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1.
Future Oncol ; 2024 May 09.
Article En | MEDLINE | ID: mdl-38722138

Aim: This study aimed to systematically evaluate the value of miRNA-143 in the early detection of bladder cancer (BCa). Methods: CNKI, WanFang, PubMed and Wiley Online Library databases were explored according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. A random-effects model was used to obtain pooled sensitivity, specificity and other related indicates. Results: Six studies were included for analysis. The overall pooled sensitivity and specificity were 0.80 (95% CI: 0.74-0.85) and 0.85 (95% CI: 0.78-0.91), and the area under the curve was 0.88 (95% CI: 0.85-0.91). Coupled with miR-100, it showed better diagnostic power (area under the curve: 0.95). Conclusion: miRNA-143 may serve as a promising noninvasive tool for the early detection of BCa.


Bladder cancer (BCa) is a common and deadly malignant tumor worldwide; however, noninvasive diagnosis can significantly improve the prognosis of patients. Recently, miRNAs have emerged as potential diagnostic biomarkers for BCa. Among them, miRNA-143 has shown promising results in several studies. This meta-analysis aimed to evaluate the overall diagnostic accuracy of miRNA-143 for BCa through a systematic review and meta-analysis of six published articles. Excitingly, the results of this meta-analysis suggest that miRNA-143 has potential diagnostic value in BCa. Particularly, miRNA-143 combined with miRNA-100 maintained better competence. Besides, miRNA-143 in plasma exhibited better diagnostic strength than that in urine. The authors believe that their study provides valuable insights into the use of miRNA-143 as a diagnostic biomarker for BCa.

2.
Clin Exp Immunol ; 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38651179

Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease.

3.
Expert Rev Anticancer Ther ; : 1-9, 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38606888

INTRODUCTION: Bladder cancer (BCa) exhibits a relatively high prevalence, yet convenient tools for its early detection are lacking. Our study aims to assess the diagnostic value of Urothelial Carcinoma-Associated 1 (UCA1) in the early detection of BCa. METHODS: Systematic searches were performed in electronic databases (PubMed, Web of Science, Science Direct, CNKI, Wanfang, and VIP) until 20 July 2023. QUADAS-2 was used for quality assessment, while Meta-DiSc 1.4 and STATA 14.0 were employed for statistical analysis. RESULTS: A total of 1252 BCa patients and 779 controls, from 12 identified articles, were included. UCA1 showed strong discriminatory ability in BCa detection, with an overall sensitivity of 0.84 specificity of 0.91, and a 0.91 area under the curve (AUC). Strikingly, UCA1 expressed in urine and tissue exhibited higher diagnostic value (0.92 AUC) compared to that in blood (0.86 AUC). Furthermore, urine UCA1 demonstrated remarkable diagnostic performance with 91% sensitivity and 98% specificity. Deeks' funnel plot detected no substantial publication bias. CONCLUSION: UCA1 could serve as a potential biomarker for BCa detection with good diagnostic performance. Besides, compared to UCA1 in blood, urine and tissue UCA1 exhibited higher diagnostic value. Further prospective clinical research is needed to corroborate the conclusion. PROSPERO REGISTRATION: CRD42023463210.

4.
Discov Med ; 36(183): 788-798, 2024 Apr.
Article En | MEDLINE | ID: mdl-38665027

BACKGROUND: High-salt diet (HSD) is a pivotal risk factor for osteoporosis (OP). Accumulating evidence has supported that tauroursodeoxycholic acid (TUDCA), a naturally produced hydrophilic bile acid, exerts positive effects on the treatment of OP. This study is committed to shedding light on the impacts of TUDCA on high salt-treated osteoblasts and probing into its underlying mechanisms of action. METHODS: Cell counting kit-8 (CCK-8) assay was used to determine the viability of osteoblasts. Alkaline phosphatase (ALP) staining and Alizarin red S (ARS) staining were used to measure osteoblast differentiation. Reverse transcription-quantitative PCR (RT-qPCR) and western blot were used to examine the expression of osteogenic markers. Western blot was also used to analyze the expression of superoxide dismutase-2 (SOD2), peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), and NADPH oxidase 1 (NOX1). The production of reactive oxygen species (ROS) was evaluated via dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Following PGC-1α knockdown in TUDCA-pretreated osteoblasts exposed to NaCl, the aforementioned functional experiments were implemented again. RESULTS: MC3T3-E1 cell viability was not significantly impacted by increasing concentrations of TUDCA. However, in NaCl-exposed MC3T3-E1 cells, the viability loss, oxidative stress, and decline of differentiation were all dose-dependently obstructed by TUDCA treatment. Moreover, NaCl exposure reduced PGC-1α expression and increased NOX1 expression, which was then reversed by TUDCA. PGC-1α deletion partially abolished the effects of TUDCA on PGC-1α and NOX1, differentiation, and oxidative stress in NaCl-treated osteoblasts. CONCLUSIONS: TUDCA might protect against high salt-induced OP via modulation of NOX1 mediated by PGC-1α.


