CD276 enhances sunitinib resistance in clear cell renal cell carcinoma by promoting DNA damage repair and activation of FAK-MAPK signaling pathway.

OBJECTIVE: This study aimed to explore the effect of CD276 expression on the sunitinib sensitivity of clear cell renal cell carcinoma (ccRCC) cell and animal models and the potential mechanisms involved. METHODS: CD276 expression levels of ccRCC and normal samples were analyzed via online databases and real-time quantitative PCR (RT-qPCR). CD276 was knocked down in ccRCC cell models (sunitinib-resistant 786-O/R cells and sunitinib-sensitive 786-O cells) using shRNA transfection, and the cells were exposed to a sunitinib (2 µM) environment. Cells proliferation was then analyzed using MTT assay and colony formation experiment. Alkaline comet assay, immunofluorescent staining, and western blot experiments were conducted to assess the DNA damage repair ability of the cells. Western blot was also used to observe the activation of FAK-MAPK pathway within the cells. Finally, a nude mouse xenograft model was established and the nude mice were orally administered sunitinib (40 mg/kg/d) to evaluate the in vivo effects of CD276 knockdown on the therapeutic efficacy of sunitinib against ccRCC. RESULTS: CD276 was significantly upregulated in both ccRCC clinical tissue samples and cell models. In vitro experiments showed that knocking down CD276 reduced the survival rate, IC50 value, and colony-forming ability of ccRCC cells. Knocking down CD276 increased the comet tail moment (TM) values and γH2AX foci number, and reduced BRCA1 and RAD51 protein levels. Knocking down CD276 also decreased the levels of p-FAK, p-MEK, and p-ERK proteins. CONCLUSION: Knocking down CD276 effectively improved the sensitivity of ccRCC cell and animal models to sunitinib treatment.

Bioinformatic Analysis and Clinical Case Studies Identify CD276 as a Promising Diagnostic Biomarker for Clear Cell Renal Cell Carcinoma.

OBJECTIVE: This study aimed to explore the relationship between CD276 and clear cell renal carcinoma (ccRCC) and assess the diagnostic value of CD276 in ccRCC. METHODS: Expression levels of CD276 in ccRCC and para-cancer tissues were compared and analyzed retrospectively using data obtained from TCGA and GEO databases. The clinical data was analyzed prospectively. Immunohistochemistry and RT-PCR analyses were used to analyze the expression of CD276 at the mRNA and protein levels. These analyses compared the expression between ccRCC tissues and para-cancer tissues obtained from 70 patients with ccRCC. Next, ELISA was used to analyze peripheral blood samples from 70 patients with ccRCC and 72 healthy individuals, facilitating the differentiation of ccRCC patients from normal controls. Finally, we utilized the Kaplan-Meier method to generate ROC curves for assessing the diagnostic value of CD276 for ccRCC. RESULTS: Analysis of TCGA and GEO data revealed that the mRNA expression of CD276 was higher in ccRCC tissues than in para-cancer tissues (P < .05). Clinical validation using IHC and RT-PCR confirmed that the expression of CD276 was higher in ccRCC tissues than in para-cancer tissues, both at the mRNA and protein levels (P < .05). ELISA demonstrated that the expression of CD276 was higher in ccRCC patients than in normal individuals, and patients with a higher pathological grade showed higher expression of CD276 in the peripheral blood than those with a lower pathological grade (P < .05). ROC curves drawn from the above three datasets demonstrated that CD276 had a high diagnostic value for ccRCC (AUC = .894, .795, .938, respectively). CONCLUSION: The expression of CD276 was higher in ccRCC tissues and positively associated with the pathological grade. Therefore, CD276 may serve as a molecular biomarker for ccRCC prediction.

Pro-cancer role of CD276 as a novel biomarker for clear cell renal cell carcinoma.

