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BACKGROUND: Observational studies have documented increased serum IL-6 levels in elderly individuals afflicted with sarcopenia. Nevertheless, the relationship between serum IL-6 concentrations and sarcopenia prevalence in the aging population is yet to be defined. METHODS: We executed a systematic review and meta-analysis of cross-sectional studies that scrutinized serum IL-6 levels in older adults with and without sarcopenia. Relevant studies were sourced from PubMed, Scopus, Embase, Cochrane Library, and Web of Science from inception until 10 September 2023. The standard mean differences (SMDs) in serum IL-6 levels between studies were synthesized using a random-effects model. To examine the influence of demographic and clinical factors on these outcomes, we performed subgroup analyses and meta-regression, focusing on variables such as sex, age, and body mass index (BMI). We also assessed the relationship between serum IL-6 levels and the defining components of sarcopenia: muscle mass, muscle strength, and physical performance. We used Fisher's Z transformation to standardize the interpretation of effect sizes from these relationships. The transformed values were then converted to summary correlation coefficients (r) for a clear and unified summary of the results. RESULTS: We included twenty-one cross-sectional studies involving 3,902 participants. Meta-analysis revealed significantly elevated serum IL-6 levels in older adults with sarcopenia compared with those without sarcopenia (SMD = 0.31; 95% CI 0.18, 0.44). The difference was highly pronounced in the subgroups of male and those with female percentage below 50% or a mean BMI below 24 kg/m2. Serum IL-6 levels were inversely correlated with muscle mass (summary r = -0.18; 95% CI -0.30, -0.06), but not with handgrip strength (summary r = -0.10; 95%CI: -0.25, 0.05) or gait speed (summary r = -0.09; 95%CI: -0.24, 0.07). CONCLUSIONS: This meta-analysis establishes a link between increased serum IL-6 levels and sarcopenia in the elderly, particularly in relation to decreased muscle mass.
Several studies have demonstrated elevated serum IL-6 levels in elderly individuals with sarcopenia, while the relationship between serum IL-6 levels and sarcopenia remains unclear.This is a systematic review and meta-analysis of 21 cross-sectional studies for the relationship between serum IL-6 levels and sarcopenia.Elevated serum IL-6 levels appear to be associated with sarcopenia in older adults, especially in relation to reduced muscle mass.
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Interleucina-6 , Sarcopenia , Humanos , Sarcopenia/sangre , Interleucina-6/sangre , Estudios Transversales , Anciano , Masculino , Femenino , Fuerza Muscular/fisiología , Índice de Masa Corporal , Anciano de 80 o más AñosRESUMEN
Host-guest complexation offers a promising approach for mitigating surface defects in perovskite solar cells (PSCs). Crown ethers are the most widely used macrocyclic hosts for complexing perovskite surfaces, yet their supramolecular interactions and functional implications require further understanding. Here we show that the dipole moment of crown ethers serves as an indicator of supramolecular interactions with both perovskites and precursor salts. A larger dipole moment, achieved through the substitution of heteroatoms, correlates with enhanced coordination with lead cations. Perovskite films incorporating aza-crown ethers as additives exhibited improved morphology, reduced defect densities, and better energy-level alignment compared to those using native crown ethers. We report power-conversion efficiencies (PCEs) exceeding 25% for PSCs, which show enhanced long-term stability, and a record PCE of 21.5% for host-guest complexation-based perovskite solar modules with an active area of 14.0 cm2.
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Perovskite solar cells (PSCs) are usually modified and passivated to improve their performance and stability. The interface modification and bulk doping are the two basic strategies. Fluorine (F)-containing materials are highly favored because of their unique hydrophobicity and coordination ability. This review discusses the basic characteristics of F, and the basic principles of improving the photovoltaic performance and stability of PSC devices using F-containing materials. We systematically summarized the latest progress in the application of F-containing materials to achieve efficient and stable PSCs on several key interface layers. It is believed that this work will afford significant understanding and inspirations toward the future application directions of F-containing materials in PSCs, and provide profound insights for the development of efficient and stable PSCs.