NADPH Oxidase 1 , Osteoblasts , Oxidative Stress , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Taurochenodeoxycholic Acid , Animals , Mice , Cell Differentiation/drug effects , NADPH Oxidase 1/metabolism , NADPH Oxidase 1/genetics , Osteoblasts/drug effects , Osteoblasts/metabolism , Oxidative Stress/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Reactive Oxygen Species/metabolism , Taurochenodeoxycholic Acid/pharmacology
5.
Sci Rep ; 14(1): 3112, 2024 02 07.
Article En | MEDLINE | ID: mdl-38326407

Corticotropin-releasing hormone-binding protein (CRHBP) is involved in many physiological processes. However, it is still unclear what role CRHBP has in tumor immunity and prognosis prediction. Using databases such as the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Tumor Protein Database, Timer Database, and Gene Expression Profiling Interactive Analysis (GEPIA), we evaluated the potential role of CRHBP in diverse cancers. Further research looked into the relationships between CRHBP and tumor survival prognosis, immune infiltration, immune checkpoint (ICP) indicators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), DNA methylation, tumor microenvironment (TME), and drug responsiveness. The anticancer effect of CRHBP in liver hepatocellular carcinoma (LIHC) was shown by Western blotting, EdU staining, JC-1 staining, transwell test, and wound healing assays. CRHBP expression is significantly low in the majority of tumor types and is associated with survival prognosis, ICP markers, TMB, and microsatellite instability (MSI). The expression of CRHBP was found to be substantially related to the quantity of six immune cell types, as well as the interstitial and immunological scores, showing that CRHBP has a substantial impact in the TME. We also noticed a link between the IC50 of a number of anticancer medicines and the degree of CRHBP expression. CRHBP-related signaling pathways were discovered using functional enrichment. Cox regression analysis showed that CRHBP expression was an independent prognostic factor for LIHC. CRHBP has a tumor suppressor function in LIHC, according to cell and molecular biology trials. CRHBP has a significant impact on tumor immunity, treatment, and prognosis, and has the potential as a cancer treatment target and prognostic indicator.


Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Microsatellite Instability , Prognosis , Databases, Protein , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Tumor Microenvironment/genetics
6.
Eur J Pediatr ; 183(3): 1389-1401, 2024 Mar.
Article En | MEDLINE | ID: mdl-38165464

Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases in children. This study aimed to identify demographic features, clinical presentation and prognosis of children with CM. Clinical characteristics and prognostic factors associated with mortality were evaluated by Cox proportional hazards regression analyses. Genetic testing was also conducted on a portion of patients. Among the 317 patients, 40.1%, 25.2%, 24.6% and 10.1% were diagnosed with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular noncompaction cardiomyopathy (LVNC) and restrictive cardiomyopathy (RCM), respectively. The most common symptom observed was dyspnea (84.2%). Except for HCM, the majority of patients were classified as NYHA/Ross class III or IV. The five-year survival rates were 75.5%, 67.3%, 74.1% and 51.1% in DCM, HCM, LVNC and RCM, respectively. The ten-year survival rates were 60.1%, 56.1%, 57.2% and 41.3% in DCM, HCM, LVNC and RCM, respectively. Survival was inversely related to NYHA/Ross class III or IV in patients with DCM, HCM and RCM. Out of 42 patients, 32 were reported to carry gene mutations. CONCLUSIONS: This study demonstrates that CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause. TRIAL REGISTRATION: MR-50-23-011798. WHAT IS KNOWN: • Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases and one of the leading causes of heart failure in children due to the lack of effective treatments. • There remains scarce data on Asian pediatric populations though emerging studies have assessed the clinical characteristics and outcomes of CM. WHAT IS NEW: • A retrospective study was conducted and the follow-up records were established to investigate the clinical characteristics, the profile of gene mutations and prognostic outcomes of children with CM in Western China. • CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause.


