Identifying IDH-mutant and 1p/19q noncodeleted astrocytomas from nonenhancing gliomas: Manual recognition followed by artificial intelligence recognition.

Background: The T2-FLAIR mismatch sign (T2FM) has nearly 100% specificity for predicting IDH-mutant and 1p/19q noncodeleted astrocytomas (astrocytomas). However, only 18.2%-56.0% of astrocytomas demonstrate a positive T2FM. Methods must be considered for distinguishing astrocytomas from negative T2FM gliomas. In this study, positive T2FM gliomas were manually distinguished from nonenhancing gliomas, and then a support vector machine (SVM) classification model was used to distinguish astrocytomas from negative T2FM gliomas. Methods: Nonenhancing gliomas (regardless of pathological type or grade) diagnosed between January 2022 and October 2022 (N = 300) and November 2022 and March 2023 (N = 196) will comprise the training and validation sets, respectively. Our method for distinguishing astrocytomas from nonenhancing gliomas was examined and validated using the training set and validation set. Results: The specificity of T2FM for predicting astrocytomas was 100% in both the training and validation sets, while the sensitivity was 42.75% and 67.22%, respectively. Using a classification model of SVM based on radiomics features, among negative T2FM gliomas, the accuracy was above 85% when the prediction score was greater than 0.70 in identifying astrocytomas and above 95% when the prediction score was less than 0.30 in identifying nonastrocytomas. Conclusions: Manual screening of positive T2FM gliomas, followed by the SVM classification model to differentiate astrocytomas from negative T2FM gliomas, may be a more effective method for identifying astrocytomas in nonenhancing gliomas.

Distinguishing Tumor Cell Infiltration and Vasogenic Edema in the Peritumoral Region of Glioblastoma at the Voxel Level via Conventional MRI Sequences.

RATIONALE AND OBJECTIVES: The peritumoral region of glioblastoma (GBM) is composed of infiltrating tumor cells and vasogenic edema, which are difficult to distinguish manually on MRI. To distinguish tumor cell infiltration and vasogenic edema in GBM peritumoral regions, it is crucial to develop a method that is precise, effective, and widely applicable. MATERIALS AND METHODS: We retrieved the image characteristics of 379,730 voxels (marker of tumor infiltration) from 28 non-enhanced gliomas and 365,262 voxels (marker of edema) from the peritumoral edema region of 14 meningiomas on conventional MRI sequences (T1-weighted image, the contrast-enhancing T1-weighted image, the T2-weighted image, the T2-fluid attenuated inversion recovery image, and the apparent diffusion coefficient map). Using the SVM classifier, a model for predicting tumor cell infiltration and vasogenic edema at the voxel level was developed. The accuracy of the model's predictions was then evaluated using 15 GBM patients who underwent stereotactic biopsies. RESULTS: The area under the curve (AUC), accuracy, sensitivity, and specificity of the prediction model were 0.93, 0.84, 0.83, and 0.85 in the training set, and 0.90, 0.82, 0.83, and 0.83 in the test set (704,992 voxels), respectively. The pathology verification of 28 biopsy points with an accuracy of 0.79. CONCLUSION: At the voxel level, it seems possible to forecast tumor cell infiltration and vasogenic edema in the peritumoral region of GBM based on conventional MRI sequences.

Personalised neoantigen-based therapy in colorectal cancer.

Colorectal cancer (CRC) has become one of the most common tumours with high morbidity, mortality and distinctive evolution mechanism. The neoantigens arising from the somatic mutations have become considerable treatment targets in the management of CRC. As cancer-specific aberrant peptides, neoantigens can trigger the robust host immune response and exert anti-tumour effects while minimising the emergence of adverse events commonly associated with alternative therapeutic regimens. In this review, we summarised the mechanism, generation, identification and prognostic significance of neoantigens, as well as therapeutic strategies challenges of neoantigen-based therapy in CRC. The evidence suggests that the establishment of personalised neoantigen-based therapy holds great promise as an effective treatment approach for patients with CRC.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictive markers in hepatoblastoma.

