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1.
World J Psychiatry ; 14(8): 1165-1173, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39165558

ABSTRACT

Patients with hematological tumors experience physical and psychological stress, and negative psychological states. Baduanjin, an emerging psychological rehabilitation method combined with resistance exercise, has received widespread attention. This study reviews the current status of the application of Baduanjin combined with resistance exercise in improving the negative psychological state of patients with hematological tumors and discusses its problems and prospects. Through a literature review and comprehensive analysis, the application of Baduanjin and resistance exercise in the psychological rehabilitation of patients with hematological tumors was identified and evaluated. The results showed that Baduanjin with resistance exercise had a positive effect on improving negative psychological states of patients with hematological tumors, which can alleviate anxiety, depression, and other adverse emotions, and improve quality of life. However, there is a lack of unified and standardized exercise intervention programs for practical application, and patient participation and compliance must be improved. Baduanjin combined with resistance exercise can potentially improve the negative psychological status of patients with hematological tumors; however, it is still necessary to further standardize and improve the exercise program improving patient participation and compliance. Future studies should strengthen theoretical exploration and empirical research, providing more effective psychological rehabilitation strategies for patients with hematological tumors.

2.
Med Sci Monit ; 30: e944556, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39161055

ABSTRACT

BACKGROUND Previous studies have suggested that autophagy, a cellular process regulated by ATG7, plays a critical role in ovarian physiology and pathology. In this study, our objective was to examine ATG7 levels in women with and without polycystic ovary syndrome (PCOS) and to explore potential associations between serum ATG7 levels and PCOS. MATERIAL AND METHODS The study included 188 women diagnosed with PCOS, matched with an equal number of healthy women for comparison. Serum levels of ATG7 were determined using the ELISA technique, and the difference was assessed using an independent samples t test. The association between ATG7 serum levels and the risk of developing PCOS was evaluated by using a multivariable logistic regression model. Additionally, the potential of ATG7 to predict PCOS was investigated through logistic regression and receiver operating characteristic (ROC) analysis. RESULTS Our study found that women with PCOS had significantly lower serum ATG7 levels than their healthy counterparts. Lower ATG7 levels were associated with a higher risk of developing PCOS after adjusting for various confounding variables. The combination of ATG7 with HOMA-IR performed well in predicting PCOS, with an AUC of 92.3%, a sensitivity of 88.3%, and a specificity of 85.3%. CONCLUSIONS Our study found that serum ATG7 levels were significantly lower in women with PCOS and were associated with an increased risk of developing PCOS. This suggests that ATG7 could potentially serve as a biomarker for diagnosing and managing PCOS.


Subject(s)
Autophagy-Related Protein 7 , Insulin Resistance , Polycystic Ovary Syndrome , ROC Curve , Humans , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/metabolism , Female , Adult , Autophagy-Related Protein 7/metabolism , Case-Control Studies , Logistic Models , Biomarkers/blood , Autophagy , Young Adult
3.
J Biotechnol Biomed ; 7(2): 214-220, 2024.
Article in English | MEDLINE | ID: mdl-39086601

ABSTRACT

The COVID-19 pandemic introduced an urgent need for rapid and high-throughput testing for SARS-CoV-2. RNA extraction is a major bottleneck for RT-qPCR. We describe a semi-automated, extraction-free RT-qPCR assay for detection of SARS-CoV-2 in nasal swab and saliva samples on a single platform. With a limit of detection of 4 copies/mL, this laboratory developed test performed equivalently to established methods requiring nucleic acid extraction. Five technologists staffing two shifts per day (80 person-hours) processed more than 400,000 samples over 10 months. Patients opted to provide nasal swab samples (83.6%) more frequently than saliva (16.4%), creating the added challenge of producing swab collection kits. Real-world testing data indicated a higher frequency of SARS-CoV-2 detection in saliva (10.1%) compared to nasal swab (7.7%). This cost-effective and quickly scalable approach is suitable for pandemic preparedness planning related to surveillance and diagnostic testing.