Cardiomyopathies , Cardiomyopathy, Dilated , Cardiomyopathy, Hypertrophic , Cardiomyopathy, Restrictive , Child , Humans , Retrospective Studies , Genetic Profile , Cardiomyopathies/genetics , Cardiomyopathy, Restrictive/complications , Cardiomyopathy, Restrictive/genetics , Cardiomyopathy, Dilated/genetics
7.
Article En | MEDLINE | ID: mdl-38061619

The experiment was conducted to investigate the effects of Bisphenol S (BPS) on growth, physiological and biochemical indices, and the expression of ecdysteroid receptor (ECR) of the red swamp crayfish (Procambarus clarkii). The gene encoding ECR was isolated from red swamp crayfish by homologous cloning and rapid amplification of cDNA ends (RACE). The ECR transcripts were 1757 bp long and encoded proteins of 576 amino acids. The quantitative real-time PCR (qRT-PCR) analysis showed that the ECR gene was expressed in various tissues under normal conditions, and the highest level was observed in the ovary and the lowest level was observed in the muscle (P < 0.05). Then, the experiment was designed with four different BPS concentrations (0, 1, 10, and 100 µg/L), BPS exposure for 14 days, three parallel groups, and a total of 240 red swamp crayfish. At 100 µg/L BPS, the survival rate, weight gain rate, and relative length rate were decreased significantly (P < 0.05). Malonaldehyde (MDA) content reached the highest level at 100 µg/L BPS. When BPS concentration was higher than 10 µg/L, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly lower than those of the control group (P < 0.05). The expression levels of the ECR gene in ovary, intestinal, gill, and hepatopancreas tissues were significantly increased after BPS exposure (P < 0.05). The ECR gene expression in ovaries and Y-organs was significantly higher than other groups in 10 µg/L BPS (P < 0.05). The expressions of the tumor necrosis factor -α (TNF-α) and interleukin-6 (IL-6) genes in the hepatopancreas gradually increased, and the highest expression was observed exposed in 100 µg/L BPS (P < 0.05). This research will provide novel insights into the health risk assessment of BPS in aquatic organisms.


Astacoidea , Receptors, Steroid , Animals , Female , Astacoidea/genetics , Receptors, Steroid/genetics , Gene Expression
8.
Eur J Nucl Med Mol Imaging ; 51(2): 380-394, 2024 Jan.
Article En | MEDLINE | ID: mdl-37792026

PURPOSE: The high expression of the transmembrane glycoprotein trophoblast cell-surface antigen 2 (Trop2) was strongly associated with the progression of solid tumors, including pancreatic and gastric cancers. Our study aimed to construct Trop2-specific immuno-positron emission tomography (immunoPET) probes and assess the diagnostic abilities in preclinical pancreatic and gastric cancer models. METHODS: The expression of Trop2 in pancreatic cancer was determined by single-cell sequencing and immunohistochemistry on tissue microarray (TMA). Flow cytometry was used to screen the expression of Trop2 in pancreatic cancer cell lines. Two nanobodies (i.e., RTD98 and RTD01) targeting Trop2 were developed and labeled with gallium-68 (68Ga, T1/2 = 1.1 h) to construct immunoPET imaging probes. The agents were researched in cell-derived pancreatic and patient-derived gastric cancer models expressing varying Trop2. RESULTS: Single-cell sequencing results showed high expression of Trop2 in pancreatic ductal cells as well as acinar cells and immunohistochemical staining of TMA from pancreatic cancers showed significantly higher expression of Trop2 in cancerous than in paracancerous tissues. ImmunoPET utilizing [68Ga]Ga-NOTA-RTD98 could clearly delineate subcutaneous tumors, both in cell-derived pancreatic cancer models and patient-derived gastric cancer models, superior to imaging using [18F]-FDG or a non-specific probe [68Ga]Ga-NOTA-RTD161. Another probe with improved pharmacokinetics targeting Trop2, [68Ga]Ga-NOTA-RTD01, was further prepared and showed advantageous diagnostic capabilities in preclinical pancreatic cancer models. CONCLUSION: In the work, we reported two nanobody tracers targeting human Trop2 which may facilitate better use of Trop2-targeted therapeutics by noninvasively displaying expression dynamics of the target.


Pancreatic Neoplasms , Stomach Neoplasms , Humans , Cell Line, Tumor , Gallium Radioisotopes , Immunohistochemistry , Pancreatic Neoplasms/metabolism , Positron-Emission Tomography/methods
9.
Biomed Pharmacother ; 170: 116069, 2024 Jan.
Article En | MEDLINE | ID: mdl-38147736

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide. Its occurrence and progression involve the process from simple hepatic steatosis to metabolic dysfunction associated steatohepatitis (MASH), which could develop into advanced liver fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). Growing evidences support that the pathogenesis and progression of MASLD are closely related to immune system dysfunction. This review aims to summarize the association of MASLD with immune disorders and the prospect of using immunotherapy for MASLD.