Background: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been presented to be a prognostic indicator in several cancers. We were supposed to evaluate the prognostic role of such inflammatory markers in hepatoblastoma (HB). Methods: Total of 101 children, diagnosed with hepatoblastoma between January 2010 and January 2018, were enrolled before treatment in the study. The clinicopathological parameters, and outcomes were collected through laboratory analyses and patient follow-up. The association between NLR, PLR, and clinicopathological characters were analyzed with Wilcoxon test, Chi-Squared test, Kaplan-Meier, Log-rank and Cox regression analyses. Results: NLR and PLR were significantly elevated in HB patients (P < 0.001), and related to age (P < 0.001), risk stratification system (P < 0.001), and pretreatment extent of disease (P < 0.0001). NLR was significantly related to alpha-fetoprotein (P = 0.034) and lactate dehydrogenase (P = 0.026). The 3-year overall survival (OS) and event-free survival (EFS) were poor in the high-NLR group (OS: 44.3% vs. 90.3%, P < 0.0001, EFS: 38.6% vs. 80.6%, P = 0.0001). The 3-year OS and EFS were poor in the high-PLR group (OS: 49.1% vs. 68.8%, P = 0.016, EFS: 39.6% vs. 64.6%, P = 0.0117). The multivariate analysis suggested that NLR (HR: 11.359, 95% CI: 1.218-105.947; P = 0.033) and risk stratification (HR: 44.905, 95% CI: 2.458-820.36; P = 0.01), were independent predictors of OS. Conclusion: Our research showed that elevated NLR and PLR were the poor prognostic factors in HB patients before treatment. The NLR was an independent prognostic factor for OS.

Bioinspired Total Synthesis of Complex Nucleoside Antibiotics A201A, A201D and A201E.

Herein, bioinspired total syntheses of A201A, A201D, and A201E based on a previously reported biosynthetic pathway are presented. The challenging 1,2-cis-furanoside, a core structure of the A201 family, was obtained by remote 2-quinolinecarbonyl-assisted glycosylation. We accomplished the total synthesis of A201A and A201E based on the critical 1,2-cis-furanoside moiety through late-stage glycosylation without any interference from basic dimethyl adenosine. We also confirmed the absolute configuration of A201E by total synthesis. This modular synthesis strategy enables efficient preparation of A201 family antibiotics, allowing the study of their structure-activity relationships and mode of action. This study satisfies the increasing demand for developing novel antibiotics inspired by the A201 family.

Inflammation-related pathways involved in damaged articular cartilage of rats exposed to T-2 toxin based on RNA-sequencing analysis.

Many studies have shown that ingestion of the T-2 toxin is harmful to articular cartilage. However, the mechanisms underlying damaged articular cartilage induced by T-2 toxin have not been elucidated. Twenty-four SD rats were randomly divided into T-2 toxin and control groups. In the control group, the 12 rats were administered 4% absolute ethanol by gavage, and in the T-2 toxin group, the 12 rats were administered T-2 toxin (100 ng/g, BW/day) by gavage. After the rats were sacrificed, the knee joints were collected, and RNA was extracted using TRIzol reagent for RNA sequencing (RNA-seq). Differentially expressed mRNA was identified based on p < 0.05 and | log2 (fold change) | > 1. The T-2 toxin-related genes were obtained from the GeneCards database. An online tool (https://www.bioinformatics.com.cn) was used for enrichment analysis. Hematoxylin and eosin (H&E) staining was used to observe damaged articular cartilage, and immunohistochemical (IHC) staining was used to validate differentially expressed proteins. The H&E staining shows the number of cells decreased significantly, and the arrangement of chondrocytes became disordered in the T-2 toxin group. RNA-seq analysis identified 195 upregulated and 89 downregulated mRNAs in the T-2 toxin group. The top immune-related biological processes (Gene Ontology) were regulation of hormone secretion, regulation of peptide hormone secretion, and regulation of transcription involved in cell fate commitment. KEGG pathway enrichment analysis revealed that the IL-17 and tumor necrosis factor signaling pathways were significantly expressed, and the IL-17 signaling pathway was also identified in the enrichment analysis of T-2 toxin-related genes. Also, Mmp3, Tnf, Mapk10, Ccl11, Creb5, Cxcl2, and Cebpb were significantly enriched in the two pathways. The immunohistochemical staining showed that the levels of Mmp3 and Tnf proteins were significantly increased in the T-2 toxin group, which was consistent with the RNA-seq results. This study revealed the critical roles of IL-17 and TNF signaling pathways in damaged cartilage induced by T-2 toxin.

YAP Activation in Promoting Negative Durotaxis and Acral Melanoma Progression.

