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2.
Acta Pharm Sin B ; 14(4): 1483-1493, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572111

RESUMO

Cardiac resident macrophages (CRMs) are the main population of cardiac immune cells. The role of these cells in regeneration, functional remodeling, and repair after cardiac injury is always the focus of research. However, in recent years, their dynamic changes and contributions in physiological states have a significant attention. CRMs have specific phenotypes and functions in different cardiac chambers or locations of the heart and at different stages. They further show specific differentiation and development processes. The present review will summarize the new progress about the spatiotemporal distribution, potential developmental regulation, and their roles in cardiac development and aging as well as the translational potential of CRMs on cardiac diseases. Of course, the research tools for CRMs, their respective advantages and disadvantages, and key issues on CRMs will further be discussed.

3.
Urolithiasis ; 52(1): 59, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568426

RESUMO

To evaluate the safety and efficacy of tubeless percutaneous nephrolithotomy (PCNL) in patients with Escherichia coli (E. coli) bacteriuria. We conducted a retrospective review of 84 patients with E. coli bacteriuria who underwent PCNL. Patients were divided into two groups according to whether a nephrostomy tube is placed at the end of the procedure. Preoperative clinical data, surgical outcomes, and postoperative complications were compared. Then, regression analysis of factors predicting success rate of PCNL in patients with E. coli bacteriuria was performed. After PCNL, residual fragments ≤ 4 mm were considered as success. At baseline, the two groups were similar with regard to age, gender, BMI, underlying disease, hydronephrosis, stone characteristics, and urinalysis. Postoperative fever occurred in 1 patient (3.8%) in the tubeless PCNL group, and in 5 patients (8.6%) in the conventional PCNL group (p > 0.05). There were no significant differences in terms of successful rate, decrease in hemoglobin, pain scores, blood transfusion, and hospitalization expenses. However, the tubeless PCNL group had significantly shorter operative time (60 vs. 70 min, p = 0.033), indwelling time of catheter (2 vs. 4 days, p < 0.001), and hospital stays (3 vs. 5 days, p < 0.001) than the conventional PCNL group. In the analysis of factors predicting success, the stone diameter, stone burden, and operative time were associated with success rate of PCNL. It is safe and effective to perform tubeless PCNL in patients with E. coli bacteriuria. Compared to conventional PCNL, tubeless PCNL accelerates patient recovery and shortens hospital stays.


Assuntos
Bacteriúria , Nefrolitotomia Percutânea , Humanos , Nefrolitotomia Percutânea/efeitos adversos , Escherichia coli , Catéteres , Hospitalização
4.
Artigo em Inglês | MEDLINE | ID: mdl-38573593

RESUMO

Neointimal hyperplasia causes the failure of coronary artery bypass grafting (CABG). Our previous studies have found that endothelial dysfunction is one candidate for triggering neointimal hyperplasia, but which factors are involved in this process is unclear. Glutathione S-transferase α4 (GSTA4) play an important role in metabolizing 4-hydroxynonenal (4-HNE), a highly reactive lipid peroxidation product, which causes endothelial dysfunction or death. Here, we investigated the role of GSTA4 in neointima formation after arteriovenous grafts (AVGs) with or without high-fat diet (HFD). Compared with normal diet (ND), HFD caused endothelial dysfunction and increased neointima formation, concomitantly accompanied by downregulated expression of GSTA4 at the mRNA and protein levels. In vitro, overexpression of GSTA4 attenuated 4-HNE-induced endothelial dysfunction and knockdown of GSTA4 aggravated endothelial dysfunction. Furthermore, silencing GSTA4 expression facilitated the activation of 4-HNE induced endoplasmic reticulum stress (ERS) and inhibition of ERS pathway alleviated 4-HNE-induced endothelial dysfunction. Additionally, compared with wild-type (WT) mice, mice with knockout of endothelial-specific GSTA4 (GSTA4 EC KO) exhibited exacerbated vascular endothelial dysfunction and increased neointima formation caused by HFD. Together, these results demonstrate the critical role of GSTA4 in protecting the function of endothelial cells and in alleviating hyperlipidemia-induced vascular neointimal hyperplasia in arteriovenous grafts.

