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1.
Pediatr Res ; 96(2): 494-501, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38514858

RESUMO

BACKGROUND: IFN-induced protein 44-like (IFI44L) promoter methylation has been demonstrated to serve as an effective blood diagnostic biomarker for adult-onset SLE. However, its utility as a diagnostic marker for childhood-onset SLE (cSLE) remains to be verified. METHODS: Initially, we conducted a differential analysis of gene methylation and mRNA expression patterns in cSLE whole blood samples obtained from the public GEO database to determine IFI44L gene expression and assess the methylation status at its CpG sites. Subsequently, we collected clinical whole blood samples from 49 cSLE patients and 12 healthy children, employing an HRM-qPCR-based IFI44L methylation detection technique to evaluate its diagnostic efficacy in pediatric clinical practice. RESULTS: A total of 26 hypomethylated, highly expressed genes in cSLE were identified by intersecting differentially expressed genes (DEGs) and differentially methylation genes (DMGs). GO enrichment analysis for these 26 genes indicated a robust association with type I IFN. Among the overlapping genes, IFI44L exhibited the most pronounced differential expression and methylation. In subsequent clinical validation experiments, IFI44L methylation was confirmed as an effective blood-based diagnostic biomarker for cSLE, achieving an AUC of 0.867, a sensitivity of 0.753, and a specificity of 1.000. CONCLUSIONS: IFI44L methylation is a promising blood biomarker for cSLE. IMPACT: IFI44L promoter methylation was reported to serve as a highly sensitive and specific diagnostic marker for adult-onset SLE. However, the diagnostic efficacy of IFI44L in childhood-onset SLE (cSLE) still remains to be confirmed. In this study, we utilized bioinformatics analysis and conducted clinical experiments to demonstrate that IFI44L methylation can also serve as a promising blood biomarker for cSLE. The findings of this study can facilitate the diagnosis of cSLE and broaden our understanding of its molecular mechanisms, with a particular focus on those related to type I interferons.


Assuntos
Biomarcadores , Metilação de DNA , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/diagnóstico , Feminino , Criança , Biomarcadores/sangue , Masculino , Estudos de Casos e Controles , Regiões Promotoras Genéticas , Ilhas de CpG , Adolescente , Idade de Início , Perfilação da Expressão Gênica , Proteínas Supressoras de Tumor
2.
BMC Public Health ; 24(1): 1783, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965535

RESUMO

PURPOSE: To investigate the associations between the most popular social media platform WeChat usage and cognitive performance among the middle-aged and older Chinese population using data from a nationally representative survey. METHODS: In total, 17,472 participants (≥ 45 years old) from the China Health and Retirement Longitudinal Study (CHARLS, Wave 4, 2018) were analyzed. Cognitive performance including episodic memory and executive function was assessed using Mini-Mental Status Examination (MMSE). Other confounding variables included socio-economic characteristics, medical status, and lifestyle-related information. Multiple linear regression models were used to test the association between cognitive performance and WeChat usage by introducing covariates hierarchically. Subgroup analyses of age and gender were conducted to estimate the robustness of the primary findings. RESULTS: After adjusting for multiple confounders across all linear models, WeChat usage is significantly associated with executive function, episodic memory, and global cognitive performance (all p values<0.05). Such results remained robust in subgroup analyses, stratified by age and gender, and also verified according to longitudinal analyses. Compared to 'Chat-only' users who only used WeChat for online interpersonal communication, further usage of WeChat functions such as using 'Moments' appeared to be significantly associated with better cognitive performance, especially for episodic memory. CONCLUSION: Social media usage is significantly and positively associated with better cognitive performance among the middle-aged and older Chinese population. Along with point-to-point messaging, using 'Moments' and extended social media platform functions may correlate to better cognitive performance.


