Systematic analysis of IGF2BP family members in non-small-cell lung cancer.

BACKGROUND: The insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, and IGF2BP3) are known to be involved in tumorigenesis, metastasis, prognosis, and cancer immunity in various human cancers, including non-small cell lung cancer (NSCLC). However, the literature on NSCLC largely omits the specific context of lung squamous cell carcinoma (LUSC), an oversight we aim to address. METHODS: Our study evaluated the differential expression of IGF2BP family members in tumors and normal tissues. Meta-analyses were conducted to assess the prognostic value of IGF2BPs in lung adenocarcinoma (LUAD) and LUSC. Additionally, correlations between IGF2BPs and tumor immune cell infiltration, mutation characteristics, chemotherapy sensitivity, and tumor mutation burden (TMB) were investigated. GSEA was utilized to delineate biological processes and pathways associated with IGF2BPs. RESULTS: IGF2BP2 and IGF2BP3 expression were found to be upregulated in LUSC patients. IGF2BP2 mRNA levels were correlated with cancer immunity in both LUSC and LUAD patients. A higher frequency of gene mutations was observed in different IGF2BP1/2/3 expression groups in LUAD compared to LUSC. Meta-analyses revealed a significant negative correlation between overall survival (OS) and IGF2BP2/3 expression in LUAD patients but not in LUSC patients. GSEA indicated a positive association between VEGF and IGF2BP family genes in LUAD, while matrix metallopeptidase activity was inversely correlated with IGF2BP family genes in LUSC. Several chemotherapy drugs showed significantly lower IC50 values in high IGF2BP expression groups in both LUAD and LUSC. CONCLUSION: Our findings indicated that IGF2BPs play different roles in LUAD and LUSC. This divergence highlights the need for tailored therapeutic strategies and prognostic tools, cognizant of the unique molecular profiles of LUAD and LUSC.

Extracorporeal Versus Conventional Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest: A Propensity Score Matching Cohort Study.

OBJECTIVE: Comparing the effects of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) on outcomes in patients with in-hospital cardiac arrest (IHCA) in China. The benefits of ECPR over CCPR in patients with IHCA remain controversial. DESIGN: This article analyzed data from the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA) study, which consecutively enrolled patients with IHCA from July 1, 2019, to December 31, 2020. Patients who received ECPR were selected as the case group and matched with patients who received CCPR as the control group by propensity score at a ratio of 1:4. A parallel questionnaire survey of participating hospitals was conducted, to collect data on ECPR cases from January 1, 2021 to November 30, 2021. The primary outcome was survival to discharge or 30-day survival. SETTING: We included 39 hospitals across 31 provinces in China. PATIENTS: Patients receiving cardiopulmonary resuscitation and without contraindications to ECPR were selected from the BASIC-IHCA database. Patients older than 75 years, not witnessed, or with cardiopulmonary resuscitation duration less than 10 min were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 4853 patients met the inclusion criteria before matching, with 34 undergoing ECPR (median age, 56.5 yr; 67.65% male) and 4819 underwent CCPR (median age, 59 yr; 64.52% male). There were 132 patients receiving CCPR and 33 patients receiving ECPR who were eventually matched. The ECPR group had significantly higher survival rates at discharge or 30-day survival (21.21% vs. 7.58%, p = 0.048). The ECPR group had significantly lower mortality rates (hazard ratio 0.57; 95% CI, 0.38-0.91) than the CCPR group at discharge or 30 days. Besides the BASIC-IHCA study, the volume of ECPR implementations and the survival rate of patients with ECPR (29.4% vs. 10.4%. p = 0.004) in participating hospitals significantly improved. CONCLUSIONS: ECPR may be beneficial compared with CCPR for patient survival after IHCA and should be considered for eligible patients with IHCA.

Pangenome analysis and virulence profiling of Streptococcus intermedius.