Carcinoma, Hepatocellular , Fatty Liver , Liver Neoplasms , Metabolic Diseases , Humans , Liver Cirrhosis
10.
Lipids Health Dis ; 22(1): 174, 2023 Oct 18.
Article En | MEDLINE | ID: mdl-37853414

BACKGROUND: The widely reported associations between body mass index (BMI) and various chronic diseases, such as hypertension and asthma, have garnered significant attention. Nonetheless, there remains a dearth of research dedicated to understanding the health impacts of medical school on the students, who experience considerable academic pressure. In that context, this study was driven by the goal of investigating the intricate interplay between BMI, blood pressure (BP), and vital capacity among medical students. METHODS: This study included a cohort of 843 medical students enrolled at Southern Medical University who were selected through random cluster sampling. Within this cohort, measurements of height, weight, BP, and vital capacity were taken. Subsequently, both BMI and vital capacity index (VCI) were calculated for each participant. By categorizing the subjects into four groups according to BMI classifications, a comprehensive analysis that included correlation assessments and binomial logistic regression was conducted. RESULTS: Within the participant pool, 9.4% and 3.8% of participants were classified as overweight and obese, respectively. Additionally, the prevalence of prehypertension, hypertension, and poor VCI was 18.1%, 2.7%, and 13.5%, respectively. Notably, male students exhibited a higher prevalence of the aforementioned health issues than their female counterparts. Correlation analysis revealed that BMI displayed positive associations with systolic blood pressure (SBP), diastolic blood pressure (DBP), and vital capacity (r = 0.372, 0.257, 0.428; P < 0.001). However, an inverse correlation emerged between BMI and VCI (r = -0.284, P < 0.001). Further analysis revealed that overweight and obese individuals faced an elevated risk of high blood pressure ([OR 2.05, 95% CI 1.15-3.67] and [OR 5.44, 95% CI 2.28-13.02], respectively) compared to their normal-weight counterparts. Moreover, these groups also exhibited a higher risk of poor VCI ([OR 5.25, 95% CI 3.04-9.06] and [OR 15.61, 95% CI 6.81-35.81], respectively), while underweight subjects experienced a reduced risk ([OR 0.19, 95% CI 0.07-0.52]). CONCLUSIONS: BMI demonstrated a notably strong positive correlation with both BP and vital capacity and a negative correlation with VCI. Therefore, for medical students as well as the daily health care of patients, weight control is recommended to better combat obesity-related diseases, for example, cardiopulmonary diseases, gout and diabetes.


Hypertension , Students, Medical , Humans , Male , Female , Body Mass Index , Blood Pressure/physiology , Overweight/complications , Risk Factors , Obesity/complications , Vital Capacity , Prevalence
11.
Int. j. morphol ; 41(5): 1527-1536, oct. 2023. ilus
Article En | LILACS | ID: biblio-1521022

SUMMARY: The 12C6+ heavy ion beam irradiation can cause bystander effects. The inflammatory cytokines, endocrine hormones and apoptotic proteins may be involved in 12C6+ irradiation-induced bystander effects. This study characterized the protective effects and mechanisms of Huangqi decoction (HQD) against 12C6+ radiation induced bystander effects. Wistar rats were randomly divided into control, 12C6+ heavy ion irradiation model, and high-dose/medium-dose/low-dose HQD groups. HE staining assessed the pathological changes of brain and kidney. Peripheral blood chemical indicators as well as inflammatory factors and endocrine hormones were detected. Apoptosis was measured with TUNEL. Proliferating cell nuclear antigen (PCNA) expression was determined with real-time PCR and Western blot.Irradiation induced pathological damage to the brain and kidney tissues. After irradiation, the numbers of white blood cells (WBC) and monocyte, and the expression of interleukin (IL)-2, corticotropin-releasing hormone (CRH) and PCNA decreased. The damage was accompanied by increased expression of IL-1β, IL-6, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) as well as increased neuronal apoptosis. These effects were indicative of radiation-induced bystander effects. Administration of HQD attenuated the pathological damage to brain and kidney tissues, and increased the numbers of WBC, neutrophils, lymphocyte and monocytes, as well as the expression of IL-2, CRH and PCNA. It also decreased the expression of IL-1β, IL-6, CORT and ACTH as well as neuronal apoptosis. HQD exhibits protective effects against 12C6+ radiation-induced bystander effects. The underlying mechanism may involve the promotion of the production of peripheral blood cells, inhibition of inflammatory factors and apoptosis, and regulation of endocrine hormones.