Assuntos
Cognição , Mídias Sociais , Humanos , Masculino , Feminino , China , Pessoa de Meia-Idade , Idoso , Estudos Longitudinais , Mídias Sociais/estatística & dados numéricos , Função Executiva , Memória Episódica , Inquéritos e Questionários , População do Leste Asiático
3.
Altern Ther Health Med ; 30(11): 472-480, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38430174

RESUMO

Objective: To explore the effect of evidence-based care plus aerobic exercise on blood pressure control and pregnancy outcome in patients with hypertensive disorders during pregnancy. Methods: A total of 100 patients diagnosed with hypertensive disorder in pregnancy treated in our hospital between February 2020 and November 2021 were recruited, analyzed and assigned at a ratio of 1:1 to receive routine nursing (control group) or evidence-based care plus aerobic exercise (experimental group) via random number table method. Outcome measures included blood pressure, negative emotions, sleep duration, and pregnancy outcome. Results: The blood pressure of both groups decreased after nursing, and the diastolic and systolic blood pressure of patients in the experimental group (79.84±5.18 mmHg, 111.62±7.96 mmHg) were lower than those in the control group (88.65±5.69 mmHg, 132.15±8.14 mmHg) (P < .05). After the completion of the nursing period, assessments using the Self-Rating Anxiety Scale and Hamilton Depression Scale were conducted. The results revealed significantly lower scores in the experimental group, which received evidence-based care along with aerobic exercise, compared to the control patients who received routine care. The sleep duration was prolonged in both groups after nursing, and patients in the experimental group got longer sleep duration than those in the control group (P < .05). The experimental group showed a significantly lower incidence of adverse pregnancy outcomes than the control group (P < .05). Limitations: While our study demonstrates the positive impact of evidence-based care combined with moderate aerobic exercise on patients with hypertensive disorders during pregnancy, it is essential to acknowledge some notable limitations. First, the sample size was relatively small, which may limit the generalizability of our findings to a larger population. Furthermore, our study primarily focused on short-term outcomes, and future research could explore the sustained benefits of this approach. Finally, individual variations in exercise tolerance and compliance may also affect the effectiveness of the intervention. Despite these limitations, our findings hold promise and provide a foundation for further research in this area. Conclusion: Evidence-based care combined with moderate aerobic exercise has proven to be an effective approach in enhancing the overall management of patients with hypertensive disorders during pregnancy. This combined intervention not only effectively regulates blood pressure levels but also mitigates adverse emotional states, enhances sleep quality, and ultimately leads to improved pregnancy outcomes. These findings hold significant promise for clinical application. Healthcare providers may consider implementing this approach to improve the well-being of pregnant individuals with hypertensive disorders, potentially reducing the risk of complications and enhancing the overall quality of care. Pregnant individuals, on the other hand, can benefit from a more comprehensive and holistic approach to their care, which may result in better health and pregnancy outcomes. Future research in this area could explore the long-term sustainability and cost-effectiveness of this intervention, as well as its potential applicability to diverse patient populations and healthcare settings.


Assuntos
Exercício Físico , Hipertensão Induzida pela Gravidez , Resultado da Gravidez , Humanos , Feminino , Gravidez , Adulto , Hipertensão Induzida pela Gravidez/terapia , Pressão Sanguínea/fisiologia , Terapia por Exercício/métodos
4.
Altern Ther Health Med ; 30(9): 234-240, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38290439

RESUMO

Objective: This study aimed to evaluate the impact of quality care on maternal and infant outcomes in patients with hypertensive disorders complicating pregnancy (HDCP) complicated by cerebral hemorrhage. Methods: From February 2020 to September 2021, 68 women with HDCP complicated by cerebral hemorrhage hospitalized at our hospital were included and divided into a routine group (standard care) and a quality group (quality care). Outcome measures included National Institutes of Health Stroke Scale (NIHSS) scores, blood pressure, self-rating anxiety scale (SAS) scores, self-rating depression scale (SDS) scores, and maternal and infant outcomes. Results: Patients in the quality group (3.22±1.89) had significantly lower NIHSS scores aftercare than those in the routine group (6.15±3.24) (P < .05). Quality care resulted in lower diastolic blood pressure (Quality group:81.23±6.15; Routine: 90.58±7.98), systolic blood pressure (Quality group:125.49±13.37; Routine: 139.74±16.67), SAS scores (Quality group: 48.42±2.65; Routine: 58.15±2.43), and SDS scores versus routine care (Quality group:48.42±2.65; Routine: 58.15±2.43)(P < .05). The quality group showed a lower incidence of adverse maternal and infant pregnancy outcomes than the routine group (P < .05). Conclusion: The findings underscore the positive impact of quality care in reducing adverse maternal and newborn pregnancy outcomes. This reduction is particularly significant for clinical practice, as it is achieved through the amelioration of various factors, such as neurological impairments, blood pressure regulation, and the alleviation of negative emotions, including anxiety and depression, in patients with HDCP complicated by cerebral hemorrhage. The practical implications of these findings for healthcare providers and patients are substantial. They highlight the potential to improve patient outcomes, enhance the overall quality of care, and reduce the burden on healthcare systems. By addressing these factors, healthcare providers can enhance the well-being of both mothers and newborns, leading to improved clinical outcomes and increased patient satisfaction.


