Development of a prognostic nomogram for patients with malignant mesothelioma with bone metastasis.

Malignant mesothelioma (MM) is a rare aggressive tumor, and bone metastasis often occurs in later stages of this disease. This study aimed to establish a nomogram to predict the prognosis of bone metastasis of patients with MM. Data from the Surveillance, Epidemiology, and End Results database were screened and retrieved. This study included 311 patients with MM with bone metastases. Prognostic factors were analyzed using the Kaplan-Meier method and Cox proportional hazards model. A nomogram for overall survival (OS) was established and evaluated using statistically significant prognostic factors, and cancer-specific survival (CSS) analysis was performed to investigate its prognostic factors. In addition, the metastasis patterns of patients with MM were investigated, and the effects of different sites of metastasis on survival were compared using the Kaplan-Meier method. Age, sex, histological type, and chemotherapy were identified as the independent risk factors for OS. The 1-, 2-, and 3-year areas under the curve of the nomogram were 0.792, 0.774, and 0.928, and 0.742, 0.733, and 0.733 in the training and validation sets, respectively. Compared to OS, histological type, radiotherapy, and chemotherapy were independent risk factors for CSS. Different metastatic sites in MM have significantly different effects on prognosis.

Clinical value of lymphocyte count in autoimmune diabetic nephropathy. / æ·‹å·´ç»†èƒžè®¡æ•°åœ¨è‡ªèº«å ç–«æ€§ç³–å°¿ç— è‚¾ç— ä¸­çš„ä¸´åºŠä»·å€¼ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: In recent years, the prevalence of diabetic nephropathy (DN) has increased significantly. An increasing number of studies have shown that lymphocyte-associated inflammatory responses play a role in DN. This study aims to investigate the relationship between lymphocytes and DN in patients with autoimmune diabetes. METHODS: The clinical data of 226 patients with Type 1 diabetes (T1D) and 79 patients with latent autoimmune diabetes in adults (LADA) were retrospectively studied and stratified according to the urinary albumin to creatinine ratio (ACR). Risk factors associated with DN were analyzed using correlation analysis and logistic regression. RESULTS: In T1D and LADA patients, systolic blood pressure (SBP), uric acid duration, and diabetes duration in patients with normoalbuminuria were lower or shorter than those in patients with macroalbuminuria (P<0.05). The lymphocyte count of T1D patients was significantly higher than that in LADA patients (P<0.05), while the neutrophil to lymphocyte ratio (NLR) of T1D patients was significantly lower than that in LADA patients (P<0.05). The lymphocyte count in the T1D patients with normoalbuminuria was lower than that those with macroalbuminuria (P<0.05). The NLR was lower in the T1D patients with macroalbuminuria than those with microalbuminuria and normoproteinuria (all P<0.01). Based on logistic regression analysis, lymphocytes were independently associated with DN in T1D after adjusting for various known risk factors such as course of disease, age, gender, dyslipidemia, hypertension, and smoking status. Analysis of the receiver operating characteristic curve of subjects predicting lymphocytes in normoalbuminuria showed that the area under the curve was 0.601 (95% CI 0.510 to 0.693, P=0.039), and when the cutoff value of lymphocytes was 2.332, the sensitivity was 37.0%, and the specificity was 82.5%. CONCLUSIONS: Lymphocyte counts in autoimmune diabetic patients are closely associated with DN, suggesting that lymphocyte-mediated inflammation may be involved in the pathogenesis of DN in autoimmune diabetic patients. This study provides a possible perspective for using lymphocytes as a potential biomarker for the early identification of individuals at risk for DN and potential therapeutic targets for DN.

Preliminary Investigation of Iron Acquisition in Hypervirulent Klebsiella pneumoniae Mediated by Outer Membrane Vesicles.