La irradiación con haz de iones pesados 12C6+ puede provocar efectos secundarios. Las citoquinas inflamatorias, las hormonas endocrinas y las proteínas apoptóticas pueden estar involucradas en los efectos secundarios inducidos por la irradiación 12C6+. Este estudio caracterizó los efectos y mecanismos protectores de la decocción de Huangqi (HQD) contra los efectos externos inducidos por la radiación 12C6+. Las ratas Wistar se dividieron aleatoriamente en grupos control, modelo de irradiación de iones pesados 12C6+ y grupos de dosis alta/media/baja de HQD. La tinción con HE evaluó los cambios patológicos del cerebro y el riñón. Se detectaron indicadores químicos de sangre periférica, así como factores inflamatorios y hormonas endocrinas. La apoptosis se midió con TUNEL. La expresión del antígeno nuclear de células en proliferación (PCNA) se determinó mediante PCR en tiempo real y transferencia Western blot. La irradiación indujo daños patológicos en los tejidos cerebrales y renales. Después de la irradiación, disminuyó el número de glóbulos blancos (WBC) y monocitos, y la expresión de interleucina (IL)-2, hormona liberadora de corticotropina (CRH) y PCNA. El daño estuvo acompañado por una mayor expresión de IL-1β, IL-6, corticosterona (CORT) y hormona adrenocorticotrópica (ACTH), así como un aumento de la apoptosis neuronal. Estas alteraciones fueron indicativas de efectos inducidos por la radiación. La administración de HQD atenuó el daño patológico a los tejidos cerebrales y renales, y aumentó el número de leucocitos y monocitos, así como la expresión de IL-2, CRH y PCNA. También disminuyó la expresión de IL-1β, IL-6, CORT y ACTH, así como la apoptosis neuronal. HQD exhibe mecanismos protectores contra los efectos externos inducidos por la radiación 12C6+. El mecanismo subyacente puede implicar la promoción de la producción de células sanguíneas periféricas, la inhibición de factores inflamatorios y la apoptosis y la regulación de hormonas endocrinas.


Animals , Female , Rats , Drugs, Chinese Herbal , Protective Agents/administration & dosage , Heavy Ions/adverse effects , Scutellaria baicalensis/chemistry , Brain/drug effects , Brain/radiation effects , Corticotropin-Releasing Hormone , Enzyme-Linked Immunosorbent Assay , Rats, Wistar , Apoptosis/drug effects , Apoptosis/radiation effects , Adrenocorticotropic Hormone , Proliferating Cell Nuclear Antigen , Endocrine System/drug effects , Endocrine System/radiation effects , Immunologic Factors/antagonists & inhibitors , Kidney/drug effects , Kidney/radiation effects
12.
J Orthop Translat ; 42: 43-56, 2023 Sep.
Article En | MEDLINE | ID: mdl-37637777

Background: Tendinopathy is a common motor system disease that leads to pain and reduced function. Despite its prevalence, our mechanistic understanding is incomplete, leading to limited efficacy of treatment options. Animal models contribute significantly to our understanding of tendinopathy and some therapeutic options. However, the inadequacies of animal models are also evident, largely due to differences in anatomical structure and the complexity of human tendinopathy. Different animal models reproduce different aspects of human tendinopathy and are therefore suitable for different scenarios. This review aims to summarize the existing animal models of tendinopathy and to determine the situations in which each model is appropriate for use, including exploring disease mechanisms and evaluating therapeutic effects. Methods: We reviewed relevant literature in the PubMed database from January 2000 to December 2022 using the specific terms ((tendinopathy) OR (tendinitis)) AND (model) AND ((mice) OR (rat) OR (rabbit) OR (lapin) OR (dog) OR (canine) OR (sheep) OR (goat) OR (horse) OR (equine) OR (pig) OR (swine) OR (primate)). This review summarized different methods for establishing animal models of tendinopathy and classified them according to the pathogenesis they simulate. We then discussed the advantages and disadvantages of each model, and based on this, identified the situations in which each model was suitable for application. Results: For studies that aim to study the pathophysiology of tendinopathy, naturally occurring models, treadmill models, subacromial impingement models and metabolic models are ideal. They are closest to the natural process of tendinopathy in humans. For studies that aim to evaluate the efficacy of possible treatments, the selection should be made according to the pathogenesis simulated by the modeling method. Existing tendinopathy models can be classified into six types according to the pathogenesis they simulate: extracellular matrix synthesis-decomposition imbalance, inflammation, oxidative stress, metabolic disorder, traumatism and mechanical load. Conclusions: The critical factor affecting the translational value of research results is whether the selected model is matched with the research purpose. There is no single optimal model for inducing tendinopathy, and researchers must select the model that is most appropriate for the study they are conducting. The translational potential of this article: The critical factor affecting the translational value of research results is whether the animal model used is compatible with the research purpose. This paper provides a rationale and practical guide for the establishment and selection of animal models of tendinopathy, which is helpful to improve the clinical transformation ability of existing models and develop new models.