Assuntos
Hemorragia Cerebral , Hipertensão Induzida pela Gravidez , Resultado da Gravidez , Qualidade da Assistência à Saúde , Humanos , Feminino , Gravidez , Adulto , Hemorragia Cerebral/complicações , Hemorragia Cerebral/terapia , Recém-Nascido , Hipertensão Induzida pela Gravidez/terapia
5.
Sensors (Basel) ; 24(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38894393

RESUMO

As the global aging population increases, the demand for rehabilitation of elderly hand conditions has attracted increased attention in the field of wearable sensors. Owing to their distinctive anti-electromagnetic interference properties, high sensitivity, and excellent biocompatibility, optical fiber sensors exhibit substantial potential for applications in monitoring finger movements, physiological parameters, and tactile responses during rehabilitation. This review provides a brief introduction to the principles and technologies of various fiber sensors, including the Fiber Bragg Grating sensor, self-luminescent stretchable optical fiber sensor, and optic fiber Fabry-Perot sensor. In addition, specific applications are discussed within the rehabilitation field. Furthermore, challenges inherent to current optical fiber sensing technology, such as enhancing the sensitivity and flexibility of the sensors, reducing their cost, and refining system integration, are also addressed. Due to technological developments and greater efforts by researchers, it is likely that wearable optical fiber sensors will become commercially available and extensively utilized for rehabilitation.


Assuntos
Fibras Ópticas , Dispositivos Eletrônicos Vestíveis , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Tecnologia de Fibra Óptica/instrumentação , Reabilitação/instrumentação , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(8): 835-839, 2024 Aug 15.
Artigo em Zh | MEDLINE | ID: mdl-39148388

RESUMO

OBJECTIVES: To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN. METHODS: A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated. RESULTS: The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL. CONCLUSIONS: Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.


Assuntos
Complemento C1q , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Complemento C1q/imunologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/sangue , Feminino , Criança , Masculino , Lúpus Eritematoso Sistêmico/imunologia , Estudos Retrospectivos , Adolescente , Autoanticorpos/sangue , Pré-Escolar , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia
7.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(8): 823-828, 2024 Aug 15.
Artigo em Zh | MEDLINE | ID: mdl-39148386

RESUMO

OBJECTIVES: To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022. RESULTS: Among the AAV children, there were 5 males and 20 females, with a median age of onset of 11.0 years. Involvement of the urinary system was seen in 18 cases (72%); respiratory system involvement in 10 cases (40%); skin involvement in 6 cases (24%); eye, ear, and nose involvement in 5 cases (20%); joint involvement in 4 cases (16%); digestive system involvement in 2 cases (8%). Eleven cases underwent kidney biopsy, with 5 cases (46%) showing focal type, 2 cases (18%) showing crescentic type, 2 cases (18%) showing mixed type, and 2 cases (18%) showing sclerotic type. Immune complex deposits were present in 5 cases (45%). Seven cases reached chronic kidney disease (CKD) stage V, with 2 cases resulting in death. Two cases underwent kidney transplantation. At the end of the follow-up period, 2 cases were at CKD stage II, and 1 case was at CKD stage III. Of the 16 cases of microscopic polyangiitis (MPA) group, 13 (81%) involved the urinary system. Of the 9 cases of granulomatosis with polyangiitis (GPA), 6 cases (66%) had sinusitis. Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group (P<0.05), while red blood cell count and glomerular filtration rate were lower in the MPA group (P<0.05). CONCLUSIONS: AAV is more common in school-age female children, with MPA being the most common clinical subtype. The onset of AAV in children is mainly characterized by renal involvement, followed by respiratory system involvement. The renal pathology often presents as focal type with possible immune complex deposits. Children with MPA often have renal involvement, while those with GPA commonly have sinusitis. The prognosis of children with AAV is poor, often accompanied by renal insufficiency.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Feminino , Masculino , Criança , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Estudos Retrospectivos , Adolescente , Pré-Escolar , Insuficiência Renal Crônica/etiologia
8.
Chemistry ; 29(14): e202203420, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36464909

