A combination of radiomic features, clinic characteristics, and serum tumor biomarkers to predict the possibility of the micropapillary/solid component of lung adenocarcinoma.

BACKGROUND: Invasive lung adenocarcinoma with MPP/SOL components has a poor prognosis and often shows a tendency to recurrence and metastasis. This poor prognosis may require adjustment of treatment strategies. Preoperative identification is essential for decision-making for subsequent treatment. OBJECTIVE: This study aimed to preoperatively predict the probability of MPP/SOL components in lung adenocarcinomas by a comprehensive model that includes radiomics features, clinical characteristics, and serum tumor biomarkers. DESIGN: A retrospective case control, diagnostic accuracy study. METHODS: This study retrospectively recruited 273 patients (males: females, 130: 143; mean age ± standard deviation, 63.29 ± 10.03 years; range 21-83 years) who underwent resection of invasive lung adenocarcinoma. Sixty-one patients (22.3%) were diagnosed with lung adenocarcinoma with MPP/SOL components. Radiomic features were extracted from CT before surgery. Clinical, radiomic, and combined models were developed using the logistic regression algorithm. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC). Studies were scored according to the Radiomics Quality Score and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines. RESULTS: The radiomics model achieved the best AUC values of 0.858 and 0.822 in the training and test cohort, respectively. Tumor size (T_size), solid tumor size (ST_size), consolidation-to-tumor ratio (CTR), years of smoking, CYFRA 21-1, and squamous cell carcinoma antigen were used to construct the clinical model. The clinical model achieved AUC values of 0.741 and 0.705 in the training and test cohort, respectively. The nomogram showed higher AUCs of 0.894 and 0.843 in the training and test cohort, respectively. CONCLUSION: This study has developed and validated a combined nomogram, a visual tool that integrates CT radiomics features with clinical indicators and serum tumor biomarkers. This innovative model facilitates the differentiation of micropapillary or solid components within lung adenocarcinoma and achieves a higher AUC, indicating superior predictive accuracy.

A new tool to predict aggressive lung cancer types before surgeryWe developed a tool to help doctors determine whether lung cancer is one of the more dangerous types, called micropapillary (MPP) or solid (SOL) patterns, before surgery. These patterns can be more harmful and spread quickly, so knowing they are there can help doctors plan the best treatment. We looked at the cases of 273 lung cancer patients who had surgery and found that 61 of them had these aggressive cancer types. To predict these patterns, we used a computer process known as logistic regression, analyzing CT scan details, health information, and blood tests for cancer markers. Based on CT scans, our tool was very good at predicting whether these patterns were present in two patient groups. However, predictions using only basic health information like the size of the tumor and whether the patient smoked needed to be more accurate. We found a way to make our predictions even better. Combining all information into one chart, known as a nomogram, significantly improved our ability to predict these dangerous cancer patterns. This combined chart could be a big help for doctors. It gives them a clearer picture of the cancer's aggressiveness before surgery, which can guide them to choose the best treatment options. This approach aims to offer a better understanding of the tumor, leading to more tailored and effective treatments for patients facing lung cancer.

A combinatorial MRI sequence-based radiomics model for preoperative prediction of microsatellite instability status in rectal cancer.

This study aimed to develop an optimal radiomics model for preoperatively predicting microsatellite instability (MSI) in patients with rectal cancer (RC) based on multiparametric magnetic resonance imaging. The retrospective study included 308 RC patients who did not receive preoperative antitumor therapy, among whom 51 had MSI. Radiomics features were extracted and dimensionally reduced from T2-weighted imaging (T2WI), T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI), and T1-weighted contrast enhanced (T1CE) images for each patient, and the features of each sequence were combined. Multifactor logistic regression was used to screen the optimal feature set for each combination. Different machine learning methods were applied to construct predictive MSI status models. Relative standard deviation values were determined to evaluate model performance and select the optimal model. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses were performed to evaluate model performance. The model constructed using the k-nearest neighbor (KNN) method combined with T2WI and T1CE images performed best. The area under the curve values for prediction of MSI with this model were 0.849 (0.804-0.887), with a sensitivity of 0.784 and specificity of 0.805. The Delong test showed no significant difference in diagnostic efficacy between the KNN-derived model and the traditional logistic regression model constructed using T1WI + DWI + T1CE and T2WI + T1WI + DWI + T1CE data (P > 0.05) and the diagnostic efficiency of the KNN-derived model was slightly better than that of the traditional model. From ROC curve analysis, the KNN-derived model significantly distinguished patients at low- and high-risk of MSI with the optimal threshold of 0.2, supporting the clinical applicability of the model. The model constructed using the KNN method can be applied to noninvasively predict MSI status in RC patients before surgery based on radiomics features from T2WI and T1CE images. Thus, this method may provide a convenient and practical tool for formulating treatment strategies and optimizing individual clinical decision-making for patients with RC.