5.
Adv Sci (Weinh) ; : e2404433, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39005186

ABSTRACT

Growing demand for wound care resulting from the increasing chronic diseases and trauma brings intense pressure to global medical health service system. Artificial skin provides mechanical and microenvironmental support for wound, which is crucial in wound healing and tissue regeneration. However, challenges still remain in the clinical application of artificial skin since the lack of the synergy effect of necessary performance. In this study, a multi-functional artificial skin is fabricated through microfluidic spinning technology by using core-shell gel nanofiber scaffolds (NFSs). This strategy can precisely manipulate the microstructure of artificial skin under microscale. The as-prepared artificial skin demonstrates superior characteristics including surface wettability, breathability, high mechanical strength, strain sensitivity, biocompatibility and biodegradability. Notably, this artificial skin has the capability to deliver medications in a controlled and sustained manner, thereby accelerating the wound healing process. This innovative approach paves the way for the development of a new generation of artificial skin and introduces a novel concept for the structural design of the unique core-shell gel NFSs.

6.
Int J Biol Macromol ; 276(Pt 1): 133652, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38971273

ABSTRACT

Eighteen S rRNA factor 1 (ESF1) is a predominantly nucleolar protein essential for embryogenesis. Our previous studies have suggested that Esf1 is a negative regulator of the tumor suppressor protein p53. However, it remains unclear whether ESF1 contributes to tumorigenesis. In this current research, we find that increased ESF1 expression correlates with poor survival in multiple tumors including pancreatic cancer. ESF1 is able to regulate cell proliferation, migration, DNA damage-induced apoptosis, and tumorigenesis. Mechanistically, ESF1 physically interacts with MDM2 and is essential for maintaining the stability of MDM2 protein by inhibiting its ubiquitination. Additionally, ESF1 also prevented stress-induced stabilization of p53 in multiple cancer cells. Hence, our findings suggest that ESF1 is a potent regulator of the MDM2-p53 pathway and promotes tumor progression.


Subject(s)
Carcinogenesis , Cell Proliferation , Proto-Oncogene Proteins c-mdm2 , Tumor Suppressor Protein p53 , Ubiquitination , Proto-Oncogene Proteins c-mdm2/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Humans , Carcinogenesis/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Cell Line, Tumor , Animals , Gene Expression Regulation, Neoplastic , Apoptosis/genetics , Mice , DNA Damage , Cell Movement
7.
Discov Oncol ; 15(1): 309, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060620

ABSTRACT

Cancer-associated fibroblasts (CAFs), integral components of the tumor microenvironment, play a pivotal role in tumor proliferation, metastasis, and clinical outcomes. However, its specific roles in Kidney Renal Clear Cell Carcinoma (KIRC) remain poorly understood. Employing the established Seurat single-cell analysis pipeline, we identified 21 CAFs marker genes. Subsequently, a prognostic signature consisting of 6 CAFs marker genes (RGS5, PGF, TPM2, GJA4, SEPT4, and PLXDC1) was developed in a cohort through univariate and LASSO Cox regression analyses. The model's efficacy was then validated in an external cohort, with a remarkable predictive performance in 1-, 3-, and 5-year. Patients in the high-risk group exhibited significantly inferior survival outcomes (p < 0.001), and the risk score was an independent prognostic factor (p < 0.05). Distinct differences in immune cell profiles and drug susceptibility were observed between the two risk groups. In KIRC, the PGF-VEGFR1 signaling pathway displayed a notable increase. PGF expression was significantly elevated in tumor tissues, as demonstrated by quantitative real-time polymerase chain reaction. In vitro, transwell assays and CCK8 revealed that recombinant-PGF could enhance the capability of cell proliferation, migration, and invasion in 769P and 786-O cells. This study firstly developed a novel predictive model based on 6 CAFs genes for KIRC. Additionally, PGF may present a potential therapeutic target to enhance KIRC treatment.

8.
J Immunother Cancer ; 12(7)2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39067872

ABSTRACT

OBJECTIVE: Hepatocellular carcinoma (HCC) poses a significant clinical challenge because the long-term benefits of immune checkpoint blockade therapy are limited. A comprehensive understanding of the mechanisms underlying immunotherapy resistance in HCC is imperative for improving patient prognosis. DESIGN: In this study, to systematically investigate the characteristics of cancer-associated fibroblast (CAF) subsets and the dynamic communication among the tumor microenvironment (TME) components regulated by CAF subsets, we generated an HCC atlas by compiling single-cell RNA sequencing (scRNA-seq) datasets on 220 samples from six datasets. We combined spatial transcriptomics with scRNA-seq and multiplexed immunofluorescence to identify the specific CAF subsets in the TME that determine the efficacy of immunotherapy in HCC patients. RESULTS: Our findings highlight the pivotal role of POSTN+ CAFs as potent immune response barriers at specific tumor locations, as they hinder effective T-cell infiltration and decrease the efficacy of immunotherapy. Additionally, we elucidated the interplay between POSTN+ CAFs and SPP1+ macrophages, whereby the former recruits the latter and triggers increased SPP1 expression via the IL-6/STAT3 signaling pathway. Moreover, we demonstrated a spatial correlation between POSTN+ CAFs and SPP1+ macrophages, revealing an immunosuppressive microenvironment that limits the immunotherapy response. Notably, we found that patients with elevated expression levels of both POSTN+ CAFs and SPP1+ macrophages achieved less therapeutic benefit in an immunotherapy cohort. CONCLUSION: Our research elucidates light on the role of a particular subset of CAFs in immunotherapy resistance, emphasizing the potential benefits of targeting specific CAF subpopulations to improve clinical responses to immunotherapy.