5.
Int Immunopharmacol ; 133: 112133, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38652962

RESUMO

There is an increasing tendency for sepsis patients to suffer from diaphragm atrophy as well as mortality. Therefore, reducing diaphragm atrophy could benefit sepsis patients' prognoses. Studies have shown that Anisodamine (Anis) can exert antioxidant effects when blows occur. However, the role of Anisodamine in diaphragm atrophy in sepsis patients has not been reported. Therefore, this study investigated the antioxidant effect of Anisodamine in sepsis-induced diaphragm atrophy and its mechanism. We used cecal ligation aspiration (CLP) to establish a mouse septic mode and stimulated the C2C12 myotube model with lipopolysaccharide (LPS). After treatment with Anisodamine, we measured the mice's bodyweight, diaphragm weight, fiber cross-sectional area and the diameter of C2C12 myotubes. The malondialdehyde (MDA) levels in the diaphragm were detected using the oxidative stress kit. The expression of MuRF1, Atrogin1 and JAK2/STAT3 signaling pathway components in the diaphragm and C2C12 myotubes was measured by RT-qPCR and Western blot. The mean fluorescence intensity of ROS in C2C12 myotubes was measured by flow cytometry. Meanwhile, we also measured the levels of Drp1 and Cytochrome C (Cyt-C) in vivo and in vitro by Western blot. Our study revealed that Anisodamine alleviated the reduction in diaphragmatic mass and the loss of diaphragmatic fiber cross-sectional area and attenuated the atrophy of the C2C12 myotubes by inhibiting the expression of E3 ubiquitin ligases. In addition, we observed that Anisodamine inhibited the JAK2/STAT3 signaling pathway and protects mitochondrial function. In conclusion, Anisodamine alleviates sepsis-induced diaphragm atrophy, and the mechanism may be related to inhibiting the JAK2/STAT3 signaling pathway.


Assuntos
Diafragma , Janus Quinase 2 , Atrofia Muscular , Fator de Transcrição STAT3 , Sepse , Transdução de Sinais , Alcaloides de Solanáceas , Animais , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Sepse/tratamento farmacológico , Sepse/complicações , Alcaloides de Solanáceas/uso terapêutico , Alcaloides de Solanáceas/farmacologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Diafragma/efeitos dos fármacos , Diafragma/patologia , Diafragma/metabolismo , Masculino , Linhagem Celular , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/etiologia , Modelos Animais de Doenças , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Proteínas Musculares/metabolismo , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/metabolismo , Atrofia
6.
Biomedicines ; 12(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38672256

RESUMO

(1) Background: Sepsis-induced muscle atrophy is characterized by a loss of muscle mass and function which leads to decreased quality of life and worsens the long-term prognosis of patients. N-acetylcysteine (NAC) has powerful antioxidant and anti-inflammatory properties, and it relieves muscle wasting caused by several diseases, whereas its effect on sepsis-induced muscle atrophy has not been reported. The present study investigated the effect of NAC on sepsis-induced muscle atrophy and its possible mechanisms. (2) Methods: The effect of NAC on sepsis-induced muscle atrophy was assessed in vivo and in vitro using cecal ligation and puncture-operated (CLP) C57BL/6 mice and LPS-treated C2C12 myotubes. We used immunofluorescence staining to analyze changes in the cross-sectional area (CSA) of myofibers in mice and the myotube diameter of C2C12. Protein expressions were analyzed by Western blotting. (3) Results: In the septic mice, the atrophic response manifested as a reduction in skeletal muscle weight and myofiber cross-sectional area, which is mediated by muscle-specific ubiquitin ligases-muscle atrophy F-box (MAFbx)/Atrogin-1 and muscle ring finger 1 (MuRF1). NAC alleviated sepsis-induced skeletal muscle wasting and LPS-induced C2C12 myotube atrophy. Meanwhile, NAC inhibited the sepsis-induced activation of the endoplasmic reticulum (ER) stress signaling pathway. Furthermore, using 4-Phenylbutyric acid (4-PBA) to inhibit ER stress in LPS-treated C2C12 myotubes could partly abrogate the anti-muscle-atrophy effect of NAC. Finally, NAC alleviated myotube atrophy induced by the ER stress agonist Thapsigargin (Thap). (4) Conclusions: NAC can attenuate sepsis-induced muscle atrophy, which may be related to downregulating ER stress.

