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1.
J Endocrinol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954845

RESUMO

Irisin is a recently discovered myokine that facilitates the browning of white adipose tissue, increases glucose uptake in skeletal muscle, and influences metabolic processes in the liver. However, its potential effects on amino acid absorption remained largely unexplored. This study aimed to elucidate the role of irisin in modulating amino acid uptake and delineate the underlying molecular mechanisms involved. To this end, juvenile tilapia were administered intraperitoneal irisin injections at 100 ng/g body weight over eight weeks. Evaluation of various physiological parameters revealed that irisin supplementation significantly improved the specific growth rate and feed conversion efficiency while reducing feed consumption. Muscle tissue analysis revealed that irisin significantly modified the proximate composition by increasing protein content and reducing lipid levels. It also significantly raised the levels of both essential and non-essential amino acids in the muscle. Histological analysis demonstrated that irisin stimulated muscle growth through hyperplasia rather than hypertrophy, corroborated by upregulated IGF-1 mRNA and downregulated myostatin mRNA expression. Mechanistic studies in cultured tilapia muscle cells elucidated that irisin activated integrin receptors on muscle cells, which subsequently engaged IGF-1/IGF-1R signaling. Downstream of IGF-1R activation, irisin simultaneously stimulates the ERK1/2 and PI3K/mTORC2/Akt pathways. The convergence of these pathways upregulates L-type amino acid transporter 1 expression, thereby augmenting amino acid uptake into muscle cells. In summary, irisin supplementation in tilapia leads to improved muscle growth, predominantly via hyperplasia and augmented amino acid assimilation, governed by intricate cellular signaling pathways. These findings provide valuable aquaculture applications and novel insights into muscle development.

2.
Res Sq ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38947095

RESUMO

Internalized pools of membrane attack complexes (MACs) promote NF-kB and dysregulated tissue inflammation. Here, we show that C9, a MAC-associated protein, promotes loss of proteostasis to become intrinsically immunogenic. Surface-bound C9 is internalized into Rab5 + endosomes whose intraluminal acidification promotes C9 aggregates. A region within the MACPF/CDC domain of C9 stimulates aggrephagy to induce NF-kB, inflammatory genes, and EC activation. This process requires ZFYVE21, a Rab5 effector, which links LC3A/B on aggresome membranes to RNF34-P62 complexes to mediate C9 aggrephagy. C9 aggregates form in human tissues, C9-associated signaling responses occur in three mouse models, and ZFYVE21 stabilizes RNF34 to promote C9 aggrephagy in vivo. Gene-deficient mice lacking ZFYVE21 in ECs showed reduced MAC-induced tissue injury in a skin model of chronic rejection. While classically defined as cytotoxic effectors, MACs may impair proteostasis, forming aggregates that behave as intracellular alarmins.

3.
Clin Rheumatol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976092

RESUMO

OBJECTIVE: The aim of this study was to investigate the status of health-related quality of life in Chinese patients with ankylosing spondylitis (AS) and to analyze factors associated with the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) in AS and its relationship with disease activity and psychological status. METHODS: A cross-sectional study of 484 patients with AS attending 10 hospitals in China from March 2021 to September 2023 was recruited. The ASAS-HI assessed general health and functional status; the Depression Anxiety Stress Scales (DASS-21) assessed psychological disorders such as anxiety, depression, and stress; and the Functional Assessment of Chronic illness Therapy-Fatigue Scale (FACIT-F) assessed patients' fatigue symptoms; the Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Measurement Index (BASMI) were used to assess patients' disease activity and functional impairment. The correlation between ASAS-HI and the ASDAS, poor psychological status, and fatigue symptoms was observed. Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of ASAS-HI. RESULTS: A total of 484 patients were included in this study of whom 162 were in poor health, 139 in moderate health, and 183 in good health. On univariate analysis, disease activity is an important factor affecting ASAS-HI. People with extremely high disease activity (ASDAS ≥ 3.5) had a 12 times elevated risk of having poor health status (OR = 12.53; P < 0.001). Other significant covariates included age ≥ 36 (OR = 1.58; P = 0.015), BMI ≥ 24 kg/m2 (OR = 2.93; P = 0.013), smoke (OR = 1.96; P = 0.002), BASFI (OR = 1.49; P < 0.001), BASMI (OR = 1.22; P < 0.001), fatigue (OR = 6.28; P < 0.001), and bad psychological conditions such as depression (OR = 10.86; P < 0.001), anxiety (OR = 3.88; P < 0.001), and stress (OR = 4.65; P < 0.001). The use of bMARDs is inversely associated with the appearance of adverse health status (OR = 0.54; P = 0.012). There was no significant relationship between HLA-B27 and sex. Multivariable logistic regression showed that higher disease activity (ASDAS ≥ 3.5) (OR = 5.14; P = 0.005), higher scores of BASMI (OR = 1.10; P = 0.009), self-reported depression (OR = 3.68; P = 0.007), and fatigue (OR = 2.76; P < 0.001) were factors associated with adverse health status. CONCLUSION: The health status of AS patients is related to age, BMI, smoking, disease activity, poor psychological status, and fatigue and is influenced by a combination of multiple factors such as emotional state, economic level, pain, and dysfunction. Therefore, clinicians should pay attention to the early assessment of ASAS-HI in order to improve the prognosis of the disease. Key Points •Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease with a long course and heavy disease burden, which greatly affects patients' quality of life. Therefore, this study aims to evaluate the health status of ankylosing spondylitis in the Chinese population and its influencing factors. •This is a multi-center cross-sectional study in China, which can better reflect the overall situation of the Chinese population.