Predictive value of platelet-related hematological markers in indicating the outcomes after laparoscopic intraperitoneal onlay mesh repair (IPOM).

BACKGROUND: The predictive value of hematological markers in the outcomes after laparoscopic intraperitoneal onlay mesh repair (IPOM) remains to be investigated. We aim to evaluate the role of platelet-related parameters after laparoscopic IPOM in patients with incisional hernias. METHODS: The data of 95 patients who underwent laparoscopic IPOM for appendicectomy-related incisional hernias were retrospectively analyzed. The complete blood count analyses were measured preoperatively, and the outcomes were obtained from hospital records and follow-up calls to patients. Platelet-multiple-lymphocyte index (PLM), neutrophil-leukocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) values were calculated. The patients were grouped based on the recurrence and the postoperative complications after surgery. RESULTS: Using cutoff values acquired by the Youden Index, we found platelet levels < 212.0 × 1000/µl, NLR > 2.33, LMR < 3.17, and PLM < 365.5 were revealed to be statistically significant in the recurrence of hernias based on univariant or multivariant analysis (p = < 0.05). We further divided the patients into two groups based on the cutoff value of PLM and found that a PLM value < 365.5 was significantly associated with the recurrence of incisional hernia (p = 0.018), the occurrence of postoperative seroma (p = 0.044), and there is a tendency that patients with PLM < 365.5 may suffer from other postoperative complications such as cardiopathy, respiratory infection, and hypoproteinemia (p = 0.089). CONCLUSION: The preoperative hematological values, especially PLM, may indicate the outcomes in incisional hernias after laparoscopic IPOM.

Nuclear Membrane Protein SUN5 Is Highly Expressed and Promotes Proliferation and Migration in Colorectal Cancer by Regulating the ERK Pathway.

SUN5 was first identified as a nuclear envelope protein involved in spermatocyte division. We found that SUN5 was highly expressed in some cancers, but its function and mechanism in cancer development remain unclear. In the present study, we demonstrated that SUN5 was highly expressed in colorectal cancer (CRC) tissues and cells, as indicated by bioinformatics analysis, and SUN5 promoted cell proliferation and migration in vitro. Moreover, the overexpression of SUN5 upregulated phosphorylated ERK1/2 (pERK1/2), whereas the knockdown of SUN5 yielded the opposite results. PD0325901 decreased the level of pERK1/2 to inhibit cell proliferation and migration, which was partially reversed by SUN5 overexpression, indicating that drug resistance existed in patients with high SUN5 expression. The xenograft transplantation experiment showed that SUN5 accelerated tumor formation in vivo. Furthermore, we found that SUN5 regulated the ERK pathway via Nesprin2 mediation and promoted the nuclear translocation of pERK1/2 by interacting with Nup93. Thus, these findings indicated that highly expressed SUN5 promoted CRC proliferation and migration by regulating the ERK pathway, which may contribute to the clinical diagnosis and new treatment strategies for CRC.

Correlation between apparent diffusion coefficient and tumor-stroma ratio in hybrid 18F-FDG PET/MRI: preliminary results of a rectal cancer cohort study.

