus, exploring its mechanism is conducive to the comprehensive governance of social security. This study conducts a case study on the anti-pandemic public opinion guidance and analyzes the public opinion representation and the internal mechanism of public opinion guidance in the context of the COVID-19 in China. The findings suggest that the public opinion on the COVID-19 manifested a three-stage progressive and stable tendency and witnessed the strength of China, specifically, benefiting from the systematic and complete integration and release mechanism for anti-pandemic information, the three-dimensional mechanism for the dissemination of knowledge related to pandemic prevention and health, the innovative disclosure mechanism for precise information, and diversified channels for international public opinion guidance. The guidance mechanism proposed in this study provides significant suggestions for the public opinion guidance of global major public health incidents in future.

10.
Invest Ophthalmol Vis Sci ; 63(8): 9, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35816041

RESUMO

Purpose: Retinal neovascularization is a major cause of blindness. This study aimed to investigate the effects of IL-19 and the underlying mechanisms in a mouse model of oxygen-induced retinopathy (OIR). Methods: C57BL/6J wild-type mice and IL-19 knockout (KO) mice were used to establish an OIR mouse model. Bone marrow-derived macrophages (BMDMs) with or without recombinant IL-19 (rIL-19) stimulation were injected intravitreally. Reverse transcription-quantitative polymerase chain reaction was used to determine the mRNA expressions. ELISA and western blotting were performed to assess the protein levels. Immunofluorescence staining was applied to assess retinal neovascularization. Human retinal endothelial cells (HRECs) stimulated with rIL-19 were cultured to evaluate the effects on cell proliferation and migration. Results: The level of IL-19 was significantly elevated at postnatal day 17 in OIR retinas. Both the avascular areas and pathological neovascular tufts were significantly increased in rIL-19-treated OIR retinas and suppressed in IL-19 KO retinas. IL-19 KO mice suppressed expression of ARG1, VEGFA, and pSTAT3. Moreover, BMDMs stimulated by rIL-19 enhanced that expression and suppressed the expression of inducible nitric oxide synthase (iNOS). The proliferation and migration of HRECs were significantly augmented by rIL-19. In addition, intravitreal injection of BMDMs stimulated by rIL-19 enhanced retinal neovascularization. Conclusions: These findings suggest that IL-19 enhances pathological neovascularization through a direct effect on microvascular endothelial cells and the promotion of M2 macrophage polarization. The inhibition of IL-19 may be a potential treatment for retinal neovascularization.


Assuntos
Doenças Retinianas , Neovascularização Retiniana , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Humanos , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxigênio/metabolismo , Oxigênio/toxicidade , Doenças Retinianas/metabolismo , Neovascularização Retiniana/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Soft Matter ; 18(29): 5465-5473, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35822864

RESUMO

Wrinkles are commonly observed in uniaxially stretched hyperelastic membranes and eventually disappear with the increase of stretching. The widely used scheme at present assumes the material parameters to be empirical values and straightforwardly considers some constitutive models to explore the wrinkling and restabilization behavior. However, this simple treatment may cause deviation from experiment by ignoring the applicability of the models and the authenticity of the input parameters, prompting us to report based on realistic material parameters. This paper presents an experimental, theoretical and numerical investigation on the wrinkling and restabilization behavior of hyperelastic materials. By fitting experimental stress-strain curves of PDMS films, we confirm that the 3-term Ogden model bears a closer resemblance to the experimental data than the widely used neo-Hookean, Mooney-Rivlin, and Arruda-Boyce models under certain circumstances. The simulation results indicate that different constitutive models quantitatively affect the critical buckling strain, wrinkling amplitudes, and restabilization points. Furthermore, the isolated central bifurcation point solved by Koiter stability theory agrees well with the simulation and experimental results. A 3D phase diagram of stability boundaries was established to gain a comprehensive insight into the effects of geometric parameters (length, width, and thickness) on wrinkling.

12.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(7): 866-872, 2022 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-35848184