Directed cell migration towards a softer environment is called negative durotaxis. The mechanism and pathological relevance of negative durotaxis in tumor progression still requires in-depth investigation. Here, we report that YAP promotes the negative durotaxis of melanoma. We uncovered that the RhoA-myosin II pathway may underlie the YAP enhanced negative durotaxis of melanoma cells. Acral melanoma is the most common subtype of melanoma in non-Caucasians and tends to develop in a stress-bearing area. We report that acral melanoma patients exhibit YAP amplification and increased YAP activity. We detected a decreasing stiffness gradient from the tumor to the surrounding area in the acral melanoma microenvironment. We further identified that this stiffness gradient could facilitate the negative durotaxis of melanoma cells. Our study advanced the understanding of mechanical force and YAP in acral melanoma and we proposed negative durotaxis as a new mechanism for melanoma dissemination.

New NNN pincer copper complexes as potential anti-prostate cancer agents.

Eleven novel NNN Cu(II) complexes supported by a tridentate bis(imidazo[1,2-α]pyridin-2-yl)pyridine ligand were synthesized and characterized by elemental analysis, HRMS, and X-ray determination. Target prediction and docking studies indicated that these pincer complexes formed hydrogen bonds with Asp33 and Gly35 of Cathepsin D protein, which is highly associated with prognosis of advanced prostate cancer. Furthermore, they exhibited anti-proliferation activity in both androgen-sensitive and androgen-insensitive prostate cancer cells according to WST-1 assay results. Mechanistic study showed that pincer complexes arrested cell cycle progression at G0/G1 phase and inhibited Cathepsin D regulated signaling pathways. Most importantly, new pincer copper complexes significantly inhibited xenograft prostate cancer growth along with a promising in vivo safety profile. In summary, these results suggest the applicability of the developed novel pincer copper complexes as promising anticancer agents for prostate cancer treatment.

The Novel Function of Unsymmetrical Chiral CCN Pincer Nickel Complexes as Chemotherapeutic Agents Targeting Prostate Cancer Cells.

We report that the pincer nickel complexes display prostate cancer antitumor properties through inhibition of cell proliferation. Notably, they display better antitumor properties than cisplatin. Mechanistic studies reveal that these pincer nickel complexes trigger cell apoptosis, most likely due to cell cycle arrest. Interestingly, these complexes also inhibit androgen receptor (AR) and prostate-specific antigen (PSA) signaling, which are critical for prostate cancer survival and progression. Our study reveals a novel function of pincer nickel complexes as potential therapeutic drugs in prostate cancer.

Development and validation of a novel survival prediction model for newly diagnosed lower-grade gliomas.

OBJECTIVE: Diffuse gliomas are the most common primary gliomas with a poor prognosis. This study aimed to develop and validate prognostic models for predicting the survival probability in newly diagnosed lower-grade glioma (LGG) patients. METHODS: Detailed data were obtained for newly diagnosed LGG from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) cohorts. Survival was assessed using Cox proportional hazards regression with adjustment for known prognostic factors. The model was established using the TCGA cohort, and independently validated using the CGGA cohort, to predict the 3-, 5-, and 10-year survival probabilities of patients. RESULTS: Data from 293 patients with newly diagnosed LGG from the TCGA cohort were used to establish a prognostic model, and from 232 patients with primary LGG in the CGGA cohort to validate the model. Age, tumor grade, molecular subtype, tumor resection, and preoperative neurological deficits were included in the prediction model. The Cox regression model had a satisfactory corrected concordance index of 0.8508, 0.8510, and 0.8516 in the internal bootstrap validation at 3, 5, and 10 years, respectively. The calibration plots demonstrated high consistency of the predicted and observed outcomes. The CGGA cohort was used for external validation and showed satisfactory discrimination of 0.7776, 0.7682, and 0.7051 at 3, 5, and 10 years, respectively. The calibration plots demonstrated an acceptable calibration capability in the external validation. CONCLUSIONS: This study established and validated a prognostic model to predict the survival probability of patients with newly diagnosed LGG. The model performed well in discrimination and calibration with ease of use, speed, accessibility, interpretability, and generalizability. An easily used nomogram based on the Cox model was established for clinical application. Moreover, a free, easy-to-use software interface based on the nomogram is provided online.