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Background: The influence of patella morphology and horizontal alignment on knee joint kinematics and kinetics remains uncertain. This study aimed to assess patella morphology and transverse alignment in relation to knee kinetics and kinematics in individuals without knee conditions. A secondary objective was to investigate the impact of femur and tibia alignment and shape on knee gait within this population. Patients and methods: We conducted a prospective collection of data, including full-leg anteroposterior and skyline X-ray views and three-dimensional gait data, from a cohort comprising 54 healthy individuals aged 40 years and older. Our study involved correlation and logistic regression analyses to examine the influence of patella, femur, and tibia morphology and alignment on knee gait. Results: The patellar tilt angle or the patella index did not show any significant relationships with different aspects of gait in the knee joint, such as velocity, angle, or moment (p > 0.05, respectively). Using multivariate logistic regression analysis, we found that the tibiofemoral angle and the Q angle both had a significant effect on the adduction angle (OR = 1.330, 95%CI 1.033-1.711, p = 0.027; OR = 0.475, 95%CI 0.285-0.792, p = 0.04; respectively). The primary variable influencing the knee adduction moment was the tibiofemoral angle (OR = 1.526, 95% CI 1.125-2.069, p = 0.007). Conclusion: In healthy Chinese individuals aged over 40, patella morphology and transverse alignment do not impact knee gait. However, the femoral-tibial angle has a big impact on the knee adduction moment.
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Interface modification and bulk doping are two major strategies to improve the photovoltaic performance of perovskite solar cells (PSCs). Dipolar molecules are highly favored due to their unique dipolarity. This review discusses the basic concepts and characteristics of dipoles. In addition, the role of dipoles in PSCs and the corresponding conventional characterization methods for dipoles are introduced. Then, we systematically summarize the latest progress in achieving efficient and stable PSCs in dipole materials at several key interfaces. Finally, we look forward to the future application directions of dipole molecules in PSCs, aiming at providing deep insight and inspiration for developing efficient and stable PSCs.
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BACKGROUND: Dysmobility syndrome based on osteoporosis (ODS) is a disease characterized by low bone mass and low muscle mass. Its features are high fracture and high fall risk. Falls and fractures are the most important factors affecting the quality of life and lifespan of ODS. However, there is no serum marker for the evaluation of ODS patients.Our previous studies have shown that the expression of circulating miRNA is stable and is a good marker for disease diagnosis. Therefore, this study aims to explore potential serum markers of ODS. METHODS: A total of 78 subjects were included in this study. The data including appendicular skeletal muscle mass index, bone mineral density, bone metabolism markers, and other relevant information were collected for analysis. Real-time quantitative polymerase chain reaction was used to detect 19 miRNAs associated with muscle mass reduction. The correlation of quantitative data was analyzed by Pearson. The receiver operating characteristic curve was used to evaluate the performance of miRNA as a biomarker. RESULTS: In this study, we found that the muscle mass and strength of patients with ODS are significantly reduced and are negatively correlated with the risk of fracture. The hsa-miR-499a-5p is specifically downregulated in ODS, and is positively correlated with muscle mass and strength, and negatively correlated with the risk of fracture. Compared with muscle mass and strength, hsa-miR-499a-5p has better sensitivity and specificity as a diagnostic marker. CONCLUSION: hsa-miR-499a-5p is a potential serum biomarker for assessing muscle function and predicting fall or fracture risk in the ODS population.
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Biomarcadores , MicroARNs , Osteoporosis , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Densidad Ósea , Fracturas Óseas/etiología , Fracturas Óseas/sangre , MicroARNs/sangre , Músculo Esquelético , Osteoporosis/sangre , Osteoporosis/diagnóstico , SíndromeRESUMEN
Introducing fluorine (F) groups into a passivator plays an important role in enhancing the defect passivation effect for the perovskite film, which is usually attributed to the direct interaction of F and defect states. However, the interaction between electronegative F and electron-rich passivation groups in the same molecule, which may influence the passivation effect, is ignored. We herein report that such interactions can vary the electron cloud distribution around the passivation groups and thus changing their coordination with defect sites. By comparing two fluorinated molecules, heptafluorobutylamine (HFBM) and heptafluorobutyric acid (HFBA), we find that the F/-NH2 interaction in HFBM is stronger than the F/-COOH one in HFBA, inducing weaker passivation ability of HFBM than HFBA. Accordingly, HFBA-based perovskite solar cells (PSCs) provide an efficiency of 24.70 % with excellent long-term stability. Moreover, the efficiency of a large-area perovskite module (14.0â cm2 ) based on HFBA reaches 21.13 %. Our work offers an insight into understanding an unaware role of the F group in impacting the passivation effect for the perovskite film.