BACKGROUND: Streptococcus intermedius, a member of the S. anginosus group, is a commensal bacterium present in the normal microbiota of human mucosal surfaces of the oral, gastrointestinal, and urogenital tracts. However, it has been associated with various infections such as liver and brain abscesses, bacteremia, osteo-articular infections, and endocarditis. Since 2005, high throughput genome sequencing methods enabled understanding the genetic landscape and diversity of bacteria as well as their pathogenic role. Here, in order to determine whether specific virulence genes could be related to specific clinical manifestations, we compared the genomes from 27 S. intermedius strains isolated from patients with various types of infections, including 13 that were sequenced in our institute and 14 available in GenBank. RESULTS: We estimated the theoretical pangenome size to be of 4,020 genes, including 1,355 core genes, 1,054 strain-specific genes and 1,611 accessory genes shared by 2 or more strains. The pangenome analysis demonstrated that the genomic diversity of S. intermedius represents an "open" pangenome model. We identified a core virulome of 70 genes and 78 unique virulence markers. The phylogenetic clusters based upon core-genome sequences and SNPs were independent from disease types and sample sources. However, using Principal Component analysis based on presence/ absence of virulence genes, we identified the sda histidine kinase, adhesion protein LAP and capsular polysaccharide biosynthesis protein cps4E as being associated to brain abscess or broncho-pulmonary infection. In contrast, liver and abdominal abscess were associated to presence of the fibronectin binding protein fbp54 and capsular polysaccharide biosynthesis protein cap8D and cpsB. CONCLUSIONS: Based on the virulence gene content of 27 S. intermedius strains causing various diseases, we identified putative disease-specific genetic profiles discriminating those causing brain abscess or broncho-pulmonary infection from those causing liver and abdominal abscess. These results provide an insight into S. intermedius pathogenesis and highlights putative targets in a diagnostic perspective.

Exploration of severe Covid-19 associated risk factor in China: Meta-analysis of current evidence.

AIM: This meta-analysis aimed to explore potential risk factors for severe Covid-19. METHODS: We systemically and comprehensively retrieved the eligible study evaluating clinical differences between severe vs non-severe Covid-19. Main effect sizes were demographic characteristics, comorbidities, signs and symptoms, laboratory findings as well as radiological features of chest CT. RESULTS: A total of 2566 Covid-19 people (771 in the severe group and 1795 in the non-severe group) from 14 studies were eligible for this meta-analysis. It was demonstrated that older age and males were more likely to have severe Covid-19. Patients with underlying comorbidities, such as hypertension, diabetes, heart disease and COPD were significantly more susceptible to severe Covid-19. Patients with dyspnoea were more likely to be severely ill. Depressed total lymphocytes were observed in this article. Meanwhile, although reticulation (30.8%), intrathoracic lymph node enlargement (20.5%) and pleural effusions (30.8%) were relatively infrequent, meta-analysis revealed that patients with these presentations in chest CT were associated with increased risk of severe Covid-19. CONCLUSIONS: There are significant differences in clinical characteristics between the severe and non-severe Covid-19 patients. Many factors are related to the severity of the disease, which can help clinicians to differentiate severe patients from non-severe patients.

Quality of life among patients after cystoprostatectomy as the treatment for locally advanced prostate cancer with bladder invasion.

PURPOSE: This study aimed to evaluate the changes of patients' quality of life (QoL) after cystoprostatectomy as a treatment for locally advanced prostate cancer (LAPC) with the bladder invasion and to determine risk factors for postoperative poor QoL. MATERIALS AND METHODS: Between Jan 2012 and December 2015, 27 patients who received cystoprostatectomy for LAPC with the bladder invasion were retrospectively included. QoL was assessed with the functional assessment of cancer therapy-prostate (FACT-P) questionnaire scores. Determinants for postoperative poor QoL were investigated using univariate and multivariate regression analysis. RESULTS: Three-year overall survival, biochemical progression-free survival, and clinical progress-free survival were 88.89%, 62.96% and 77.78%, respectively. Preoperative symptoms of hematuria, urinary frequency, and dysuria were well alleviated after cystoprostatectomy. Moreover, FACT-P questionnaire scores at 6 months and 1 year after cystoprostatectomy were significantly higher than preoperative scores. Univariate and multivariable analysis (p < .05) showed that postoperative complication was the independent risk factor for the loss of postoperative QoL. CONCLUSIONS: Patients' QoL can be improved after cystoprostatectomy as the treatment for LAPC with the bladder invasion, which is associated with ameliorative urinary symptoms after the surgery. Besides, surgical complication is identified to be a risk factor for postoperative poor QoL.