RESUMO

Dehydratase (DH), a domain located at polyketide synthase (PKS) modules, commonly catalyzes the dehydration of ß-hydroxy to an α,ß-unsaturated acyl intermediate. As a unique bifunctional dehydratase, AmbDH3 (the DH domain of module 3 of the ambruticin PKS) is verified to be responsible for both dehydration and the following pyran-forming cyclization. Besides, in vitro studies showed that its catalytic efficiency varies with different chiral substrates. However, the detailed molecular mechanism of AmbDH3 remains unclear. In this work, the structural rationale for the substrate specificity (2R/2S- and 6R/6S-substrates) in AmbDH3 was elucidated and the complete reaction pathways including dehydration and cyclization were presented. Both MD simulations and binding free energy calculations indicated AmbDH3 had a stronger preference for 2R-substrates (2R6R-2, 2R6S-3) than 2S-substrates (2S6R-1), and residue H51 and G61 around the catalytic pocket were emphasized by forming stable hydrogen bonds with 2R-substrates. In addition, AmbDH3's mild tolerance at C6 was explained by comparison of substrate conformation and hydrogen bond network in 6S- and 6R-substrate systems. The QM/MM results supported a consecutive one-base dehydration and cyclization mechanism for 2R6S-3 substrate with the energy barrier of 25.2 kcal mol-1 and 24.5 kcal mol-1 , respectively. Our computational results uncover the substrate recognition and catalytic process of the first bifunctional dehydratase-cyclase AmbDH3, which will shed light on the application of multifunctional DH domains in PKSs for diverse natural product analogs and benefit the chemoenzymatic synthesis of stereoselective pyran-containing products.


Assuntos
Desidratação , Policetídeo Sintases , Humanos , Especificidade por Substrato , Policetídeo Sintases/química , Piranos/química , Hidroliases/química
9.
Int Microbiol ; 26(4): 1009-1020, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37067733

RESUMO

Ectoine is a natural amino acid derivative and one of the most widely used compatible solutes produced by Halomonas species that affects both cellular growth and osmotic equilibrium. The positive effects of UV mutagenesis on both biomass and ectoine content production in ectoine-producing strains have yet to be reported. In this study, the wild-type H. campaniensis strain XH26 (CCTCCM2019776) was subjected to UV mutagenesis to increase ectoine production. Eight rounds of mutagenesis were used to generate mutated XH26 strains with different UV-irradiation exposure times. Ectoine extract concentrations were then evaluated among all strains using high-performance liquid chromatography analysis, alongside whole genome sequencing with the PacBio RS II platform and comparison of the wild-type strain XH26 and the mutant strain G8-52 genomes. The mutant strain G8-52 (CCTCCM2019777) exhibited the highest cell growth rate and ectoine yields among mutated strains in comparison with strain XH26. Further, ectoine levels in the aforementioned strain significantly increased to 1.51 ± 0.01 g L-1 (0.65 g g-1 of cell dry weight), representing a twofold increase compared to wild-type cells (0.51 ± 0.01 g L-1) when grown in culture medium for ectoine accumulation. Concomitantly, electron microscopy revealed that mutated strain G8-52 cells were obviously shorter than wild-type strain XH26 cells. Moreover, strain G8-52 produced a relatively stable ectoine yield (1.50 g L-1) after 40 days of continuous subculture. Comparative genomics analysis suggested that strain XH26 harbored 24 mutations, including 10 nucleotide insertions, 10 nucleotide deletions, and unique single nucleotide polymorphisms. Notably, the genes orf00723 and orf02403 (lipA) of the wild-type strain mutated to davT and gabD in strain G8-52 that encoded for 4-aminobutyrate-2-oxoglutarate transaminase and NAD-dependent succinate-semialdehyde dehydrogenase, respectively. Consequently, these genes may be involved in increased ectoine yields. These results suggest that continuous multiple rounds of UV mutation represent a successful strategy for increasing ectoine production, and that the mutant strain G8-52 is suitable for large-scale fermentation applications.