Background: To explore possible correlations between the tumor-stroma ratio (TSR) and different imaging features of fluorine-18-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) in untreated rectal cancer patients. Methods: A patients with rectal cancer were included in this study. All participants were examined preoperatively with whole-body 18F-FDG PET/MRI. Two pathologists evaluated the TSR of tumors together. Apparent diffusion coefficient (ADC) values and PET-related parameters of the primary lesions were measured and compared between the stroma-high and stroma-low groups. Pearson's correlation or Spearman's rank correlation were used to evaluate the correlation between the ADC values, PET-related parameters, and pathological indices. Results: Our results showed that in the untreated rectal cancer patients, the ADC mean values correlated with the TSR (r=0.327; P=0.007), and stroma-high (low TSR) rectal cancer corresponded to relatively lower ADC mean values (813.54±88.68 vs. 879.92±133.18; P=0.018). The ADC mean and ADC minimum (ADCmin) values were found to be negatively correlated with the pathological T stages (r=-0.384, P=0.001; r=-0.416, P=0.001, respectively) as well as the largest tumor diameters (r=-0.340, P=0.005; r=-0.314, P=0.010, respectively) of rectal cancer. In addition, the pathological T stages correlated with all PET-related metabolic parameters, including mean standard uptake value (SUV), maximum SUV (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) (r=0.338, P=0.006; r=0.350, P=0.004; r=0.326, P=0.007; and r=0.472, P<0.001, respectively). Our results also identified associations between the ADCmin values and SUVmean, SUVmax, and TLG (r=-0.335, P=0.006; r=-0.343, P=0.005; and r=-0.343, P=0.005, respectively). However, there were no statistical correlations between the PET/MRI parameters and the immunohistochemical (IHC) results. Conclusions: This study indicated that the intratumoral heterogeneity measured by PET/MRI may reflect characteristics of the tumor microenvironment. Hence, PET/MRI parameters might be helpful in predicting tumor aggressiveness and prognosis.

Bioinformatics Methods Reveal the Biomarkers and the miRNA-mRNA Network in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has threatened the health of humans, and few therapeutic strategies can completely uproot this illness. Bioinformatics methods have been widely used for investigating the pathological mechanisms of disease. In this study, datasets including GSE20077 and GSE108724, obtained from the Gene Expression Omnibus (GEO) database, were used for investigating the biomarker and molecular mechanism of HCC. The differentially expressed genes (DEGs) in the datasets were identified, and the targets of the miRNAs were searched in the miRDIP and miRNET databases. Enrichment analysis was performed for delving the molecular mechanism of DEGs, and protein-protein interaction (PPI) networks and miRNA-mRNA networks were used to reveal the hub nodes and the related interaction relationships. Moreover, the expression and diagnostic values of hub nodes were analyzed with the GEPIA2 database. The results showed that 53 upregulated miRNAs and 48 downregulated miRNAs were found in GSE20077, and 55 upregulated miRNAs and 69 downregulated miRNAs were found in GSE108724. Moreover, seven common miRNAs including miR-146b-5p, miR-338-3p, miR-375, miR-502-3p, miR-532-3p, miR-532-5p, and miR-557 were found in the datasets. The targets of the common miRNAs were related with the P53, HIF1, Wnt, and NF-κB pathways. Besides, YWHAZ and CDC42 were identified as the hub nodes and served as the downstream targets of miR-375-3p. The GEPIA2 database showed that YWHAZ and CDC42 were related with the survival rate of the patients. In conclusion, this study suggests that miR-375-3p functions as a tumor suppressor which could inhibit the progression of HCC via targeting YWHAZ and CDC42.

Rat BAT xenotransplantation recovers the fertility and metabolic health of PCOS mice.

Polycystic ovarian syndrome (PCOS) is a major severe ovary disorder affecting 5-10% of reproductive women around the world. PCOS can be considered a metabolic disease because it is often accompanied by obesity and diabetes. Brown adipose tissue (BAT) contains abundant mitochondria and adipokines and has been proven to be effective for treating various metabolic diseases. Recently, allotransplanted BAT successfully recovered the ovarian function of PCOS rat. However, BAT allotransplantation could not be applied to human PCOS; the most potent BAT is from infants, so voluntary donors are almost inaccessible. We recently reported that single BAT xenotransplantation significantly prolonged the fertility of aging mice and did not cause obvious immunorejection. However, PCOS individuals have distinct physiologies from aging mice; thus, it remains essential to study whether xenotransplanted rat BAT can be used for treating PCOS mice. In this study, rat-to-mouse BAT xenotransplantation, fortunately, did not cause severe rejection reaction, and significantly recovered ovarian functions, indicated by the recovery of fertility, oocyte quality, and the levels of multiple essential genes and kinases. Besides, the blood biochemical index, glucose resistance, and insulin resistance were improved. Moreover, transcriptome analysis showed that the recovered PCOS F0 mother following BAT xenotransplantation could also benefit the F1 generation. Finally, BAT xenotransplantation corrected characteristic gene expression abnormalities found in the ovaries of human PCOS patients. These findings suggest that BAT xenotransplantation could be a novel therapeutic strategy for treating PCOS patients.