OBJECTIVE: Renal cell carcinoma (RCC) is a common malignant tumor with a high incidence in males and the elderly, and clear cell RCC (ccRCC) is the most common RCC subtype. ccRCC is highly metastatic with a poor prognosis. Therefore, it is crucial to obtain a detailed understanding of the molecular mechanism of ccRCC and to identify suitable biomarkers to realize early diagnosis and improve prognosis. METHODS: We analyzed data from the Cancer Genome Atlas, investigated the overall differential expression of CD276 in ccRCC, and evaluated the influence of CD276 on patient survival and prognosis. We also performed gene set enrichment analysis (GSEA) and pathway enrichment analysis and investigated cell infiltration and drug responsiveness to further assess the regulatory effect of CD276 on ccRCC. Furthermore, we verified CD276 expression in RCC cell lines and control cell lines. RESULTS: The CD276 expression level in ccRCC samples was higher than that in corresponding samples adjacent to the tumors. Moreover, high CD276 expression levels were positively correlated with poor prognosis in patients with RCC. GSEA revealed that CD276 was significantly involved in immune-related pathways, and the level of CD276 expression was confirmed as associated with immune cell infiltration to some extent. Notably, some drugs were predicted to act on CD276, and this was confirmed by molecular docking. Furthermore, high levels of CD276 expression in RCC cell lines were verified. CONCLUSION: CD276 expression was significantly increased in ccRCC tissues and cells and positively correlated with patient prognosis. CD276 is a potential prognostic biomarker of ccRCC. Overall, this study provides a potential therapeutic strategy for ccRCC.

Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts.

BACKGROUND: Prostate cancer (PCa) is a widespread malignancy, predominantly affecting elderly males, and current methods for diagnosis and treatment of this disease continue to fall short. The marker Ki-67 (MKI67) has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells, including those of PCa. Hence, verifying the association between MKI67 and the diagnosis and prognosis of PCa, using bioinformatics databases and clinical data analysis, carries significant clinical implications. AIM: To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa. METHODS: For cohort 1, the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. For cohort 2, the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa. RESULTS: In cohort 1, MKI67 expression was correlated with prostate-specific antigen (PSA), Gleason Score, T stage, and N stage. The receiver operating characteristic (ROC) curve showed a strong diagnostic ability, and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval (PFI). The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa. In cohort 2, MKI67 expression was significantly related to the Gleason Score, T stage, and N stage; however, it was negatively associated with the PFI. The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa. Multivariate COX regression analysis was performed to select risk factors, including PSA level, N stage, and MKI67 expression. A nomogram was established to predict the 3-year PFI. CONCLUSION: MKI67 expression was positively associated with the Gleason Score, T stage, and N stage and showed a strong diagnostic and prognostic ability in PCa.

Cation-π interactions enabled water-stable perovskite X-ray flat mini-panel imager.

Sensitive and stable perovskite X-ray detectors are attractive in low-dosage medical examinations. The high sensitivity, tunable chemical compositions, electronic dimensions, and low-cost raw materials make perovskites promising next-generation semiconductors. However, their ionic nature brings serious concerns about their chemical and water stability, limiting their applications in well-established technologies like crystal polishing, micro-processing, photolithography, etc. Herein we report a one-dimensional tryptamine lead iodide perovskite, which is stable in water for several months as the strong cation-π interactions between organic cations. The one-dimensional and two-dimensional tryptamine lead iodide perovskite tablets are switchable through thermal-annealing or water-soaking treatments to relax microstrains. The water-stable and microstrain-free one-dimensional perovskite tablets yield a large sensitivity of 2.5 × 106 µC Gyair-1 cm-2 with the lowest detectable dose rate of 5 nGyair s-1. Microelectrode arrays are realized by surface photolithography to construct high-performance X-ray flat mini-panels with good X-ray imaging capability, and a record spatial resolution of 17.2 lp mm-1 is demonstrated.

Activation of assembly factor for spindle microtubules triggers progression of renal cell carcinoma via Wnt3a pathway.

Renal cell carcinoma, shorted as RCC is a well-known urological cancer with high level of morbidity and mortality. Although the regulatory role of the spindle microtubule assembly factor (ASPM) in tumor progression has been established, its relationship to the development of RCC remains unclear. To determine the significance of this gene in RCC, we examined its expression in RCC patients in the TCGA database and compared ASPM level between clinical samples of normal tissues and RCC tissues collected at our center. The prognostic relevance of ASPM was assessed by generating Kaplan-Meier survival curves and log-rank functions. Following alteration of ASPM expression using sh-ASPM or oe-ASPM transfection, RCC cell characteristics were evaluated through CCK-8, Transwell, and colony formation assays. Western blot analysis was conducted to measure levels of genes affected by ASPM, and rescue experiments were performed to explore the involvement of Wnt3a signaling in ASPM-mediated malignancy in RCC. Our findings indicate that ASPM is upregulated in RCC samples, and its levels are associated with the long-term survival of RCC patients. ASPM promotes the migration, proliferation, and invasiveness of RCC cells, and the Wnt3a pathway may be implicated in this process. In conclusion, these results indicate that ASPM contributes to the cancer progression of RCC by targeting the Wnt3a signaling pathway.