Assuntos
Halomonas , Halomonas/genética , Halomonas/metabolismo , Raios Ultravioleta , Genômica , Nucleotídeos/metabolismo
10.
Sensors (Basel) ; 23(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37687808

RESUMO

Compared with lever-type amplification mechanisms, bridge-type flexible amplification mechanisms have advantages in terms of amplification ratio and structural compactness. Therefore, they can effectively replace the lever-type amplification mechanism in the existing hair-like sensors and realize the development of miniature hair-like sensors with high sensitivity. With that in mind, a highly sensitive hair-like sensor based on a bridge-type amplification mechanism with distributed flexibility is presented to measure the airflow rate. First, the structural composition and operating principle of the hair-like sensor are described. Then, detailed design and analysis of the hair-like sensor are carried out, focusing on the design of the hair post structure, amplification mechanism, and resonator. Furthermore, the designed hair-like sensor is processed and prepared, and some experimental studies are conducted. The experimental results demonstrate that the developed hair-like sensor can measure the airflow rate with high sensitivity up to 8.56 Hz/(m/s)2. This provides a new concept for the structural design of hair-like sensors and expands the application of bridge-type flexible amplification mechanisms in the field of micro/nano sensors.

11.
Asia Pac J Clin Nutr ; 32(1): 26-32, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36997482

RESUMO

BACKGROUND AND OBJECTIVES: The impacts of nutritional status on clinical outcomes in children receiving umbilical cord blood stem cell transplantation (UCBT) are not fully described. We evaluated the risk for malnutrition before transplantation admission and influence of weight loss during hospitalization on short-term clinical outcomes in children with UCBT. METHODS AND STUDY DESIGN: We conducted a retrospective study of pediatric patients up to age 18 years who received UCBT and were treated at the Children's Hospital of Fudan University between January 2019 and December 2020. RESULTS: The mean age of the 91 patients was 1.3 years, with 78 (85.7%) men and 13 (14.3%) women (p<0.001). UCBT was performed mostly for primary immunodeficiency disease (PID) (83, 91.2%). The weight loss differences among children with different primary diseases were statistically significant (p=0.003). Children with a large amount of weight loss during hospitalization (n = 24) had higher risks of skin graft-versus-host disease (GVHD) (multivariate OR=5.01, 95% CI: 1.35-18.65), intestinal GVHD (multivariate OR=7.27, 95% CI: 1.74-30.45), a longer median hospital stay (p=0.004), higher antibiotic costs (p=0.008) and higher total hospitalization costs (p=0.004). Malnutrition on admission was significantly positively correlated with longer parenteral nutrition (PN) time (p=0.008). Early nutritional intervention effects on clinical outcomes need further assessment. CONCLUSIONS: Underweight recipient child and excessive weight loss during transplantation increases the length and cost of hospital stay, and is associated with a high incidence of GVHD, which affects the prognosis of transplantation and medical resources consumption.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Desnutrição , Masculino , Criança , Humanos , Feminino , Lactente , Adolescente , Estado Nutricional , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/etiologia , Desnutrição/complicações
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(8): 785-790, 2023 Aug 15.
Artigo em Zh | MEDLINE | ID: mdl-37668024

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ systems, presenting a complex and diverse clinical manifestation. The heterogeneous treatment response and prognosis of SLE pose significant challenges to its diagnosis, classification, and homogeneous treatment. The emergence of new technologies and fields, such as synthetic biology, genomics, and proteomics, has contributed to a deeper exploration of the pathogenesis and biomarkers of SLE, facilitating precision diagnosis and treatment. This review summarizes the latest research data and achievements in SLE for the years 2021-2022, providing an overview and summary of relevant studies conducted in the past two years.