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Cerebral Aspergillosis.

Purpose: Cerebral aspergillosis (CA) is a rare but often fatal, difficult-to-diagnose, opportunistic infection. The utility of metagenomic next-generation sequencing (mNGS) for diagnosis of CA is unclear. We evaluated the usefulness of mNGS of the cerebrospinal fluid (CSF) for the diagnosis of CA. Methods: This prospective study involved seven consecutive patients with confirmed CA in whom CSF mNGS was performed. Serum (1→3)-ß-D-glucan and galactomannan levels were determined, and histopathological examination and mNGS of the CSF were conducted. CSF specimens from three non-infected patients were used as positive controls. Results: mNGS of the CSF was positive in six of the seven confirmed CA cases (85.71% sensitivity). In the cryptococcal meningitis group (control), mNGS of the CSF was positive for Aspergillus in two patients (84.62% specificity). The positive likelihood ratio, negative likelihood ratio, and Youden's index of mNGS for CA in the CSF were 5.565, 0.169, and 0.7, respectively. Among the six mNGS-positive cases, more than two Aspergillus species were found in four (4/6, 66.67%). In the positive controls, the addition of one A. fumigatus spore yielded a standardised species-specific read number (SDSSRN) of 25.45 by mNGS; the detection rate would be 0.98 if SDSSRN was 2. Conclusion: mNGS facilitates the diagnosis of CA and may reduce the need for cerebral biopsy in patients with suspected CA. Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR1800020442.

MAFG-AS1 promotes tumor progression via regulation of the HuR/PTBP1 axis in bladder urothelial carcinoma.

Long noncoding RNAs (lncRNAs) play a crucial role in progression of bladder urothelial carcinoma (BUC). However, the molecular mechanisms behind this role have not been elucidated yet. Here, we found that the lncRNA MAFG-AS1, which is highly expressed in BUC, is correlated with aggressive characteristics and poor prognosis of BUC. We demonstrate that MAFG-AS1 can promote BUC proliferation, invasion, metastasis, and epithelial-mesenchymal transition in vitro and in vivo. Mechanistically, MAFG-AS1 direct binding to Hu antigen R (HuR) could recruit ubiquitin-specific proteinase 5 (USP5) to prevent HuR from degrading by ubiquitination. We further demonstrate that overexpression of MAFG-AS1 can upregulate the expression of polypyrimidine tract-binding protein 1 (PTBP1) through promoting its stability mediated by bound HuR. In conclusion, these findings indicate that MAFG-AS1 promotes the progression of BUC via regulation of the HUR/PTBP1 axis. Targeting MAFG-AS1 may provide a novel strategy for individualized therapy and a potential biomarker for prognosis of BUC.

LINC00968 can inhibit the progression of lung adenocarcinoma through the miR-21-5p/SMAD7 signal axis.

BACKGROUND: Long non-coding RNAs (LncRNAs) have been associated with several types of cancer. However, little is known about their role in lung adenocarcinoma (LUAD). RESULTS: LINC00968 was significantly differentially expressed in LUAD tissues. Downregulated LINC00968 was associated with clinicopathological features of LUAD. LINC00968 inhibited cell growth and metastasis by regulating the Hippo signaling pathway We demonstrated that LINC00968 acts as a ceRNA to consume miR-21-5p, enhancing the accumulation of SMAD7, a miR-21-5p target. CONCLUSIONS: LINC00968 limits LUAD progression via the miR-21-5p/SMAD7 axis and may serve as a prognostic biomarker and therapeutic target for LUAD. METHODS: We conducted comprehensive data mining on LINC00968 based on the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. The expression of LINC00968 in LUAD cells was determined using in situ hybridization. We detected LINC00968 function in LUAD cells using the MTT, clone formation, and transwell assays, and tumor xenografts. Label-free quantitative proteomics, western blotting, a dual-luciferase reporter assay, immunofluorescence, and RNA immunoprecipitation assays were used to determine the correlations among LINC00968, miR-21-5p, and SMAD7. Gain- and loss-function approaches were used to explore the effects of LINC00968, miR-21-5p, and SMAD7 on cell proliferation, migration, and invasion.

Downregulation of the ubiquitin ligase KBTBD8 prevented epithelial ovarian cancer progression.

