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Background Lung endothelial barrier injury plays an important role in the pathophysiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) therapy has shown promise in ARDS treatment and restoration of the impaired barrier function. It has been reported that Wnt5a shows protective effects on endothelial cells. Therefore, the study aimed to investigate whether overexpression of Wnt5a could promote the protective effects of MSCs on Lipopolysaccharide (LPS)-induced endothelial cell injury. Methods To evaluate the protective effects of MSCs overexpressing Wnt5a, we assessed the migration, proliferation, apoptosis, and angiogenic ability of endothelial cells. We assessed the transcription of protective cellular factors using qPCR and determined the molecular mechanism using Western blot analysis. Results Overexpression of Wnt5a upregulated the transcription of protective cellular factors in MSCs. Co-culture of MSC Wnt5a promoted endothelial migration, proliferation and angiogenesis, and inhibited endothelial cell apoptosis through the PI3K/AKT pathway. Conclusions Overexpression of Wnt5a promoted the therapeutic effect of MSCs on endothelial cell injury through the PI3K/AKT signaling. Our study provides a novel approach for utilizing genetically modified MSCs in the transplantation therapy for ARDS.

Background: This study compared the analytical performance of the Elecsys 602 (Roche Diagnostics) system with the I2000 (Abbott laboratories) system for the quantitative measurement of squamous cell carcinoma antigen (SCCA) to assess its role as an indicator in pan squamous cell carcinoma. Methods: 435 serum samples included pan squamous cell cancer group (n = 318) and healthy subjects (n = 52) and non-squamous cell group (n = 41) and benign diseases group (n = 24) were measured by 2 systems and compared. Results: The within-run precision coefficient of variation (CV) for Abbott and Roche systems were 3.34-4.88% and 0.95 -1.96%, and the total precision CV were 2.89-9.48% and 3.97-5.38%, respectively. Good correlation was showed in Abbott and Roche systems (slopes = 0.749, r = 0.9658). Serum SCCA in the groups of nasopharyngeal carcinomas, lung squamous cell carcinoma, esophageal squamous cell carcinoma, bladder cancer and cervical squamous cell carcinoma under the curve area (AUC) was more than 0.5, while the AUC in the non- nasopharyngeal carcinomas head and neck squamous cell carcinoma was less than 0.5. The AUC of 2 systems was statistically different in lung squamous cell carcinoma and nasopharyngeal carcinomas (P < 0.05). The levels of SCCA of 2 systems were similarities in esophageal squamous cell carcinoma(stage IV vs. stage 0a-II)and bladder cancer(stage I vs. stage Oa)and cervical squamous cell carcinoma(stage IIB-III vs. stage I-IIA), which advanced stage had higher level of SCCA than early stage. But the SCCA levels of 2 systems were inconsistent in bladder cancer (stage II-IV vs. stage Oa in Abbott), head and neck squamous cell carcinoma (stage IV vs. stage Oa-I in the Roche) and lung squamous cell carcinoma (stage III vs. stage I-II in the Roche). (P < 0.05) Conclusions: 2 systems correlated well in SCCA detection of squamous cell carcinoma, but there were individual differences. Serum SCCA may also contribute to the diagnosis of bladder cancer.

Background The prognosis of non-small cell lung cancer (NSCLC) with brain metastases (BMs) had been researched in some researches, but the combination of clinical characteristics and serum inflammatory indexes as a noninvasive and more accurate model has not been described. Methods We retrospectively screened patients with BMs at the initial diagnosis of NSCLC at Sun Yat-Sen University Cancer Center. LASSO-Cox regression analysis was used to establish a novel prognostic model for predicting OS based on blood biomarkers. The predictive accuracy and discriminative ability of the prognostic model was compared to Adjusted prognostic Analysis (APA), Recursive Partition Analysis (RPA), and Graded Prognostic Assessment (GPA) using concordance index (C-index), time-dependent receiver operating characteristic (td-ROC) curve, Decision Curve Analysis(DCA), net reclassification improvement index (NRI), and integrated discrimination improvement index (IDI). Results 10-parameter signature's predictive model for the NSCLC patients with BMs was established according to the results of LASSO-Cox regression analysis. The C-index of the prognostic model to predict OS was 0.672 (95% CI = 0.609 ~ 0.736) which was significantly higher than APA,RPA and GPA. The td-ROC curve and DCA of the predictive model also demonstrated good predictive accuracy of OS compared to APA, RPA and GPA. Moreover, NRI and IDI analysis indicated that the prognostic model had improved prediction ability compared with APA, RPA and GPA. Conclusion The novel prognostic model demonstrated favorable performance than APA, RPA, and GPA for predicting OS in NSCLC patients with BMs.