OBJECTIVE: To investigate the role of outer membrane vesicles (OMVs) and related proteins in iron acquisition of hypervirulent Klebsiella pneumoniae (HVKP) and classic Klebsiella pneumoniae (cKP). METHODS: The OMVs of HVKP and cKP under iron-deficient and iron-sufficient media were extracted and purified by ultracentrifugation. Transmission electron microscopy (TEM) was used to identify OMVs. The quantitative proteomics were performed based on mass spectrometry. RESULTS: Four OMVs samples secreted by HVKP and cKP under iron-deficient and iron-sufficient environment were isolated and collected (HVKP OMVs under iron-deficient environment (A1), HVKP OMVs under iron-sufficient environment (A2), cKP OMVs under iron-deficient environment (B1), cKP OMVs under iron-sufficient environment (B2)). The amount of OMVs released by HVKP in iron-deficient medium was significantly larger than that in iron-sufficient medium (P < 0.05). HVKP secreted more OMVs than cKP in iron-deficient medium (P < 0.05). A total of 1074 kinds of proteins were identified in four samples. A comparison between the iron-deficient vs iron-sufficient environment showed that 61 proteins in HVKP OMVs were identified with a significant change in abundance under iron-deficient environment. Among them, 17 proteins were related to iron acquisition and transportation systems. While in cKP OMVs, 62 proteins significantly changed under iron-deficient environment in which 5 proteins were related to iron acquisition and transportation systems. Upon comparison of the HVKP vs cKP OMVs under iron deficiency, 81 proteins were detected with a significant change in which 8 proteins were related to iron acquisition and transportation systems. CONCLUSION: Above all, the results of this study suggest a potential role for OMVs in iron acquisition of HVKP and provide evidence of potential connections between OMVs and strong iron-acquisition ability of HVKP during iron limitation.

Correlations between Serum P2X7, Vitamin A, 25-hydroxy Vitamin D, and Mycoplasma Pneumoniae Pneumonia.

BACKGROUND: Identifying new molecular diagnostic markers for Mycoplasma Pneumoniae Pneumonia (MPP) has always been an essential topic since MPP cases have increased every year, especially among children. Here, we examined the correlation between serum level of Purinergic receptor P2X7, vitamin A, and 25-hydroxy vitamin D (25(OH)D) and the severity of MPP, aiming to identify molecules that have the potential to become diagnostic markers. METHODS: This study was conducted on 186 cases aged 1-14 (136 MPP and 50 non-MPP patients). Serum levels of Purinergic receptor P2X7, vitamin A, 25(OH)D, and multiple inflammatory and immune factors were measured, compared, and tested for statistical significance. RESULTS: Serum P2X7, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels were significantly increased in severe MPP patients, while serum vitamin A, 25(OH)D, IgA, and IgG levels were significantly decreased. CONCLUSION: Our results demonstrated a positive correlation between serum P2X7 level and the severity of MPP, and negative correlations between serum levels of vitamin A and 25(OH)D and the severity of MPP, suggesting that high serum levels of P2X7 and low serum levels of vitamin A and 25(OH)D may indicate relatively severer MPP.

Ångstrom-scale silver particle-embedded carbomer gel promotes wound healing by inhibiting bacterial colonization and inflammation.

Poor wound healing after diabetes or extensive burn remains a challenging problem. Recently, we presented a physical approach to fabricate ultrasmall silver particles from Ångstrom scale to nanoscale and determined the antitumor efficacy of Ångstrom-scale silver particles (AgÅPs) in the smallest size range. Here we used the medium-sized AgÅPs (65.9 ± 31.6 Å) to prepare carbomer gel incorporated with these larger AgÅPs (L-AgÅPs-gel) and demonstrated the potent broad-spectrum antibacterial activity of L-AgÅPs-gel without obvious toxicity on wound healing-related cells. Induction of reactive oxygen species contributed to L-AgÅPs-gel-induced bacterial death. Topical application of L-AgÅPs-gel to mouse skin triggered much stronger effects than the commercial silver nanoparticles (AgNPs)-gel to prevent bacterial colonization, reduce inflammation, and accelerate diabetic and burn wound healing. L-AgÅPs were distributed locally in skin without inducing systemic toxicities. This study suggests that L-AgÅPs-gel represents an effective and safe antibacterial and anti-inflammatory material for wound therapy.

Collagen-tussah silk fibroin hybrid scaffolds loaded with bone mesenchymal stem cells promote skin wound repair in rats.

This study demonstrates the efficacy of collagen/tussah silk fibroin (Col/TSF) hybrid scaffolds loaded with bone mesenchymal stem cells (BMSCs) in skin repair. Collagen (Col) and tussah silk fibroin (TSF) were extracted from bovine tendons and tussah cocoons, respectively. Col/TSF scaffolds were obtained using a freeze-drying method and were characterised using fourier transform infrared spectroscopy, scanning electron microscopy, porosity, water retention, thermal stability, and biocompatibility. The results revealed that addition of TSF to scaffolds could enhance their moisturising ability and cell infiltration. The antibacterial properties of Col/TSF scaffolds loaded with antibiotics were also excellent. BMSCs cultured in contact with developed Col/TSF scaffolds showed increased cell adhesion, viability, and differentiation. An in vivo study on rats showed that the Col/TSF scaffold seeded with BMSCs was more conducive to wound healing compared to the Col/TSF scaffold alone. The present study suggests that Col/TSF scaffold seeded with BMSCs could be a promising candidate for skin tissue engineering, due to its excellent skin affinity, good air and water permeability, and improved wound healing potential.