Exophytic benign prostatic hyperplasia presenting as a polycystic pelvic mass.

We report a case of an exophytic benign prostatic hyperplasia presenting as a polycystic pelvic mass. A 69-year-old man presented with an incidental finding of a pelvic mass of over 18 years. Digital rectal examination revealed a mass on the right anterior rectal wall 8 cm from the anal opening. His current prostate-specific antigen was 3.187 ng/mL. Enhanced computed tomography and magnetic resonance imaging demonstrated an occupancy in the right pelvis. A laparoscopic resection of the pelvic tumor was performed and pathologists identified it as an exophytic benign prostatic hyperplasia nodule. No significant recurrence was found at the 6-month follow-up.

KL is a favorable prognostic factor related immune for clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a prevalent cancer in adult urology, often leading to metastasis and poor prognosis. Recently, advances in tumor immunology and aging research have opened up new possibilities for the treatment of kidney cancer. Therefore, the identification of potential targets and prognostic biomarkers for immunotherapy has become increasingly urgent. METHODS: Using GSE168845 data, we identified immune-aging-associated differentially expressed genes (IAR-DEGs) by intersecting differentially expressed immune-related genes and aging-related genes. The prognostic value of IAR-DEGs was determined via univariate and multivariate Cox regression analysis, revealing KL as an independent prognostic factor for ccRCC. We also investigated the correlation between KL and various immune-related factors, including immune cell infiltration, immune score, immune checkpoint, MSI, and TIED score. To confirm the expression of KL in ccRCC, we conducted qRT-PCR assays on both ccRCC cell lines and clinical tissue samples, and compared KL expression levels between normal kidney cell line (HK-2) and ACHN, a ccRCC cell line. Finally, we assessed KL protein expression levels in tissues using immunohistochemistry (IHC). RESULTS: In this study, we utilized Venn diagram analysis to identify 17 co-expressed immune-aging related DEGs from GSE168845, import database, and MSigDB database. GO and KEGG analysis revealed that the functions of the 17 IAR-DEGs were primarily related to "aging". Univariate and multivariate Cox analysis validated these 17 genes, and KL was determined to be an independent prognostic factor for ccRCC. The downregulation of KL was observed in ccRCC tissues and was negatively associated with T stage, M stage, pathological stage, and histologic grade (p < 0.05). This downregulation indicated disease deterioration and a shortened overall survival period. Our calibration curves and nomogram demonstrated the excellent predictive potential of KL. GSEA analysis showed that KL gene mediated immune and aging-related pathways, and was significantly correlated with immune infiltration and MS and TIED score. More research has revealed a significant reduction in KL mRNA expression levels in human renal cancer cells, particularly in ccRCC tissues compared to adjacent normal kidney tissues. Moreover, immunohistochemistry data have demonstrated a marked decrease in KL protein expression levels in ccRCC cells when compared to adjacent normal tissues. CONCLUSIONS: KL was a potential aging-related target for immunotherapy and valid prognostic biomarker for ccRCC patients.

Assessing the Relationship Between Gut Microbiota and Posttransplant Diabetes Mellitus.