RESUMO

Objective: To investigate the influence of axis pedicle and intra-axial vertebral artery (IAVA) alignment on C 2 pedicle screw placement by measuring the data of head and neck CT angiography. Methods: The axis pedicle diameter (D), isthmus height (H), isthmus thickness (T), and IAVA alignment types were measured in 116 patients (232 sides) who underwent head and neck CT angiography examinations between January 2020 and June 2020. Defined the IAVA offset direction by referencing the vertical line through the center of C 3 transverse foramen on the coronal scan, it was divided into lateral (L), neutral (N), and medial (M). Defined the IAVA high-riding degree by referencing the horizontal line through the outlet of the C 2 transverse foramen, it was divided into below (B), within (W), and above (A). The rate of pedicle stenosis, high-riding vertebral artery, and different IAVA types were calculated, and their relationships were analysed. Simulative C 2 pedicle screws were implanted by Mimics 19.0 software, and the interrelation among the rates of pedicle stenosis, high-riding vertebral artery, IAVA types, and vertebral artery injury were analyzed. Results: The rate of C 2 pedicle stenosis was 33.6% (78/232), and the rate of high-riding vertebral artery was 35.3% (82/232). According to the offset direction and the degree of riding, IAVA was divided into 9 types, among which the N-W type (29.3%) was the most, followed by the L-W type (19.0%) and the L-B type (12.9%), accounting for 60.9%. The vertebral artery injury rate of simulative implanted C 2 pedicle screws was 35.3% (82/232). The vertebral artery injury rate in patients with pedicle stenosis and high-riding vertebral artery was significantly higher than that who were not ( P<0.001). The rate of pedicle stenosis, high-riding vertebral artery, and vertebral artery injury were significantly different among IAVA types ( P<0.001), and M-A type was the most common. Conclusion: Vertebral artery injury is more common in pedicle stenosis and/or high-riding vertebral artery and/or IAVA M-A type. Preoperative head and neck CT angiography examination has clinical guiding significance.


Assuntos
Parafusos Pediculares , Vértebras Cervicais/cirurgia , Constrição Patológica , Humanos , Tomografia Computadorizada por Raios X , Artéria Vertebral/lesões , Artéria Vertebral/cirurgia
13.
ISME J ; 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35869388

RESUMO

The interactions between Emiliania huxleyi and E. huxleyi virus (EhV) regulate marine carbon and sulfur biogeochemical cycles and play a prominent role in global climate change. As a large DNA virus, EhV has developed a novel "virocell metabolism" model to meet its high metabolic needs. Although it has been widely demonstrated that EhV infection can profoundly rewire lipid metabolism, the epigenetic regulatory mechanisms of lipid metabolism are still obscure. MicroRNAs (miRNAs) can regulate biological pathways by targeting hub genes in the metabolic processes. In this study, the transcriptome, lipidome, and miRNAome were applied to investigate the epigenetic regulation of lipid metabolism in E. huxleyi cells during a detailed time course of viral infection. Combined transcriptomic, lipidomic, and physiological experiments revealed reprogrammed lipid metabolism, along with mitochondrial dysfunction and calcium influx through the cell membrane. A total of 69 host miRNAs (including 1 known miRNA) and 7 viral miRNAs were identified, 27 of which were differentially expressed. Bioinformatic prediction revealed that miRNAs involved in the regulation of lipid metabolism and a dual-luciferase reporter assay suggested that phosphatidylinositol 3-kinase (PI3K) gene might be a target of ehx-miR5. Further qPCR and western blot analysis showed a significant negative correlation between the expression of ehx-miR5 and its target gene PI3K, along with the lower activity of its downstream components (p-Akt, p-TOR, SREBP), indicating that lipid metabolism might be regulated by ehx-miR5 through the PI3K-Akt-TOR signaling pathway. Our findings reveal several novel mechanisms of viral strategies to manipulate host lipid metabolism and provide evidence that ehx-miR5 negatively modulates the expression of PI3K and disturbs lipid metabolism in the interactions between E. huxleyi and EhV.

14.
Front Immunol ; 13: 925217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795680

RESUMO

Therapeutic tumor vaccines have become an important breakthrough in the treatment of various solid tumors including lung cancer. Dendritic cells (DCs)-based tumor vaccines targeting tumor-associated antigens (TAAs) play a key role in immunotherapy and immunoprevention. However, the weak immunogenicity of TAAs and low immune response rates are a major challenge faced in the application of therapeutic tumor vaccines. Here, we tested whether targeting an attractive target Mesothelin (MSLN) and PD-L1 immune checkpoint molecule to DCs in vivo would elicit therapeutic antitumor cytotoxic T lymphocyte (CTL) response. We generated specific MSLN fragment combined with PD-L1 and GM-CSF peptide immunogen (MSLN-PDL1-GMCSF) based on the novel anti-PD-L1 vaccination strategy we recently developed for the cancer treatment and prevention. We found that DCs loaded with MSLN-PDL1-GMCSF vaccine elicited much stronger endogenous anti-PD-L1 antibody and T cell responses in immunized mice and that antigen specific CTLs had cytolytic activities against tumor cells expressing both MSLN and PD-L1. We demonstrated that vaccination with MSLN-PDL1-GMCSF potently inhibited the tumor growth of MSLN+ and PD-L1+ lung cancer cells, exhibiting a significant therapeutic anti-tumor potential. Furthermore, PD-1 blockade further improved the synergistic antitumor therapeutic efficacy of MSLN-PDL1-GMCSF vaccine in immunized mice. In summary, our data demonstrated for the first time that this PD-L1-containing MSLN therapeutic vaccine can induce persistent anti-PD-L1 antibody and CTL responses, providing an effective immunotherapeutic strategy for lung cancer immunotherapy by combining MSLN-PDL1-GMCSF vaccine and PD-1 blockade.


