Regulatory role of exosome-derived miRNAs and other contents in adipogenesis.

Intramuscular fat (IMF) content significantly impacts meat quality. influenced by complex interactions between skeletal muscle cells and adipocytes. Adipogenesis plays a pivotal role in IMF formation. Exosomes, extracellular membranous nanovesicles, facilitate intercellular communication by transporting proteins, nucleic acids (DNA and RNA), and other biomolecules into target cells, thereby modulating cellular behaviors. Recent studies have linked exosome-derived microRNAs (miRNAs) and other cargo to adipogenic processes. Various cell types, including skeletal muscle cells, interact with adipocytes via exosome secretion and uptake. Exosomes entering adipocytes regulate adipogenesis by modulating key signaling pathways, thereby influencing the extent and distribution of IMF deposition. This review comprehensively explores the origin, formation, and mechanisms of exosome action, along with current research and their applications in adipogenesis. Emphasis is placed on exosome-mediated regulation of miRNAs, non-coding RNAs (ncRNAs), proteins, lipids, and other biomolecules during adipogenesis. Leveraging exosomal contents for genetic breeding and treating obesity-related disorders is discussed. Insights gathered contribute to advancing understanding and potential therapeutic applications of exosome-regulated adipogenesis mechanisms.

A Pioglitazone Nanoformulation Designed for Cancer-Associated Fibroblast Reprogramming and Cancer Treatment.

The recent focus of cancer therapeutics research revolves around modulating the immunosuppressive tumor microenvironment (TME) to enhance efficacy. The tumor stroma, primarily composed of cancer-associated fibroblasts (CAFs), poses significant obstacles to therapeutic penetration, influencing resistance and tumor progression. Reprogramming CAFs into an inactivated state has emerged as a promising strategy, necessitating innovative approaches. This study pioneers the design of a nanoformulation using pioglitazone, a Food and Drug Administration-approved anti-diabetic drug, to reprogram CAFs in the breast cancer TME. Glutathione (GSH)-responsive dendritic mesoporous organosilica nanoparticles loaded with pioglitazone (DMON-P) are designed for the delivery of cargo to the GSH-rich cytosol of CAFs. DMON-P facilitates pioglitazone-mediated CAF reprogramming, enhancing the penetration of doxorubicin (Dox), a therapeutic drug. Treatment with DMON-P results in the downregulation of CAF biomarkers and inhibits tumor growth through the effective delivery of Dox. This innovative approach holds promise as an alternative strategy for enhancing therapeutic outcomes in CAF-abundant tumors, particularly in breast cancer.

Design, selective synthesis and biological activities evaluation of novel thiazol-2-ylbenzamide and thiazole-2-ylbenzimidoyl chloride derivatives.

To promote the development and exploitation of novel antifungal agents, a series of thiazol-2-ylbenzamide derivatives (3A-3V) and thiazole-2-ylbenzimidoyl chloride derivatives (4A-4V) were designed and selective synthesis. The bioassay results showed that most of the target compounds exhibited excellent in vitro antifungal activities against five plant pathogenic fungi (Valsa mali, Sclerotinia scleotiorum, Botrytis cinerea, Rhizoctonia solani and Trichoderma viride). The antifungal effects of compounds 3B (EC50 = 0.72 mg/L) and 4B (EC50 = 0.65 mg/L) against S. scleotiorum were comparable to succinate dehydrogenase inhibitors (SDHIs) thifluzamide (EC50 = 1.08 mg/L) and boscalid (EC50 = 0.78 mg/L). Especially, compounds 3B (EC50 = 0.87 mg/L) and 4B (EC50 = 1.08 mg/L) showed higher activity against R. solani than boscalid (EC50 = 2.25 mg/L). In vivo experiments in rice leaves revealed that compounds 3B (86.8 %) and 4B (85.3 %) exhibited excellent protective activities against R. solani comparable to thifluzamide (88.5 %). Scanning electron microscopy (SEM) results exhibited that compounds 3B and 4B dramatically disrupted the typical structure and morphology of R. solani mycelium. Molecular docking demonstrated that compounds 3B and 4B had significant interactions with succinate dehydrogenase (SDH). Meanwhile, SDH inhibition assay results further proved their potential as SDHIs. In addition, acute oral toxicity tests on A. mellifera L. showed only low toxicity for compounds 3B and 4B to A. mellifera L. populations. These results suggested that these two series of compounds had merit for further investigation as potential low-risk agricultural SDHI fungicides.