Differential expression profiles and functional analysis of plasma miRNAs associated with chronic myeloid leukemia phases.

AIM: This study was aimed to investigate the expression profiles and biological function of plasma miRNAs at different phases of chronic myeloid leukemia (CML). MATERIALS & METHODS: Differentially expressed miRNAs were identified by microarray. The candidate miRNAs were validated by quantitative real-time PCR at chronic phase, accelerated phase and blast crisis. The functional analysis of miRNAs was carried out by using DAVID. RESULTS: The putative targets of dysregulated miRNAs were involved in important signaling pathways. Plasma let-7b-5p and miR-451a expression was lower in CML patients, and plasma miR-451a gradually decreased from chronic phase to accelerated phase and blast crisis. CONCLUSION: Dysregulated plasma miRNAs maybe play regulatory roles in pathogenesis of CML. Let-7b-5p and miR-451a can be used as potential biomarkers for the diagnosis and prognosis of CML.

Clostridium difficile toxin B recombinant protein inhibits tumor growth and induces apoptosis through inhibiting Bcl-2 expression, triggering inflammatory responses and activating C-erbB-2 and Cox-2 expression in breast cancer mouse model.

Clostridium difficile toxin B (cdtB) is a critical virulence factor characterized with potential cytotoxicity and pro-inflammatory activity. This study aims to investigate anti-tumor effects of cdtB on breast cancer development. Clostridium difficile strain was cultured and cdtB recombinant protein (rcdtB) was synthesized. Breast cancer cell line, MDA-MB-231, was divided into Normal control, rcdtB 50, 100, 200 and 400 ng/ml group in vitro. Mice were divided into Normal control and rcdtB treatment group (400 ng/ml) in vivo. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to evaluate inhibitive effects of rcdtB on cell growth. Flow cytometry and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) were employed to examine apoptosis in vitro and in vivo, respectively. Cell cycle distribution was analyzed by utilizing commercial kit. B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were examined using western blot. Inflammatory response was detected using haematoxylin and eosin (HE). Erythroblastic leukemia viral oncogene homolog 2 (C-erbB-2) and cyclooxygenase-2 (Cox-2) were examined using immunohistochemical and immunofluorescence assay, respectively. The results indicated that rcdtB significantly induced MDA-MB-231 death, inhibited growth and decreased S-phase cells compared to Normal control group (P < 0.05). rcdtB significantly induced early and late apoptosis, and decreased Bcl-2 levels compared to Normal control group (P < 0.05). rcdtB significantly inhibited cell migration compared to Normal control group (P < 0.05). rcdtB significantly inhibited tumor growth and activated inflammation of breast cancer model compared to Normal control group (P < 0.01). rcdtB significantly reduced C-erbB-2 and Cox-2 in tumor tissues compared to Normal control group (P < 0.01). In conclusion, rcdtB treatment inhibited tumor growth and induced apoptosis through inhibiting Bcl-2 expression, inflammatory responses, and activating C-erbB-2 and Cox-2 expression in breast cancer mouse model.

Methylation of PRDM2, PRDM5 and PRDM16 genes in lung cancer cells.

AIMS: To investigate the changes of expression and methylation status of PRDM2, PRDM5, PRDM16 in lung cancer cells after treatment with demethylation agent. METHODS: A549 (lung adenocarcinoma cell line), HTB-182 (lung squamous cell carcinoma cell line) and HBE (normal bronchial cell line) were treated with 5-aza-2dC. The methylation state of PRDM2, PRDM5, PRDM16 was detected by MSP. The expression of PRDM2, PRDM5, PRDM16 was detected by RT-PCR and Western blot analysis. Cell growth was detected by MTT assay. RESULTS: 5-aza-2-dC reduced the methylation of PRDM2, PRDM5, PRDM16 gene in A549 and HTB-182 cells but not in HBE cells. Consistently, 5-aza-2dC increased mRNA and protein expression of PRDM2, PRDM5, PRDM16 in A549 and HTB-182 cells but not in HBE cells. Furthermore, 5-aza-2dC inhibited the growth of A549 and HTB-182 cells but not HBE cells. CONCLUSIONS: PRDM2, PRDM5, PRDM16 promoters are methylated and their expression is suppressed in lung cancer cells. Demethylation drug 5-aza-2dC could upregulate the expression of PRDM2, PRDM5, PRDM16 and suppress lung cancer cell growth. 5-aza-2dC has potential to be used for lung cancer therapy by epigenetic mechanism.

Promoter methylation-mediated downregulation of PRDM5 contributes to the development of lung squamous cell carcinoma.