4.
J Vis Exp ; (207)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38856215

RESUMO

This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 transarterial radioembolization (TARE) and Programmed Cell Death-1 (PD-1) inhibitors as neoadjuvant therapy. Highlighted through a case report, it offers a step-by-step reference for similar therapeutic interventions. A retrospective analysis was conducted on a patient who underwent hepatectomy following Y-90 TARE and PD-1 inhibitor treatment. Key demographic and clinical details were recorded at admission to guide therapy selection. Y-90 TARE suitability and dosage calculation were based on Technetium-99m (Tc-99m) macroaggregated albumin (MAA) perfusion mapping tests. Lesion coverage by Y-90 microspheres was confirmed through single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging, and adverse reactions and follow-up outcomes were meticulously documented. The patient, with a 7.2 cm HCC in the right hepatic lobe (T1bN0M0, BCLC A, CNLC Ib) and an initial alpha-fetoprotein (AFP) level of 66,840 ng/mL, opted for Y-90 TARE due to high recurrence risk and initial surgery refusal. The therapy's parameters, including the lung shunting fraction (LSF) and non-tumor ratio (TNR), were within therapeutic limits. A total of 1.36 GBq Y-90 was administered. At 1 month post-therapy, the tumor shrank to 6 cm with partial necrosis, and AFP levels dropped to 21,155 ng/mL, remaining stable for 3 months. After 3 months, PD-1 inhibitor treatment led to further tumor reduction to 4 cm and AFP decrease to 1.84 ng/mL. The patient then underwent hepatectomy; histopathology confirmed complete tumor necrosis. At 12 months post-surgery, no tumor recurrence or metastasis was observed in follow-up sessions. This protocol demonstrates the effective combination of Y-90 TARE and PD-1 inhibitor as a bridging strategy to surgery for HCC patients at high recurrence risk, providing a practical guide for implementing this approach.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Terapia Neoadjuvante , Radioisótopos de Ítrio , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Terapia Neoadjuvante/métodos , Embolização Terapêutica/métodos , Radioisótopos de Ítrio/uso terapêutico , Masculino , Estudos Retrospectivos , Inibidores de Checkpoint Imunológico/uso terapêutico , Pessoa de Meia-Idade , Idoso , Compostos Radiofarmacêuticos/uso terapêutico
5.
Kidney Int ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38797325