Assuntos
Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Proteômica
13.
Biochem Cell Biol ; 100(1): 9-16, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34658256

RESUMO

Cardiovascular and related metabolic diseases are significant global health challenges. Glucagon-like peptide 1 (GLP-1) is a brain-gut peptide secreted by the ileal endocrine system and is now an established drug target in type 2 diabetes (T2DM). GLP-1 targeting agents have been shown not only to treat T2DM, but also to exert cardiovascular protective effects by regulating multiple signaling pathways. The mitogen-activated protein kinase (MAPK) pathway, a common signal transduction pathway for transmitting extracellular signals to downstream effector molecules, is involved in regulating diverse cellular physiological processes, including cell proliferation, differentiation, stress, inflammation, functional synchronization, transformation, and apoptosis. The purpose of this review is to highlight the relationship between GLP-1 and cardiovascular disease (CVD) and discuss how GLP-1 exerts cardiovascular protective effects through the MAPK signaling pathway. This review also discusses the future challenges in fully characterizing and evaluating the CVD protective effects of GLP-1 receptor agonists (GLP-1RA) at the cellular and molecular levels. A better understanding of the MAPK signaling pathway that is dysregulated in CVD may aid in the design and development of promising GLP-1RA.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais
14.
Cytokine ; 159: 156000, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36058192

RESUMO

BACKGROUND: Renal interstitial fibrosis (RIF) is the main pathological change of a variety of chronic kidney diseases (CKD). Epigenetic modifications of fibrosis-prone genes regulate RIF progression. This study aimed to investigate long non-coding RNA (lncRNA) N6-methyladenosine (m6A) modification and its role in regulating RIF progression. METHODS: Unilateral ureteral occlusion (UUO) was employed to construct the RIF in vivo model; and TGF-ß1-treated HK-2 and HKC-8 cells were used for in vitro experiments. The mRNA and protein expressions were assessed using qRT-PCR and western blot. The proliferation and migration were evaluated by EdU assay and transwell assay, respectively. In addition, levels of inflammatory cytokines were determined by ELISA assay and qRT-PCR. Moreover, lncRNA GAS5 m6A level was detected using Me-RIP assay. HE and Masson staining were employed to evaluate fibrotic lesions of the kidney. RESULTS: FTO expression was elevated in HK-2 and HKC-8 cells after TGF-ß1 treatment and mouse kidney tissue following UUO, and lncRNA GAS5 was downregulated. LncRNA GAS5 overexpression or FTO silencing suppressed TGF-ß1-induced the increase of EMT-related proteins (Vimentin, Snail and N-cadherin) and inflammatory cytokines (IL-6, IL-1ß and TNF-α) levels in HK-2 cells. FTO suppressed lncRNA GAS5 expression by reducing the m6A modification of lncRNA GAS5. Additionally, FTO knockdown could suppress EMT process and inflammation response induced by TGF-ß1 and UUO in vitro and in vivo. As expected, FTO knockdown abrogated the promotion effects of lncRNA GAS5 silencing on TGF-ß1-induced EMT process and inflammation response in HK-2 and HKC-8 cells. CONCLUSION: FTO promoted EMT process and inflammation response through reducing the m6A modification of lncRNA GAS5.