Effects of exogenous ghrelin on the tissue structure and somato-statin secretion in the pancreas of African ostrich chicks / Efectos de la grelina exógena en la estructura del tejido y la secreción de somato-estatinas en el páncreas de los polluelos de avestruz africanos

SUMMARY: This study aimed to investigate the effect of exogenous ghrelin on pancreatic growth and development in African ostrich chicks. Sixteen 40-day-old African ostrich chicks (male or female) were randomly divided into four groups and injected intravenously metatarsal vein with saline (control) or ghrelin (10, 50, and 100 μg/kg) for 6 days. Body and pancreas weight were determined, structural characteristics were observed using HE staining, somatostatin-immunopositive cells were detected using immunohistochemistry. The results were as follows: 1. The 50 and 100 μg/kg groups showed lower relative pancreas weight than the control group (P 0.05. Moreover, compared with the control, the islet cells in treatment groups were loosely arranged and showed reduced cytoplasm. In the exocrine pancreas, the volume of acinar cells in the 10, 50, and 100 μg/kg groups all decreased to varying degrees. 3. Somatostatin immunopositive cells were mainly located around the periphery of the islets and sporadically distributed in the center. The density of the somatostatin immunopositive cells in the 10, 50, and 100 μg/kg groups was higher than that in the control (P < 0.05). These findings suggest that exogenous ghrelin increases the area and number of islets and number of somatostatin immunopositive cells but reduces relative pancreas weight and effects the morphological and structural development of the pancreas, which may inhibit the pancreatic growth and development in African ostrich chicks.

RESUMEN: Este estudio tuvo como objetivo investigar el efecto de la grelina exógena sobre el crecimiento y desarrollo del páncreas en polluelos de avestruz africana. Dieciséis pollos de avestruz africana de 40 días (machos o hembras) se dividieron al azar en cuatro grupos y se inyectaron por vía intravenosa con solución salina (control) o grelina (10, 50 y 100 μg / kg) durante 6 días. determinadas, se observaron las características estructurales mediante tinción Hematoxilina-Eosina, se detectaron células inmunopositivas a somatostatina mediante inmunohistoquímica. Los resultados fueron los siguientes: ¨Los grupos de 50 y 100 μg / kg mostraron un menor peso relativo del páncreas que el grupo de control (P <0,05). El área de islotes por unidad de área del páncreas fue mayor en los grupos de 10, 50 y 100 μg / kg grupos que en el grupo de control (P <0,05). El número de islotes por unidad de área del páncreas fue menor en el grupo de 10 μg / kg que en el control (P <0,05). Además, en comparación con el control, las células de los islotes en los grupos de tratamiento estaban dispuestas de forma holgada y mostraban un citoplasma reducido. En el páncreas exocrino, el volumen de células acinares en los grupos de 10, 50 y 100 μg / kg disminuyó en diversos grados. Las células inmunopositivas de somatostatina se ubicaron principalmente alrededor de la periferia de los islotes y se distribuyeron esporádicamente en el centro. La densidad de las células inmunopositivas a la somatostatina en los grupos de 10, 50 y 100 μg / kg fue mayor que la del control (P <0,05). Estos hallazgos sugieren que la grelina exógena aumenta el área y el número de islotes y el número de células inmunopositivas a la somatostatina, pero reduce el peso relativo del páncreas, lo que puede inhibir el crecimiento y desarrollo pancreático en los polluelos de avestruz africana.

Effectiveness and safety of ultrasound-guided hydrostatic reduction for children with acute intussusception.

OBJECTIVE: This study aims to explore the effectiveness and safety of the new-type ultrasound-guided hydrostatic reduction for children with acute intussusception. METHODS: The clinical data of 364 children with primary acute intussusception who underwent nonsurgical reduction in our hospital between January 2016 and May 2019 were retrospectively analyzed. Among the 364 children, 119 formed the hydrostatic reduction group. There were 89 males and 30 females, and the average age of admission was 25.13 ± 1.43 months. Among the pneumatic reduction group of 245 patients, there were 163 males and 82 females. The average age of admission was 22.47 ± 1.52 months. The reduction rate, length of stay, and perforation rate were compared between the two groups. RESULTS: Univariate analysis showed that the reduction rate in the hydrostatic group (94.96%) was higher than in the pneumatic group (85.31%) (p = 0.007), and the hospital stay (2.76 ± 0.15 days) of the hydrostatic reduction group was shorter than that of the pneumatic reduction group (3.56 ± 0.35 days) (p = 0.038). In children with intussusception time >48 h, the reduction rate was 95.45% in the hydrostatic reduction group and 86.20% in the pneumatic reduction group. CONCLUSION: The new-type ultrasound-guided hydrostatic reduction has a higher reduction rate in the treatment of acute intussusception in children results in a shortened hospital stay, It is effective, safe, and avoids radiation exposure.

Reduced survival of young patients under 55 years with metastatic prostate cancer: a population-based study.

