MAOB expression correlates with a favourable prognosis in prostate cancer, and its genetic variants are associated with the metastasis of the disease.

Monoamine oxidase B (MAOB), a neurotransmitter-degrading enzyme, was reported to reveal conflicting roles in various cancers. However, the functional role of MAOB and impacts of its genetic variants on prostate cancer (PCa) is unknown. Herein, we genotyped four loci of MAOB single-nucleotide polymorphisms (SNPs), including rs1799836 (A/G), rs3027452 (G/A), rs6651806 (A/C) and rs6324 (G/A) in 702 PCa Taiwanese patients. We discovered that PCa patients carrying the MAOB rs6324 A-allele exhibited an increased risk of having a high initial prostate-specific antigen (iPSA) level (>10 ng/mL). Additionally, patients with the rs3027452 A-allele had a higher risk of developing distal metastasis, particularly in the subpopulation with high iPSA levels. In a subpopulation without postoperative biochemical recurrence, patients carrying the rs1799836 G-allele had a higher risk of developing lymph node metastasis and recurrence compared to those carrying the A-allele. Furthermore, genotype screening in PCa cell lines revealed that cells carrying the rs1799836 G-allele expressed lower MAOB levels than those carrying the A-allele. Functionally, overexpression and knockdown of MAOB in PCa cells respectively suppressed and enhanced cell motility and proliferation. In clinical observations, correlations of lower MAOB expression levels with higher Gleason scores, advanced clinical T stages, tumour metastasis, and poorer prognosis in PCa patients were noted. Our findings suggest that MAOB may act as a suppressor of PCa progression, and the rs3027452 and rs1799836 genetic variants of MAOB are linked to PCa metastasis within the Taiwanese population.

Functional variants of the chitinase 3-like 1 gene are associated with clinicopathologic outcomes and progression of prostate cancer.

Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in advanced stages of several cancer types, including prostate cancer (PCa). Impacts of genetic variants of CHI3L1 on PCa development have not yet been investigated. The most common well-studied genetic variations are single-nucleotide polymorphisms (SNPs). Therefore, the objective of this study was to explore associations of CHI3L1 SNPs with both the susceptibility to PCa and its clinicopathological development. Three promoter SNPs, rs6691378 (-1371, G>A), rs10399805 (-247, G>A) and rs4950928 (-131, C>G), and one non-synonymous SNP, rs880633 (+2950, T>C), were analysed using a TaqMan allelic discrimination assay for genotyping in a cohort of 701 PCa patients and 701 healthy controls. Results indicated that there were no significant associations of PCa susceptibility with these four CHI3L1 SNPs. However, among elderly PCa patients (aged >65 years), it was observed that polymorphic variants (GA + AA) of CHI3L1 rs6691378 and 10399805 were significantly linked to reduced risks of several clinicopathological characteristics, including a high Gleason grade, advanced pathologic T stage and tumour cell invasion. Moreover, analyses of The Cancer Genome Atlas database revealed that CHI3L1 expression levels were elevated in PCa tissues compared with normal tissues. Interestingly, higher CHI3L1 expression levels were found to be associated with longer progression-free survival rates in PCa patients. Our findings indicated that levels of CHI3L1 may influence the progression of PCa, and the rs6691378 and 10399805 SNP genetic variants of CHI3L1 are linked to the clinicopathological development of PCa within a Taiwanese population.

Genetic variants of dipeptidyl peptidase IV are linked to the clinicopathologic development of prostate cancer.

CD26/dipeptidyl peptidase IV (DPP4) is a multifunctional cell-surface glycoprotein widely found in many cell types, and a soluble form is present in body fluids. There is longstanding evidence indicating a tumour-promoting or -suppressive role of DPP4 in different cancer types. However, studies focusing on the impacts of genetic variants of DPP4 on cancers are very rare. Herein, we conducted a case-control study to evaluate whether single-nucleotide polymorphisms (SNPs) of DPP4 were associated with the risk or clinicopathologic development of prostate cancer (PCa). We genotyped four loci of DPP4 SNPs, including rs7608798 (A/G), rs3788979 (C/T), rs2268889 (T/C) and rs6741949 (G/C), using a TaqMan allelic discrimination assay in 704 PCa patients and 704 healthy controls. Our results showed that PCa patients with the DPP4 rs7608798 AG+GG genotype or rs2268889 TC+CC genotype had a higher risk of developing an advanced clinical primary tumour (cT) stage (adjusted odds ratio (AOR): 1.680, 95% confidence interval (CI): 1.062-2.659, p = 0.025; AOR: 1.693, 95% CI: 1.092-2.624, p = 0.018). Additionally, in The Cancer Genome Atlas (TCGA) database, we observed that lower DPP4 expression levels were correlated with higher Gleason scores, advanced cT and pathological stages, tumour metastasis, and shorter progression-free survival rates in PCa patients. Furthermore, overexpression of DPP4 suppressed migration/invasion of metastatic PC3 PCa cells. Our findings suggest that DPP4 levels may affect the progression of PCa, and the DPP4 rs7608798 and rs2268889 SNPs are associated with the clinicopathologic development of PCa in a Taiwanese population.