PRDM5 has been proposed as a tumor suppressor frequently downregualted in tumor. In this study, lung squamous cell carcinoma tissues and adjacent nontumorous normal tissues were collected from 30 patients. PRDM5 expression was detected by reverse transcription polymerase chain reaction and Western blot analysis, DNA methylation of PRDM5 promoter was analyzed by methylation-specific PCR. SK-MES-1 cells or xenografts in nude mice were treated with 5-aza-2'-deoxycitydine, and cell proliferation and tumor growth in nude mice were examined. We found that PRDM5 promoter was methylated and PRDM5 expression at both mRNA and protein levels was reduced in lung squamous cell carcinoma tissues. Furthermore, PRDM5 promoter methylation was significantly correlated with tumor differentiation and lymph node metastasis of lung squamous cell carcinoma, but not with age, gender, smoking, or tumor grade. 5-aza-2'-deoxycitydine inhibited the proliferation of SK-MES-1 cells and the growth of xenografts in nude mice, accompanied by reduced methylation of PRDM5 promoter and increased expression of PRDM5. Taken together, our data suggest that PRDM5 is a tumor suppressor in lung cancer and is a promising target for the diagnosis, prognosis, and therapy of lung squamous cell carcinoma.

Lactobacillus acidophilus ATCC 4356 attenuates the atherosclerotic progression through modulation of oxidative stress and inflammatory process.

The aim of this study was to investigate the effect of Lactobacillus (L.) acidophilus ATCC 4356 on the progression of atherosclerosis in Apoliprotein-E knockout (ApoE(-/-)) mice and the underlying mechanisms. Eight week-old ApoE(-/-) mice were treated with L. acidophilus ATCC 4356 daily for 12 weeks. The wild type (WT) mice or ApoE(-/-) mice in the vehicle group were treated with saline only. Body weights, serum lipid levels, aortic atherosclerotic lesions, and tissue oxidative and inflammatory statuses were examined among the groups. As compared to ApoE(-/-) mice in the vehicle group, ApoE(-/-) mice treated with L. acidophilus ATCC 4356 had no changes in body weights and serum lipid profiles, but showed decreased atherosclerotic lesion size in en face aorta. In comparison with WT mice, ApoE(-/-) mice in the vehicle group showed higher levels of serum malondialdehyde (MDA), oxidized low density lipoprotein (oxLDL) and tumor necrosis factor-alpha (TNF-α), but lower levels of interleukin-10 (IL-10) and superoxide dismutase (SOD) activities in serum. Administration of L. acidophilus ATCC 4356 could reverse these trends in a dose-dependent manner in ApoE(-/-) mice. Furthermore, ApoE(-/-) mice treated with L. acidophilus ATCC 4356 showed an inhibition of translocation of NF-κB p65 from cytoplasm to nucleus, suppression of degradation of aortic IκB-α, and improvements of gut microbiota distribution, as compared to ApoE(-/-) mice in the vehicle group. Our findings suggest that administration of L. acidophilus ATCC 4356 can attenuate the development of atherosclerotic lesions in ApoE(-/-) mice through reducing oxidative stress and inflammatory response.

[Cytomegalovirus infection and immunosuppressant treatment in allogeneic hematopoietic stem cell transplantation recipients].

OBJECTIVE: To explore the correlation between peripheral blood cytomegalovirus (CMV) DNA level and cyclosporine A (CsA) plasma concentration among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients who received immunosuppressant treatment, and to evaluate the potential clinical value. METHODS: A total of 32 allo-HSCT patients were enrolled and their data were analyzed retrospectively. Ganciclovir was used to prevent CMV infection before the transplantation. Routine fluorescence PCR was admitted to test the blood CMV DNA level. The patients were divided into 2 groups: a CMV DNA positive group and a CMV DNA negative group. Enzyme multiplied immunoassay technique was adopted regularly to monitor the blood CsA concentration. The correlation between CMV DNA level and CsA concentration was analyzed. RESULTS: The CMV infection rate in patients who received allo-HSCT was 53.13%. The blood CsA concentration in the CMV DNA positive group was significantly higher than that in the CMV DNA negative group (P<0.05). Through the ROC curve, the area under the curve on Day 1, 7, and 14 had statistical significance compared with 0.5, and the corresponding blood CsA concentration was 203.15, 215.55, and 302.65 ng/mL, respectively. CONCLUSION: Immunosuppressive drug concentration can affect the dynamic changes of CMV DNA. High blood CsA concentration may be one of the reasons for CMV infection. Monitoring the blood CsA concentration may provide guidance for clinical treatment.