OBJECTIVES: The incidence of diabetes significantly increases after kidney transplant, and the associated gut microbiota are closely related to diabetes. However, the gut microbiota of recipients with diabetes after kidney transplant remain unexplored. MATERIALS AND METHODS: Feces samples from recipients with diabetes 3 months after kidney transplant were collected and analyzed using high-throughput 16S rRNA gene sequencing. RESULTS: Our study included 45 transplant recipients: 23 posttransplant diabetes mellitus recipients, 11 recipients without diabetes mellitus, and 11 recipients with preexisting diabetes mellitus. No significant differences in intestinal flora richness and α diversity were observed among the 3 groups. However, principal coordinate analysis based on UniFrac distance revealed significant differences in ß diversity. At the phyla level, the abundance of Proteobacteria in posttransplant diabetes mellitus recipients decreased (P = .028), whereas that of Bactericide (P = .004) increased. At the class level, the abundance of Gammaproteobacteria (P = .037) decreased, whereas thatofBacteroidia (P=.004)increased.Attheorderlevel, the abundanceof Enterobacteriales (P = .039)decreased, whereasBacteroidales (P=.004)increased.Atthe family level, the abundance of Enterobacteriaceae (P = .039) and Peptostreptococcaceae (P = .008) decreased, whereas Bacteroidaceae (P = .010) increased. At the genus level,the abundance of Lachnospiraceae incertae sedis (P = .008) decreased, whereas Bacteroides (P = .010) increased. Furthermore, KEGG analysis identified 33 pathways, among which the biosynthesis of unsaturated fatty acids was closely related to gut microbiota and posttransplant diabetes mellitus. CONCLUSIONS: To our knowledge, this is the first comprehensive analysis of the gut microbiota from posttransplant diabetes mellitus recipients. The microbial composition of stool samples of post- transplant diabetes mellitus recipients was significantly different from recipients without diabetes and with preexisting diabetes. The number of bacteria producing short-chain fatty acids decreased, whereas pathogenic bacteria increased.

Up-regulation of PRKDC was associated with poor renal dysfunction after renal transplantation: A multi-centre analysis.

Renal transplantation is the only efficacious treatment for end-stage kidney disease. However, some people have developed renal insufficiency after transplantation, the mechanisms of which have not been well clarified. Previous studies have focused on patient factors, while the effect of gene expression in the donor kidney on post-transplant renal function has been less studied. Donor kidney clinical data and mRNA expression status were extracted from the GEO database (GSE147451). Weight gene co-expression network analysis (WGCNA) and differential gene enrichment analysis were performed. For external validation, we collected data from 122 patients who accepted renal transplantation at several hospitals and measured the level of target genes by qPCR. This study included 192 patients from the GEO data set, and 13 co-expressed genes were confirmed by WGCNA and differential gene enrichment analysis. Then, the PPI network contained 17 edges as well as 12 nodes, and four central genes (PRKDC, RFC5, RFC3 and RBM14) were identified. We found by collecting data from 122 patients who underwent renal transplantation in several hospitals and by multivariate logistic regression that acute graft-versus-host disease postoperative infection, PRKDC [Hazard Ratio (HR) = 4.44; 95% CI = [1.60, 13.68]; p = 0.006] mRNA level correlated with the renal function after transplantation. The prediction model constructed had good predictive accuracy (C-index = 0.886). Elevated levels of donor kidney PRKDC are associated with renal dysfunction after transplantation. The prediction model of renal function status for post-transplant recipients based on PRKDC has good predictive accuracy and clinical application.

Identification of a New Prediction Model for Bladder Cancer Related to Immune Functions and Chemotherapy Using Gene Sets of Biological Processes.

Background: Biological processes serve crucial functions in the initiation and development of cancer. Therefore, we constructed and validated a model for bladder cancer (BLCA) with good predictive power for immunity, prognosis, and therapy. Methods: Using the expression of the gene sets based on biological processes, BLCA patients were divided into three clusters by consensus cluster analysis. By performing LASSO regression analysis twice, key genes were selected, and the biological processes-related genes' (BPRG) score was calculated. Differences in immune infiltration, tumor microenvironment, tumor mutation burden, immunotherapy, and sensitivity towards chemotherapy were analyzed between two groups divided by BPRG score. Results: Good accuracy was observed for the three clusters. They showed different prognoses and levels of immune cell infiltration. The selected key genes were mainly enriched in immune-related pathways. The high-BPRG score group was related to poor prognosis, higher immune cell infiltration, interstitial scores, and increased tumor mutation. Moreover, the effects of immunotherapy were good, and those of chemotherapy were poor. Conclusion: Overall, key genes may be involved in various complex immune regulation processes. Therefore, the quantification and verification of the BPRG score are expected to facilitate the understanding of the immunosuppressive microenvironment in BLCA and guide the choice of chemotherapeutic drugs and immunotherapeutic regimens and help predict the prognoses of patients with BLCA.

Compound synthesizing profiling based on quantitative HPLC fingerprints combined with antioxidant activity analysis for Zhizi Jinhua pills.