Integration of Multivariate Statistical Control Chart and Machine Learning to Identify the Abnormal Process Parameters for Polylactide with Glass Fiber Composites in Injection Molding; Part I: The Processing Parameter Optimization for Multiple Qualities of Polylactide/Glass Fiber Composites in Injection Molding.

This paper discusses the mixing of polylactide (PLA) and glass fiber which use injection molding to produce a functional composite material with glass fiber properties. The injection molding process explores the influence of glass fiber ratio, melt temperature, injection speed, packing pressure, packing time and cooling time on the mechanical properties of composite. Using the orthogonal table planning experiment of the Taguchi method, the optimal parameter level combination of a single quality process is obtained through main effect analysis (MEA) and Analysis of variance (ANOVA). Then, the optimal parameter level combination of multiple qualities is obtained through principal component analysis (PCA) and data envelopment analysis (DEA), respectively. It is observed that if all the quality characteristics of tensile strength, hardness, impact strength and bending strength are considered at the same time, the optimal process conditions are glass fiber addition 20 wt %, melt temperature 185 °C, injection speed 80 mm/s, holding pressure 60 MPa, holding time 1 s and cooling time 15 s, and the corresponding mechanical properties are tensile strength 95.04 MPa, hardness 86.52 Shore D, impact strength 4.4408 J/cm2, bending strength 119.89 MPa. This study effectively enhances multiple qualities of PLA/GF composite.

Proteoglycan SPOCK1 as a Poor Prognostic Marker Promotes Malignant Progression of Clear Cell Renal Cell Carcinoma via Triggering the Snail/Slug-MMP-2 Axis-Mediated Epithelial-to-Mesenchymal Transition.

Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) has been reported to play an oncogenic role in certain cancer types; however, the role of SPOCK1 in the progression of clear cell renal cell carcinoma (ccRCC) remains elusive. Here, higher SPOCK1 transcript and protein levels were observed in ccRCC tissues compared to normal tissues and correlated with advanced clinical stages, larger tumor sizes, and lymph node and distal metastases. Knockdown and overexpression of SPOCK1 in ccRCC cells led to decreased and increased cell clonogenic and migratory/invasive abilities in vitro as well as lower and higher tumor growth and invasion in vivo, respectively. Mechanistically, the gene set enrichment analysis (GSEA) database was used to identify the gene set of epithelial-to-mesenchymal transition (EMT) pathways enriched in ccRCC samples with high SPOCK1 expression. Further mechanistic investigations revealed that SPOCK1 triggered the Snail/Slug-matrix metalloproteinase (MMP)-2 axis to promote EMT and cell motility. Clinical ccRCC samples revealed SPOCK1 to be an independent prognostic factor for overall survival (OS), and positive correlations of SPOCK1 with MMP-2 and mesenchymal-related gene expression levels were found. We observed that patients with SPOCK1high/MMP2high tumors had the shortest OS times compared to others. In conclusion, our findings reveal that SPOCK1 can serve as a useful biomarker for predicting ccRCC progression and prognosis, and as a promising target for treating ccRCC.

Synergistic Benefit of Adoptive T Cells in Combination With Chemoradiotherapy Against Metastatic Prostate Cancer Cells.