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Carbonyl functional materials as additives are extensively applied to reduce the defects density of the perovskite film. However, there is still a lack of comprehensive understanding for the effect of carbonyl additives to improve device performance. In this work, we systematically study the effect of carbonyl additive molecules on the passivation of defects in perovskite films. After a comprehensive investigation, the results confirm the importance of molecular dipole in amplifying the passivation effect of additive molecules. The additive with strong molecular dipole possesses the advantages of enhancing the efficiency and stability of perovskite solar cells (PSCs). After optimization, the companion efficiency of PSCs is 23.20 %, and it can maintain long-term stability under harsh conditions. Additionally, a large-area solar cell module-modified DLBA was 20.18 % (14â cm2 ). This work provides an important reference for the selection and designing of efficient carbonyl additives.
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BACKGROUND & AIMS: Capsaicin receptor, also known as transient receptor potential vanilloid 1 (TRPV1), is involved in pain physiology and neurogenic inflammation. Herein, we discovered the presence of TRPV1 in hepatic stellate cells (HSCs) and aimed to delineate its function in this cell type and liver fibrosis. METHODS: TRPV1 expression was examined in liver biopsies from patients with liver fibrosis using quantitative real-time PCR and immunostaining. Its contribution to liver fibrosis was examined in Trpv1-/- mice, upon lentiviral delivery of the TRPV1 gene, and in human and mouse primary HSCs, using patch clamp, intracellular Ca2+ mobilization determination, FACS analyses and gain/loss of function experiments. Binding of sterile alpha and Toll/interleukin-1 receptor motif-containing protein 1 (SARM1) to TRPV1 was determined using mass spectrometry, co-immunoprecipitation, surface plasmon resonance, bioluminescence resonance energy transfer, and NanoBiT. RESULTS: TRPV1 mRNA levels are significantly downregulated in patients with liver fibrosis and mouse models, showing a negative correlation with F stage and α-smooth muscle actin expression, a marker of HSC activation. TRPV1 expression and function decrease during HSC activation in fibrotic livers in vivo or during culture. Genetic and pharmacological inhibition of TRPV1 in quiescent HSCs leads to NF-κB activation and pro-inflammatory cytokine production. TRPV1 requires binding of its N-terminal ankyrin repeat domain to the TIR-His583 (Toll/interleukin-1 receptor) domain of SARM1 to prevent HSCs from pro-inflammatory activation. Trpv1-/- mice display increased HSC activation and more severe liver fibrosis, whereas TRPV1 overexpression is antifibrotic in various disease models. CONCLUSION: The antifibrotic properties of TRPV1 are attributed to the prevention of HSC activation via the recruitment of SARM1, which could be an attractive therapeutic strategy against liver fibrosis. IMPACT AND IMPLICATIONS: We identified the neuronal channel protein TRPV1 as a gatekeeper of quiescence in hepatic stellate cells, a key driver of liver fibrogenesis and chronic liver disease. Physiologically expressed in healthy liver and consistently downregulated during liver fibrosis development, its therapeutic re-expression is expected to have few side effects, making it an attractive target diagnostic tool and drug candidate for industry and clinicians.