Pioglitazone decreased renal calcium oxalate crystal formation by suppressing M1 macrophage polarization via the PPAR-γ-miR-23 axis.

Interaction of pioglitazone (PGZ) and macrophages (Mps) in renal crystal formation remains unclear. In the present study, we investigated the possible mechanisms involved with Mps of PGZ in suppressing renal crystal formation. Crystal formation in the mouse kidney was detected using polarized light optical microscopy and Pizzolato staining. Gene expression was detected by Western blot analysis, quantitative RT-PCR, immunohistochemistry, immunofluorescence, and ELISA. Mp phenotypes were identified by flow cytometric analysis. Cell apoptosis was detected with TUNEL assay, and tubular injury was detected with periodic acid-Schiff staining. Interaction of peroxisome proliferator-activated receptor (PPAR)-γ and promoter was determined by chromatin immunoprecipitation assay. Luciferase reporter assay was performed to authenticate target genes of miRNA-23 (miR-23). Recombinant adenovirus was used to elucidate the role of miR-23 in vivo. Renal crystal formation, inflammation, tubular injury, and cell apoptosis were significantly marked in glyoxylic acid-treated groups and significantly decreased in PGZ-treated groups. PGZ significantly reduced Mp infiltration and M1 Mp polarization in the kidney. In vitro, PGZ shifted crystal-stimulated M1-predominant Mps to M2-predominant Mps, which were anti-inflammatory. PPAR-γ could directly bind to one PPAR-γ regulatory element in the promoter of pre-miR-23 to promote expression of miR-23 in Mps. We identified two downstream target genes of miR-23, interferon regulatory factor 1 and Pknox1. Moreover, miR-23 decreased crystal deposition, M1 Mp polarization, and injury in the kidney. This study has proven that PGZ decreased renal calcium oxalate crystal formation and renal inflammatory injury by suppressing M1 Mp polarization through a PPAR-γ-miR-23-interferon regulatory factor 1/Pknox1 axis. PGZ is liable to be a potential therapeutic medicine for treating urolithiasis.

Hydroxycitric Acid Tripotassium Inhibits Calcium Oxalate Crystal Formation in the Drosophila Melanogaster Model of Hyperoxaluria.

BACKGROUND Hydroxycitric acid is a potential lithontriptic agent for calcium oxalate (CaOx) stones in the kidneys. This study aimed to evaluate the safety and efficiency of hydroxycitric acid tripotassium (K-HCA) against CaOx crystal formation using Drosophila melanogaster hyperoxaluria models. MATERIAL AND METHODS Wild-type D. melanogaster were fed standard medium with ethylene glycol or sodium oxalate added to induce hyperoxaluria. Their Malpighian tubules were dissected and observed under a microscope every 3 days. Crystal deposit score of each Malpighian tubule were evaluated under a magnification of ×200. Using hyperoxaluria Drosophila models, we investigated the inhibitory efficiency of hydroxycitrate acid tripotassium and citric acid tripotassium (K-CA) against CaOx crystal formation. The survival rate of each group was also assessed. RESULTS When fed with 0.05% NaOx, the CaOx formation in Malpighian tubules increased significantly, without reduction of life span. Therefore, we selected 0.05% NaOx-induced hyperoxaluria models for the further investigations. After treatment, the stone scores showed that K-CA and K-HCA both significantly inhibit the formation of CaOx crystals in a dose-dependent manner, and with smaller dosage (0.01%), K-HCA was more efficient than K-CA. Moreover, after treatment of K-CA or K-HCA, the life span in different groups did not change, reflecting the safety to life. CONCLUSIONS The hyperoxaluria Drosophila models fed on 0.05% NaOx diet might be a useful tool to screen novel agents for the management of CaOx stones. K-HCA may be a promising agent for the prevention CaOx stones, with satisfying efficiency and acceptable safety.