RESUMO

ZFYVE21 is an ancient, endosome-associated protein that is highly expressed in endothelial cells (ECs) but whose function(s) in vivo are undefined. Here, we identified ZFYVE21 as an essential regulator of vascular barrier function in the aging kidney. ZFYVE21 levels significantly decline in ECs in aged human and mouse kidneys. To investigate attendant effects, we generated EC-specific Zfyve21-/- reporter mice. These knockout mice developed accelerated aging phenotypes including reduced endothelial nitric oxide (ENOS) activity, failure to thrive, and kidney insufficiency. Kidneys from Zfyve21 EC-/- mice showed interstitial edema and glomerular EC injury. ZFYVE21-mediated phenotypes were not programmed developmentally as loss of ZFYVE21 in ECs during adulthood phenocopied its loss prenatally, and a nitric oxide donor normalized kidney function in adult hosts. Using live cell imaging and human kidney organ cultures, we found that in a GTPase Rab5- and protein kinase Akt-dependent manner, ZFYVE21 reduced vesicular levels of inhibitory caveolin-1 and promoted transfer of Golgi-derived ENOS to a perinuclear Rab5+ vesicular population to functionally sustain ENOS activity. Thus, our work defines a ZFYVE21- mediated trafficking mechanism sustaining ENOS activity and demonstrates the relevance of this pathway for maintaining kidney function with aging.

6.
Materials (Basel) ; 17(10)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38793357

RESUMO

In deep underground engineering, the deformation, failure characteristics, and mechanism of surrounding rock under the influence of grain sizes and mineral compositions are not clear. Based on CJPL-II variously colored marbles, the differences in grain size and mineral composition of the marble were analyzed by thin-section analysis and XRD tests, and the effect of intermediate principal stress on the mechanical properties of marble was investigated. Both SEM and microfracture analysis were coupled to reveal the failure mechanisms. The results highlight that the crack initiation strength, damage strength, peak strength, and elasticity modulus of Jinping marble exhibit an increasing trend with an increase in intermediate principal stress, while the peak strain initially increases and subsequently decreases. Moreover, this study established negative correlations between marble strength, brittleness characteristics, and fracture angle with grain size, whereas positive correlations were identified with the content of quartz, sodium feldspar, and the magnitude of the intermediate principal stress. The microcrack density in marble was found to increase with larger grain sizes and decrease with elevated quartz and sodium feldspar content, as well as with increasing intermediate principal stress. Notably, as the intermediate principal stress intensifies and grain size diminishes, the transgranular tensile failure of marble becomes more conspicuous. These research findings contribute to the effective implementation of disaster prevention and control strategies.

7.
Exp Ther Med ; 27(6): 259, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38756898

RESUMO

The present retrospective study was designed to explore the value of conventional ultrasound (US) and Virtual Touch Tissue Imaging and Quantification (VTIQ) in the assessment of mesenteric lymphadenitis (ML) in a paediatric population. A total of 103 patients with ML and 60 healthy paediatric patients were examined. VTIQ was performed to assess mesenteric lymph node (MLN) stiffness via shear-wave velocity (SWV). Univariate and multivariate logistic regression analyses were conducted to reveal independent variables for the identification of ML. The diagnostic performance of US, and US combined with VTIQ, were compared. All the quantitative VTIQ parameters (including the SWVMean, SWVMax and SWVMin) were significantly greater for MLNs in the control group than for MLNs in the ML group (all P<0.001). The SWV values in the control group were nearly 2-fold greater than that in the ML group. According to the multivariate logistic regression analysis, the longest diameter [odds ratio (OR)=6.042; P=0.046] was revealed to be the strongest independent predictor for ML, followed by the CRP level (OR=2.310; P<0.001) and the SWVMean (OR=0.106; P<0.001). According to the receiver operating characteristic analysis, the area under the curve (AUC) for US combined with VTIQ was 0.890 (95% CI: 0.831-0.949) with a greater sensitivity of 91.26% and a greater specificity of 86.67% than that for US alone (AUC: 0.798; 95% CI: 0.724-0.872; sensitivity: 79.61%; specificity: 80.00%). A significant negative correlation between increased VTIQ parameters and ML was observed. Utilizing VTIQ to assess MLN stiffness offers a non-invasive, convenient, reliable and reproducible approach for identifying mesenteric lymphadenopathy.