13.
Transpl Immunol ; 80: 101889, 2023 10.
Article En | MEDLINE | ID: mdl-37414263

BACKGROUND: Acute renal injury (AKI) is a common complication of lung transplantation. However, there has been no related research on whether the relationship between fluid balance and input and output influences the occurrence of early AKI. This study aimed to explore the relationship between early fluid balance and input and output on the incidence of early AKI after lung transplantation. METHODS: Data from 31 patients who underwent lung transplantation in the Department of Intensive Care Medicine of the Sichuan Academy of Medical Sciences, Sichuan People's Hospital, from August 2018 to July 2021 were collected. To summarize the occurrence of early AKI after lung transplantation, The main indicators of lung transplantation patients were collected. The risk factors for early AKI after lung transplantation were analyzed. RESULTS: Among the 31 patients who underwent lung transplantation, 21 had early postoperative AKI, with an incidence rate of 67.7%. Compared with the non-AKI group, the hospitalization and ICU hospitalization times of the AKI group were longer (P < 0.05). Multivariate regression analysis showed that intraoperative input volume, BMI, and fluid balance on the first day after lung transplantation were independent risk factors for AKI. CONCLUSION: Intraoperative input volume, BMI, and fluid balance on the first day after lung transplantation were independent risk factors for AKI.


Acute Kidney Injury , Lung Transplantation , Humans , Incidence , Retrospective Studies , Risk Factors , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Lung Transplantation/adverse effects , Postoperative Complications/epidemiology
14.
Br J Cancer ; 129(3): 541-550, 2023 08.
Article En | MEDLINE | ID: mdl-37311977

BACKGROUND: PD-L1 promotes glycolysis in tumour cells. We observed a correlation between high PD-L1 expression and high 18F-FDG uptake in patients with pancreatic ductal adenocarcinoma (PDAC) in a previous study. This study aims to determine the usefulness of 18F-FDG PET/CT for evaluating the PD-L1 status in PDAC and to elucidate its rationality by integrated analyses. METHODS: For bioinformatics analysis, WGCNA, GSEA and TIMER were applied to analyse the pathways and hub genes associated with PD-L1 and glucose uptake. 18F-FDG uptake assay was used to determine the glucose uptake rate of PDAC cells in vitro. Related genes expression were verified by RT-PCR and western blot. A retrospective analysis was performed on 47 patients with PDAC who had undergone 18F-FDG PET/CT. Maximum standardised uptake values (SUVmax) were determined. The usefulness of SUVmax for evaluating PD-L1 status was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: Bioinformatics analysis showed that several signalling pathways are associated with both PD-L1 expression and tumour glucose uptake, among which JAK-STAT may be an important one. By in vitro experiments, the regulatory role of PD-L1 on glucose uptake was demonstrated, and its dependency on the JAK-STAT pathway was also verified by the rescue study. The SUVmax of PD-L1-positive patients was significantly higher than PD-L1-negative in tumour cells (TCs) (6.1 ± 2.3 vs. 11.1 ± 4.2; P < 0.001), and in tumour-infiltrating immune cells (TIICs) (6.4 ± 3.2 vs. 8.4 ± 3.5; P < 0.001). In a multivariate analysis, SUVmax was significantly associated with PD-L1 expression in TCs and TIICs (P < 0.001 and P = 0.018, respectively). Using SUVmax cut-off values of 8.15 and 7.75, PD-L1 status in TCs and TIICs could be predicted with accuracies of 91.5% and 74.5%, respectively. CONCLUSION: Higher 18F-FDG uptake by PDAC is associated with elevated PD-L1 expression. JAK-STAT is an important pathway that mediates PD-L1 to promote glucose uptake in PDAC.


Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , B7-H1 Antigen/metabolism , Retrospective Studies , Janus Kinases/metabolism , Signal Transduction , STAT Transcription Factors/metabolism , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/genetics , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/genetics , Glucose , Pancreatic Neoplasms
15.
Eur J Nucl Med Mol Imaging ; 50(9): 2683-2691, 2023 07.
Article En | MEDLINE | ID: mdl-37039900