Efficacy and safety of PDE5-Is and α-1 blockers for treating lower ureteric stones or LUTS: a meta-analysis of RCTs.

BACKGROUND: Lower ureteric stones and lower urinary tract symptoms are common in urology.Drug treatment is one of standard therapy,but the efficacy was controversial.Thus we aimed to investigate the efficacy and safety of monotherapy or combination therapy of adrenoceptor1 blockers and phosphodiesterase5 inhibitors for treatment. METHODS: Randomized controlled trials up to November 2016 were retrieved from PubMed, the Cochrane Library, Web of Science and Embase. A total of 17 studies were included. We analyzed data through random or fixed effect models. The heterogeneity between studies was assessed by the I2 test statistic. RESULTS: As for lower ureter stones, our analysis demonstrated tadalafil had a significantly lower incidence of abnormal ejaculation than adrenoceptor1 blockers (2.31 95%CI 0.22to0.84, P = 0.01),while combination therapy had a higher expulsion rate (2.49 95%CI 1.44to4.29, P = 0.001) and shorter expulsion time (- 1.98 95%CI -3.08to0.88, P = 0.0004) than tamsulosin. As for lower urinary tract symptoms, our analysis indicated adrenoceptor1 blockers was more effective than phosphodiesterase5 inhibitors on decreasing International Prostate Symptom Score (1.96 95%CI 0.03to3.89, P = 0.05) and Post-Void Residual (9.41 95%CI 1.40to14.41, P = 0.02) and phosphodiesterase5 inhibitors showed a greater effect than adrenoceptor1 blockers on improving Erectile Dysfunction (2.23 95%CI 1.24to3.22, P<0.0001).Combination therapy had a significantly better effect on International Prostate Symptom Score (1.47 95%CI 1.25to1.69, P<0.0001), Maximum flow rate (0.87 95%CI 0.71to1.04, P<0.0001), Post-Void Residual (10.74 95%CI 3.53to17.96,P = 0.004) and Quality of life (0.59 95%CI 0.22to0.97, P = 0.002) but was associated with higher incidences of adverse events (3.40 95%CI 1.82to6.36, P = 0.0001) than adrenoceptor1 blockers. Combination therapy had a significantly better effect on International Prostate Symptom Score (4.19 95%CI 3.34to5.04, P<0.0001), Maximum flow rate (1.86 95%CI 1.32to2.39, P<0.0001), Post-Void Residual (22.58 95%CI 9.13to36.04, P = 0.001) and Quality of life (0.68 95%CI 0.37to1.00, P<0.0001) without higher incidences of adverse events than PDE5-Is. CONCLUSIONS: In conclusion, this meta-analysis suggested combination therapy had a best efficacy of therapy for lower ureteric stones or lower urinary tract symptoms correlated with benign prostatic hyperplasia than monotherapy. Adrenoceptor1 blockers was more effective than phosphodiesterase5 inhibitors on International Prostate Symptom Score and Post-Void Residual. Both monotherapy and combination therapy were safe.

Botulinum Toxin to Improve the Prognosis of Skin Transplantation: A Short Narrative Review.

Skin transplantation is a traditional and well-established method of repairing skin loss, especially deep second-degree postburn wounds. Complications often happen amid the healing process, including necrosis and skin contracture, which has raised widespread concern from patients and doctors. Since the first recorded medical application of botulinum toxin for strabismus, accumulating evidence has enclosed all-round potential of botulinum toxin, more than aesthetic management. In recent decades, botulinum toxin also has been revealed to improve the prognosis of skin grafts. This literature review aims to briefly summarize the history and latest advances of its use for skin transplantation.