8.
Polymers (Basel) ; 16(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38675028

RESUMO

The mechanical recycling of discarded plastic products as resources for environmental preservation has recently gained research attention. In this context, it is necessary to use waste materials for fiber-reinforced thermoplastics (FRTP). Glass and carbon fibers are often damaged by shear and compression during melt-forming processes. To achieve a sustainable society, it is necessary for thermal recycling to produce minimal to no residue and for mechanical recycling to maintain the length of fibers used in FRTP to preserve their performance as a reinforcing agent. Aramid fibers (AFs) do not shorten during the melt-molding process, and their composites have excellent impact strength. On the other hand, plastics reinforced with glass or carbon fibers are reported to have a superior strength and modulus of elasticity compared to aramid fibers. This study investigates the dispersion of a carbon nanofiber (CNF), a whisker, as the third component in aramid-fiber-reinforced polypropylene (PP/AF). The results and discussion sections demonstrate how the dispersion of CNF in PP/AF can enhance the mechanical properties of injection-molded products without compromising their impact resistance. The proposed composition will have excellent material recyclability and initial mechanical properties compared to glass-fiber-reinforced thermoplastics.

9.
Polymers (Basel) ; 16(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38611141

RESUMO

Short fiber-reinforced thermoplastic polymers (SFRTPs) are commonly used in various molding methods due to their high specific elasticity and strength. To evaluate the interfacial strength, several determination methods have been proposed, including the interfacial shear strength (IFSS). In previous research, an IFSS evaluation method based on the short beam shear method was proposed. However, this method is only applicable to micrometer-sized fibers with high stiffness levels that are not easily bent. When utilizing cellulose fiber, the interfacial shear strength (IFSS) results frequently exhibit significant deviations. To tackle this issue, we suggest an enhanced experimental technique that employs beam-shaped specimens with welding points based on the short beam shear test. Furthermore, we conducted a three-dimensional analysis of the original method to determine the fiber orientation angle and IFSS. The outcomes were compared with previously reported determinations. The IFSS achieved through the novel method proposed in this paper exhibits high precision and reliability, rendering it suitable for use with soft and flexible fibers.

10.
Diagnostics (Basel) ; 14(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38611644

RESUMO

The glymphatic system suggests the convective bulk flow of cerebrospinal fluid (CSF) through perivascular spaces and the interstitial spaces of the brain parenchyma for the rapid removal of toxic waste solutes from the brain. However, the presence of convective bulk flow within the brain interstitial spaces is still under debate. We first addressed this argument to determine the involvement of the glymphatic system in brain waste clearance utilizing contrast-enhanced 3D T1-weighted imaging (T1WI), diffusion tensor imaging (DTI), and confocal microscopy imaging. Furthermore, perivascular macrophages (PVMs), which are immune cells located within perivascular spaces, have not been thoroughly explored for their association with the glymphatic system. Therefore, we investigated tracer uptake by PVMs in the perivascular spaces of both the arteries/arterioles and veins/venules and the potential association of PVMs in assisting the glymphatic system for interstitial waste clearance. Our findings demonstrated that both convective bulk flow and diffusion are responsible for the clearance of interstitial waste solutes from the brain parenchyma. Furthermore, our results suggested that PVMs may play an important function in glymphatic system-mediated interstitial waste clearance. The glymphatic system and PVMs could be targeted to enhance interstitial waste clearance in patients with waste-associated neurological conditions and aging.

11.
NMR Biomed ; 37(8): e5132, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38465514

RESUMO

The glymphatic system is a system of specialized perivascular spaces in the brain that facilitates removal of toxic waste solutes from the brain. Evaluation of glymphatic system function by means of magnetic resonance imaging (MRI) has thus far been largely focused on rodents because of the limitations of intrathecal delivery of gadolinium-based contrast agents to humans. This review discusses MRI methods that can be employed clinically for glymphatic-related measurements intended for early diagnosis, prevention, and the treatment of various neurological conditions. Although glymphatic system-based MRI research is in its early stages, recent studies have identified promising noninvasive MRI markers associated with glymphatic system alterations in neurological diseases. However, further optimization in data acquisition, validation, and modeling are needed to investigate the glymphatic system within the clinical setting.