BACKGROUND/AIM: Prostate cancer (PC) is one of the major diseases that affects male health and ranks as the second most frequent cancer in men worldwide. Although most newly-diagnosed PCs are well-differentiated tumors with a high cure probability, there are some patients with aggressive malignancies that show potential for recurrence and metastasis. Cytotoxic T lymphocytes are a specific immune effector cell population that mediates immune responses against cancer. MATERIALS AND METHODS: In the present study, the cytotoxicity of peripheral blood mononuclear cells (PBMCs)-derived γδ T cells and cytokine-induced killer (CIK) cells in combination with chemoradiotherapy against PC cells was evaluated using Alamar blue cell viability and cell membrane permeability assays. RESULTS: Advanced PC-3 cells, which were more resistant to docetaxel (Doc), also showed higher viability following pretreatment with radiation. The cell proliferation inhibition was significantly increased upon additional γδ T or CIK treatment. Furthermore, the proportion of apoptotic cells was significantly (p<0.05) increased in the Doc-γδ T cell co-treatment group as compared with the Doc or γδ T cell treated alone group. CONCLUSION: γδ T cell therapy may provide additional benefit compared to traditional chemoradiotherapy for PC treatment.

Serum vitamin D levels in females with urinary incontinence: a meta-analysis of observational trials.

INTRODUCTION AND HYPOTHESIS: The association of vitamin D deficiency with female urinary incontinence is unclear. METHODS: A systematic review of English and non-English articles was conducted. All observational studies in databases including PubMed, EMBASE, the Cochrane Library Trials Register, and Google Scholar were searched until 5 October 2020. Additional studies were identified by contacting clinical experts and searching the bibliographies and abstracts of the compiled articles. Search terms included urinary incontinence and vitamin D. Article data, including study quality indicators, were independently extracted by two authors using predefined data fields. RESULTS: Two cohort studies, four case-control studies and five cross-sectional studies were included in the qualitative synthesis. Two cohort studies and one cross-sectional study, with a total of 2501 females, were included in the meta-analysis. Heterogeneity among the three studies was not observed (I2 = 0.0%, P = 0.69). All pooled analyses were based on fixed-effects models. No difference in vitamin D level was observed between the urinary incontinence group and the control group (mean difference 0.07 ng/ml; 95% confidence interval [CI] -0.57-0.72, P = 0.81, I2 = 0%). CONCLUSIONS: Our meta-analysis revealed that adult females with urinary incontinence did not have lower serum vitamin D levels than control females.

Effects of Concurrent Chemoradiotherapy on the Metastasis and the Mesenchymal Transition of Bladder Urothelial Carcinoma Cells.

BACKGROUND/AIM: Cancer stem cells (CSCs) have been suggested playing a crucial role in the tumorigenesis and tumor progression. Clinically, concurrent chemoradiotherapy (CCRT) after transurethral resection of the bladder is the widely accepted treatment option for high-grade bladder urothelial carcinoma (UC); however, a proportion of bladder UC patients still suffer from recurrence and metastasis. In the present study, we investigated the stemness properties of bladder UC cells with respect to various disease stages. The metastatic capability and epithelial-mesenchymal transition (EMT) of the parental cells and the CSC cells of bladder UC, after chemotherapy with cisplatin alone or CCRT were also studied, respectively. MATERIALS AND METHODS: The aldehyde dehydrogenase (ALDH)-positive cells were analyzed by a flow cytometer. The inhibitory effects of radiation in combination with cisplatin on the cell viability, migration, invasion and EMT characteristics were also examined. RESULTS: We found that the proportion of ALDH+-CSCs of bladder UC cells and the disease grading were independent. Furthermore, cisplatin alone significantly (p<0.05) enhanced the migration of both grade-III T24 cells and advanced-stage HT1197 cells, while CCRT treatment significantly (p<0.05) inhibited the T24 cell migration capability, compared to the cisplatin alone group. Interestingly, we found that the cell invasion capability was obviously increased upon the treatment with CCRT in both T24 and HT1197 CSCs. Furthermore, cisplatin played a promoting role in EMT whether in the presence or absence of irradiation. CONCLUSION: CSCs as well as EMT signaling might contribute to the resistance and metastasis of one-shot CCRT in malignant bladder cancer.

Malakoplakia and xanthogranulomatous pyelonephritis treated with nephrectomy: A case report.