Catalytic NIR chemiluminescence sensor with enhanced persistence and intensity for in vivo imaging.

Chemiluminescence (CL) is a self-illumination phenomenon that involves the emission of light from chemical reactions, and it provides favorable spatial and temporal information on biological processes. However, it is still a great challenge to construct effective CL sensors that equip strong CL intensity, long emission wavelength, and persistent luminescence for deep tissue imaging. Here, we report a liposome encapsulated polymer dots (Pdots)-based system using catalytic CL substrates (L-012) as energy donor and fluorescent polymers and dyes (NIR 695) as energy acceptors for efficient Near-infrared (NIR) CL in vivo imaging. Thanks to the modulation of paired donor and acceptor distance and the slow diffusion of biomarker by liposome, the Pdots show a NIR emission wavelength (λ em, max = 720 nm), long CL duration (>24 h), and a high chemiluminescence resonance energy transfer efficiency (46.5 %). Furthermore, the liposome encapsulated Pdots possess excellent biocompatibility, sensitive response to H2O2, and persistent whole-body NIR CL imaging in the drug-induced inflammation and the peritoneal metastatic tumor mouse model. In a word, this NIR-II CL nanoplatform with long-lasting emission and high spatial-temporal resolution will be a concise strategy in deep tissue imaging and clinical diagnostics.

(+)-Borneol Protects Dopaminergic Neuronal Loss in Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson's Disease Mice: A Study of Dopamine Level using In Vivo Brain Microdialysis.

Considerable research efforts have been directed toward the symptom relief of Parkinson's disease (PD) by attenuating dopamine (DA) depletion. One common feature of these existing therapies is their unavailability of preventing the neurodegenerative process of dopaminergic neurons. (+)-Borneol, a natural highly lipid-soluble bicyclic monoterpene, has been reported to regulate the levels of monoamine neurotransmitters in the central nervous system and exhibit neuroprotective effects. However, the effect of (+)-borneol on the dopaminergic neuronal loss of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice is not defined. Herein, we first report that 30 mg/kg (+)-borneol significantly attenuated the motor deficits of PD mice, which benefits from markedly increasing the level of DA and decreasing the metabolic rate of DA in the striatum of conscious and freely moving mouse detected by ultraperformance liquid chromatography tandem mass spectrometry online combined with in vivo brain microdialysis sampling. It is worth noting that the enhanced level of DA by (+)-borneol was enabled by the reduction in loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons in the substantia nigra and striatum and promotion of reserpine- or nomifensine-induced DA release in PD mice. Interestingly, (+)-borneol evidently inhibited the decreased expression levels of DA transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) on the MPTP mouse model of PD. Moreover, (+)-borneol suppressed the neuroinflammation by inhibiting the production of IL-1ß, IL-6, and TNF-α and attenuated oxidative stress by decreasing the level of MDA and increasing the activities of SOD and GSH-px in PD mice. These findings demonstrate that (+)-borneol protects DA neurons by inhibiting neuroinflammation and oxidative stress. Further research work for the neuroprotection mechanism of (+)-borneol will focus on reactive oxygen species-mediated apoptosis. Therefore, (+)-borneol is a potential therapeutic candidate for retarding the neurodegenerative process of PD.

New gene signature from the dominant infiltration immune cell type in osteosarcoma predicts overall survival.