Subject(s)
Cancer-Associated Fibroblasts , Carcinoma, Hepatocellular , Immunotherapy , Liver Neoplasms , Tumor Microenvironment , Humans , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/immunology , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/immunology , Immunotherapy/methods , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/genetics , Mice
9.
PLoS One ; 19(7): e0304809, 2024.
Article in English | MEDLINE | ID: mdl-38995923

ABSTRACT

Supporting cells(SCs) have been demonstrated to be a reliable source for regenerating hair cells(HCs). Previous research has reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo. However, there is limited knowledge about the impact of the material on Lgr5+ cells. In this study, Lgr5+ cells were isolated from neonatal Lgr5-EGFP-CreERT2 transgenic mice by flow cytometry and then plated on self-assembled silica beads (SB). Lgr5+ cell differentiation was observed by immunofluorescence. We found that in the direct differentiation assay, the SB group generated more hair cells than the control group(*p < 0.05). Especially in the SB group, Lgr5+ progenitors generated significantly more Myo7a+ HCs outside of the colony than in the control group(**p < 0.01). In the sphere differentiation assay, we found that the diameter of spheres in the SB group was significantly larger compared to those of the control group(**p < 0.01). However, the difference in the ratio of myo7a+ cell counts was not obvious(P>0.05). The experiment proved that the self-assembled silica beads could promote the differentiation of Lgr5+ progenitors in vitro. Our findings implicate that nanostructures of self-assembled silica beads can be used as vectors for stem cell research in the inner ear.


Subject(s)
Cell Differentiation , Mice, Transgenic , Nanostructures , Receptors, G-Protein-Coupled , Silicon Dioxide , Stem Cells , Animals , Silicon Dioxide/chemistry , Receptors, G-Protein-Coupled/metabolism , Stem Cells/cytology , Stem Cells/metabolism , Mice , Nanostructures/chemistry , Cells, Cultured
10.
J Phys Chem A ; 128(30): 6216-6228, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39023240

ABSTRACT

In this work, a quantitative structure-antioxidant activity relationship of flavonoids was performed using a machine learning (ML) method. To achieve lipid-soluble, highly antioxidant flavonoids, 398 molecular structures with various substitute groups were designed based on the flavonoid skeleton. The hydrogen dissociation energies (ΔG1, ΔG2, and ΔG3) related to multiple hydrogen atom transfer processes and the solubility parameter (δ) of flavonoids were calculated using molecular simulation. The group decomposition results and the calculated antioxidant parameters constituted the ML data set. The artificial neural network and random forest models were constructed to predict and analyze the contribution of the substitute groups and positions to the antioxidant activity. The results showed the hydroxyl group at positions B4', B5', and B6' and the branched alkyl group at position C3 in the flavonoid skeleton were the optimal choice for improving antioxidant activity and compatibility with apolar organic materials. Compared to the pyrogallol group-grafted flavonoid, the designed potent flavonoid decreased ΔG1 and δ by 2.2 and 15.1%, respectively, while ΔG2 and ΔG3 kept the favorable lower values. These findings suggest that an efficient flavonoid prefers multiple ortho-phenolic hydroxyl groups and suitable sites with hydrophobic groups. The combination of molecular simulation and the ML method may offer a new research approach for the molecular design of novel antioxidants.