Construction of Dual-Channel Water Transport in Mesoporous Silica Low Humidity Sensors to Achieve High Sensitivity.

In this paper, strong hydrophilic poly(ionic liquid)s (PILs) are selectively grafted on different positions (mesoporous channels and outer surface) of mesoporous silica via thiol-ene click chemical reaction. The purposes of selective grafting are on the one hand, to explore the differences of adsorption and transportation of water molecules in mesoporous channels and on the outer surface, and on the other hand, to combine the two approaches (intra-pore grafting and external surface grafting) to reasonably design SiO2 @PILs low humidity sensing film with synergetic function to achieve high sensitivity. The results of low relativehumidity （RH） sensing test show that the sensing performance of humidity sensor based on mesoporous silica grafted with PILs in the channels is better than that of humidity sensor based on mesoporous silica grafted with PILs on the outer surface. Compared with water molecules transport single channel, the construction of dual-channel water transport significantly improves the sensitivity of the low humidity sensor, and the response of the sensor is up to 4112% in the range of 7-33% RH. Moreover, the existence of micropores and the formation of dual-channel water transport affect the adsorption/desorption behaviors of the sensor under different humidity ranges, especially below 11% RH.

Research progress of intramuscular fat formation based on co-culture.

Intramuscular fat (IMF) is closely related to the meat quality of livestock and poultry. As a new cell culture technique in vitro, cell co-culture has been gradually applied to the related research of IMF formation because it can simulate the changes of microenvironment in vivo during the process of IMF cell formation. In the co-culture model, in addition to studying the effects of skeletal muscle cells on the proliferation and differentiation of IMF, we can also consider the role of many secretion factors in the formation of IMF, thus making the cell research in vitro closer to the real level in vivo. This paper reviewed the generation and origin of IMF, summarized the existing co-culture methods and systems, and discussed the advantages and disadvantages of each method as well as the challenges faced in the establishment of the system, with emphasis on the current status of research on the formation of IMF for human and animal based on co-culture technology.

Putrescine (1,4-Diaminobutane) enhances antifungal activity in postharvest mango fruit against Colletotrichum gloeosporioides through direct fungicidal and induced resistance mechanisms.

Anthracnose decay caused by Colletotrichum gloeosporioides greatly shortens the shelf life and commercial quality of mango fruit. Putrescine (1,4-Diaminobutane) is involved in modulating plant defense to various environmental stresses. In this research, in vivo and in vitro tests were used to explore the antifungal activity and the underlying mechanism of putrescine against C. gloeosporioides in mango fruit after harvested. In vivo tests suggested that putrescine markedly delayed the occurrence of disease and limited the spots expansion on inoculated mango fruit. Further analysis exhibited that putrescine treatment enhanced disease resistance, along with enhanced activities of chitinase (CHI), ß-1,3-glucanase (GLU), phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-coumarate coenzyme A ligase (4CL), polyphenol oxidase (PPO) and the accumulation of lignin, flavonoid, phenolics, and anthocyanin in infected mango fruit. In addition, in vitro tests showed that putrescine exerted strongly antifungal activity against C. gloeosporioides. Putrescine induced the production of reactive oxygen species (ROS) and severe lipid peroxidation damage in C. gloeosporioides mycelia, resulting in the leakage of soluble protein, soluble sugar, nucleic acids, K+ and Ca2+ of C. gloeosporioides mycelia. The mycelium treated with putrescine showed severe deformity and shrinkage, and even cracking. Taken together, putrescine could effectively reduce the incidence rate and severity of anthracnose disease possibly through direct fungicidal effect and indirect induced resistance mechanism, thus showing great potential to be applied to disease control.

Association of PFKM gene polymorphisms and susceptibility to cryptorchidism in a Chinese Han population.