Assuntos
RNA Longo não Codificante , Insuficiência Renal Crônica , Obstrução Ureteral , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Animais , Caderinas , Transição Epitelial-Mesenquimal/genética , Fibrose , Inflamação/genética , Inflamação/patologia , Interleucina-6/farmacologia , Rim/metabolismo , Camundongos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Obstrução Ureteral/genética , Obstrução Ureteral/metabolismo , Vimentina
15.
Extremophiles ; 26(1): 14, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35229247

RESUMO

Halophilic bacteria such as the genus Halomonas are promising candidates in diverse industrial, agricultural and biomedical applications. Here, we successfully isolated a halophilic Halomonas alkaliphila strain XH26 from Xiaochaidan Salt Lake, and studied its osmoadaptation strategies using transcriptome and ectoine analysis. Divergent mechanisms were involved in osmoadaptation at different salinities in H. alkaliphila XH26. At moderate salinity (6% NaCl), increased transcriptions of ABC transporters related to iron (III), phosphate, phosphonate, monosaccharide and oligosaccharide import were observed. At high salinity (15% NaCl), transcriptions of flagellum assembly and cell motility were significantly inhibited. The transcriptional levels of ABC transporter genes related to iron (III) and iron3+-hydroxamate import, glycine betaine and putrescine uptake, and cytochrome biogenesis and assembly were significantly up-regulated. Ectoine synthesis and accumulation was significantly increased under salt stress, and the increased transcriptional expressions of ectoine synthesis genes ectB and ectC may play a key role in high salinity induced osmoadaptation. At extreme high salinity (18% NaCl), 5-hydroxyectoine and ectoine worked together to maintain cell survival. Together these results give valuable insights into the osmoadaptation mechanisms of H. alkaliphila XH26, and provide useful information for further engineering this specific strain for increased ectoine synthesis and related applications.


Assuntos
Diamino Aminoácidos , Halomonas , Diamino Aminoácidos/metabolismo , Halomonas/genética , Halomonas/metabolismo , Estresse Salino , Transcriptoma
16.
Antonie Van Leeuwenhoek ; 115(4): 545-559, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35243586

RESUMO

Here, we report the whole genome of a novel halophilic Halomonas species strain XH36 with high ectoine production potential. The genome was 3,818,310 bp in size with a GC content of 51.97%, and contained 3533 genes, 61 tRNAs and 18 rRNAs. The phylogenetic analysis using the 16s rRNA genes, the UBCGs and the TYGS database indicated that XH36 belongs to a novel Halomonas species, which we named as Halomonas qaidamensis. Osmoadaptation related genes including Na(+) and K(+) transport and compatible solute accumulation were both present in the XH36 genome, the latter of which mainly contained ectoine, 5-hydroxyectoine and betaine. HPLC validation studies showed that H. qaidamensis XH36 accumulated ectoine to cope with salt stress, and the content of ectoine could be as high as 315 mg/g CDW under 3 mol/l NaCl. Our results show that XH36 is a new promising industrial strain for ectoine production, and the genomic analysis will guide us to better understand its salt-induced osmoadaptation mechanisms, and provide theoretical references for future application research of ectoine.


Assuntos
Diamino Aminoácidos , Halomonas , Halomonas/genética , Filogenia , RNA Ribossômico 16S/genética , Sequenciamento Completo do Genoma
17.
Sensors (Basel) ; 22(12)2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35746289

RESUMO

In this paper, a novel near-field high-resolution image focusing technique is proposed. With the emergence of Millimeter-wave (mmWave) devices, near-field synthetic aperture radar (SAR) imaging is widely used in automotive-mounted SAR imaging, UAV imaging, concealed threat detection, etc. Current research is mainly confined to the laboratory environment, thus ignoring the adverse effects of the non-ideal experimental environment on imaging and subsequent detection in real scenarios. To address this problem, we propose an optimized Back-Projection Algorithm (BPA) that considers the loss path of signal propagation among space by converting the amplitude factor in the echo model into a beam-weighting. The proposed algorithm is an image focusing algorithm for arbitrary and irregular arrays, and effectively mitigates sparse array imaging ghosts. We apply the 3DRIED dataset to construct image datasets for target detection, comparing the kappa coefficients of the proposed scheme with those obtained from classic BPA and Range Migration Algorithm (RMA) with amplitude loss compensation. The results show that the proposed algorithm attains a high-fidelity image reconstruction focus.