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Células Estrelladas Hepáticas , Canales Catiónicos TRPV , Humanos , Ratones , Animales , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/farmacología , Células Estrelladas Hepáticas/metabolismo , Hígado/patología , Cirrosis Hepática/patología , Regulación de la Expresión Génica , Proteínas del Citoesqueleto/metabolismo , Proteínas del Citoesqueleto/farmacología , Proteínas del Dominio Armadillo/genética , Proteínas del Dominio Armadillo/metabolismoRESUMEN
BACKGROUND: We aimed to investigate the utility of Hounsfield units (HU) obtained from different regions of interest in opportunistic lumbar computed tomography (CT) to predict osteoporosis coupling with data of dual-energy X-ray absorptiometry (DXA). METHODS: A total of 100 patients who attended a university hospital in Shanghai, China, and had undergone CT and DXA tests of the lumbar spine within 3 months were included in this retrospective review. Images were reviewed on axial sections, and regions of interest (ROI) markers were placed on the round, oval, anterior, left, and right of the L1-L4 vertebra to measure the HU. The mean values of CT HU were then compared to the bone mineral density (BMD) measured by DXA. Receiver operator characteristic curves were generated to determine the threshold for diagnosis and its sensitivity and specificity values. RESULTS: The differences in CT HU of different ROI based on DXA definitions of osteoporosis, osteopenia, and normal individuals were statistically significant (p < 0.01). The HU values of the different ROI correlated well with the BMD values (Spearman coefficient all > 0.75, p < 0.01). The threshold for diagnosing osteoporosis varies from 87 to 111 HU in different ROIs, and the threshold for excluding osteoporosis or osteopenia is 99-125 HU. CONCLUSION: This is the first study on osteoporosis diagnosis of different ROI with routine CT lumbar scans. There is a strong correlation between CT HU of different ROI in the lumbar spine and BMD, and HU measurements can be used to predict osteoporosis.
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Enfermedades Óseas Metabólicas , Osteoporosis , Absorciometría de Fotón/métodos , Densidad Ósea , Enfermedades Óseas Metabólicas/diagnóstico por imagen , China , Humanos , Vértebras Lumbares/diagnóstico por imagen , Osteoporosis/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND AND AIMS: Patients with liver fibrosis who have pain in the liver region may have changed nerve factors. The expression of neurokines and hepatic nerves in liver fibrosis, however, was little understood. In order to better understand how liver fibrosis develops, we plan to look into the hepatic nerve and neurokine changes and how they relate to hepatic stellate cells (HSCs). METHODS: The expression of neurokines in liver samples from 55 chronic hepatitis B patients and the carbon tetrachloride (CCl4) animal model were studied. The co-staining of Nissl and α-SMA allowed us to investigate the neurons and their interaction with α-SMA in fibrotic livers, as well as the expression of the glial cell marker glial fibrillary acidic protein (GFAP) and its relationship with α-SMA, a marker of HSCs. SH-SY5Y cells were treated with a fibrotic serum to imitate the hepatic microenvironment on neuronal cells. We also used brain-derived neurotrophic factor (BDNF) to stimulate mouse primary HSCs and LX2. RESULTS: The levels of mRNA for neurokines such as BDNF, GFAP, and growth-associated protein (GAP43) are significantly increased in both human and animal liver fibrosis. As liver fibrosis advances, we found that Nissl bodies and α-SMA may co-localize, suggesting a connection between hepatic nerves and HSCs. Human fibrotic serum may increase neurkines, notably BDNF, in SH-SY5Y cells. We also found that BDNF increased pro-inflammatory cytokines and fibrogenic markers in hHSCs. CONCLUSIONS: Patients with hepatic fibrosis had significantly higher levels of BDNF, GFAP, GAP43, and nerve fibers. HSC and nerve fibers interact, and nerves also create neurogenic substances that promote liver fibrosis and HSC activation.
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Células Estrelladas Hepáticas , Neuroblastoma , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Tetracloruro de Carbono/toxicidad , Citocinas/metabolismo , Fibrosis , Proteína Ácida Fibrilar de la Glía/metabolismo , Células Estrelladas Hepáticas/metabolismo , Humanos , Hígado/metabolismo , Cirrosis Hepática/patología , Ratones , Neuroblastoma/patología , ARN Mensajero/metabolismo , Microambiente TumoralRESUMEN
Objectives: We assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients. Methods: A total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis. Results: We showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80-0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79-0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson's trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p < 0.001) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10-17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3. Conclusion: Using serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients.