7.
Sci Rep ; 14(1): 2914, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316888

RESUMO

To explore the preference for diagnosing and treating renal colic during pregnancy among Chinese urologists. A questionnaire was designed using the Sojump® platform. WeChat, the largest social networking platform in China, was used to distribute the questionnaire to urologists at hospitals of all levels in China. In total, 110 responses were included. Of the respondents, 100.0% used ultrasound to diagnose renal colic during pregnancy, followed by magnetic resonance imaging (17.3%) and low-dose CT (3.6%). Phloroglucinol (80.9%) and progesterone (72.7%) were the most commonly used antispasmodics and analgesics. Opioid analgesics were not commonly used (12.7%). Most of the respondents (63.6%) indicated that no more than 20% of the patients needed surgical intervention. If surgery was unavoidable, 95.5% preferred temporary renal drainage, including ureteral stenting (92.7%) and percutaneous nephrostomy (2.7%). However, some respondents still preferred definitive stone treatment, such as ureteroscopy lithotripsy (3.6%) and percutaneous nephrolithotomy (0.9%). Moreover, there were no differences in the choices of urologists with different professional titles regarding diagnostic tools, most therapeutic medications, or surgical methods (p > 0.05). Ultrasound is the preferred tool for diagnosing renal colic during pregnancy. Low-dose CT is still not widely accepted. Pregnant patients with renal colic are initially treated conservatively. Urologists prefer ureteral stenting when there are clinical indications for intervention.


Assuntos
Cólica Renal , Ureter , Cálculos Ureterais , Gravidez , Feminino , Humanos , Cólica Renal/diagnóstico , Cólica Renal/terapia , Urologistas , Ureteroscopia/métodos , Inquéritos e Questionários , Cálculos Ureterais/terapia
8.
Acta Psychol (Amst) ; 243: 104149, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38245937

RESUMO

Insomnia, which is highly prevalent among college students, has been identified as one of the negative consequences of childhood maltreatment. While prior studies have uncovered distinct correlations between childhood maltreatment, insomnia, and other variables, the potential underlying mechanisms need to be further explored. This study focused on the chain-mediating role of alexithymia and psychological distress in the relationship between childhood maltreatment and insomnia. An online cross-sectional survey was conducted among Chinese college students, yielding 999 valid questionnaires that included demographic information, the Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Toronto Alexithymia Scale (TAS), the 21-item Depression Anxiety Stress Scales (DASS-21), and the Insomnia Severity Index (ISI). A chain-mediating model was then tested. The results revealed significant positive correlations between each pair of the four variables. Alexithymia and psychological distress separately mediated the link between childhood maltreatment and insomnia (effect of alexithymia was 0.06 with 95 % CI [0.03, 0.09]; effect of psychological distress was 0.24 with 95 % CI [0.19, 0.29]). Additionally, a chain-mediating effect of alexithymia and psychological distress was observed (chain-mediating effect was 0.12 with 95 % CI [0.09, 0.15]). The findings suggest that emotional interventions may mitigate the long-term effect of childhood maltreatment on sleep problems among college students, by improving the ability to recognize emotions and decreasing emotional problems.