Background: In recent studies, microRNAs have been demonstrated as stable detectable biomarkers in blood for cancer. In addition, computer-aided biomarker discovery has now become an attractive paradigm for precision diagnosis. Methods: In this study, we identified and evaluated miR-139-3p as a biomarker for screening of esophageal squamous cell carcinoma using the Cancer Genome Atlas and Gene Expression Omnibus database analyses. We identified possible miR-139-3p target genes through the predicted database and esophageal squamous cell carcinoma upregulated genes from the Cancer Genome Atlas and Gene. Bioinformatics analysis was performed to determine key miR-139-3p targets and pathways associated with esophageal carcinoma. Finally, the expression and expected significance of hub genes were evaluated via the Genotype-Tissue Expression project. Results: MiR-139-3p was significantly downregulated in patients with esophageal squamous cell carcinoma/esophageal carcinoma. In GSE 122497, the area under the curve-receiver operating characteristic value, sensitivity, and specificity for serum miR-139-3p were 0.754, 67.49%, and 80.00%, respectively. The pattern specification process, skeletal system development, and regionalization process were the most enriched interactions in esophageal carcinoma. In addition, Epstein-Barr virus infection, human T-cell leukemia virus 1 infection, and human cytomegalovirus infection were identified as crucial pathways. Six hub genes (CD1A, FCGR2A, ANPEP, CD1B, membrane metalloendopeptidase, and TWIST1) were found, and FCGR2A and membrane metalloendopeptidase were further confirmed by genotype-tissue expression. High expression of membrane metalloendopeptidase correlated with a better overall survival but not with disease-free survival of patients with esophageal carcinoma. Conclusions: MiR-139-3p was identified as a candidate biomarker for predicting esophageal squamous cell carcinoma based on network analysis. MiR-139-3p acted as a tumor suppressor by targeting membrane metalloendopeptidase in esophageal carcinoma, and low expression of membrane metalloendopeptidase may indicate a better prognosis of patients with esophageal carcinoma.

The lineage commitment and differentiation of mesenchymal stem cells (MSCs) play a crucial role in bone homeostasis. MAPK7 (Mitogen-activated protein kinase 7), a member of MAPK family, controls cell differentiation, proliferation and survival. However, the specific role of Mapk7 in regulating osteogenic and adipogenic differentiation of MSCs remains to be determined. In this study, depletion of Mapk7 in MSCs by crossing Prx1 -Cre mice to Mapk7 flox/flox resulted in severe low bone mass and accumulation of fat in bone marrow exhibiting osteoporosis (OP) in mice. Mapk7 promoted osteogenic differentiation and inhibited adipogenic differentiation of MSCs after knocking out and over-expressing Mapk7 in vitro. Mechanistically, Mapk7 activated Wnt/β-catenin signaling by phosphorylating Lrp6 at Ser1490, which ultimately enhanced osteogenesis and suppressed adipogenesis of MSCs. This is of great clinical and scientific significance for understanding biological function of Mapk7 and developing potential therapeutic targets for treatment of MSCs differentiation imbalance related bone diseases, such as, osteoporosis. Mapk7 regulates bone mass and bone marrow adiposity by controlling mesenchymal stem cells fate transition through phosphorylation of Ser1490 of LRP6 and promoting nuclear translocation of β-catenin.

Osteosarcoma (OSC) is a high-morbidity bone cancer with an unsatisfactory prognosis. Timely and accurate assessment the overall survival (OS) and progression-free survival (PFS) in patients with OSC are required to guide and select the best treatment. This study aimed to develop a simple, convenient and low-cost prognostic model based on clinical characteristics and blood biomarkers for predicting OS and PFS in OSC patients. Overall, 158 patients with OSC included from the Sun Yat-sen University Cancer Center in this retrospective study. LASSO-Cox algorithm was used to shrink predictive factor size and established a prognostic risk model for predicting OS and PFS in OSC patients. The predictive ability of the survival model was compared to the Tumor Node Metastasis (TNM) stage and clinical treatment by concordance index (C-index), time-dependent receiver operating characteristic (td-ROC) curve, decision curve analysis (DCA), net reclassification improvement index (NRI), and integrated discrimination improvement index (IDI). Based on results from the LASSO-Cox method, gender, family history of cancer, monocyte (M), red blood cell (RBC), lactic dehydrogenase (LDH), and cystatin C (Cys-C) were identified to construct a novel predictive model for the OSC patients. The C-index of the prognostic model to predict OS and PFS were 0.713 (95% CI = 0.630 - 0.795) and 0.636 (95% CI = 0.577 - 0.696), respectively, which were higher than the OS and PFS of TNM stage and clinical treatment. Td-ROC curve and DCA of the predictive model also demonstrated good predictive accuracy and discriminatory power of OS and PFS compared to TNM stage and treatment. Moreover, the prognostic model performed well across all time frames (1-, 3-, and 5-year) with regards to the IDI and NRI in comparison to the TNM stage, and clinical treatment. The simple, convenient and low-cost prognostic model we developed demonstrated favorable performance for predicting OS and PFS in OSC patients, which may serve as a useful tool for physicians to provide personalized survival prediction for OSC patients.