The immune microenvironment of osteosarcoma (OS) has been reported to play an important role in disease progression and prognosis. However, owing to tumor heterogeneity, it is not ideal to predict OS prognosis by examining only infiltrating immune cells. This work aimed to build a prognostic gene signature based on similarities in the immune microenvironments of OS patients. Public datasets were used to examine the correlated genes, and the most consistent dominant infiltrating immune cell type was identified. The LASSO Cox regression model was used to establish a multiple-gene risk prediction signature. A nine-gene prognostic signature was generated from the correlated genes for M0 macrophages and then proven to be effective and reliable in validation cohorts. Signature comparison indicated the priority of the signature. Multivariate Cox regression models indicated that the signature risk score is an independent prognostic factor for OS patients regardless of the Huvos grade in all datasets. In addition, the results of the association between the signature risk score and chemotherapy sensitivity also showed that there was no significant difference in the sensitivity of any drugs between the low- and high-risk groups. A GSEA of GO and KEGG pathways found that antigen processing- and presentation-related biological functions and olfactory transduction receptor signaling pathways have important roles in signature functioning. Our findings showed that M0 macrophages were the dominant infiltrating immune cell type in OS and that the new gene signature is a promising prognostic model for OS patients.

A novel cuproptosis-related lncRNA prognostic signature in thyroid cancer.

Aims: We aimed to investigate the value of cuproptosis-related lncRNA in screening out high-risk thyroid cancer patients. Materials & methods: RNA sequencing data of thyroid cancer were obtained from The Cancer Genome Atlas. A cuproptosis-related lncRNA signature was constructed by using Cox regression. Results: Four cuproptosis-related lncRNAs were used to construct a survival prognosis model for thyroid cancer. The receiver operating characteristic curve showed that the area under the curve reached 0.830 at 1 year, 0.790 at 3 years and 0.824 at 5 years. Conclusion: The model may help to screen out thyroid cancer patients at high risk, and thus develop more appropriate treatment strategies.

The incidence of thyroid cancer (TC) is increasing and in most patients the standard treatment is effective. However, a regional recurrence or distant metastasis is observed in some patients with aggressive TC. Hence, finding reliable biomarkers to predict patients at risk of recurrence or distant metastasis and formulating effective treatment strategies have important clinical significance. In this study, we proposed a novel prediction model for TC patients. The model may help to screen out TC patients at risk of local recurrence or distant metastasis, and thus develop more appropriate treatment strategies.

Effect of TRPC6 knockdown on puromycin aminonucleoside-induced podocyte injury.

This study was aimed to construct eukaryotic expression vectors carrying the small hairpin RNA (shRNA) targeting TRPC6 gene and investigate the effect of TRPC6 knockdown on puromucin aminonucleoside (PAN)-induced podocyte injury. Two DNA sequences containing the small hairpin structure targeting TRPC6 were designed, synthesized and then inserted into the green fluorescence protein (GFP)-contained plasmids (pGC) to establish the plasmids pGCsi-TRPC6A and pGCsi-TRPC6B. Plasmids expressing scrambled shRNA were used as negative control and named pGCsi-NC. These plasmids were transfected into a conditionally immortalized murine podocyte cell line by using liposome. Flow cytometry was used to examine the transfection efficiency. TRPC6 mRNA and protein expression levels were detected by RT-PCR and Western blotting. Cultured podocytes were divided into four groups: control group, PAN treatment group, PAN+TRPC6 shRNA transfected group and PAN+scrambled shRNA transfected group. The paracelluar permeability to BSA was evaluated by Millicell-PCF Inserts and cell viability was measured by the trypan blue assay. Immunofluorescent assay was used to observe the distribution of α-actinin-4 and α-tubulin. The results showed that the transfection efficiency of the shRNA expression vector was about 45%. Expression levels of TRPC6 mRNA and protein were downregulated after transfection with pGCsi-TRPC6A and pGCsi-TRPC6B. Knocking down TRPC6 gene could effectively reverse the PAN-induced increase in the paracelluar permeability to BSA. The distribution of α-actinin-4 and α-tubulin was disrupted after treatment with PAN, which was reversed by knocking down TRPC6 gene. It was concluded that knocking down TRPC6 gene could effectively prevent podocytes from the permeability increase induced by PAN, which may be related to the regulation of podocyte cytoskeleton.