OBJECTIVES: Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue. METHODS: We first examine KBTBD8 expression in EOC tissues and cells. Next, we performed RNA sequencing to reveal the overall mechanism. Then we investigated the roles of KBTBD8 in the proliferation, migration, and health status of cultured EOC cells. Finally, we employed tumor xenograft models to evaluate the role of KBTBD8 in vivo. RESULTS: First, KBTBD8 level was significantly higher in EOC tissues and cells. Next, comparative RNA sequencing identified more tumorigenesis-related genes that KBTBD8 might regulate. Then we found that KBTBD8 knockdown significantly decreased EOC cell proliferation, migration, and the activities of multiple tumorigenesis-related kinases. Finally, KBTBD8 knockdown significantly diminished ovarian tumor formation in vivo. CONCLUSION: Proper KBTBD8 level is essential for the healthy growth of ovarian somatic cells, such as ovarian epithelial cells. Excessive KBTBD8 might be a significant impetus for EOC progression. KBTBD8 reduction greatly inhibits EOC proliferation and migration.

SIRT1 Regulates N6 -Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2-Dependent FTO SUMOylation.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is associated with high malignancy rates. Recently, a known deacetylase silent information regulator 1 (SIRT1) was discovered in HCC, and its presence is positively correlated with malignancy and metastasis. N6 -methyladenosine (m6 A) is the most prominent modification, but the exact mechanisms on how SIRT1 regulates m6 A modification to induce hepatocarcinogenesis remain unclear. APPROACH AND RESULTS: Here we demonstrate that SIRT1 exerts an oncogenic role by down-regulating fat mass and obesity-associated protein (FTO), which is an m6 A demethylase. A crucial component of small ubiquitin-related modifiers (SUMOs) E3 ligase, RANBP2, is activated by SIRT1, and it is indispensable for FTO SUMOylation at Lysine (K)-216 site that promotes FTO degradation. Moreover, Guanine nucleotide-binding protein G (o) subunit alpha (GNAO1) is identified as m6 A downstream targets of FTO and tumor suppressor in HCC, and depletion of FTO by SIRT1 improves m6 A+ GNAO1 and down-regulates its mRNA expression. CONCLUSIONS: We demonstrate an important mechanism whereby SIRT1 destabilizes FTO, steering the m6 A+ of downstream molecules and subsequent mRNA expression in HCC tumorigenesis. Our findings uncover a target of SIRT1 for therapeutic agents to treat HCC.

Brain Atrophy Associated with Primary Diffuse Meningeal Melanomatosis.

BACKGROUND: Primary meningeal melanomatosis is a rare leptomeningeal tumor, and the diagnosis is challenging due to nonspecific clinical symptoms and radiologic findings. CASE DESCRIPTION: A 21-year-old man presented with recurrent seizure and impaired memory. Cranial magnetic resonance imaging showed obvious brain atrophy with bilateral extensive meningeal enhancement in the supratentorial region. Diffusion-weighted imaging and fluid-attenuated inversion recovery showed slightly hyperintensive signals in the cortex. Microscopic examination revealed invasion of pigment into the Virchow-Robin space and cortex. Immunohistochemical examination of biopsy samples showed that cells were immunopositive for HMB45 and S-100 and immunonegative for melan-A with a Ki-67-positive percentage of 3%. No obvious atypia or nuclear mitosis was observed. Pathohistologic results of biopsied meninges confirmed the diagnosis of diffuse meningeal melanomatosis. The disease was aggravated with the occurrence of brain atrophy, recurrent seizure, and declined higher cortical function. CONCLUSIONS: This case report illustrates that brain atrophy in meningeal melanomatosis is associated with a progressive decline of higher cortical function.

miR-26a-5p protects against myocardial ischemia/reperfusion injury by regulating the PTEN/PI3K/AKT signaling pathway.