Assuntos
Vacinas Anticâncer , Neoplasias Pulmonares , Animais , Antígenos de Neoplasias , Fatores Imunológicos , Imunoterapia , Neoplasias Pulmonares/terapia , Mesotelina , Camundongos , Receptor de Morte Celular Programada 1
15.
Front Endocrinol (Lausanne) ; 13: 913370, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903272

RESUMO

Purpose: We sought to reveal the expression profiles of transfer RNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) in the vitreous humor of patients with proliferative diabetic retinopathy (PDR). Methods: Vitreous humor samples were obtained from PDR patients and a control group for this study. Sequencing of small RNAs was conducted to assess the expression profiles of tsRNAs and miRNAs in both groups, which was followed by validation using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatics analyses were conducted to predict the target genes and their potential biological functions and signaling pathways. Results: A total of 37 tsRNAs and 70 miRNAs with significant differences were screened out from the vitreous humor samples of PDR patients compared to controls. Following validation by RT-qPCR, the target genes of the validated tsRNAs and miRNAs were predicted, and Gene Ontology analysis indicated that the target genes of the tsRNAs were most enriched in the cellular macromolecule metabolic process, cytoplasm, and ion-binding, while those of the miRNAs were most abundant in the regulation of major metabolic process, cytoplasm, and protein-binding. In addition, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the target genes of said tsRNAs and miRNAs were most enriched in the adenosine monophosphate-activated protein kinase signaling pathway and Th17 cell differentiation, respectively. Conclusions: The present study identified altered tsRNAs and miRNAs in vitreous humor samples of PDR patients, which may play important roles in the pathogenesis of PDR and could be considered potential therapeutic targets in the treatment of PDR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , MicroRNAs , Diabetes Mellitus/patologia , Retinopatia Diabética/metabolismo , Ontologia Genética , Humanos , MicroRNAs/metabolismo , RNA de Transferência/metabolismo , Corpo Vítreo/metabolismo , Corpo Vítreo/patologia
16.
Chemosphere ; : 135612, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35817188

RESUMO

Zero-valent iron (ZVI, Fe0) enables chemical reduction of environmental pollutants coupled with reactivity loss due to surface oxidation. During ZVI treatment process, however, microbial community stability in terms of resistance and resilience remains largely unclear. Here, we monitored bacterial community succession over a 4 weeks period in soil microcosms with or without 2% (w/w) Fe0 amendment. To simulate soil pollution, 100 µg g-1 chlorinated pesticide lindane (γ-hexachlorocyclohexane) was added to the microcosms as a model contaminant. In addition to microbial activity as measured by soil organic carbon mineralization, bacterial abundance, diversity and composition were determined using qPCR and high-throughput sequencing of 16S rRNA genes. Co-occurrence analysis was performed to reveal the interaction patterns within the bacterial communities. The results indicated that ZVI caused near-complete transformation of lindane, while in the microcosms without Fe0 amendment the pesticide was recalcitrant. ZVI strongly inhibited CO2-efflux at the early stage of incubation, but the bacterial community appeared to be less sensitive to Fe0 amendment. The ratios of negative to positive correlations between network nodes suggested that Fe0 had marginal influence on community stability compared to the lindane treatments, which destabilized the bacterial community. Community succession occurred in the presence of ZVI, as exemplified by a dominancy transition from anaerobic to aerobic taxa. Yet, ZVI alleviated the stress of lindane on soil bacteria by improving community structure and increasing network complexity. Taken together, these findings demonstrate the stability of soil bacterial community under Fe0 stress, which might be conducive to functional recovery of soil microorganisms following ZVI remediation.

17.
Front Pharmacol ; 13: 888588, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35662709

RESUMO

IKKε (inhibitor of nuclear factor kappa-B kinase ε) is a member of the noncanonical NF-κB pathway. It participates in the inflammatory response and innate immunity against bacteria. In recent decades, IKKε has been closely associated with metabolic regulation. Inhibition of the IKKε pathway can improve fat deposition in the liver, reduce subcutaneous fat inflammation, and improve liver gluconeogenesis in obesity. IKKε is expected to be a new therapeutic target for metabolic diseases such as nonalcoholic fatty liver disease, diabetes, and obesity. Herein, we summarize the structural characterization, physiological function, and pathological role of IKKε in metabolic diseases and small molecule inhibitors of IKKε.