MiR-483 Promotes Colorectal Cancer Cell Biological Progression by Directly Targeting NDRG2 through Regulation of the PI3K/AKT Signaling Pathway and Epithelial-to-Mesenchymal Transition.

BACKGROUND: Colorectal cancer is the third frequent tumor in the whole world. MiR-483, located at the 11p15.5 locus, acts as an oncogene in multiple tumors. The purpose of this study is to explore the important roles of miR-483 in colorectal cancer. MATERIALS AND METHODS: RT-qPCR and western blot were applied to calculate the mRNA levels of miR-483 and genes. The Kaplan-Meier method was conducted to calculate the survival of patients with colorectal cancer. The proliferation and invasive abilities were measured by Methyl Thiazolyl Tetrazolium (MTT) and transwell assays. RESULTS: MiR-483 was upregulated in colorectal cancer tissues, and the upregulation of miR-483 predicted poor prognosis of colorectal cancer patients. NDRG2 was a target gene of miR-483 in colorectal cancer. Furthermore, miR-483 has been reported to promote colorectal cancer cell proliferation and invasion through targeting NDRG2 by the PI3K/AKT pathway and epithelial-to-mesenchymal transition (EMT). In addition, the overexpression of miR-483 promoted xenograft growth of LOVO cells. CONCLUSION: MiR-483 promoted cell proliferation through the NDRG2/PI3K/AKT pathway and invasion-mediated EMT in colorectal cancer. In view of the multiple mechanisms of molecular immunotherapy, it is necessary to further study the relationship between miR-483 and colorectal cancer, so as to find a more direct and effective treatment method to prevent colorectal cancer.

Discovery and Validation of a SIT1-Related Prognostic Signature Associated with Immune Infiltration in Cutaneous Melanoma.

Signaling threshold regulating transmembrane adaptor 1 (SIT1) encodes a disulfide-linked homodimeric lymphocyte-specific glycoprotein involved in immune cell activation. However, the relationship between SIT1 and the prognosis of skin cutaneous melanoma (SKCM) and tumor-infiltrating lymphocytes remains elusive. Here, we first compared the differences in SIT1 expression levels between SKCM tissues and adjacent normal tissues. Next, we found that the immune cell infiltration levels and signature pattern of immune infiltration were positively associated with the SIT1 gene mRNA levels. TCGA_SKCM RNA-seq data unveiled that the SIT1 upregulated several immune-associated signaling pathways in GSEA analysis. The high expression of SIT1 was closely related to improved survival in patients with SKCM. A pathway enrichment analysis of SIT1-associated immunomodulators indicated the involvement of the NF-κB signaling pathways. Based on SIT1-associated immunomodulators, we built a 13-gene signature by LASSO Cox regression which served as an independent prognostic factor for the survival of melanoma patients. By using the signature risk score, we achieved a good prediction result for the immunotherapy response and survival of SKCM patients. Our findings provided evidence for SIT1's implication in tumor immunity and survival of SKCM patients. The nominated immune signature is a promising predictive model for prognosis and immunotherapy sensitivity in SKCM patients.

Role of CD2-associated protein in albumin overload-induced apoptosis in podocytes.