Subject(s)
Antioxidants , Flavonoids , Machine Learning , Quantitative Structure-Activity Relationship , Flavonoids/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Molecular Structure , Molecular Dynamics Simulation , Drug Design , Thermodynamics
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 789-793, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926968

ABSTRACT

OBJECTIVE: To investigate the relative expression level and clinical significance of LINC00475 in serum of patients with multiple myeloma (MM). METHODS: The expression of LINC00475 in serum of 108 MM patients and five MM cell lines including RPMI 8226, NCI-H929, U266, OPM2 and CAG were detected by real-time fluorescence quantitative PCR. The diagnostic value of LINC00475 in MM was evaluated by receiver operating characteristic (ROC) curve analysis. The correlation of LINC00475 with patients' characteristics was analyzed. RESULTS: Compared with control groups, the expression of LINC00475 was up-regulated in serum of MM patients and MM cell lines (all P < 0.05). ROC curve analysis showed that the optimal cut-off value of LINC00475 was 262.4, the area under curve (AUC) was 0.924(95%CI : 0.884-0.964), and sensitivity and specificity was 83.3% and 91.7%, respectively, which indicated that LINC00475 had good evaluation value in MM patients. Compared with low-LINC00475 expression group, patients in high-LINC00475 expression group had higher levels of ß2microglobulin (ß2-MG) and Cystatin C (Cys-C) but lower albumin (ALB) (all P < 0.05). Compared with MM patients with International Staging System (ISS) stage I, the expression level of LINC00475 was significantly higher in patients with stage II and III (both P < 0.05). CONCLUSION: LINC00475 is helpful to distinguish MM patients from healthy adults, which is correlated with the prognostic indicators such as ß2-MG, ALB, and ISS stage.


Subject(s)
Multiple Myeloma , RNA, Long Noncoding , Humans , Multiple Myeloma/genetics , RNA, Long Noncoding/genetics , Cell Line, Tumor , beta 2-Microglobulin , ROC Curve , Clinical Relevance
12.
Front Psychol ; 15: 1372694, 2024.
Article in English | MEDLINE | ID: mdl-38882513

ABSTRACT

Background: The interplay between teaching engagement and performance has garnered attention in both theoretical and empirical research, primarily due to its influence on student academic achievement, teacher well-being, and the realization of institutional goals. This is especially pertinent in the realm of preschool education, where the scope of learning extends beyond academic content to encompass the broader socialization of children. Drawing from Affective Neuroscience research, this study investigates the role of affective tendencies as mediators in the relationship between work engagement and job performance. Objective: The primary aim of this research is to examine a chain mediation model that hypothesizes the predictive role of teacher engagement. This model posits the intermediary influence of four basic emotions-CARING, SEEKING, ANGER, and FEAR-followed by the mediating effect of job satisfaction on teacher job performance. Method: The study utilized a sample of 842 Chinese preschool teachers. Data were collected through an online questionnaire, employing a time-lagged design. The analysis was conducted using Model 80 of the PROCESS Macros. Results: The findings reveal that both positive and negative emotions significantly predict teachers' job satisfaction. However, job satisfaction does not influence job performance. The analysis confirmed the direct and total effects of teacher engagement, as well as the indirect effects, particularly through the positive emotion of Caring. Implications: The results are instrumental in informing and refining interventions designed to enhance teacher engagement and performance, underscoring the importance of emotional factors in the educational environment.

14.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167276, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38844114

ABSTRACT

The role of hypoxia in the tumor microenvironment of intrahepatic cholangiocarcinoma (iCCA) remains unclear. Here, we generated a comprehensive atlas of the entire tumor microenvironment and delineated the multifaceted cell-cell interactions to decipher hypoxia-induced pro-tumor immune suppression. We discovered hypoxia is significantly associated with iCCA progression via the activation of HIF1A expression. Moreover, hypoxia-dependent PPARγ-mediated fatty acid oxidation in APOE+ TAMs promoted M2 macrophage polarization by activating the HIF1A-PPARG-CD36 axis. These polarized APOE+ TAMs recruited Treg cell infiltration via the CCL3-CCR5 pair to form an immunosuppressive microenvironment. APOE+ TAMs tended to co-localize spatially with Treg cells in the malignant tissue based on spatial transcriptome data and immunofluorescence analysis results. We identified tumor-reactive CXCL13+ CD8-PreTex with specific high expression of ENTPD1 and ITGAE, which acted as precursors of CD8-Tex and had higher cytotoxicity, lower exhaustion, and more vigorous proliferation. Consequently, CXCL13+ CD8-PreTex functioned as a positive regulator of antitumor immunity by expressing the pro-inflammatory cytokines IFNG and TNF, associated with a better survival outcome. Our study reveals the mechanisms involved in hypoxia-induced immunosuppression and suggests that targeting precursor-exhausted CXCL13+CD8+ T cells might provide a pratical immunotherapeutic approach.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Single-Cell Analysis , Tumor Microenvironment , Cholangiocarcinoma/immunology , Cholangiocarcinoma/pathology , Cholangiocarcinoma/metabolism , Tumor Microenvironment/immunology , Humans , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/immunology , Bile Duct Neoplasms/metabolism , Animals , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Mice , Cell Line, Tumor , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/pathology
15.
Oncogene ; 43(31): 2389-2404, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38890429