Assuntos
Sistema Glinfático , Imageamento por Ressonância Magnética , Sistema Glinfático/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Animais , Encéfalo/diagnóstico por imagem
12.
Biomedicines ; 12(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38398003

RESUMO

The glymphatic system has recently been shown to be important in neurological diseases, including diabetes. However, little is known about how the progressive onset of diabetes affects the glymphatic system. The aim of this study is to investigate the glymphatic system response to the progressive onset of diabetes in a rat model of type 2 diabetic mellitus. Male Wistar rats (n = 45) with and without diabetes were evaluated using MRI glymphatic tracer kinetics, functional tests, and brain tissue immunohistochemistry. Our data demonstrated that the contrast agent clearance impairment gradually progressed with the diabetic duration. The MRI data showed that an impairment in contrast clearance occurred prior to the cognitive deficits detected using functional tests and permitted the detection of an early DM stage compared to the immuno-histopathology and cognitive tests. Additionally, the quantitative MRI markers of brain waste clearance demonstrated region-dependent sensitivity in glymphatic impairment. The improved sensitivity of MRI markers in the olfactory bulb and the whole brain at an early DM stage may be attributed to the important role of the olfactory bulb in the parenchymal efflux pathway. MRI can provide sensitive quantitative markers of glymphatic impairment during the progression of DM and can be used as a valuable tool for the early diagnosis of DM with a potential for clinical application.

13.
Neurobiol Dis ; 192: 106426, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331353

RESUMO

The term "glymphatic" emerged roughly a decade ago, marking a pivotal point in neuroscience research. The glymphatic system, a glial-dependent perivascular network distributed throughout the brain, has since become a focal point of investigation. There is increasing evidence suggesting that impairment of the glymphatic system appears to be a common feature of neurodegenerative disorders, and this impairment exacerbates as disease progression. Nevertheless, the common factors contributing to glymphatic system dysfunction across most neurodegenerative disorders remain unclear. Inflammation, however, is suspected to play a pivotal role. Dysfunction of the glymphatic system can lead to a significant accumulation of protein and waste products, which can trigger inflammation. The interaction between the glymphatic system and inflammation appears to be cyclical and potentially synergistic. Yet, current research is limited, and there is a lack of comprehensive models explaining this association. In this perspective review, we propose a novel model suggesting that inflammation, impaired glymphatic function, and neurodegenerative disorders interconnected in a vicious cycle. By presenting experimental evidence from the existing literature, we aim to demonstrate that: (1) inflammation aggravates glymphatic system dysfunction, (2) the impaired glymphatic system exacerbated neurodegenerative disorders progression, (3) neurodegenerative disorders progression promotes inflammation. Finally, the implication of proposed model is discussed.


Assuntos
Sistema Glinfático , Doenças Neurodegenerativas , Humanos , Encéfalo/metabolismo , Doenças Neurodegenerativas/metabolismo , Aquaporina 4 , Inflamação/metabolismo
14.
ACS Appl Mater Interfaces ; 16(7): 9303-9312, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38343044

RESUMO

Daytime radiative cooling technology offers a low-carbon, environmentally friendly, and nonpower-consuming approach to realize building energy conservation. It is important to design materials with high solar reflectivity and high infrared emissivity in atmospheric windows. Herein, a porous calcium silicate composite SiO2 aerogel water-borne coating with strong passive radiative cooling and high thermal insulation properties is proposed, which shows an exceptional solar reflectance of 94%, high sky window emissivity of 96%, and 0.0854 W/m·K thermal conductivity. On the SiO2/CaSiO3 radiative cooling coating (SiO2-CS-coating), a strategy is proposed to enhance the atmospheric window emissivity by lattice resonance, which is attributed to the eight-membered ring structure of porous calcium silicate, thereby increasing the atmospheric window emissivity. In the daytime test (solar irradiance 900W/m2, ambient temperature 43 °C, wind speed 0.53 m/s, humidity 25%), the temperature inside the box can achieve a cooling temperature of 13 °C lower than that of the environment, which is 30 °C, and the theoretical cooling power is 96 W/m2. Compared with the commercial white coating, SiO2-CS-coating can save 70 kW·h of electric energy in 1 month, and the energy consumption is reduced by 36%. The work provides a scalable, widely applicable radiative-cooling coating for building comfort, which can greatly reduce indoor temperatures and is suitable for building surfaces.