Assuntos
Maus-Tratos Infantis , Angústia Psicológica , Testes Psicológicos , Autorrelato , Distúrbios do Início e da Manutenção do Sono , Criança , Humanos , Sintomas Afetivos/epidemiologia , Sintomas Afetivos/psicologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudos Transversais , Maus-Tratos Infantis/psicologia , Estudantes/psicologia
9.
Sci Rep ; 14(1): 1447, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228655

RESUMO

Premature ovarian failure (POF) caused by chemotherapy is a growing concern for female reproductive health. The use of metformin (MET), which has anti-oxidative and anti-inflammatory effects, in the treatment of POF damaged by chemotherapy drugs remains unclear. In this study, we investigated the impact of MET on POF caused by cyclophosphamide (CTX) combined with busulfan (BUS) and M1 macrophages using POF model mice and primary granule cells (GCs). Our findings demonstrate that intragastric administration of MET ameliorates ovarian damage and alleviates hormonal disruption in chemotherapy-induced POF mice. This effect is achieved through the reduction of inflammatory and oxidative stress-related harm. Additionally, MET significantly relieves abnormal inflammatory response, ROS accumulation, and senescence in primary GCs co-cultured with M1 macrophages. We also observed that this protective role of MET is closely associated with the AMPK/PPAR-γ/SIRT1 pathway in cell models. In conclusion, our results suggest that MET can protect against chemotherapy-induced ovarian injury by inducing the expression of the AMPK pathway while reducing oxidative damage and inflammation.


Assuntos
Antineoplásicos , Metformina , Insuficiência Ovariana Primária , Humanos , Camundongos , Feminino , Animais , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/prevenção & controle , Insuficiência Ovariana Primária/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Metformina/uso terapêutico , Células da Granulosa/metabolismo , Antineoplásicos/farmacologia
10.
Biomol Biomed ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236204

RESUMO

Sepsis, a life-threatening condition characterized by organ dysfunction, results from a complex series of pathophysiological mechanisms including immune dysfunction, an uncontrolled inflammatory response, and coagulation abnormalities. It is a major contributor to global mortality and severe disease development. Platelets, abundant in the circulatory system, are sensitive to changes in the body's internal environment and are among the first cells to respond to dysregulated pro-inflammatory and pro-coagulant reactions at the onset of sepsis. In the initial stages of sepsis, the coagulation cascade, inflammatory response, and endothelial tissue damage perpetually trigger platelet activation. These activated platelets then engage in complex inflammatory and immune reactions, potentially leading to organ dysfunction. Therefore, further research is essential to fully understand the role of platelets in sepsis pathology and to develop effective therapeutic strategies targeting the associated pathogenic pathways. This review delves into the involvement of platelets in sepsis and briefly outlines the clinical applications of associated biomarkers.

11.
Behav Res Methods ; 56(3): 2273-2291, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37311866

RESUMO

Careless responding, where participants do not fully engage with item content, is pervasive in survey research. Left undetected, carelessness can compromise the interpretation and use of survey results, including information about participant locations on the construct, item difficulty, and the psychometric quality of the instrument. We present and illustrate a sequential procedure for evaluating response quality in survey research using indicators from Mokken scale analysis (MSA). We use a real data illustration and a simulation study to compare a sequential procedure to a standalone procedure. We also consider how identifying and removing responses with evidence of poor measurement properties affects item quality indicators. Results suggest that the sequential procedure was effective in identifying potentially problematic response patterns that may not always be captured by traditional methods for identifying careless responders but was not always sensitive to specific carelessness patterns. We discuss implications for research and practice.


Assuntos
Projetos de Pesquisa , Humanos , Inquéritos e Questionários , Psicometria/métodos , Simulação por Computador
12.
Adv Mater ; 36(2): e2305479, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37705254