Reperfusion strategies in acute myocardial infarction (AMI) can cause a series of additional clinical damage, defined as myocardial ischemia/reperfusion (I/R) injury, and thus there is a need for effective therapeutic methods to attenuate I/R injury. miR-26a-5p has been proven to be an essential regulator for biological processes in different cell types. Nevertheless, the role of miR-26a-5p in myocardial I/R injury has not yet been reported. We established an I/R injury model in vitro and in vivo. In vitro, we used cardiomyocytes to simulate I/R injury using hypoxia/reoxygenation (H/R) assay. In vivo, we used C57BL/6 mice to construct I/R injury model. The infarct area was examined by TTC staining. The level of miR-26a-5p and PTEN was determined by bioinformatics methods, qRT-PCR, and western blot. In addition, the viability and apoptosis of cardiomyocytes were separately detected by MTT and flow cytometry. The targeting relationship between miR-26a-5p and PTEN was analyzed by the TargetScan website and luciferase reporter assay. I/R and H/R treatment induced myocardial tissue injury and cardiomyocyte apoptosis, respectively. The results showed that miR-26a-5p was down-regulated in myocardial I/R injury. PTEN was found to be a direct target of miR-26a-5p. Furthermore, miR-26a-5p effectively improved viability and inhibited apoptosis in cardiomyocytes upon I/R injury by inhibiting PTEN expression to activate the PI3K/AKT signaling pathway. miR-26a-5p could protect cardiomyocytes against I/R injury by regulating the PTEN/PI3K/AKT pathway, which offers a potential approach for myocardial I/R injury treatment.

miR-26a-5p protects against myocardial ischemia/reperfusion injury by regulating the PTEN/PI3K/AKT signaling pathway

Reperfusion strategies in acute myocardial infarction (AMI) can cause a series of additional clinical damage, defined as myocardial ischemia/reperfusion (I/R) injury, and thus there is a need for effective therapeutic methods to attenuate I/R injury. miR-26a-5p has been proven to be an essential regulator for biological processes in different cell types. Nevertheless, the role of miR-26a-5p in myocardial I/R injury has not yet been reported. We established an I/R injury model in vitro and in vivo. In vitro, we used cardiomyocytes to simulate I/R injury using hypoxia/reoxygenation (H/R) assay. In vivo, we used C57BL/6 mice to construct I/R injury model. The infarct area was examined by TTC staining. The level of miR-26a-5p and PTEN was determined by bioinformatics methods, qRT-PCR, and western blot. In addition, the viability and apoptosis of cardiomyocytes were separately detected by MTT and flow cytometry. The targeting relationship between miR-26a-5p and PTEN was analyzed by the TargetScan website and luciferase reporter assay. I/R and H/R treatment induced myocardial tissue injury and cardiomyocyte apoptosis, respectively. The results showed that miR-26a-5p was down-regulated in myocardial I/R injury. PTEN was found to be a direct target of miR-26a-5p. Furthermore, miR-26a-5p effectively improved viability and inhibited apoptosis in cardiomyocytes upon I/R injury by inhibiting PTEN expression to activate the PI3K/AKT signaling pathway. miR-26a-5p could protect cardiomyocytes against I/R injury by regulating the PTEN/PI3K/AKT pathway, which offers a potential approach for myocardial I/R injury treatment.

Glutamate dehydrogenase inhibits tumor growth in gastric cancer through the Notch signaling pathway.

Glutamate dehydrogenase (GDH) is a key enzyme in glutaminolysis and can regulate allosteric functions. Immunohistochemical study found that GDH expressed in gastric cancer cell cytoplasm and membrane, and a few located in the nucleus, ranging from light yellow to tan to sepia. According to the analysis by Kaplan Meier survival curve and the Log-Rank test, the median survival of GDH high expression in patients was 51.7 months with 95% confidence intervals (CI) was 41.138-55.262. The expression level of GDH was significantly reduced after silencing GDH gene in gastric cancer cells and tissues. Further, after silencing GDH gene, gastric cancer cell migration and invasion ability were decreased significantly. Protein expression of. In addition, tumor growth was significantly reduced after silencing GDH gene. In vivo and in vitro experiments suggest that GDH can decrease gastric cancer cell migration and invasion, thus inhibiting tumor growth.

Enhanced antitumor effect of cytotoxic T lymphocytes induced by dendritic cells pulsed with colorectal cancer cell lysate expressing α-Gal epitopes.

Colorectal cancer (CRC) is one of the most common types of gastrointestinal malignancy. Traditional therapeutic options for CRC exhibit a limited effect. Adoptive cellular therapy has emerged as a new treatment strategy for CRC. Dendritic cells (DCs) are potent antigen-presenting cells. Specific cytotoxic T lymphocytes (CTLs) activated by DCs pulsed with tumor lysate have been reported to be a safe and promising treatment approach for CRC. However, the antitumor effect of specific CTLs remains limited. The low immunogenicity of tumor-associated antigens (TAAs) is the main reason for this limited therapeutic effect. In the present study, α-gal epitopes were synthesized on the CRC cell line SW620 to increase the immunogenicity of TAAs. DCs were pulsed with α-gal-expressing tumor lysate and CTLs were activated by these DCs. The cytotoxicity of CTLs was measured in vitro. The results demonstrated that DCs pulsed with α-gal-expressing tumor lysate can increase the frequency of CD3+CD8+ CTLs and natural killer T cells, increase the level of tumor necrosis factor-α produced by CTLs and enhance the cytotoxicity of CTLs against tumor cells. Therefore, this novel approach may be an effective treatment strategy for patients with CRC.