ABSTRACT

The role of tumor-resident microbiota in modulating tumor immunity remains unclear. Here, we discovered an abundance of intra-tumoral bacteria, such us E.coli, residing and resulting in Colorectal cancer liver metastasis (CRLM). E.coli enhanced lactate production, which mediated M2 macrophage polarization by suppressing nuclear factor-κB -gene binding (NF-κB) signaling through retinoic acid-inducible gene 1 (RIG-I) lactylation. Lactylation of RIG-I suppressed recruitment of NF-κB to the Nlrp3 promoter in macrophages, thereby reducing its transcription. This loss of Nlrp3 affected the immunosuppressive activities of regulatory T cells (Tregs) and the antitumor activities of and CD8+ T cells. Small-molecule compound screening identified a RIG-I lactylation inhibitor that suppressed M2 polarization and sensitized CRLM to 5-fluorouracil (5-FU). Our findings suggest that tumor-resident microbiota may be a potential target for preventing and treating CRLM.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , NF-kappa B , Colorectal Neoplasms/pathology , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/immunology , Liver Neoplasms/secondary , Liver Neoplasms/microbiology , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Animals , Humans , Mice , NF-kappa B/metabolism , Microbiota/immunology , Macrophages/immunology , Macrophages/metabolism , Escherichia coli , T-Lymphocytes, Regulatory/immunology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Cell Line, Tumor , Fluorouracil/pharmacology , Signal Transduction
16.
Plant Cell Environ ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38770581

ABSTRACT

Mitogen-activated protein kinase (MAPK) signalling cascades are functionally important signalling modules in eukaryotes. Transcriptome reprogramming of immune-related genes is a key process in plant immunity. Emerging evidence shows that plant MAPK cascade is associated with processing (P)-body components and contributes to transcriptome reprogramming of immune-related genes. However, it remains largely unknown how this process is regulated. Here, we show that OsMPK12, which is induced by Magnaporthe oryzae infection, positively regulates rice blast resistance. Further analysis revealed that OsMPK12 directly interacts with enhancer of mRNA decapping protein 4 (OsEDC4), a P-body-located protein, and recruits OsEDC4 to where OsMPK12 is enriched. Importantly, OsEDC4 directly interacts with two decapping complex members OsDCP1 and OsDCP2, indicating that OsEDC4 is a subunit of the mRNA decapping complex. Additionally, we found that OsEDC4 positively regulates rice blast resistance by regulating expression of immune-related genes and maintaining proper mRNA levels of some negatively-regulated genes. And OsMPK12 and OsEDC4 are also involved in rice growth and development regulation. Taken together, our data demonstrate that OsMPK12 positively regulates rice blast resistance via OsEDC4-mediated mRNA decay of immune-related genes, providing new insight into not only the new role of the MAPK signalling cascade, but also posttranscriptional regulation of immune-related genes.

17.
Nanoscale ; 16(25): 12007-12012, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38805180

ABSTRACT

Polyvinyl alcohol (PVA) fiber materials have gained immense recognition due to their good biocompatibility and wide applications. However, methods allowing the synergistic enhancement of mechanical strength and toughness of PVA fibers still remain a key challenge. To this end, we developed covalently cross-linked ultrastrong SiO2-loaded polyvinyl alcohol fibers via a microfluidic spinning chemistry strategy. The thermal stretching and annealing processes not only promote the ordered arrangement of molecules, but also facilitate the ring opening reaction and increase crystallinity. Thus, the resulting fiber has a high tensile strength of 866 MPa, a specific toughness of 288 J g-1 and a tensile strain of 80%. This work provides a covalent cross-linking reinforcement method to prepare ultrastrong composite fibers assisted by microfluidic spinning chemistry and thermal stretching, which would lead to the fabrication of mechanically strong fiber materials through a simple pathway.