RESUMO

On-skin electronics require minimal thicknesses and decent transparency for conformal contact, imperceptible wearing, and visual aesthetics. It is challenging to search for advanced ultrathin dielectrics capable of supporting the active components while maintaining bending softness, easy handling, and wafer-scale processability. Here, self-delaminated aramid nanodielectrics (ANDs) are demonstrated, enabling any skin-like electronics easily exfoliated from the processing substrates after complicated nanofabrication. In addition, ANDs are mechanically strong, chemically and thermally stable, transparent and breathable, therefore are ideal substrates for soft electronics. As demonstrated, compliant epidermal electrodes comprising silver nanowires and ANDs can successfully record high-quality electromyogram signals with low motion artifacts and satisfying sweat and water resistance. Furthermore, ANDs can serve as both substrates and dielectrics in single-walled carbon nanotube field-effect transistors (FETs) with a merely 160-nm thickness, which can be operated within 4 V with on/off ratios of 1.4 ± 0.5 × 105 , mobilities of 39.9 ± 2.2 cm2 V-1 s-1 , and negligible hysteresis. The ultraconformal FETs can function properly when wrapped around human hair without any degradation in performance.

13.
J Drug Target ; 31(9): 920-930, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37724808

RESUMO

Gynecological cancers are the second most common types of cancer in women. Clinical diagnosis of these cancers is often delayed or misdiagnosed due to lack of insight into their tumorigenesis mechanism and specific diagnostic biomarkers. Many studies have demonstrated that competing endogenous RNAs (ceRNAs) modulate the progression and resistance of gynecological cancer through microRNA (miRNA)-mediated mechanisms, which affect gene expression in multiple cancer-related pathways. Here we review studies on the involvement of the ceRNA hypothesis in the progression and resistance of gynaecological cancers to validate some ceRNAs as therapeutic targets and predictive biomarkers.


Assuntos
MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , Feminino , RNA Mensageiro/metabolismo , Redes Reguladoras de Genes , Regulação Neoplásica da Expressão Gênica/genética , RNA Longo não Codificante/genética , Neoplasias/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores
14.
J Intell ; 11(7)2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37504774

RESUMO

The hypermedia environment is among the most prevalent contemporary self-regulated learning (SRL) environments; however, methods for improving the effectiveness of students' multi-session SRL in such environments remain under discussion. In this study, two experiments were conducted to explore whether and how prompts and feedback benefit performance during multi-session SRL in a hypermedia learning environment. A total of 76 senior students participated in Experiment 1, which used a mixed 2 (prompting condition: prompt, no prompt) × 2 (feedback condition: feedback, no feedback) × 2 (learning session: Session 1 and Session 2) design to explore the effects of prompting and feedback on the multi-session learning process in a hypermedia environment. The results indicated that, in learning Session 1, performance in the prompt condition was significantly better than in the unprompted condition, with or without feedback; in learning Session 2, participants in the prompt condition with feedback performed significantly better than those in the other three conditions. Students in the group with a prompt and feedback had the most accurate meta-comprehension absolute accuracy in both learning sessions. Experiment 2 recruited 94 secondary school students to further explore whether the combination of prompts and different types of feedback led to different learning outcomes according to the division of feedback timing. A mixed 2 (prompt condition: prompt, no prompt) × 3 (feedback condition: delayed feedback, immediate feedback, no feedback) × 2 (learning session: Session 1 and Session 2) design was used. The results indicated that, in learning Session 1, the prompt condition outperformed the unprompted condition with or without feedback; in learning Session 2, students with prompted delayed feedback outperformed the other five conditions. We also found that although there was no significant difference in meta-comprehension monitoring accuracy between delayed and immediate feedback, both groups performed significantly better than those in the no feedback condition. These results suggest that the combination of prompts and feedback in hypermedia environments facilitates student performance better than prompts or feedback alone; this improvement may be related to the correction of poor internal student feedback.

15.
Small ; 19(29): e2207785, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37052516

RESUMO

Supramolecular rather than covalent molecular engineering on Feringa motors can provide an alternative toolkit for tuning the properties of motorized materials through appropriate supramolecular structural perturbations, which are underexplored. Herein, a multicomponent supramolecular gel system is successfully prepared by employing an ultra-low molecular weight gelator and a modulator-Feringa motor. The electron microscopic, spectroscopic, and rheological data revealed that the morphology and mechanical properties of the gel can be tuned via a crystallographic mismatch branching (CMB) mechanism simply by adding varied amounts of motor modulators. Notably, the rotary motion of the motor is preserved in such a multicomponent gel system, and the morphology and rheology of the gel can be further altered by the motor's rotary motion that promotes the structural perturbation, resulting in seldomly seen gel-to-gel transition events. The work shown here offers prospects to utilize a supramolecular perturbation strategy to deliver responsiveness from molecular motors to the corresponding bulk materials.