15.
Aging Dis ; 15(2): 584-600, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37611901

RESUMO

The accumulation of harmful substances has long been recognized as a likely cause of many neurodegenerative diseases. The two classic brain clearance pathways are cerebrospinal fluid (CSF) and vascular circulation systems. Since the discovery of the glymphatic system, research on the CSF pathway has gained momentum, and impaired CSF clearance has been implicated in virtually all neurodegenerative animal models. However, the contribution of the direct participation of vascular transport across the blood-brain barrier in clearing substances is often ignored in glymphatic papers. Supportive evidence for the direct involvement of parenchymal vasculature in substance clearance is accumulated. First, multiple mechanisms have been proposed for the vascular drainage of exogenous and endogenous substances across the blood-brain barriers. Second, the "traditional" role of arachnoid villi and granulations as the main site for CSF draining into the vasculature system has been questioned. Third, MRI studies using different CSF tracers indicate that parenchymal vasculature directly participates in tracer efflux, consistent with immunohistochemical findings. Here we will review evidence in the literature that supports the direct participation of the parenchymal vascular system in substance clearance, in addition to the CSF clearance pathways.


Assuntos
Encéfalo , Sistema Glinfático , Animais , Encéfalo/metabolismo , Barreira Hematoencefálica , Transporte Biológico
16.
Cell Oncol (Dordr) ; 47(1): 303-319, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37702916

RESUMO

PURPOSE: We aimed to investigate the role of ubiquilin-4 in predicting the immunotherapy response in gastric cancer. METHODS: Retrospective RNA-sequencing and immunohistochemical analysis were performed for patients with gastric cancer who received programmed death-1 blockade therapy after recurrence. Multiplex immunohistochemistry identified immune cell types in gastric cancer tissues. We used immunocompetent 615 mice and immunodeficient nude mice to perform tumorigenic experiments. RESULTS: Ubiquilin-4 expression was significantly higher in responders (p < 0.05, false discovery rate > 2.5) and showed slight superiority over programmed death ligand 1 in predicting programmed death-1 inhibitor therapy response (area under the curve: 87.08 vs. 72.50). Ubiquilin-4-high patients exhibited increased CD4+ and CD8+ T cells, T follicular helper cells, monocytes, and macrophages. Ubiquilin-4-overexpressed mouse forestomach carcinoma cells showed significantly enhanced growth in immunocompetent mice but not in immunodeficient mice. Upregulation or downregulation of ubiquilin-4 synergistically affected programmed death ligand 1 at the protein and messenger RNA levels. Functional enrichment analysis revealed significant enrichment of the Notch, JAK-STAT, and WNT signaling pathways in ubiquilin-4-high gastric cancers. Ubiquilin-4 promoted Numb degaration, activating the Notch signaling pathway and upregulating programmed death ligand 1. CONCLUSIONS: Ubiquilin-4 may contribute to immune escape in gastric cancer by upregulating programmed death ligand 1 expression in tumor cells through Notch signaling activation. Thus, ubiquilin-4 could serve as a predictive marker for programmed death ligand 1 inhibitor therapy response in gastric cancer.


Assuntos
Proteínas de Transporte , Proteínas Nucleares , Neoplasias Gástricas , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos , Camundongos Nus , Estudos Retrospectivos , Transdução de Sinais , Neoplasias Gástricas/genética , Proteínas Nucleares/metabolismo , Proteínas de Transporte/metabolismo
17.
Fish Shellfish Immunol ; 144: 109245, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38000652

RESUMO

Irisin, a secreted myokine generated by fibronectin type III domain-containing protein 5, has recently shown the potential to alleviate inflammation. Cholecystokinin-octapeptide (CCK-8) is closely associated with the inflammatory factor TNF-α, a central cytokine in inflammatory reactions. However, the interactions between irisin and CCK-8 in regulating TNF-α production and the underlying mechanism have not yet been elucidated. In the present study, irisin treatment inhibited the basal and the CCK-8-induced TNF-α production in vivo. Additionally, neutralizing circulating irisin using an irisin antiserum significantly augmented the CCK-8-induced stimulation of TNF-α levels. Moreover, the incubation of head kidney cells with irisin or CCK-8 has opposite effects on TNF-α secretion. Notably, irisin treatment inhibited basal and CCK-8-stimulated TNF-α release and gene transcription in head kidney cells. Mechanistically, the inhibitory actions of irisin on basal and CCK-8-induced TNF-α production could be negated by co-administered with the selective integrin αVß5 inhibitor cilengitide. In addition, the inhibitory effect of irisin on basal and CCK-8-triggered TNF-α production could be abolished by the inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, irisin impeded CCK-8-induced phosphorylation and degradation of IκBα, simultaneously inhibiting NF-κB phosphorylation, preventing its translocation into the nucleus, and suppressing its DNA-binding activity induced by CCK-8. Collectively, these results suggest that the inhibitory effect of irisin on TNF-α production caused by CCK-8 is mediated via the integrin αVß5-NF-κB signaling pathways in tilapia.