The MRVI1-AS1/ATF3 signaling loop sensitizes nasopharyngeal cancer cells to paclitaxel by regulating the Hippo-TAZ pathway.

Long non-coding RNA (lncRNA) plays an important role in malignant tumor occurrence, development, and chemoresistance, but the mechanism of how they affect nasopharyngeal cancer (NPC) paclitaxel chemosensitivity is unclear. In this study, lncRNA array of CNE-1 and HNE-2 paclitaxel-resistant cells and their parental strains revealed that the paclitaxel-resistant strains had significantly lower MRVI1-AS1 (murine retrovirus integration site 1 homolog antisense RNA 1) expression than the parental strains, and that MRVI1-AS1 overexpression in vitro and in vivo increased paclitaxel chemosensitivity. Further, MRVI1-AS1 upregulated ATF3 (activating transcription factor 3) by simultaneously inhibiting miR-513a-5p (microRNA-513a-5p) and miR-27b-3p expression levels to increase NPC paclitaxel chemosensitivity. Chromatin immunoprecipitation and quantitative real-time PCR showed that ATF3 could feed-back MRVI1-AS1 regulation positively. Furthermore, MRVI1-AS1 and ATF3 could form a positive feedback loop, which promoted the expression of RASSF1 (Ras association domain family member 1), a Hippo-TAZ (tafazzin) signaling pathway regulatory factor, thereby inhibiting TAZ expression. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide) assay and flow cytometry showed that the decreased TAZ increased NPC cell paclitaxel chemosensitivity. Overall, the results indicate that the MRVI1-AS1/ATF3 signaling pathway can increase NPC paclitaxel chemosensitivity by modulating the Hippo-TAZ signaling pathway. Therefore, targeting the loop may be a new NPC treatment strategy.

Apparent performance of metagenomic next-generation sequencing in the diagnosis of cryptococcal meningitis: a descriptive study.

INTRODUCTION: In recent years, metagenomic next-generation sequencing (mNGS) has become widely used in medical microbiology to detect pathogen infection. AIM: We aimed to assess the diagnostic performance of mNGS of cerebrospinal fluid (CSF) for prediction of cryptococcal meningitis (CM). METHODOLOGY: A comparative evaluation of mNGS (performed on CSF samples) and conventional methods, including India ink staining, culture for fungi and cryptococcal-antigen (CrAg) detection by enzyme immunoassay, was performed on 12 consecutive non-HIV-infected patients with chronic or subacute CM. RESULTS: India ink staining and culture of the CSF were positive for Cryptococcus in 83.33 % (10/12) of the samples; 100 % (11/11) were positive via CrAg EIA. The mNGS results of the CSF identified DNA sequences corresponding to Cryptococcus in 75 % of samples (9/12). However, the DNA of both C. neoformans s.l. and C. gattii s.l. was detected concurrently in 33.33 % (4/12). CONCLUSION: mNGS is helpful for identifying Cryptococcus species. The application of mNGS, together with India ink staining, culture methods, and CrAg, may significantly improve the diagnostic precision in CM, thereby informing choice of appropriate antifungal treatment courses.

Synthesis, characterization and antibacterial activity of Zn(II) coordination polymer.

In this study, the zinc(II)-based coordination polymer, [Zn(CPDA)(NO3)2)](CPDA = 1,2-cyclopentanedicarboxylic acid) (1), had been successfully synthesized according to the hydrothermal method. Afterwards, 1 had been characterized by means of single crystal and power X-ray diffraction, elemental analysis, thermogravimetric analysis and infrared spectrum techniques. In addition, the antibacterial activities in vitro had been evaluated towards Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively, through the growth inhibition and inhibition zone experimental methods. Our results indicated that 1 had displayed favorable antibacterial activity compared with the Zinc nitrate and the CPDA ligand. These findings had revealed that the antibacterial mechanism of 1 might be correlated with the production of reactive oxygen species (ROS) in cells.