18.
BMC Med Genomics ; 15(1): 126, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668409

RESUMO

BACKGROUND: The deletion of a short arm fragment on chromosome 8 is a rare cause of Kallmann syndrome and spherocytosis due to deletion of the FGFR1 and ANK1 genes. CASE PRESENTATION: This case study describes a 4-month-old child with growth and psychomotor retardation, auricle deformity, microcephaly, polydactyly, a heart abnormality, and feeding difficulties. An approximately 12.00 MB deletion was detected in the 8p11.22-p21.2 region of chromosome 8. After sequencing, we found that 65 protein genes had been deleted, including FGFR1, which resulted in Kallmann syndrome. There was no deletion of the ANK1 gene associated with spherocytosis, consistent with the phenotype. CONCLUSION: This patient is a new case of short arm deletion of chromosome 8, resulting in novel and previously unreported clinical features.


Assuntos
Transtornos Cromossômicos , Síndrome de Kallmann , Esferocitose Hereditária , Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 22 , Humanos , Síndrome de Kallmann/genética , Esferocitose Hereditária/genética
19.
Environ Pollut ; 308: 119620, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35709920

RESUMO

Per- and polyfluoroalkyl substances (PFAS) are complex emerging pollutants that are widely distributed in soils. The compositions of PFAS vary according to the emission sources. However, the soil distributions of PFAS from different sources are still poorly understood. In this study, the concentrations and compositions of 18 PFAS in soils close to potential sources (industrial areas, airports, landfills, fire stations and agricultural areas) were investigated in Shanghai. The total PFAS concentrations varied from 0.64 to 294 µg kg-1d.w.. Among the sites, the highest PFAS concentration was found near the fire station (average = 57.9 µg kg-1d.w.), followed by the industrial area (average = 8.53 µg kg-1d.w.). The detection frequencies of the 18 PFAS ranged from 47.5% to 100%. Perfluorooctanoic acid (PFOA) and perfluoroheptanoic acid (PFHpA) were detected in all samples. The detection frequencies of PFAS near the fire station were higher than those near other sources. The PFAS in soils were mainly composed of short-chain perfluoroalkyl carboxylic acids (C ≤ 8). Elevated concentrations of long-chain perfluoroalkyl carboxylic acids (C > 12) were found in industrial area. Principal component analysis revealed that long-chain PFAS had different factor loadings compared to short-chain PFAS. With the exception of agricultural soils, the correlations between individual PFAS were more positive than negative. Strong positive correlations were found within three groups of perfluoroalkyl carboxylic acids (C5-C7, C9-C12, and C14-C18), suggesting their similar inputs and transportation pathways. The PFAS in soils around the fire station were likely directly emitted from a point source. In contrast, the PFAS in soils near the other sites had multiple input pathways, including both direct emission and precursor degradation.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Poluentes Químicos da Água , Ácidos Alcanossulfônicos/análise , Ácidos Carboxílicos , China , Fluorcarbonetos/análise , Solo , Poluentes Químicos da Água/análise
20.
J Arthroplasty ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35490981

RESUMO

BACKGROUND: Different bearings have been used in total hip arthroplasty (THA), but the long-term performance is still controversial. The purpose of this study was to investigate whether there are differences when comparing THAs with 5 different bearings at a long-term follow-up of more than 10 years. METHODS: From January 2010 to May 2012, 101 THA patients (134 hips) were divided into metal-on-metal group (MoM, 31 hips), metal-on-polyethylene group (MoP, 23 hips), ceramic-on-metal group (CoM, 21 hips), ceramic-on-ceramic group (CoC, 33 hips), and ceramic-on-polyethylene group (CoP, 26 hips). The mean follow-up period was 10.3 years. The Harris hip score (HSS), Western Ontario and McMaster Universities Osteoarthritis Index scores (WOMAC), range of motion (ROM), blood cell count, and liver-kidney function were measured. Serum and urine metal ion levels were measured using high-resolution inductively coupled plasma-mass spectrometry (ICP-MS) and a blood lymphocytes analysis was counted by flow cytometry. RESULTS: No difference was observed in the HSS, WOMAC, ROM, blood cell count, or liver-kidney function among any of the 5 groups. Metal ion levels were significantly elevated in metal-containing bearings. Flow cytometry showed that no differences were found. Revision was performed due to pseudotumor in 3 patients. The implant survival rate was 96.7% and 93.3% for the MoM and CoC groups, which was significantly lower compared with other groups. CONCLUSIONS: Metal ion levels were elevated significantly in metal-containing bearings, especially in MoM THA patients. The implant survival rate was significantly lower in CoC and MoM THAs, which was mainly due to pseudotumor formation. LEVEL OF EVIDENCE: Therapeutic Level II.

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