BACKGROUND: Cryptorchidism is one of the most common congenital anomalies in newborn boys. There are various risk factors that have been verified to have relationship with cryptorchidism, including exogenous and genetic, but the pathogenesis of cryptorchidism remains unclear. PFKM gene is a critical gene encodes for a regulatory enzyme, which limits the rate in the pathway of glycolysis. We assumed that cryptorchidism risk may associated with PFKM gene single-nucleotide polymorphisms (SNPs). Thus we selected three tag SNPs in the PFKM gene and aimed to investigate the possible association between PFKM gene polymorphisms and cryptorchidism risk. METHODS: The SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. 140 cases and 227 controls were enrolled in this study, including 105 unilateral cryptorchidism and 35 bilateral cases. The testis position was decided by the higher one in bilateral cases. RESULTS: The frequency of allele G of SNP rs2228500 is increased in cryptorchidism patients compared to that in controls (p < 0.05). Genotypic frequencies of rs2228500 are associated with the susceptibility of cryptorchidism in the codominant model (p < 0.05). And compared with G/G genotype in the dominant model, notable decreased frequencies of A carriers (A/G-A/A genotypes) were observed in cryptorchidism patients (p = 0.0069, OR = 1.80, 95% CI 1.17-2.75). CONCLUSIONS: This research first revealed that PFKM gene polymorphisms were associated with cryptorchidism in a Chinese Han population. We have offered primary evidence that the G allele and the G/G genotype of rs2228500 SNP in the PFKM gene are more frequent in patients with cryptorchidism than healthy controls.

[Association Between TAB2 Gene Polymorphisms and Susceptibility to Cryptorchidism in Han Chinese Population in Southwest China].

Objective: To conduct preliminary investigation into the correlation between transforming growth factor beta-activated protein kinase 1-binding protein 2 ( TAB2) gene and the incidence of cryptorchidism in Han Chinese population in Southwest China. Methods: A total of 259 patients with cryptorchidism and 355 healthy controls from Southwest China were enrolled for the study. Polymerase chain reaction-restriction fragment length polymorphism method was used to analyze the genotype of the 3 tag single nucleotide polymorphisms (SNPs) of TAB2 gene, i.e., rs237028, rs521845 and rs652921. The Chi-square test was used to analyze the relationship between the genotype frequency of the three tag SNPs and the incidence of cryptorchidism. Results: The distribution of the 3 tag SNPs' alleles and genotypes were in agreement with the Hardy-Weinberg equilibrium, and the genotype results of polymerase chain reaction-restriction fragment length polymorphism assay were consistent with those of Sanger sequencing. The frequency of the G allele at TAB 2 rs237028 was significantly higher in the cryptorchidism group than that in the control group (30.9% vs. 25.6%, P=0.04, OR=1.31, 95% CI: 1.01-1.70). In the dominant model, the risk of cryptorchidism was significantly higher in AG/GG genotype carriers ( P=0.006, OR=1.57, 95% CI: 1.14-2.17). In the cryptorchidism group, the TC/CC genotype frequency of the rs652921 locus were significantly higher than that of the control group (75.3% vs. 67.0%, P=0.03, OR=1.50, 95% CI: 1.05-2.14). Correlation between rs521845 and susceptibility to cryptorchidism was not observed in the Han Chinese population. Conclusion: The AG/GG genotype of rs237028 locus and the TC/CC genotype of rs652921 locus of the TAB2 gene may be associated with increased risks of cryptorchidism in Han Chinese population in southwest China.

Lipopolysaccharide Downregulates 11ß-Hydroxysteroid Dehydrogenase 2 Expression through Inhibiting Peroxisome Proliferator-Activated Receptor-γ in Placental Trophoblasts.

It is increasingly recognized that excessive glucocorticoids induce fetal intrauterine growth restriction (IUGR). Placental 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2), a glucocorticoid-catalyzing enzyme, prevents active glucocorticoids from maternal circulation into the fetus, thus protecting against IUGR. Previous studies demonstrated gestational LPS exposure caused fetal IUGR. The aim of the current study was to investigate the effects of LPS on 11ß-HSD2 in mice placentas and human placental trophoblasts. Pregnant ICR(CD-1) mice were i.p. injected with LPS (200 µg/kg) on gestational day 16. As expected, gestational LPS exposure downregulated 11ß-HSD2 in mice placentas. In vitro, LPS downregulated 11ß-HSD2 in human placental trophoblasts. Additional experiment showed that LPS, which activated NF-κB, suppressed rosiglitazone-induced activation of peroxisome proliferator-activated receptor-γ (PPARγ) in mice placentas and human placental trophoblasts. Moreover, NF-κB p65 knockdown and specific NF-κB inhibitor attenuated LPS-induced suppression of PPARγ nuclear translocation in human placental trophoblasts. In addition, NF-κB p65 knockdown attenuated LPS-induced downregulation of 11ß-HSD2 in human placental trophoblasts. Mechanically, LPS promoted physical interaction between NF-κB p65 and PPARγ in the cytoplasm and nucleus of placental trophoblasts. Finally, pretreatment with rosiglitazone, a PPARγ agonist, partially alleviated LPS-induced reduction of fetal weight and crown-rump length. Taken together, these results suggest that LPS downregulates 11ß-HSD2 through suppressing PPARγ in placental trophoblasts. Placental 11ß-HSD2 downregulation may contribute partially to LPS-induced fetal IUGR.

Gestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain.

Several studies found that reduction of 5-hydroxymethylcytosine (5hmC), a marker of DNA hydroxymethylation highly enriched in developing brain, is associated with anxiety-like behaviors. This study aimed to investigate whether gestational arsenic (As) exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain. The dams drank ultrapure water containing NaAsO2 (15 mg/L) throughout pregnancy. Anxiety-like behaviors were evaluated and developing brain 5hmC was detected. Results showed that anxiety-like behaviors were observed in As-exposed adult offspring. In addition, 5hmC content was reduced in As-exposed fetal brain. Despite no difference on Tet1, Tet2 and Tet3 expression, TET activity was suppressed in As-exposed fetal brain. Mechanistically, alpha-ketoglutarate (α-KG), a cofactor for TET dioxygenases, was reduced and Idh2, a key enzymatic gene for mitochondrial α-KG synthesis, was downregulated in As-exposed fetal brain. Of interest, ascorbic acid, a cofactor for TET dioxygenases, reversed As-induced suppression of TET activity. Moreover, ascorbic acid attenuated As-induced reduction of 5hmC in fetal brain. In addition, ascorbic acid alleviated As-induced anxiety-like behaviors in adult offspring. Taken together, these results suggest that gestational As exposure induces anxiety-like behaviors in adult offspring, possibly at part, by inhibiting DNA hydroxymethylation in developing brain.

RIP1 promotes proliferation through G2/M checkpoint progression and mediates cisplatin-induced apoptosis and necroptosis in human ovarian cancer cells.

Receptor-interacting protein 1 (RIP1, also known as RIPK1) is not only a tumor-promoting factor in several cancers but also mediates either apoptosis or necroptosis in certain circumstances. In this study we investigated what role RIP1 plays in human ovarian cancer cells. We showed that knockout (KO) of RIP1 substantially suppressed cell proliferation, accompanied by the G2/M checkpoint arrest in two human ovarian cancer cell lines SKOV3 and A2780. On the other hand, RIP1 KO remarkably attenuated cisplatin-induced cytotoxicity, which was associated with reduction of the apoptosis markers PARP cleavage and the necroptosis marker phospho-MLKL. We found that RIP1 KO suppressed cisplatin-induced ROS accumulation in both SKOV3 and A2780 cells. ROS scavenger BHA, apoptosis inhibitor Z-VAD or necroptosis inhibitor NSA could effectively suppress cisplatin's cytotoxicity in the control cells, suggesting that ROS-mediated apoptosis and necroptosis were involved in cisplatin-induced cell death. In addition, blocking necroptosis with MLKL siRNA effectively attenuated cisplatin-induced cytotoxicity. In human ovarian cancer A2780 cell line xenograft nude mice, RIP1 KO not only significantly suppressed the tumor growth but also greatly attenuated cisplatin's anticancer activity. Our results demonstrate a dual role of RIP1 in human ovarian cancer: it acts as either a tumor-promoting factor to promote cancer cell proliferation or a tumor-suppressing factor to facilitate anticancer effects of chemotherapeutics such as cisplatin.

Gestational 1-nitropyrene exposure causes gender-specific impairments on postnatal growth and neurobehavioral development in mice.