PURPOSE: Multiple myeloma (MM) is a malignant disease characterized by the secretion of monoclonal immunoglobulins and has a high demand for amino acids. [11C]methionine total-body PET is capable of noninvasive dynamic monitoring of radiotracer in vivo, thus providing a way to reveal the dynamic changes of myeloma metabolism. This study aims to analyze the metabolic process of [11C]methionine based on kinetic modeling, and to preliminary reveal its application value in MM. METHODS: Dynamic total-body [11C]methionine PET/CT was conducted with uEXPLORER in 12 subjects (9 MM patients and 3 controls). The tissue time activity curves (TACs) of organs and bone marrows were extracted. Model fitting of TACs was operated using PMOD Kinetic Modeling. After validation by Goodness of fit (GOF), the reversible two-tissue compartment model (2T4k) was used to further analysis. R software was used to analyze the correlation between kinetic parameters and clinical indicators. RESULTS: The 2T4k has passed the criterion of GOF and was used to fit the data of 0-20 minutes. The [11C]methionine net uptake rate (Ki) was significantly higher in the MM lesions than in the non-myeloma controls (control: 0.040±0.007 mL/g/min, MM: 0.171±0.108 mL/g/min, p=0.009). The Ki values were found to be correlated with M protein levels in MM patients. MM patients with t(4;14) translocations had an elevated k4 value compared with t(4;14) negative patients. CONCLUSION: MM lesions have a propensity for uptake of [11C]methionine. The serum levels of M protein are correlated with [11C]methionine uptake rate in myeloma. Metabolic classification based on the k4 value may be a promising strategy for risk stratification in MM.


Multiple Myeloma , Humans , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/pathology , Positron Emission Tomography Computed Tomography , Methionine , Positron-Emission Tomography , Bone Marrow/pathology , Racemethionine
16.
Cell Death Discov ; 9(1): 103, 2023 Mar 25.
Article En | MEDLINE | ID: mdl-36966168

The oncogene MYC is dysregulated in a host of human cancers, and as an important point of convergence in multitudinous oncogenic signaling pathways, it plays a crucial role in tumor immune regulation in the tumor immune microenvironment (TIME). Specifically, MYC promotes the expression of immunosuppressive factors and inhibits the expression of immune activation regulators. Undoubtedly, a therapeutic strategy that targets MYC can initiate a new era of cancer treatment. In this review, we summarize the essential role of the MYC signaling pathway in tumor immunity and the development status of MYC-related therapies, including therapeutic strategies targeting MYC and combined MYC-based immunotherapy. These studies have reported extraordinary insights into the translational application of MYC in cancer treatment and are conducive to the emergence of more effective immunotherapies for cancer.

17.
Mar Pollut Bull ; 188: 114706, 2023 Mar.
Article En | MEDLINE | ID: mdl-36764147

Microplastics have become the marine pollution posing a human health risk, but they are difficult to be detected and recognized for different materials, irregular shapes, and broad size distributions. Microplastics' refractive index (RI) is related to the materials and can be characterized by the Mueller matrix. In this work, the particles are suspended in water and their Mueller matrices are measured by a particulate Mueller matrix polarimetry setup. Four kinds of spherical particles including microplastics are effectively classified by their Mueller matrices. Moreover, two kinds of common microplastics with broad size distributions, irregular shapes, and random orientations are also well recognized by the Mueller matrix. These results imply that RI plays a vital role in the recognition of microplastics suspended in water. By using the Mie theory and discrete dipole approximation simulation, the discussions explain in physics origin how RI affects Mueller matrix coupling with size and structure, and give some decoupling methods. Results in this work help advance future tools to in situ recognize the microplastics in seawater.


Microplastics , Refractometry , Humans , Plastics , Seawater , Water
18.
Planta ; 257(2): 33, 2023 Jan 07.
Article En | MEDLINE | ID: mdl-36609883

MAIN CONCLUSIONS: Fully mature acorns of Quercus variabilis, Q. aliena, Q. mongolica, and Q. glandulifera are desiccation-sensitive. X-ray computer tomography showed that cotyledons shrink during drying, but embryos are protected. Information available on recalcitrant acorns of tropical and sub-tropical species of Quercus suggests that an impermeable pericarp, which limits the entry and loss of water only through the hilum (scar), is the underlying mechanism that prevents drying of the embryo axis following dispersal until the germination season. However, there is a lack of consensus supporting this proposition across species, and it is not well understood if such mechanisms occur in temperate Quercus species. This study investigated the significance of the acorn pericarp for temperate oak species and presents an ecological framework based on the post-dispersal climatic conditions. Using Quercus variabilis, Q. aliena, Q. mongolica, and Q. glandulifera acorns, the relationship between moisture content (MC) and germination was established, and X-ray computed tomography (X-ray CT) was used to understand the internal structural changes of cotyledons and embryonic axis occurring during desiccation. Water entry and exit routes through the scar, pericarp and apex were determined by imbibition and drying experiments. Climatic data and acorn morphological characteristics and germination were subjected to a principal component analysis (PCA). Freshly dispersed acorns of all species had a moisture content (MC) above 35% fresh weight (FW) basis, but drying to 15-10% MC resulted in complete loss of viability, implying recalcitrance behaviour. X-ray CT images suggested that the pericarp offers some protection to cotyledons and embryonic axis during desiccation, but it is contingent on MC. Extensive drying to a low MC with the scar and apex covered with vaseline resulted in internal tissues shrinkage, corresponding with viability loss. Water could enter or exit through the pericarp, albeit at a much slower rate than through the scar. A combination of factors including acorn anatomy, moisture content at the time of dispersal, microhabitat, the position of acorns in the soil prevent embryo desiccation below the critical MC and thus promotes survival of acorns on/in the soil during winter in temperate regions. Pericarp anatomy, to some extent, prevents excessive drying of the embryonic axis by slowing water movement, but prolonged drying or predatory pressure could result in pericarp cracks, favouring the absorption of water during sporadic rain. In the latter case, the survival of acorns possibly depends extensively on the continuous erratic rainfall, i.e. continuous wet-dry cycle, but in-situ experiments are yet to be performed to test this hypothesis.