Objective: The aim of this study was to evaluate the prognosis of patients with metastatic prostate cancer (mPCa) in different age groups. Methods: Patients with mPCa from 2004 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were identified. Seven groups were divided according to the age at diagnosis, including ≤55 years, 56-60 years, 61-65 years, 66-70 years, 71-75 years, 76-80 years and >80 years. Fine and Gray's competing risks model and Kaplan-Meier analysis were conducted to evaluate the cancer-specific survival (CSS). Results: A total of 36231 patients with mPCa were included. The CSS curves of the overall cohort showed that patients aged ≤55 years had significantly worse CSS than patients in age groups of 56-60 [HR:0.93 (0.87~1.00), p=0.039], 61-65 [HR:0.91 (0.85~0.97), p=0.003] and 66-70 [HR:0.90 (0.84~0.96), p=0.001]. After removing patients dead for other reasons, the differences of CSS curves between ≤55 years group and 56-70 years groups were not significant. However, the mean survival time of ≤55 years group (55.78±2.48 months) was still shorter than 56-60 years (57.28±2.35 months), 61-65 years (57.64±2.07 months), and 66-70 years (57.11±2.11 months). When stratified by M stages, similar results were found in M1a, M1b and M1c stage groups. According to Fine-Gray competing risks models, patient ≤55 years featured significantly higher sub-distribution hazard ratio (sdHR) than 61-65 years group [sdHR: 0.94(0.88~1.00); p=0.046]. Conclusions: The mPCa patients ≤55 years seemed to be associated with worse prognosis in comparison with patients aging 56-70 years.

Identification of a ceRNA Network in Lung Adenocarcinoma Based on Integration Analysis of Tumor-Associated Macrophage Signature Genes.

As research into tumor-immune interactions progresses, immunotherapy is becoming the most promising treatment against cancers. The tumor microenvironment (TME) plays the key role influencing the efficacy of anti-tumor immunotherapy, in which tumor-associated macrophages (TAMs) are the most important component. Although evidences have emerged revealing that competing endogenous RNAs (ceRNAs) were involved in infiltration, differentiation and function of immune cells by regulating interactions among different varieties of RNAs, limited comprehensive investigation focused on the regulatory mechanism between ceRNA networks and TAMs. In this study, we aimed to utilize bioinformatic approaches to explore how TAMs potentially influence the prognosis and immunotherapy of lung adenocarcinoma (LUAD) patients. Firstly, according to TAM signature genes, we constructed a TAM prognostic risk model by the least absolute shrinkage and selection operator (LASSO) cox regression in LUAD patients. Then, differential gene expression was analyzed between high- and low-risk patients. Weighted gene correlation network analysis (WGCNA) was utilized to identify relevant gene modules correlated with clinical characteristics and prognostic risk score. Moreover, ceRNA networks were built up based on predicting regulatory pairs in differentially expressed genes. Ultimately, by synthesizing information of protein-protein interactions (PPI) analysis and survival analysis, we have successfully identified a core regulatory axis: LINC00324/miR-9-5p (miR-33b-5p)/GAB3 (IKZF1) which may play a pivotal role in regulating TAM risk and prognosis in LUAD patients. The present study contributes to a better understanding of TAMs associated immunosuppression in the TME and provides novel targets and regulatory pathway for anti-tumor immunotherapy.

The Immune Regulatory Effect of Boron on Ostrich Chick Splenic Lymphocytes.