1-Nitropyrene (1-NP), a typical nitrated polycyclic aromatic hydrocarbon, is widely distributed in the environment and is well known for its mutagenic effects. Recently, we found that gestational 1-NP exposure induced fetal growth restriction. In this study, we further evaluated the effect of in utero 1-NP exposure on postnatal growth and neurobehavioral development in the offspring. Pregnant mice were administered with 1-NP (10 µg/kg) by gavage daily in late pregnancy (GD13-GD17). The body weight of each offspring was measured from PND1 to 12 weeks postpartum. Exploration and anxiety related activities were detected by open-field test at 6 weeks postpartum. Learning and memory were assessed by Morris Water Maze at 7 weeks postpartum. And depressive-like behaviors were estimated by sucrose preference test at 10 weeks postpartum. Significant body weight reduction was observed in 1-NP-exposed female offspring at PND1, PND14 and PND21 while the lower body weight was only found at PND1 for 1-NP-exposed male offspring. Exploration and anxiety activities at puberty, and depressive-like behavior in adulthood were not disturbed in offspring prenatally exposed to 1-NP. Interestingly, spatial learning and memory ability at puberty was impaired in females but not in males prenatally exposed to 1-NP. These findings suggest that gestational 1-NP exposure delays postnatal growth and impaired neurobehavioral development in a gender-dependent manner.

[Expression and Initial Mechanism of Nicotinamide Phosphoribosyltransferase (NAMPT) in Dilated Cardiomyopathy].

OBJECTIVE: To explore nicotinamide phosphoribosyltransferase (NAMPT) expression in dilated cardiomyopathy (DCM) and its initial mechanism in the pathogenesis of DCM. METHODS: The peripheral blood of 131 Chinese patients with DCM confirmed by West China Hospital of Sichuan University during 2010-2013 were collected. 137 cases of Chinese Han healthy persons who were randomly selected in the physical examination center of West China Hospital of Sichuan University as the control group. The serum NAMPT levels were measured by ELISA. The NAMPT mRNA levels were determined by RT-PCR. Plasmids over-expressing NAMPT and empty vector were constructed and transfected into H9C2 cells. By using WST-1 technique,cell cycle detection and flow cytometry measurements,the effect of NAMPT on H9C2 proliferation and apoptosis was studied. RESULTS: Serum NAMPT level was significantly higher in the DCM group compared with that of controls and positively associated with the grade of heart failure and the size of left ventricular in DCM patients. The NAMPT mRNA level was significantly lower in the DCM group than that in the control group. The plasmid over-expressing NAMPT promoted H9C2 cells proliferation and increased the proportion of S phase cells compared with that of empty plasmid group. Over-expressing NAMPT increased proportion of the viable cells and reduced the proportion of late apoptotic and necrotic cells than empty plasmid group in the basic situation or after being treated with different concentrations of H2O2. CONCLUSION: The high expression of plasma protein level of NAMPT while low expression of NAMPT mRNA in peripheral blood cells,contributes one of the biological characteristics to DCM. The decrease of intracellular NAMPT may be an important factor in the pathogenesis of DCM.

Association between polymorphisms in IL21 gene and risk for sepsis.

CONTEXT: Sepsis is now the leading cause of death in the noncardiovascular intensive care unit (ICU). OBJECTIVE: To investigate whether polymorphisms in IL21 gene contribute to sepsis susceptibility. MATERIALS AND METHODS: Three single-nucleotide polymorphisms of IL21 (rs907715, rs2055979, rs12508721) were genotyped by TaqMan assay in patients with sepsis and control subjects. RESULTS: Polymorphisms rs2055979 and rs12508721 in IL21 were more frequent in sepsis patients compared to general population. But allele frequency of rs907715 was not significantly different between sepsis patients and control subjects. CONCLUSION: Polymorphisms in IL21 may be associated with sepsis risk.

Significant association between IL-32 gene polymorphisms and susceptibility to endometrial cancer in Chinese Han women.

Interleukin-32 (IL-32), a pro-inflammatory chemokine, has been reported to be involved in inflammatory, infectious diseases and even cancers. This study aimed to investigate whether two genetic variants (rs28372698 and rs12934561) of IL-32 were associated with susceptibility to endometrial cancer (EC) in Chinese Han women by a hospital-based study with 272 EC patients and 337 healthy controls. Our results showed that the frequencies of TT genotype (P = 0.012, OR = 2.37, 95 % CI = 1.32-4.28) and T allele (P = 0.026, OR = 1.320, 95 % CI = 1.036-1.681) of rs28372698 in EC patients were significantly higher than controls. Clinical analyses indicated the TT genotype frequency was relevant to high clinical stage and cervical invasion. Furthermore, the frequencies of CC genotype (P = 0.0077, OR = 1.62, 95 % CI = 1.05-2.50) and C allele (P = 0.043, OR = 1.269, 95 % CI = 1.011-1.592) of rs12934561 were also significantly higher in EC patients than controls. Stratification analyses revealed that CC genotype was more frequent in endometrioid adenocarcinoma or EC without parametrial invasion. This study demonstrates that IL-32 gene polymorphisms are significantly associated with increased EC susceptibility in Chinese Han women.