Cotyledon , Quercus , Water , Seeds , Desiccation , Cicatrix
19.
Front Endocrinol (Lausanne) ; 14: 1332216, 2023.
Article En | MEDLINE | ID: mdl-38298188

Purpose: For early diagnosis of osteoporosis (OP), plasma metabolomics of OP was studied by untargeted LC/GC-MS in a Chinese elderly population to find possible diagnostic biomarkers. Methods: A total of 379 Chinese community-dwelling older adults aged ≥65 years were recruited for this study. The BMD of the calcaneus was measured using quantitative ultrasound (QUS), and a T value ≤-2.5 was defined as OP. Twenty-nine men and 47 women with OP were screened, and 29 men and 36 women were matched according to age and BMI as normal controls using propensity matching. Plasma from these participants was first analyzed by untargeted LC/GC-MS, followed by FC and P values to screen for differential metabolites and heatmaps and box plots to differentiate metabolites between groups. Finally, metabolic pathway enrichment analysis of differential metabolites was performed based on KEGG, and pathways with P ≤ 0.05 were selected as enrichment pathways. Results: We screened metabolites with FC>1.2 or FC<1/1.2 and P<0.05 and found 33 differential metabolites in elderly men and 30 differential metabolites in elderly women that could be potential biomarkers for OP. 2-Aminomuconic acid semialdehyde (AUC=0.72, 95% CI 0.582-0.857, P=0.004) is highly likely to be a biomarker for screening OP in older men. Tetradecanedioic acid (AUC=0.70, 95% CI 0.575-0.818, P=0.004) is highly likely to be a biomarker for screening OP in older women. Conclusion: These findings can be applied to clinical work through further validation studies. This study also shows that metabolomic analysis has great potential for application in the early diagnosis and recurrence monitoring of OP in elderly individuals.


Osteoporosis , Male , Humans , Aged , Female , Gas Chromatography-Mass Spectrometry/methods , Osteoporosis/diagnosis , Metabolomics/methods , Biomarkers , Liquid Chromatography-Mass Spectrometry
20.
Biomaterials ; 288: 121741, 2022 09.
Article En | MEDLINE | ID: mdl-36031458

Large bone defects that cannot form a callus tissue are often faced with long-time recovery. Developmental engineering-based strategies with mesenchymal stem cell (MSC) aggregates have shown enhanced potential for bone regeneration. However, MSC aggregates are different from the physiological callus tissues, which limited the further endogenous osteogenesis. This study aims to achieve engineering of osteo-callus organoids for rapid bone regeneration in cooperation with bone marrow-derived stem cell (BMSC)-loaded hydrogel microspheres (MSs) by digital light-processing (DLP) printing technology and stepwise-induction. The printed MSC-loaded MSs aggregated into osteo-callus organoids after chondrogenic induction and showed much higher chondrogenic efficiency than that of traditional MSC pellets. Moreover, the osteo-callus organoids exhibited stage-specific gene expression pattern that recapitulated endochondral ossification process, as well as a synchronized state of cell proliferation and differentiation, which highly resembled the diverse cell compositions and behaviors of developmentally endochondral ossification. Lastly, the osteo-callus organoids efficiently led to rapid bone regeneration within only 4 weeks in a large bone defect in rabbits which need 2-3 months in previous tissue engineering studies. The findings suggested that in vitro engineering of osteo-callus organoids with developmentally osteogenic properties is a promising strategy for rapid bone defect regeneration and recovery.


Mesenchymal Stem Cells , Organoids , Animals , Bone Regeneration , Cell Differentiation , Chondrogenesis , Osteogenesis/physiology , Rabbits , Tissue Engineering
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