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Factor Neurotrófico Derivado de la Línea Celular Glial , Hepatitis B Crónica , Cirrosis Hepática , Aspartato Aminotransferasas , Biomarcadores/sangre , Biopsia , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Hepatitis B Crónica/sangre , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/virología , Recuento de Plaquetas , ARN Mensajero , Curva ROC , Estudios RetrospectivosRESUMEN
Objective: This study aimed to assess the main components of Artemisia annua L. essential oil (AEO) and determine their effect on the proliferation and differentiation of RAW264.7 cells induced by receptor activator for nuclear factor-ligand (RANKL) in vitro. Then, we tried to explain part of the function of its possible mechanisms. Materials and Methods: Essential oil was extracted from Artemisia annua L. Osteoclasts were induced in vitro by RANKL in mouse RAW264.7 cells. The experimental group was treated with different concentrations of AEO, while the control group was not treated with AEO. CCK8 was used to detect osteoclast proliferation. The osteoclasts were stained with TRAP. Western blot was used to detect protein in the MAPK pathway and the NF-κB pathway after treatment with different concentrations of AEO. RT-PCR was used to determine the expression of osteoclast-related mRNA in cells. Results: The GC-MS analysis was used to obtain the main components of AEO, including camphor, borneol, camphor, borneol, terpinen-4-ol, p-cymene, eucalyptol, deoxyartemisinin, and artemisia ketone. The CCK8 results showed that the AEO volume ratio of 1 : 4000, 1 : 5000, and 1 : 6000 did not affect the proliferation of RAW264.7 cells. However, TRAP staining showed that AEO decreased osteoclast formation. Western blot results showed that the expression of protein TRAF6, p-p38, p-ERK, p-p65, and NFATc1 decreased in the MAPK pathway and the NF-κB pathway affected by AEO. Furthermore, RT-PCR results showed that the expression of osteoclast resorption-related mRNAs (MMP-9, DC-STAMP, TRAP, and CTSK) and osteoclast differentiation-related mRNAs (OSCAR, NFATc1, c-Src, and c-Fos) also decreased in the experimental group. Conclusions: AEO inhibits osteoclast differentiation in vitro, probably by reducing TRAF6 activation, acting on the MAPK pathway and NF-κB pathway, and inhibiting the expression of osteoclast-related genes.
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BACKGROUND: Lumbar disc herniation (LDH) is a common chronic musculoskeletal disorder that seriously affects quality of life. The percutaneous endoscopic lumbar diskectomy (PELD) technique was developed to address spinal nerve root compression through direct visualization of pathological findings while minimizing tissue destruction upon exposure. It is an effective and safe treatment for LDH. However, recurrent LDH is a major concern after lumbar discectomy for primary LDH. A considerable number of clinical studies have reported that patients with LDH with radiculopathy could benefit from manual therapy. Shi's manual therapy (SMT) was established based on traditional Chinese medicine (TCM) theory and has been shown to have a superior effect in alleviating muscle tension and loosening joints to improve lumbar and leg pain, radiculopathy, stiffness, activity discomfort, and related disorders. However, there is a lack of high-quality clinical evidence to support this conclusion. The purpose of this study is to evaluate the efficacy and safety of the combination of Shi's manual therapy (SMT) and PELD for LDH with radiculopathy. METHODS/DESIGN: A multicenter randomized controlled trial (RCT) with a 1-year follow-up period will be performed. A total of 510 participants with LDH with radiculopathy will be recruited from four clinical centers. The sample size was estimated, and statistical analysis will be performed and supervised by biostatisticians from an independent third-party research institution. Two hundred fifty-five subjects will be randomly allocated to each group. The subjects in the control group will undergo PELD. Participants in the intervention group will be treated with a combination of SMT and PELD. Recurrence rate is the primary endpoint and the survival analysis of recurrence rate is the secondary endpoint, and the primary analysis of recurrence rate is the chi-square test and the secondary analysis of recurrence rate is survival analysis. The primary outcome measure is the recurrence rate of LDH with radiculopathy at the 1-year follow-up after treatment. The secondary outcome measures will be the ODI score, the VAS score for pain for the lumbar spine and lower limbs, the straight leg raise angle, the stability of the operated lumbar segment, and the SF-36 scores. Assessments will occur at baseline, postoperation, and 1 week, 4 weeks, 13 weeks, 26 weeks, and 1 year postoperation. In addition, adverse events related to clinical symptoms and signs and the results of laboratory tests will be documented during the clinical trials. DISCUSSION: This study will provide reliable evidence of the effectiveness and safety of the combination of SMT and PELD for LDH with radiculopathy. If the results are favorable, it is expected that patients with LDH with radiculopathy will benefit from this study, and many patients could gain a good alternative treatment for LDH with radiculopathy. TRIAL REGISTRATION: China Registered Clinical Trial Registration Center ChiCTR2000036515 . Registered on 13 November 2020.