16.
J Cell Physiol ; 238(3): 582-596, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36791253

RESUMO

Endoplasmic reticulum (ER) stress is involved in skeletal muscle atrophy in various conditions, but the role of ER stress in sepsis-induced muscle atrophy is not well understood. In this study, we conducted experiments in wild-type (WT) mice and C/EBP homologous protein knockout (CHOP KO) mice to explore the role and mechanism of ER stress in sepsis-induced muscle atrophy. Cecal ligation and puncture (CLP) was used to establish a mouse model of sepsis. In WT mice, the body weight, muscle mass, and cross-sectional area of muscle fibers in CLP group both decreased significantly compared with sham group, which revealed that sepsis-induced dramatic muscle atrophy. Additionally, sepsis activated the ubiquitin-proteasome system (UPS), accompanied by the activation of ER stress. In vitro, inhibition of ER stress suppressed the activity of E3 ubiquitin ligases and alleviated the myotube atrophy. In vivo, CHOP KO also reduced the expression of E3 ubiquitin ligases and UPS-mediated protein degradation, and significantly attenuated sepsis-induced muscle atrophy. Deletion of CHOP also decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and Smad3, and inhibition of STAT3 and Smad3 partly reduced proteolysis caused by ER stress in vitro. These findings confirm that ER stress activates UPS-mediated proteolysis and promotes sepsis-induced muscle atrophy, which is partly achieved by activating STAT3 and Smad3.


Assuntos
Estresse do Retículo Endoplasmático , Atrofia Muscular , Fator de Transcrição STAT3 , Sepse , Proteína Smad3 , Animais , Camundongos , Camundongos Knockout , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Sepse/complicações , Sepse/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/metabolismo , Modelos Animais de Doenças , Ubiquitina/metabolismo , Proteólise , Fosforilação
17.
Curr Med Sci ; 43(1): 115-122, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36640244

RESUMO

OBJECTIVE: Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts (AVGs), but the factors mediating this process are unclear. The purpose of this study was to investigate the role of endoplasmic reticulum stress (ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet (HFD) mice. METHODS: CCAAT-enhancer-binding protein-homologous protein (CHOP) knockout (KO) mice were created. Mice were fed with HFD to produce HFD model. AVGs model were applied in the groups of WT ND, WT HFD, and CHOP KO HFD. Human umbilical vein endothelial cells (HUVECs) were cultured with oxidized low density lipoprotein (ox-LDL) (40 mg/L) for the indicated time lengths (0, 6, 12, 24 h). ERS inhibitor tauroursodeoxycholic acid (TUDCA) was used to block ERS. Immunohistochemical staining was used to observe the changes of ICAM1. Changes of ERS were detected by real-time RT-PCR. Protein expression levels and ERS activation were detected by Western blotting. Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay. RESULTS: HFD increased neointima formation in AVGs associated with endothelial dysfunction. At the same time, ERS was increased in endothelial cells (ECs) after AVGs in mice consuming the HFD. In vitro, ox-LDL was found to stimulate ERS, increase the permeability of the EC monolayer, and cause endothelial dysfunction. Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL. In vivo, knockout of CHOP (CHOP KO) protected the function of ECs and decreased neointima formation after AVGs in HFD mice. CONCLUSION: Inhibiting ERS in ECs could improve the function of AVGs.