BACKGROUND: Compound drug Zhizi Jinhua Pills (ZZJHP) is composed of 8 herbal medicines (HMs), and it is necessary to control the HMs to ensure its holistic quality. PURPOSE: To establish a quality monitoring method for ZZJHP from precise control of multiple active ingredients to contour control of fingerprint, to calculate the contribution of HMs and predict the quality of compound drugs. METHODS: In this study, HPLC method was established for content determination of 11 analytes and fingerprint assessment. In vivo and in vitro studies of antioxidant activity were performed, Orthogonal Partial Least Squares analysis was applied for spectrum-effect correlation between antioxidant activity and HPLC fingerprint. The compound synthesizing fingerprint (CSF) of ZZJHP was fitted with 8 HMs, and the contribution of the single herb to prescription was evaluated by Sub-quantified profiling method. RESULTS: The content of 11 analytes and fingerprints of ZZJHP were measured simultaneously, 32 batches of samples were divided into 6 grades. In vivo and in vitro researches suggested significant antioxidant activity capacity of ZZJHP. Then, spectrum-effect relationship study showed that 24 of the 30 fingerprint peaks had antioxidant activity. By prescription and decomposition profiling, the qualitative and quantitative contributions of the 8 herbs were revealed in turn. The negative solution experiment proved that CSF could accurately predict the quality of composite drugs. CONCLUSION: The intelligent prediction strategy could intervene at the source to realize rapid screening of HMs and prediction of the quality of preparations, which could provide guidance for the use of HMs and improve the quality of composite drugs.

Circular RNA circCSPP1 promotes the occurrence and development of colon cancer by sponging miR-431 and regulating ROCK1 and ZEB1.

BACKGROUND: Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms. METHODS: Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1). RESULTS: It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level. CONCLUSION: Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.

Comprehensive evaluation of Loblolly fruit by high performance liquid chromatography four wavelength fusion fingerprint combined with gas chromatography fingerprinting and antioxidant activity analysis.

Loblolly fruit (LBF) is mainly used as raw material for beverage, but there are few researches on its quality evaluation or control. The aim of this study was to develop comprehensive evaluation methods for the quality control of Loblolly fruit. firstly, double wavelength coefficient ratio spectrum was used to identify the purity of chromatographic fingerprint peak. It is very important to identify the purity of fingerprint peaks because only the quantitative determination of pure chromatographic peaks is meaningful for its efficient quality control. Then, multi-wavelength fusion fingerprint was established to avoid one-sidedness of a single wavelength for further evaluation by systematically quantified fingerprint method (SQFM). According to the outcome of Pm, 25 batches of LBF were classified into two classifications by hierarchical cluster analysis, which was consistent with the SQFM evaluation results. Two active components, gallic acid (GAC) and ethyl gallate (EGA) in LBF, were quantitatively determined by quantitative analysis of multi-components by single marker (QAMS). In addition, the fingerprint efficacy relationship was established using an off-line antioxidant system and partial least-squares model to explore the connection between chemical components and antioxidant activities. Finally, the evaluation results of high-performance liquid chromatography and gas chromatography were integrated by the mean algorithm, which could reduce the error caused by single method. The results showed that the proposed strategy could provide a method for quality evaluation of LBF and even other traditional Chinese medicines (TCMs).

Efficacy of Bladder Intravesical Chemotherapy with Three Drugs for Preventing Non-Muscle-Invasive Bladder Cancer Recurrence.

Epirubicin, gemcitabine, and pirarubicin are widely used as first-line drugs for intravesical chemotherapy to prevent tumor recurrence after transurethral bladder tumor resection for non-muscle-invasive bladder cancer (NMIBC). However, which drug is better is less discussed. A total of 335 NMIBC patients administered intravesical chemotherapy underwent transurethral bladder tumor resection (TURBT) in our hospital from October 2015 to October 2019. After TURBT, all the patients received standard intravesical chemotherapy. Through clinical data collection and telephone follow-up, the tumor recurrence and adverse reactions of all patients after bladder perfusion treatment were counted. Recurrence was defined as new tumor appearance in the bladder. Of the 335 patients who underwent intravesical chemotherapy, 109 patients received epirubicin and 114 patients and 112 patients were given gemcitabine and pirarubicin, respectively. According to the general information of the patients, the patients were divided into intermediate-risk and high-risk bladder cancer and compared separately. There was no statistical difference in clinical and pathological features between different groups (P > 0.05). The recurrence rate of intermediate-risk bladder cancer patients shows no difference between three groups (P > 0.05). As for the high-risk bladder cancer patients, it is found that the 1-year recurrence rate between three groups was not statistically significant (P > 0.05), whereas the 2-year recurrence rate of patients given gemcitabine (9.87%) was significantly lower than that of epirubicin (25.37%) and pirarubicin (24.32%), and the difference was statistically significant (P < 0.017, Bonferroni adjusted P value). The Kaplan-Meier survival curves showed that the recurrence-free survival rate of patients received gemcitabine was significantly higher than that of the other two groups. Comparing the incidence of adverse reactions during the infusion of the three groups of patients, the differences were not statistically significant (P > 0.05). In patients with high-risk non-muscle-invasive bladder cancer, the application of gemcitabine intravesical chemotherapy is related with a relatively lower recurrence rate but similar incidence of adverse reactions.