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Desplazamiento del Disco Intervertebral , Manipulaciones Musculoesqueléticas , Radiculopatía , Discectomía/efectos adversos , Endoscopía/efectos adversos , Endoscopía/métodos , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Estudios Multicéntricos como Asunto , Dolor/etiología , Radiculopatía/diagnóstico , Radiculopatía/etiología , Radiculopatía/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Alcoholic liver disease (ALD) is associated with high morbidity and mortality worldwide. The pathogenesis of ALD is not completely understood. Although accumulating evidence suggests an important role of glial cell line-derived neurotrophic factor (GDNF) in several diseases, there are no data concerning its role in ALD. This study compared patients with ALD with control subjects and used a mouse model and a cell culture model to investigate the function of GDNF in ALD and its mechanism of action in hepatocyte injury. METHODS: Serum levels of GDNF were measured in 25 patients with ALD and 25 healthy control subjects. A 4-week Lieber-DeCarli ethanol (EtOH) liquid diet combined with the Gao-Binge model was used in the mouse study. Mouse primary hepatocytes and Huh-7 cells were used for cell experiments. The parameters of liver injury, inflammatory cytokines, and lipid metabolism were measured. RESULTS: Patients with alcoholic hepatitis had higher serum GDNF than control subjects. Expression of GDNF mRNA and protein was markedly increased in mice in the chronic-plus-binge ALD mouse model. The level of GDNF mRNA was upregulated in primary hepatic stellate cells isolated from ethanol-fed mouse liver. Ethanol induced GDNF expression in LX2 cells. The levels of inflammatory cytokines (tumor necrosis factor α, interleukin 1ß, and monocyte chemotactic protein 1) were significantly increased after GDNF stimulation in primary hepatocytes and Huh-7 cells. After GDNF stimulation, levels of both p-AKT and p-NF-κB were significantly increased in primary hepatocytes and Huh-7 cells. The NF-κB activity induced by GDNF was significantly decreased by an NF-κB inhibitor, which limited hepatocyte injury and inflammation. CONCLUSIONS: The concentration of GDNF is increased in the circulation of ALD patients. GDNF promotes alcohol-induced liver injury and inflammation via the activation of NF-κB, which mediates hepatocyte injury and inflammatory cytokine expression. Based on these findings, GDNF is a potential therapeutic target for preventing or ameliorating liver injury in ALD.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Hepatopatías Alcohólicas , Animales , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Etanol/efectos adversos , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Factor Neurotrófico Derivado de la Línea Celular Glial/uso terapéutico , Humanos , Inflamación/metabolismo , Hígado/metabolismo , Hepatopatías Alcohólicas/metabolismo , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , ARN Mensajero/metabolismoRESUMEN
OBJECTIVE: The present study intends to investigate the effects and underlying molecular mechanism of Qigu Capsule (QG) on fracture healing in mice with osteoporosis. METHODS: Ten-week-old female C57BL/6 mice were ovariectomized and three weeks later were evaluated for successful modeling. Then, all mice were prepared into models of transverse fracture in the right middle femoral shaft. Mice were treated daily using a gavage with normal saline (the NS group), Qigu Capsule (the QG group), or alendronate (the ALN group) postoperatively. Fracture callus tissues were collected and analyzed by X-ray, micro-CT, western blot (WB), and transmission electron microscope (TEM) on postoperation Day 14 (POD14), POD28, and POD42. RESULTS: (1) X-ray results showed that on POD14, the QG group had the fracture healing score significantly higher than the NS and ALN groups, and on POD28, it had the fracture healing score higher than the NS group, suggesting that QG could promote fracture healing. (2) Micro-CT results showed that on POD14, the QG group had tissue bone density (TMD) significantly higher than the NS and ALN groups, and on POD28 and POD42, it had bone volume fraction, trabecular number, and TMD significantly higher than the NS group. (3) WB results showed that, compared with the NS group, the QG group had significantly increased expression of nuclear factor kappa-B (NF-κB), hypoxia-inducible factor-1α (HIF-1α), bone alkaline phosphatase (BALP), runt-related transcription factor 2 (Runx2), bone Gla protein (BGP) and collagen Iα1 (COLIα1) on POD14, significantly increased expression of NF-κB, HIF-1α, BALP and COLIα1 on POD28, and significantly increased expression of NF-κB, HIF-1α, and Runx2 on POD42. (4) TEM scanning results showed that, compared with the NS and ALN groups, the QG group had significantly increased numbers of autophagic vacuoles (AVs) in osteocytes on POD14, POD28, and POD42. CONCLUSION: QG could accelerate osteoporotic fracture healing by promoting bone formation and osteocyte autophagy, possibly through upregulating the NF-κB/HIF-1α signaling pathway.