18.
Cartilage ; : 19476035241250198, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38747467

ABSTRACT

OBJECTIVE: Knee osteoarthritis (KOA) is a complex degenerative joint disease and a major cause of joint dysfunction. This study aimed to explore the function of hsa_circ_0007482 on inflammation, proliferation, differentiation, and apoptosis in KOA. DESIGN: Real-time quantitative polymerase chain reaction (PCR) was performed to detect the expression of circ_0007482, inflammatory factors, and differentiation-related molecules in KOA chondrocytes and interleukin (IL)-1ß-stimulated chondrocytes. The correlation between the circ_0007482 expression and inflammatory factors was analyzed by the Pearson method. KOA cell model was established using IL-1ß for 24 hours. The proliferation activity of chondrocytes was evaluated by CCK-8 assay, and cell apoptosis rate was assessed by flow cytometry. The downstream miRNA of circ_0007482 was validated using dual-luciferase reporter assay. RESULTS: The circ_0007482 expression was elevated in both KOA cartilage tissues and IL-1ß-treated chondrocytes and positively correlated with inflammatory factors expression. In comparison to the control group, IL-1ß treatment diminished chondrocyte proliferation abilities and increased cell apoptosis and inflammatory factors IL-6, IL-8, and tumor necrosis factor (TNF)-α mRNA expression. Inhibition of circ_0007482 partially improved IL-1ß-induced inflammatory reaction. Circ_0007482 could negatively regulate the expression of miR-558. CONCLUSIONS: Interfering of circ_0007482 might partially promote cell proliferation and differentiation, while inhibit cell apoptosis to improve joint injury by regulating miR-558 in IL-1ß-treated chondrocyte cell model.

19.
Clin Mol Hepatol ; 30(3): 515-538, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38726504

ABSTRACT

BACKGROUND/AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH. METHODS: Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH. RESULTS: Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage ß-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression. CONCLUSION: ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.


Subject(s)
Autophagy-Related Proteins , Autophagy , Macrophages , Membrane Proteins , Animals , Mice , Autophagy-Related Proteins/metabolism , Autophagy-Related Proteins/genetics , Humans , Macrophages/metabolism , Membrane Proteins/metabolism , Membrane Proteins/genetics , Male , Disease Progression , Mice, Knockout , Disease Models, Animal , Fatty Liver/metabolism , Fatty Liver/pathology , Fatty Liver/genetics , Diet, High-Fat/adverse effects , Energy Metabolism , Liver/metabolism , Liver/pathology , Signal Transduction , Mice, Inbred C57BL
20.
Article in English | MEDLINE | ID: mdl-38642326

ABSTRACT

BACKGROUND: Air volatile organic compounds (VOCs) cause allergic reaction mainly via the respiratory tract or skin. OBJECTIVE: This study aimed to investigate the association between daily visits by patients with urticaria and short-term changes in exposure to ambient air VOCs. METHODS: The dependent variable was information from patients with urticaria at a medical center in Kaohsiung, Taiwan, from 2014/01/01 to 2018/07/31. The multivariable model included one-day average 75th percentile values of air VOCs and meteorologic data retrieved from Taiwan Air Quality Monitoring Network database, and was analyzed using a case-crossover study design and conditional logistic regression. RESULTS: Total daily clinic visits for urticaria were significantly positively associated with higher levels of 4 VOCs (ethylbenzene, toluene, m-/p-xylene, and o-xylene (adjusted odds ratio (AOR: 1.03-1.28)) on the visit days, and 10 VOC levels on the fourth lag day (benzene, ethylbenzene, toluene, m-/p-xylene, o-xylene, 1,3,5-trimethylbenzene, n-hexane, methylcyclohexane, cyclohexane, and ethylene (AOR: 1.02-3.02)). Analyses of age and gender subgroups revealed that men showed resistance on the visit day, and women, older, and younger patients were more vulnerable. Men were influenced by higher benzene levels (AOR = 1.24) on the fourth lag day. Higher values of more than 6 VOCs on the fourth lag day significantly affected women, younger and older patients (AOR: 1.04-6.5). The most notable VOCs were methylcyclohexane (women AOR = 3.28, younger AOR = 3.82) and 1,3,5-trimethylbenzene (women AOR = 2.77, older AOR = 6.5) on the fourth lag day, which had the lowest concentrations but highest influence. CONCLUSION: The concentration of certain air VOCs significantly affected daily visits for urticaria.

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