Assuntos
Ciclídeos , NF-kappa B , Animais , NF-kappa B/metabolismo , Sincalida/efeitos adversos , Fator de Necrose Tumoral alfa/farmacologia , Fibronectinas/genética , Ciclídeos/metabolismo , Transdução de Sinais , Inflamação/induzido quimicamente
18.
Oral Dis ; 30(1): 50-62, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37518974

RESUMO

AIM: The aim of the study was to observe the effect of acupuncture on regulating interleukin (IL)-17, tumor necrosis factor (TNF)-ɑ, and aquaporins (AQPs) in Sjögren's syndrome (SS) on patients and on non-obese diabetic (NOD) models. METHODS: Levels of anti-AQP 1, 5, 8, and 9 antibodies, IL-17, and TNF-ɑ in the serum of SS patients were compared prior and following 20 acupuncture treatment visits during 8 weeks. While in murine model, five groups were divided to receive interventions for 4 weeks, including control, model, acupuncture, isoflurane, and hydroxychloroquine. The submaxillofacial gland index, histology, immunohistochemistry of AQP1, 5, salivary flow, together with IL-17, and TNF-ɑ expression in peripheral blood were compared among the groups. RESULTS: Acupuncture reduced IL-17, TNF-ɑ, and immunoglobin A levels, and numeric analog scale of dryness in 14 patients with SS (p < 0.05). The salivary flow was increased, and the water intake decreased in NOD mice receiving acupuncture treatments. IL-17 and TNF-ɑ levels in peripheral serum were down-regulated (p < 0.05) and AQP1, 5 expression in the submandibular glands up-regulated in mice. CONCLUSION: The effect on relieving xerostomia with acupuncture may be achieved by up-regulating the expression of AQP1. AQP5, down-regulating levels of IL-17 and TNF-ɑ, and a decrease in inflammation of glands.


Assuntos
Terapia por Acupuntura , Síndrome de Sjogren , Humanos , Animais , Camundongos , Síndrome de Sjogren/patologia , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-17/metabolismo , Camundongos Endogâmicos NOD , Glândula Submandibular/metabolismo , Modelos Animais de Doenças
20.
Am J Transl Res ; 15(10): 6170-6179, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37969208

RESUMO

OBJECTIVE: To analyze the association between transperineal pelvic floor ultrasound findings and posterior pelvic injury and prolapse in postpartum women. METHODS: A total of 108 postpartum women received treatment from January 2020 and December 2022 were divided into 2 groups, with 53 cases in a pelvic floor disorder (PFD) group and 55 cases in the no PFD group according to whether they developed PFD after delivery. The relationship between ultrasound data and the Pelvic Floor Distress Inventory (PFDI-20) scores was analyzed by Pearson correlation. The diagnostic value of transperineal pelvic floor ultrasound for PFD was analyzed by using the receiver operating characteristic curve, and the relationship between transperineal pelvic floor ultrasound parameters and PFD was analyzed by using the RR hazard ratio. RESULTS: The distance from the bladder neck to the posterior inferior border of the pubic symphysis, the distance from the cervix to the posterior inferior border of the pubic symphysis, and the shortening rate during retraction were shorter or lower in the PFD group than those in the no PFD group. Additionally, bladder descent, cervical subluxation, urethral rotation, anterior and posterior diameters of the static levator ani muscle (LAM), anterior and posterior diameters of the retracted LAM, anterior and posterior diameters of the LAM in the maximal Valsalva maneuver, and PFDI-20 scores in the PFD group were longer or higher than those of the no PFD group (P<0.01). Shortening rate during retraction, bladder descent, cervical subluxation, urethral rotation, and elongation at maximal Valsalva maneuver were positively correlated with the PFDI-20 score (R = 0.027, 0.053, 0.102, 0.002, 0.011, 0.123, respectively, all P<0.05). CONCLUSIONS: The degree of bladder descent, cervical subluxation, urethral rotation, shortening rate during retraction, and elongation at maximal Valsalva maneuver are closely related to the PFD I-20 score.

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