Upland cotton is the most important natural-fiber crop. The genomic variation of diverse germplasms and alleles underpinning fiber quality and yield should be extensively explored. Here, we resequenced a core collection comprising 419 accessions with 6.55-fold coverage depth and identified approximately 3.66 million SNPs for evaluating the genomic variation. We performed phenotyping across 12 environments and conducted genome-wide association study of 13 fiber-related traits. 7,383 unique SNPs were significantly associated with these traits and were located within or near 4,820 genes; more associated loci were detected for fiber quality than fiber yield, and more fiber genes were detected in the D than the A subgenome. Several previously undescribed causal genes for days to flowering, fiber length, and fiber strength were identified. Phenotypic selection for these traits increased the frequency of elite alleles during domestication and breeding. These results provide targets for molecular selection and genetic manipulation in cotton improvement. The authors resequence a core collection of upland cotton ( Gossypium hirsutum ) comprising 419 accessions. They analyze genomic variation and conduct a genome-wide association study for 13 fiber quality and yield traits in 12 different environments.

Background: Fructus Meliae Toosendan (FMT) is a traditional Chinese medicine used to treat ascariasis; however, its reported hepatotoxicity limits its application. Toosendanin (TSN), as a principal active component, is recognized as the primary toxic ingredient responsible for FMT-induced hepatotoxicity, but the underlying mechanisms remain elusive. Methods: HepG2 cells were treated with TSN and analyzed using Western blotting and qPCR assays for related gene transcription and protein expression. Lipid peroxidation and ferroptosis markers were measured. Balb/c and C57BL/6 mice received various doses of TSN administration, and their liver function was assessed with serum biochemistry and histopathology. Network pharmacology and oxidative lipidomics were performed to identify key targets and metabolites. Results: TSN triggered ferroptosis both in vitro and in vivo, accompanied by the elevated expression of 5-lipoxygenase (ALOX5) and its downstream metabolites. The ALOX5 level modulated hepatocyte sensitivity to TSN-induced ferroptotic damage. An ALOX5 knockdown alleviated TSN-induced liver injury and ferroptosis in vivo. Conclusions: Our study demonstrated that TSN induces hepatotoxicity by facilitating ALOX5-mediated lipid peroxidation, thereby sensitizing cells to ferroptosis.

Background Radiotherapy is regarded as a milestone for the cure of cervical cancer. However, clinical outcome heavily be hindered by radioresistance. So, exploring the underlying mechanism of radioresistance, and find potential target, well deserve fully emphasis. Methods In this study, we developed two novel radiation resistance cervical cancer cell lines, which could mimic clinical radioresistance. In order to find new potential targets, RNA-Seq, database analysis, streptavidin-agarose and LC/MS were used. Pull-down, luciferase and rescue assays were conducted to explore the regulatory mechanisms. To further evaluate the correlation between therapeutic responses and HMGB3/hTERT expression, 172 cervical cancer patients were recruited. Results Knockdown of HMGB3 significantly inhibit the DNA damage repair and induced more γH2AX foci, leading to enhanced chemo- and radio-sensitivity in vitro and in vivo, whereas HMGB3 overexpression has the opposite effects. HMGB3 promotes cell growth and radioresistance by transcriptionally up-regulating hTERT via the specifical binding of HMGB3 at the hTERT promoter region from − 902 to − 321. HMGB3 knockdown-mediated radiosensitization could be reversed by the overexpressed hTERT in both cervical cancer cell lines and xenograft tumor mouse model. Furthermore, clinical data from 172 cervical cancer patients proved that there was a positive correlation between HMGB3 and hTERT expression, and high expression of HMGB3/hTERT predicted poor response to radiotherapy, worse TNM stages and shorter survival time. Conclusion Here, we have identified HMGB3/hTERT signaling axis as a new target for cervical cancer radioresistance. Our results provide new insights into the mechanism of cervical cancer radioresistance and indicate that targeting the HMGB3/hTERT signaling axis may benefit cervical cancer patients.

SRC2 (soybean genes regulated by cold 2) is a protein that contains a C2 domain and plays a vital role in plant stress responses. In this study, we identified a total of 15 SRC2-like genes ( ZmSRC2L1 – ZmSRC2L15 ) in maize and systematically characterized their molecular properties, genomic distribution, promoter features, subcellular localization, and expression under abiotic stress conditions. We confirmed that the ZmSRC2L genes are unevenly distributed across chromosomes 1–8, encoding proteins of 212–402 amino acids, with molecular weights (MWs) ranging from 21.93 to 42.52 kDa. These proteins retain a conserved C2_SRC2_like domain while exhibiting subfamily-specific variations. Promoter analysis revealed the presence of cis-elements enriched in light, hormones, and stress responses, and predicted regulation by multiple transcription factor families, particularly ERF and MYB. Subcellular localization analysis revealed that the ZmSRC2L proteins are distributed across multiple cellular compartments. Transcriptome and RT-qPCR analyses demonstrate that gene expression is tissue-specific under stresses such as drought, heat, and cold. Functional validation using Ds insertion mutants indicated that the loss of ZmSRC2L2 specifically impaired drought tolerance without affecting responses to heat or cold. Overall, these results provide a comprehensive framework for understanding the role of the ZmSRC2L family in abiotic stress responses and highlight ZmSRC2L2 and other members as promising targets for enhancing maize stress resistance.