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AIMS: Liver fibrosis is a chronic liver disease characterized by hepatic stellate cell (HSC) activation. Peroxisome proliferator-activated receptor gamma (PPARγ) play an important role in HSC activation. This study aimed to investigate the role of PPARγ in the progression of human hepatic fibrosis and the mechanism by which microRNA-942 regulates HSC activation. METHODS: 70 chronic hepatitis B (CHB) patients liver tissues were used to assess PPARγ, α-SMA and miR-942 levels by immunoblot and real-time PCR. Human primary HSCs or LX2 cells were used to perform multiple molecular experiments based on the transfection of small interfering RNA (siRNA) or co-transfection of microRNA inhibitor. Site-directed mutagenesis and luciferase reporter assays were used to identify miR-942 targets. miR-942 expression and localization in hepatic fibrosis and co-localization between α-SMA were determined by fluorescence in situ hybridization (FISH). KEY FINDINGS: The mRNA expression of PPARγ was decreased in activated HSCs and CHB patients with liver fibrosis, which was negatively correlated with F stage and α-SMA. miR-942 negatively regulates PPARγ expression via targeting the PPARγ 3'UTR. Inhibiting PPARγ promoted TGFß1 induced HSC activation, and this effect was blocked after inhibiting the miR-942. Moreover, miR-942 was mainly expressed in fibrous septa and negatively correlated with PPARγ in liver fibrosis. SIGNIFICANCE: PPARγ targeting by miR-942 and decreasing HSC activation in human hepatic fibrosis. Hence, regulating PPARγ may be a promising therapeutic strategy for hepatic fibrosis.
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Hepatitis B Crónica , Cirrosis Hepática , PPAR gamma/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Actinas , Secuencia de Bases , Regulación de la Expresión Génica , Células Estrelladas Hepáticas/metabolismo , Hepatitis B Crónica/metabolismo , Hepatitis B Crónica/terapia , Humanos , Cirrosis Hepática/metabolismo , Cirrosis Hepática/terapia , MicroARNs/metabolismo , Imagen Óptica/métodosRESUMEN
The reasonable selection of magnetic resonance imaging(MRI) scan sequence and parameters is very important for the objective evaluation of the results of clinical study and high quality imaging. The semi quantitative scoring system of total knee joint including Whole Organ Magnetic Resonance Imaging Score, Boston Leeds Osteoarthritis Knee Score, MRI Osteoarthritis Knee Score, Cartilage Repair Osteoarthritis Knee Score and so on. They can fully evaluate the imaging changes of various organs during the development of knee osteoarthritis. With the continuous development of MRI technology, the morphological and physiological changes of articular cartilage can be quantitatively assessed. T2 mapping, Diffusion Weighted Imaging, and delayed Gadolinium-Enhanced MRI of Cartilage can be quantitatively monitoring changes in cartilage matrix components. These quantitative and semi quantitative evaluation techniques are helpful to detect OA in its early stage, guide clinical early intervention, and also provide the possibility for the accurate evaluation of the therapeutic effect.