RATIONALE: Malakoplakia and xanthogranulomatous pyelonephritis are chronic inflammatory conditions of the kidney characterized by the infiltration of inflammatory cells. PATIENT CONCERNS: An 82-year-old female patient had a history of hypertension, type 2 diabetes mellitus, dyslipidemia, and end-stage renal disease under hemodialysis. She was admitted repeatedly 4 times within 4 months due to urosepsis. DIAGNOSIS: The enlarged right kidney with a low-density lesion at the right middle calyx, and a well-enhanced ureter were noted on the computed tomography scan. Therefore, xanthogranulomatous inflammation was suspected. Semi-rigid ureteroscopy with biopsy was performed, and xanthogranulomatous inflammation of the ureter was confirmed on the pathology report. INTERVENTIONS: After right open radical nephrectomy was performed, the final pathology report revealed malakoplakia with xanthogranulomatous pyelonephritis. OUTCOMES: After the surgery, she has no longer suffered from urosepsis for 8 months, and there were no adverse event or recurrence noted. LESSONS: With this case report, we aim to emphasize that these 2 diseases are not mutually exclusive, but they may exist simultaneously in the same patient.

Inhibition of Bruton's Tyrosine Kinase Suppresses Cancer Stemness and Promotes Carboplatin-induced Cytotoxicity Against Bladder Cancer Cells.

BACKGROUND/AIM: Bruton's tyrosine kinase (BTK) has been discovered to serve a critical role in the survival and infiltration of B-cell lymphoma. Recently, it was reported that BTK inhibitors exerted potential beneficial effects against numerous types of solid tumor, including glioblastoma multiforme and breast cancer; however, whether BTK is crucial for the progression of bladder cancer (BLCA) remains unclear. The present study investigated the in vitro function of BTK in stemness properties of BLCA cells. Furthermore, the therapeutic effects of a standard chemotherapeutic drug, carboplatin in combination with the BTK inhibitor, ibrutinib were also investigated. MATERIALS AND METHODS: The association between BTK and BLCA progression was evaluated using free databases. The in vitro stemness and metastatic properties of BLCA cells were also investigated. Finally, the cytotoxicity of carboplatin in combination with ibrutinib was determined. RESULTS: The meta-survival analysis of the association between BTK and BLCA progression revealed that the expression levels of BTK were associated with a higher risk of BLCA progression. The CD133+-side population of BLCA cells formed spheroids when cultured in serum-free conditioned medium. In addition, expression levels of BTK and activated mTOR signaling in side population cells was up-regulated compared with the parental BLCA cells. Furthermore, the transfection of short hairpin RNA targeting BTK into BLCA cells markedly reduced cell migratory ability. More importantly, in advanced BLCA cells, which were more resistant to carboplatin, it was discovered that the cell viability was significantly reduced in the presence of ibrutinib (p<0.05). CONCLUSION: The findings of the present study suggested that BTK may have a critical role in the progression of BLCA; however, the underlying mechanisms and potential therapeutic strategies involved require further investigations.

Incidence of Bladder Cancer in Type 2 Diabetes Mellitus Patients: A Population-Based Cohort Study.

Background and objectives: Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide and is associated with increased incidence of kidney cancer and bladder cancer (BC). However, studies have produced conflicting results. Therefore, we retrospectively evaluated the incidence of BC in T2DM patients using the Taiwan National Health Insurance Research Database (NHIRD). Materials and Methods: We included 31,932 patients with a diagnosis of T2DM in the study group and 63,864 age- and sex-matched patients without T2DM at a ratio of 1:2 in the control group. The primary outcome was the diagnosis of BC. Cox proportional hazards regression was used to evaluate the incidence and adjusted hazard ratio (aHR) of BC in the multivariate model. Results: After a 16-year follow-up, we found that 67 BC cases occurred in the study group and 152 BC events in the non-T2DM group without a significantly higher risk (aHR: 0.842, 95% confidence interval: 0.627-1.13). Conclusions: T2DM patients do not have a higher risk of BC.

Gamma/Delta T-Cells Enhance Carboplatin-induced Cytotoxicity Towards Advanced Bladder Cancer Cells.