Proteinuria is a well-established exacerbating factor of chronic kidney diseases. However, the harmful effects of protein overload on podocytes and the underlying mechanisms are still poorly understood. In the present study, we examined the effects of high concentrations of albumin on podocytes and investigated the role of CD2AP (CD2-associated protein) in albumin overload-induced podocyte apoptosis. Conditionally immortalized mouse podocytes were cultured in vitro and treated with different concentrations of BSA. In addition, CD2AP eukaryotic expression vector or siRNA (small interfering RNA) was transfected into podocytes before they were exposed to BSA. Podocyte apoptosis, expressions of active caspase-3 (p17) and CD2AP, and the distribution of F-actin cytoskeleton were detected by flow cytometry, Western-blot analysis and fluorescent staining respectively. It was found that exposure of podocytes to BSA induced podocyte apoptosis in a concentration-dependent manner that was accompanied by up-regulation of active caspase-3, the disruption of F-actin cytoskeleton, and decreased expression of CD2AP. Transfection of CD2AP eukaryotic expression vector into podocytes increased CD2AP expression, partially restored F-actin distribution, blocked active caspase-3 expression and inhibited podocyte apoptosis. In contrast, transfection of CD2AP siRNA deteriorated the above changes induced by BSA. It is concluded that protein overload induces podocyte apoptosis via the down-regulation of CD2AP and subsequent disruption of cytoskeleton of podocytes, and CD2AP may play an important role in protein overload-induced podocyte injury.

Protective effects of eplerenone on podocyte injury in adriamycin nephropathy rats.

To investigate the protective effects of eplerenone on adriamycin-induced renal injury and the possible mechanisms involved, 36 male Sprague-Dawley rats were randomly divided into control group, adriamycin nephropathy (AN) group and eplerenone-treated group (100 mg·kg(-1)·d(-1) eplerenone). Blood pressure, 24-h urinary protein, serum potassium, sodium and creatinine were measured 28 days after adriamycin injection (a single tail intravenous injection of 6.5 mg/kg adriamycin). The morphological changes of renal tissues were observed by light and electron microscopy. Immunohistochemistry and Western blotting were performed to examine the expression of TGF-ß(1) and desmin in renal cortex. The results showed that 28 days after adriamycin injection, there were no significant changes in the level of serum potassium, sodium, creatinine concentrations and blood pressure values in the rats of the three groups. Meanwhile, the 24-h proteinuria excretion in the AN group was significantly higher than that in the control group (P<0.01), but that in the eplerenone-treated group was substantially reduced when compared with that in the AN group (P<0.05). Mild mesangial cell proliferation and matrix expansion, diffuse deformation and confluence of foot processes in podocytes were found in the AN group. By contrast, rats in the eplerenone-treated group exhibited obvious attenuation of these morphological lesions. The protein expression of TGF-ß(1) and desmin in the AN group was markedly up-regulated in contrast to that in the control group (P<0.01), whereas that in the eplerenone-treated group was much lower than in the AN group (P<0.05). It was concluded that eplerenone may ameliorate the proteinuria and the development of pathological alteration in adriamycin-induced nephropathy presumably via the inhibition of cytokine release, and restore the morphology of podocytes independent of its blood pressure-lowing effects.

Relationship between serum cystatin-c and coronary lesion severity in coronary artery disease patients with a normal glomerular filtration rate.

OBJECTIVE: Cardiovascular disease is a major cause of death. This study evaluated the relationship between serum cystatin-c and coronary lesion severity in coronary artery disease (CAD) patients with a normal glomerular filtration rate. METHODS: Nine hundred and fifty-nine patients were retrospectively included and divided into non-CAD and CAD groups according to coronary angiography results. CAD patients were classified into three groups by Gensini score tertiles. Multivariable logistic regression was used to study the relationship between serum cystatin-c and coronary lesion severity. RESULTS: Serum cystatin-c levels were significantly higher in CAD patients than in non-CAD patients. Correlation analysis revealed significant correlations between serum cystatin-c levels with the Gensini score and the number of diseased vessels. The area under the receiver operating characteristic curve of serum cystatin-c was 0.544 and 0.555 for predicting a high Gensini score and three-vessel disease, respectively. Multivariate stepwise regression analysis demonstrated that the serum cystatin-c level was an independent predictor of a high Gensini score [odds ratio (OR) = 2.177, 95% confidence interval (CI) 1.140-3.930] and three-vessel disease (OR = 1.845, 95% CI 0.994-3.424) after adjusting for the conventional CAD risk factors. CONCLUSIONS: Serum cystatin-c was elevated in CAD patients and may be an independent predictor of CAD severity.