Assuntos
Dieta Hiperlipídica , Neointima , Humanos , Animais , Camundongos , Neointima/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Estresse do Retículo Endoplasmático
18.
Int Immunopharmacol ; 114: 109550, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36525796

RESUMO

The process of host infection by bacteria is complicated. Bacterial infections strongly induce the host immune system, which necessitates a robust clearance of the infection. However, bacteria have over time developed strategies that enable their evasion of attacks by the host immune system. One such strategy is the type VI secretion system (T6SS), a special needle-like secretion system that is widespread in Gram-negative bacteria and is responsible for delivering effector proteins into the external bacterial environment or directly into the host cell cytosol. Bacterial T6SS and its secreted effector proteins play an important role in the interaction between bacteria and host immune system. They also serve as antigens that are employed in the development of vaccines for clinical trials as well as future vaccine candidates. This review focuses mainly on aspects of T6SS effectors that impact the strength of the host immune system, including inflammation, autophagy, and apoptosis (silent programmed cell death). The T6SS-based vaccines are also described.


Assuntos
Sistemas de Secreção Tipo VI , Vacinas , Sistemas de Secreção Tipo VI/metabolismo , Proteínas de Bactérias/metabolismo , Bactérias/metabolismo , Sistema Imunitário/metabolismo
19.
Int Immunopharmacol ; 115: 109640, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36586273

RESUMO

BACKGROUND: Muscle atrophy occurs in patients with sepsis and increases mortality and disability. Remission of muscle atrophy may improve the quality of life in patients with sepsis. Astragaloside IV (ASIV) has been shown to have excellent anti-inflammatory and anti-fibrotic effects and to reduce organ damage caused by sepsis. However, the effect of ASIV on sepsis-induced muscle atrophy has not been reported. Therefore, this study explored the pharmacological effects and mechanisms of ASIV in sepsis-induced muscle atrophy. METHODS: Cecal ligation and puncture (CLP) was used to establish a mouse model of sepsis and lipopolysaccharide (LPS)-stimulated C2C12 myotubes. After administration of ASIV, the body weight, tibialis anterior (TA) and gastrocnemius muscle weight and fiber cross-sectional area of the mice were measured. The diameter of myotubes was observed by immunofluorescence staining. ELISA was used to assess inflammatory factors in plasma and cell culture supernatants. RT-PCR and Western blotting were used to detect the expression of MuRF1, Atrogin-1 and TGF-ß1/Smad signaling pathway components in TA and C2C12 myotubes. RESULTS: Our study found that ASIV reduced serum inflammatory factors and improved survival in septic mice. ASIV alleviated muscle mass reduction, myofiber cross-sectional area reduction, and C2C12 myotube atrophy by inhibiting the expression of the E3 ubiquitin ligases MuRF1 and atrogin-1. In addition, we observed that ASIV inhibited TGF-ß1/Smad signaling. Inhibition of the TGF-ß1/Smad signaling pathway partly blocked the anti-muscle atrophy effect of ASIV. CONCLUSION: ASIV can alleviate sepsis-induced muscle atrophy, which may be related to the inhibition of the TGF-ß1/Smad signaling pathway.


Assuntos
Sepse , Fator de Crescimento Transformador beta1 , Camundongos , Animais , Qualidade de Vida , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Transdução de Sinais , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo
20.
Educ Technol Res Dev ; 71(2): 767-792, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36406105

RESUMO

Most education systems were severely impacted by the COVID-19 pandemic, and as a result, learning shifted from face-to-face to online in higher education institutions. This unprecedented shift in the learning environment caused substantial challenges for students. The situation was more severe in developing nations such as Bangladesh, which lacked available resources and knowledge of online education to support their students. Recent studies suggest that students resisted online learning in various developing nations. To support online learning in developing nations, this study develops the Acceptance of Online Learning (AOL) scale comprised of both institutional and student-related factors. To validate the AOL scale, the study collected data from 441 students across 30 higher education institutions in Bangladesh to determine the factors explaining students' acceptance of online learning using AOL measurements. The results showed that institutional factors, such as technological sufficiency, instructor efficiency, and technical assistance play significant roles in students' acceptance of online learning in developing nations. These findings will help education policymakers and administrators in developing nations to assess the needs of students with respect to online learning, and the AOL scale will assist in the evaluation of students' acceptance of online learning in these nations.

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