MicroRNA miR-29a Inhibits Colon Cancer Progression by Downregulating B7-H3 Expression: Potential Molecular Targets for Colon Cancer Therapy.

MiR-29a belongs to one of the subtypes of miRNAs known as non-coding single-stranded RNAs and is preferentially expressed in normal tissues. B7-H3, a member of the B7/CD28 immunoglobulin superfamily, was shown to be overexpressed in several solid malignant tumors, including colon cancer. In addition, it is associated with tumor progression and poor prognosis. We used immunohistochemical and Western blotting to assess B7-H3 protein expression levels in colon cancer and adjacent normal tissues and then compared their relationships with clinicopathological factors. Quantitative real-time reverse-transcription PCR was used to assess B7-H3 and miRNA-29a mRNA expression levels, and then their relationship and clinical significance were evaluated. In addition, colon cancer Caco-2 cells, which constitutively overexpress B7-H3, were transfected with lentivirus particles for miR-29a upregulation. Invasion and migration assays were carried out in vitro along with the establishment of a subcutaneous xenograft model in vivo to determine the role of miRNA-29a in colon cancer progression. The B7-H3 protein showed elevated expression in colon carcinoma and was relevant to TNM staging, lymph node metastasis, and reduced survival. Meanwhile, miR-29a was preferentially expressed in normal colon tissues, while B7-H3 transcript levels had no marked differences between tumor and normal tissue specimens. In vitro, miR-29a upregulation resulted in reduced B7-H3 expression. Furthermore, miR-29a upregulation reduced the invasive and migratory abilities of colon carcinoma cells. In animal models, upregulation of miR-29a slowed down the growth of subcutaneous xenotransplanted tumors and resulted in prolonged survival time. MiR-29a downregulates B7-H3 expression and accordingly inhibits colon cancer progression, invasion, and migration, indicating miR-29a and B7-H3 might represent novel molecular targets for advanced immunotherapy in colon cancer.

Risk of osteoporosis in patients with erectile dysfunction: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Erectile dysfunction (ED) and osteoporosis are both common health problems and have similar risk factors. Recent studies have found that people with ED have a higher risk of osteoporosis.We aimed to systematically assess osteoporosis risk in patients with ED. METHODS: A systematically research was carried out in Medline via PubMed, Cochrane Library, EMBASE, and Web of Science up to June 4, 2020, to identify articles related to ED and osteoporosis. The 2 researchers independently reviewed the literature, extracted the data, and evaluated the quality of the literature. All analyses were done using RevMan5.3 and Stata14. RESULTS: A total of 4 studies involving 22,312 participants were included. The meta-analysis results showed that the risk of osteoporosis in the ED group was significantly higher than that in the non-ED group [odds ratio (OR) = 2.66, 95% confidence interval (95% CI) 1.42 to 4.98, P = .002, I2 = 68%]. Interestingly, compared with older participants, the increased risk of osteoporosis in ED patients seemed to be more pronounced in younger participants. Despite the lack of data for meta-analysis, more than half of the literature mentioned this tendency. We found the source of heterogeneity through sensitivity analysis, and there was no significant effect on the results before and after the removal of this literature, indicating that our results were robust. No obvious publication bias was found through Egger method (P = .672). CONCLUSION: People with ED have a higher risk of osteoporosis, especially among younger males. Because the assessment of osteoporosis is economical and noninvasive, ED patients should be evaluated by bone mineral density or men with osteoporosis should be further assessed for erectile function.

Serum folic acid levels and erectile dysfunction: A meta-analysis and systematic review.