BACKGROUND/AIM: Bladder cancer (BLCA, urothelial bladder cancer) is one of the most common malignancies with increasing incidence and mortality worldwide. Poor diagnosis and the limitation of treatment is still an unmet need in clinical practice. γδ T-Cells have been paid increasing attention because of their potent cytotoxicity against tumors. Herein, we investigated the cytolytic effect of γδ T-cells in combination with the chemotherapeutic drug, carboplatin, against BLCA cells. MATERIALS AND METHODS: The standard protocol for the induction and expansion of peripheral blood mononuclear cell-derived γδ T-cells was a zoledronic acid/interleukin-2-based medium system for 2 weeks. The cytotoxicity of γδ T-cells with and without carboplatin against BLCA cells was examined. RESULTS: After incubation, T-cell receptor-positive γδ T-cells showed a natural killer cell-like phenotypic characteristic and dose-dependently increased cytotoxicity against BLCA cells. Interestingly, we found that in advanced BLCA cells, which were more resistant to carboplatin, the cell viability was significantly (p<0.05) reduced in the presence of γδ T-cells. CONCLUSION: Our findings showed that γδ T-cell therapy has potent benefit in cancer treatment.

Cytokine-induced Killer T Cells Enhance the Cytotoxicity Against Carboplatin-resistant Ovarian Cancer Cells.

BACKGROUND/AIM: Ovarian cancer (OC) is typically diagnosed at an advanced stage with limitations for cure. Cytokine-induced killer (CIK) T cell therapy exerts significant cytotoxic effects against cancer cells and reduces the adverse effects of chemotherapy. Herein, we performed a flow cytometry-based method to evaluate the cytotoxicity of peripheral blood mononuclear cells-derived CIK cells against OC cells. MATERIALS AND METHODS: The CIK cells were induced and expanded using an interferon-γ/IL-2-based xeno-free medium system. The cytotoxicity of CIK cells or carboplatin against OC cells was examined. RESULTS: The CIK cells showed an NK-like phenotypic characteristic and dose-dependently increased cytotoxicity against OC cells. We found that the number of advanced OC cells, which were more resistant to carboplatin, was dramatically decreased by an additional one-shot CIK treatment. CONCLUSION: CIK cells have a potent cytotoxic ability that would be explored as an alternative strategy for cancer treatment in the near future.

Isolation and Expansion of Cytotoxic Cytokine-induced Killer T Cells for Cancer Treatment.

Adoptive cellular immunotherapy focuses on restoring cancer recognition via the immune system and improves effective tumor cell killing. Cytokine-induced killer (CIK) T cell therapy has been reported to exert significant cytotoxic effects against cancer cells and to reduce the adverse effects of surgery, radiation, and chemotherapy in cancer treatments. CIK can be derived from peripheral blood mononuclear cells (PBMCs), bone marrow, and umbilical cord blood. CIK cells are a heterogeneous subpopulation of T cells with CD3+CD56+ and natural killer (NK) phenotypic characteristics that include major histocompatibility complex (MHC)-unrestricted antitumor activity. This study describes a qualified, clinically applicable, flow cytometry-based method for the quantification of the cytolytic capability of PBMC-derived CIK cells against hematological and solid cancer cells. In the cytolytic assay, CIK cells are co-incubated at different ratios with prestained target tumor cells. After the incubation period, the number of target cells are determined by a nucleic acid-binding stain to detect dead cells. This method is applicable to both research and diagnostic applications. CIK cells possess potent cytotoxicity that could be explored as an alternative strategy for cancer treatment upon its preclinical evaluation by a cytometer setup and tracking (CS & T)-based flow cytometry system.

Mesenchymal stem cells restore the sperm motility from testicular torsion-detorsion injury by regulation of glucose metabolism in sperm.