Boron is a trace element which plays important roles in immune response. The relationship between boron and splenic lymphocyte proliferation, apoptosis, secretion of cytokines, and genes potentially related to immune response in ostrich chicks were investigated in the present study. Different concentrations of boron (0, 0.01, 0.1, 0.5, 1, 5, 10, 25, 50, and 100 mmol/L) were applied to splenic lymphocytes of African ostrich, respectively. The effect of boron on lymphocyte proliferation was checked by the CCK-8 method. Flow cytometry was used to detect the effect of boron on apoptosis. The secretion levels of IL-6 and IFN-α were determined by ELISA. Splenic lymphocyte gene expression profiles of ostrich chicks treated with boron (0, 0.1, 100 mmol/L) were studied using RNA-seq technology. The results showed that cell proliferation increased with 0.01-10 mmol/L boron, when it was 25-100 mmol/L, the cell proliferation gradually decreased as the boron concentration increased. Apoptosis ratio in ostrich splenic lymphocytes was closely related to boron concentrations. 0.01- and 0.1-mmol/L boron inhibited apoptosis in splenic lymphocytes, whereas 1, 10, 50, and 100-mmol/L boron promoted apoptosis. As the concentration of boron increased, the secretion of IL-6 gradually decreased; IFN-α was initially increased and then decreased with boron concentrations increased, reaching the maximum level with 1 mmol/L boron. In terms of the RNA-Seq data, there was no differentially expressed gene between the 0- and 0.1-mmol/L boron-treated samples; 21 differentially expressed genes were found between the 0- and 100-mmol/L boron-treated samples; 43 differentially expressed genes were found between the 0.1- and 100-mmol/L boron-treated samples. Functional analysis of the differentially expressed genes by Gene Ontology verified multiple functions associated with immune response. Pathway analysis showed that systemic lupus erythematosus, alcoholism, viral carcinogenesis, and necroptosis pathway were the major enriched pathways, and BIRC2-3, FTH1, and IL-1ß genes showed differential expression in necroptosis pathway. These results demonstrated that low concentrations (0.01-0.1 mmol/L) of boron may promote the proliferation and the secretion of cytokines, inhibit cell apoptosis of ostrich splenic lymphocytes by enhancing the function of the cell membrane and the activity of intracellular catalytic enzymes, whereas high-concentration (25-100 mmol/L) boron had opposite effects on cells. The necroptosis pathway might play a pivotal role in regulating the immune response of boron-treated splenic lymphocytes in ostrich chicks.

LINC-PINT Suppresses the Aggressiveness of Thyroid Cancer by Downregulating miR-767-5p to Induce TET2 Expression.

Long noncoding RNA (lncRNA) long intergenic nonprotein-coding RNA, p53-induced transcript (LINC-PINT) has shown anti-invasive activity in lung and colon cancer cells. However, the role of LINC-PINT in thyroid cancer is unclear. In the present work, we explored the expression of LINC-PINT in 60 paired thyroid cancer and adjacent normal tissues. The clinical significance and biological function of LINC-PINT in thyroid cancer were determined. LINC-PINT expression was downregulated in thyroid cancer relative to adjacent normal tissues (p = 0.0002). Low expression of LINC-PINT was significantly associated with advanced tumor node metastasis (TNM) stage (p = 0.0306) and lymph node metastasis (p = 0.0359). Ectopic expression of LINC-PINT suppressed the proliferation, invasion, and tumorigenesis of thyroid cancer cells. Mechanistically, LINC-PINT associated with and downregulated microRNA (miR)-767-5p. Moreover, LINC-PINT overexpression relieved miR-767-5p-mediated repression of ten-eleven translocation 2 (TET2). miR-767-5p promoted aggressiveness of thyroid cancer, which was reversed by overexpression of TET2. Coexpression of miR-767-5p or depletion of TET2 rescued the inhibitory effect of LINC-PINT on thyroid cancer cell proliferation and invasion. In addition, there was a negative correlation between miR-767-5p and LINC-PINT in thyroid cancer (r = -0.34772, p = 0.01789). Taken together, LINC-PINT functions as a tumor suppressor in thyroid cancer via the miR-767-5p/TET2 axis, representing a potential therapeutic target for thyroid cancer.

Sirt1 improves heart failure through modulating the NF-κB p65/microRNA-155/BNDF signaling cascade.

Heart failure (HF) affects over 26 million people worldwide, yet the pathologies of this complex syndrome have not been completely understood. Here, we investigated the involvement of deacetylase Sirtuin 1 (Sirt1) in HF and its downstream signaling pathways. A HF model was induced by the ligation of the left coronary artery in rats, where factors associated with left ventricular echocardiography, heart hemodynamics and ventricular mass indexes were recorded. Collagen volume fraction in heart tissues was determined by Masson's trichrome staining. Cell models of HF were also established (H2O2, 30 min) in cardiomyocytes harvested from suckling rats. HF rats presented with downregulated expressions of Sirt1, brain-derived neurotrophic factor (BDNF) and exhibited upregulated expressions of NF-κB p65 and miR-155. Repressed Sirt1 expression increased acetylation of NF-κB p65, resulting in the elevation of NF-κB p65 expression. NF-κB p65 silencing improved heart functions, decreased ventricular mass and reduced apoptosis in cardiomyocytes. MiR-155 inhibition upregulated its target gene BDNF, thereby reducing cardiomyocyte apoptosis. Sirt1 overexpression upregulated BDNF, improved heart function, and reduced apoptosis in cardiomyocytes. In conclusion, Sirt1 alleviates HF in rats through the NF-κB p65/miR-155/BDNF signaling cascade.