The aim of this study was to assess the relationship between serum folic acid (FA) levels and erectile dysfunction (ED) through a meta-analysis. A research was conducted in MEDLINE via PubMed, Cochrane Library, EMBASE and Web of Science up to 22 November 2020 to identify studies related to FA and ED. Two authors independently screened the literature, evaluated methodological quality and extracted the data. We used RevMan5.3 and STATA 14.0 for meta-analysis. A total of six studies including 1,842 participants were included, and the results showed that the FA levels in the non-ED group were significantly higher than those in the ED group (MD = 3.37, 95% CI 1.49-5.52, p = 0.004). Subgroup analysis indicated that with the increase in ED severity, the difference in FA levels between groups was more obvious (MD: 1.99 vs. 4.63 vs. 5.63). The differences in FA levels between groups seem more significant in the younger group (MD = 4.87, 95% CI 2.58-6.89, p < 0.001) than in the older group (MD = 3.15, 95% CI 2.21-4.08, p < 0.001). In conclusion, FA deficiency is closely related to ED, and the degree of FA deficiency may reflect the severity of ED. In addition, the association seems to be more pronounced in the younger group.

IL-36ß promotes anti-tumor effects in CD8+ T cells by downregulating micro-RNA let-7c-5p.

BACKGROUND: The anti-tumor effect of interleukin (IL)-36ß-mediated activation of CD8+ T cells has been reported, but the molecular mechanism is largely undefined. METHODS: The levels of IL-36ß in pancreatic cancer were examined by quantitative real-time PCR (qRT-PCR) and immunohistochemical staining. Cytology and animal experiments were performed to study the effects of IL-36ß on the growth of pancreatic cancer cells. We then examined the changes of CD8+ T cells and natural killer (NK) cells in the tumor by flow cytometry. The microRNA expression profiles were determined by microarray analysis. RESULTS: The results revealed decreased levels of IL-36ß in pancreatic cancer tissues. In addition, IL-36ß inhibited tumor growth and promoted CD8+ T and NK cell proliferation in the tumor microenvironment (TME). Moreover, IL-36ß stimulated CD8+ T cells to synthesize high amounts of interferon-gamma (IFN-γ) and IL-2. Microarray analysis showed that IL-36ß administration to human and mouse CD8+ T cells consistently downregulated the miRNA, let-7c-5p. Downregulation of let-7c-5p resulted in IFN-γ and IL-2 upregulation in CD8+ T cells, whereas its upregulation had the opposite effect. Further experiments demonstrated that IL-36ß downregulated IFN-γ in let-7c-5p+ CD8+ T cells. CONCLUSIONS: These findings suggest IL-36ß promotes IFN-γ and IL-2 production in CD8+ T cells, as well as anti-tumor effects in CD8+ T cells by downregulating let-7c-5p.

A pan-cancer study of PD-1 and CTLA-4 as therapeutic targets.

BACKGROUND: Immunotherapy is a new and powerful weapon against tumors, represented by inhibitors of programmed death-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4). This study aimed to determine the similarities and differences between PD-1 and CTLA-4 in 33 cancers in The Cancer Genome Atlas (TCGA) and the impact of subtypes of the immune environment on tumor production and treatment. METHODS: From the Xena browser, we downloaded TNM stage, immune subtypes, and tumor microenvironment scores for 33 tumors from TCGA. Expression of CTLA-4 and PD-1 in normal and tumor samples were compared for various tumors with normal tissue sample sizes greater than five. The relationship between expression and overall survival was investigated using one-way Cox analysis. The immune scores of 33 tumors were assessed using ESTIMATE prediction software to predict the degree of immune cell infiltration across tumors and calculate the correlation between PD-1 and CTLA-4 expression with the tumor microenvironment and tumor stem cells. We also examined the correlation between genes and drug sensitivity. RESULTS: PD-1 and CTLA-4 were highly expressed in breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), esophageal carcinoma (ESCA), and kidney renal clear cell carcinoma (KIRC) (P<0.05), highly correlated with immune subtypes C2 (IFN-γ-dominant) and C6 (TGF-ß-dominant), and positively correlated with tumor microenvironmental immune scores (P<0.05). In renal clear cell carcinoma, PD-1 and CTLA-4 expression was positively correlated with clinical stage and microenvironmental score (r>0.7, P<0.05). CONCLUSIONS: The finding that PD1 and CTLA-4 are associated with the prognosis of most tumour patients and are closely related to the tumour microenvironment is of great value and provides a research direction for the screening of populations benefiting from immunotherapy.