BACKGROUND: Testicular torsion is an urological emergency that may lead to infertility due to ischemic injury. Promptly surgical correction by orchiopexy is the only way to avoid infertility and no effective treatment for restoration of spermatogenesis. We previously reported that mesenchymal stem cells (MSCs), through local injection upon testicular torsion-detorsion, restored the spermatogenesis without differentiation into sperm. In this study, molecular mechanisms of MSCs in regulating germ cell activity induced by testicular torsion-detorsion were investigated. METHODS: Sixteen male Sprague-Dawley rats 6-8 weeks old received left testis 720° torsion for 3 h followed by detorsion with or without MSCs. Right inguinal skin incision without testicular torsion served as control. MSCs with 3 × 104 cells were locally injected into left testis 30 min before detorsion. Three days after the surgery, orchiectomy was executed and the testis, epididymis, and sperm were separated to each other. Functional assessments on sperm included counting sperm amount and sperm motility, staining F-actin, and quantifying adenosine triphosphate (ATP) content. The hallmarks of glycogenesis and glycolysis in each tissue segment were measured by Western blot. RESULTS: Testicular torsion-detorsion significantly decreased the amount of sperm, inhibited the motility, declined the F-actin expression, and reduced the content of ATP in sperm. Local injection of MSCs improved sperm function, particularly in sperm motility. With MSCs, ATP content and F-actin were preserved after testicular torsion-detorsion. MSCs significantly reversed the imbalance of glycolysis in sperm and testis induced by testicular torsion-detorsion, as evidenced by increasing the expression of phosphoglycerate kinase 2 and glyceraldehyde-3-phosphate dehydrogenase-spermatogenic, activating Akt, and increasing glycogen synthase kinase 3 (GSK3), which led to the increase in glycolysis cascades and ATP production. Human stem cell factor contributed the activation of Akt/GSK3 axis when sperm suffered from testicular torsion-detorsion-induced germ cell injury. CONCLUSIONS: Local injection of MSCs into a testis damaged by testicular torsion-detorsion restores sperm function mainly through the improvement of sperm motility and energy. MSCs reversed the imbalance of glycogenesis and glycolysis in sperm by regulating Akt/GSK3 axis. Thus, MSCs may potentially rescue torsion-detorsion-induced infertility via local injection.

Honokiol induces apoptotic cell death by oxidative burst and mitochondrial hyperpolarization of bladder cancer cells.

Bladder cancer is one of the most common types of malignant tumor worldwide. Current treatments, including chemo-/radiotherapy, only have limited efficacy on bladder cancer progression. Honokiol is an active component of Magnolia officinalis with multiple biological effects that may provide promising health benefits. In the present study, the anti-cancer properties of honokiol against bladder cancer cells were investigated by flow cytometric analysis. The results revealed that honokiol exhibited significant anti-proliferative effects on bladder cancer cell lines, particularly on BFTC-905 human transitional cell carcinoma cells. Furthermore, honokiol at low doses (≤25 µM) induced cell cycle arrest in G0/G1 phase, while it induced significant apoptotic cell death at high doses (≥50 µM; P<0.05). Furthermore, a significant accumulation of reactive oxygen species was identified in honokiol-treated cells. In addition, honokiol induced hyperpolarization of the mitochondrial membrane, which may lead to mitochondrial dysfunction. Finally, caspase-3/7 activation was identified in high-dose honokiol-treated bladder cancer cells. These results suggest that honokiol induces apoptosis via the mitochondrial pathway and honokiol-containing traditional herbal remedies may have a potential clinical application in the treatment of bladder cancer.

A Large Urinary Bladder Hemangioma Mimicking Urachal Cancer: A Case Report and Literature Review.

Urinary bladder hemangiomas are rare, especially in children and adolescents. We present a case of a 17-year-old young man with persistent gross hematuria for 1 month. Computed tomography revealed a 3.6 cm mass on the superior anterior wall of the urinary bladder, which was highly suspected as an urachal tumor. We carried out an en bloc resection of the urachus and bladder tumor. The pathologic report indicated a cavernous hemangioma of the urinary bladder. No tumor recurrence or bleeding was found during the 2-year follow-up. Urinary bladder hemangioma is an important differential diagnosis in young patients with hematuria.

Risk factors for complications and graft failure in kidney transplant patients with sepsis.

Immunosuppressive therapies decrease the incidence of acute kidney rejection after kidney transplantation, but also increase the risk of infections and sepsis. This study aimed to identify the risk factors associated with complications and/or graft failure in kidney transplant patients with sepsis. A total of 14,658 kidney transplant patients with sepsis, identified in the National Inpatient Sample (NIS) database (data from 2005-2014), were included in the study and classified into three groups: patients without complications or graft failure/dialysis (Group 1), patients with complications only (Group 2), and patients with complications and graft failure/dialysis (Group 3). Multinomial logistic regression analyses were conducted to evaluate factors associated with kidney transplant recipients. Multivariate analysis showed that, compared to Group 1, patients from Group 2 or Group 3 were more likely to be Black and to have cytomegalovirus infection, coagulopathy, and glomerulonephritis (p ≤ 0.041). Also, Group 2 was more likely to have herpes simplex virus infection, and Group 3 was more likely to have hepatitis C infection and peripheral vascular disorders, compared to Group 1 (p ≤ 0.002). In addition, patients in Group 3 were more likely to be Black and to have hepatitis C infection, peripheral vascular disorders, coagulopathy, and hypertension compared to Group 2 (p ≤ 0.039). Age and female gender were associated with lower odds of complications after kidney transplantation regardless of graft rejection/dialysis (p ≤ 0.049). Hyperlipidemia and diabetes decreased the chance of complications and graft failure/dialysis after kidney transplant (p < 0.001). In conclusion, the study highlights that black race, male gender, and specific comorbidities can increase the risk of complications and graft failure in kidney transplant patients with sepsis.