18.
FASEB J ; 34(1): 1398-1411, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914630

RESUMO

Atherosclerosis is a chronic disease characterized by lipid deposition and inflammatory response. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-facilitated inflammatory responses are crucial in the pathogenesis of atherosclerosis, and thus new therapeutic approaches are emerging that target NLRP3 and inflammation. Here, we explored the anti-atherosclerotic effect and mechanisms of a new rutaecarpine derivative, 5-deoxy-rutaecarpine (R3) in vitro and in vivo. R3 treatment attenuated atherosclerosis development and increased plaque stability in Apoe-/- mice fed a high-fat diet, and decreased levels of inflammatory mediators, such as interleukin-1ß, in the serum of Apoe-/- mice and in oxidized low-density lipoprotein (ox-LDL)-stimulated murine macrophages. R3 treatment inhibited NLRP3 inflammasome activation in the livers of Apoe-/- mice and ox-LDL-stimulated murine macrophages by inhibiting NF-κB and MAPK pathways. Additionally, R3 significantly decreased total cholesterol in the serum and livers of Apoe-/- mice and promoted cholesterol efflux in murine macrophages through upregulating protein expression of ATP-binding cassette subfamily A member 1 and scavenger receptor class B type I/human CD36 and lysosomal integral membrane protein-II analogous-1. Our results demonstrated that R3 prevented atherosclerotic progression via attenuating NLRP3 inflammasome-related inflammation and modulating cholesterol transport.


Assuntos
Aterosclerose/tratamento farmacológico , Colesterol/metabolismo , Alcaloides Indólicos/farmacologia , Inflamassomos/metabolismo , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Quinazolinas/farmacologia , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Transporte Biológico Ativo/efeitos dos fármacos , Colesterol/genética , Inflamassomos/genética , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/patologia , Camundongos , Camundongos Knockout para ApoE , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética
19.
Arch Microbiol ; 203(5): 2029-2042, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33554274

RESUMO

Halophilic Archaea are widely distributed globally in hypersaline environments. However, little is known of how dominant halophilic archaeal genera are distributed across environments and how they may co-associate across ecosystems. Here, the archaeal community composition and diversity from hypersaline environments (> 300 g/L salinity; total of 33 samples) in the Qaidam Basin of China were investigated using high-throughput Illumina sequencing of 16S rRNA genes. The archaeal communities (total of 3,419 OTUs) were dominated by the class Halobacteria (31.7-99.6% relative abundances) within the phylum Euryarchaeota (90.8-99.9%). Five predominant taxa, including Halorubrum, Halobacterium, Halopenitus, Methanothrix, and Halomicrobium, were observed across most samples. However, several distinct genera were associated with individual samples and were inconsistently distributed across samples, which contrast with previous studies of hypersaline archaeal communities. Additionally, co-occurrence network analysis indicated that five network clusters were present and potentially reflective of interspecies interactions among the environments, including three clusters (clusters II, III, and IV) comprising halophilic archaeal taxa within the Halobacteriaceae and Haloferacaceae families. In addition, two other clusters (clusters I and V) were identified that comprised methanogens. Finally, salinity comprising ionic concentrations (in the order of Na+ > Ca2+ > Mg2+) and pH were most correlated with taxonomic distributions across sample sites.


Assuntos
Ecossistema , Microbiologia Ambiental , Euryarchaeota/classificação , China , Euryarchaeota/genética , RNA Ribossômico 16S/genética , Salinidade , Água do Mar/microbiologia
20.
J Org Chem ; 86(18): 13011-13024, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34494838

RESUMO

An amino-controlled regiodivergent asymmetric synthesis of CF3-containing spiro-pyrrolidine-pyrazolone compounds is described. With alkaloid-derived squaramide as catalyst, the 1,3-dipolar cycloaddition of α,ß-unsaturated pyrazolone with diethyl 2-((2,2,2-trifluoroethyl)imino) malonate offered adducts in excellent yields, dr, and ee. While the cyclohexanediamine-derived squaramide was employed, the reaction afforded a series of structure isomers through a switched umpolung reaction.


Assuntos
Pirazolonas , Compostos de Espiro , Estrutura Molecular , Prótons , Pirrolidinas , Estereoisomerismo
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