Local injection of mesenchymal stem cells protects testicular torsion-induced germ cell injury.

INTRODUCTION: Testicular torsion is a urological emergency and infertility is a common complication due to ischemic injury. Surgical reduction and orchiopexy is indicated, but to date there is no effective method for restoration of spermatogenesis. The effects of mesenchymal stem cells (MSCs) on acute tissue injury have been demonstrated, and the abilities of paracrine support, differentiation and immune-modulation may benefit to testicular torsion-induced infertility. We investigate the therapeutic efficacy and the mechanisms of MSCs in testicular torsion-induced germ cell injury when injected locally. METHODS: Six to eight-week-old Sprague-Dawley rats received surgical 720 degree torsion for 3 hours, followed by detorsion on the left testis. 20 µl of phosphate-buffered saline (PBS) without or with 3 x 10(4) MSCs from human orbital fat tissues (OFSCs) were given for 10 rats, respectively, via local injection into the left testis 30 minutes before detorsion. 20 µl of PBS injection for 6 rats with surgical exposure without torsion served as sham control. Histopathology with Johnsen's score analysis, Western blot analysis for superoxide dismutase 2, Bax, Caspase-3, human insulin growth factor-1 and human stem cell factor, malondialdehyde (MDA) assay in testis and plasma, hormones level including testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by ELISA Kits, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and fluorescence staining for P450, Sox-9 and VASA were performed. RESULTS: Animals were sacrificed and bilateral orchiectomy was performed 7 days after torsion-detorsion. Local injections of OFSCs prevented torsion-induced infertility judging from Johnsen's score. TUNEL assay and Western blot analysis on caspase 3 and Bax demonstrated that OFSCs prevented ischemic/reperfusion induced intrinsic apoptosis. MDA assay revealed that OFSCs significantly reduced the oxidative stress in the damaged testicular tissues. After the OFSC injection, serum testosterone secretion was increased, while the elevation of FSH triggered by testicular injury was balanced. OFSCs also produced stem cell factor in the damaged testis. Immunofluorescence staining revealed that most transplanted cells surrounded the Leydig cells. Some of transplanted cells differentiated into p450 expressing cells within 7 days. CONCLUSIONS: Local injection of allogenic MSCs before surgical detorsion is a simple, clinical friendly procedure to rescue torsion-induced infertility.

Regulation of metastatic ability and drug resistance in pulmonary adenocarcinoma by matrix rigidity via activating c-Met and EGFR.

Lung fibrosis is a poor prognostic factor for pulmonary adenocarcinoma, and the effect of a rigid microenvironment on cancer behavior is unclear. We cultured A549 cells on matrices of 0.2, 2, and 25 kPa to mimic the rigidities of normal lung parenchyma, progressive fibrotic change, and lung fibrosis, respectively. Lung tissue from patients with pulmonary adenocarcinoma was used to confirm the in vitro findings. Increased matrix rigidity promoted cell proliferation and upregulated the epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-Met), and Snail expression in A549 cells. A549 cells became more resistant to the EGFR inhibitor (Erlotinib) and c-Met inhibitor (PHA-665752) when matrix rigidity increased; however, a high concentration of PHA-665752 reversed the rigidity-induced morphological pleomorphism. In human lung tissue, expression of type I collagen was more consistent with clinical fibrosis than the expression of alpha-smooth muscle antibody was. c-Met- and Snail-expressing tumor cells, rather than EGFR-experssing cells, were localized with lung parenchyma rich in type I collagen. Our findings suggest that c-Met causes the rigidity-induced biophysical reaction in pulmonary adenocarcinoma. Treatment targeting both EGFR and c-Met should be considered for patients with lung fibrosis and who are abundant type I collagen expression in the tumor mass.