Polymorphisms and plasma levels of IL-27: impact on genetic susceptibility and clinical outcome of bladder cancer.

BACKGROUND: Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. Few studies have investigated polymorphisms and serum/plasma levels of IL-27 in diseases including cancers. This study has analyzed the associations of IL-27 gene polymorphisms, as well as plasma levels of IL-27, with susceptibility to bladder cancer and clinical outcome. METHODS: Three hundred and thirty-two patients (nonmuscle-invasive bladder cancer (NMIBC)/muscle-invasive bladder cancer (MIBC): 176/156) included in a 60-month follow-up program and 499 controls were enrolled. Two single nucleotide polymorphisms (SNPs), rs153109 and rs17855750, were genotyped by polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP) method. Plasma concentration of IL-27 was determined by ELISA in 124 patients (NMIBC/MIBC: 50/74) and 151 controls. RESULTS: Significantly increased risk for bladder cancer was associated with AG/GG genotypes of rs153109 (P = 0.029). No GG genotype of rs17855750 was observed in controls, while 4 patients were found to be GG homozygotes, suggesting GG genotype may be associated with bladder cancer risk (P = 0.006). For bladder cancer patients, SNP rs17855750 was also associated with increased risk for MIBC. For MIBC patients, but not NMIBC, TG/GG genotypes of rs17855750 turned out to be a protective factor for overall survival (P = 0.035). Significantly reduced plasma levels of IL-27 were observed in both NMIBC and MIBC patients compared with controls (P < 0.0001). CONCLUSION: Our data suggest that polymorphisms and reduced plasma levels of IL-27 may predict the susceptibility to bladder cancer, and rs17855750 may be a useful marker to distinguish patients with high risk of death.

Association between polymorphisms in IL27 gene and renal cell carcinoma.

CONTEXT: Interleukin-27 is a new member of the IL-12 family which plays an important role in human carcinogenesis. OBJECTIVE: To investigate whether polymorphisms in IL27 contribute to renal cell carcinoma (RCC) risk. MATERIALS AND METHODS: These two polymorphisms were genotyped in 329 RCC patients and 386 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Significantly increased RCC risk was associated the G allele of both rs153109 and rs17855750 (rs153109: p = 0.006, OR = 1.364, 95%CI = 1.095-1.700; rs17855750: p = 0.001, OR = 1.768, 95%CI = 1.245-2.511). CONCLUSION: The present study provided evidence that rs153109 and rs17855750 were associated with increased risk for RCC, suggesting an important role IL-27 may play in nephrocarcinogenesis.

Prognostic value of IL-27 polymorphisms and the susceptibility to epithelial ovarian cancer in a Chinese population.

This study investigated the association between IL-27 gene polymorphisms and susceptibility to epithelial ovarian cancer in a Chinese population and discusses the risk factors associated with survival time. We collected data on 229 patients diagnosed with epithelial ovarian cancer, from 15 to 77 years of age with a long clinical follow-up period. Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the genotype of IL-27 gene polymorphisms. Ovarian cancer-specific survival (OCSS) according to genotype of IL-27 gene polymorphisms was explored by Kaplan-Meier analysis and Cox proportional hazards modeling. Significant differences for genotype frequencies of both SNP sites were found between cases and controls. Both allele G frequencies were significantly greater among the cases (rs153109: 0.404 vs. 0.303, P = 0.001, odds ratio [OR] = 1.333, 95% confidence interval [CI] = 1.133-1.567; rs17855750: 0.146 vs. 0.083, P = 0.001, OR = 1.766, 95% CI = 1.258-2.481). Haplotype analysis showed haplotypes AG, GT and GG were associated with increased ovarian cancer susceptibility while AT was a protective haplotype. Advanced FIGO stage (stages III + IV) and non-optimal cytoreductive surgery (residual tumor ≥1 cm) were poor prognostic factors in the univariate analysis (P = 0.003, P = 0.049). However, FIGO stage was found to be the only independent significant prognostic factor by Cox proportional hazards analysis (P = 0.042). IL-27p28 mRNA expression was significantly decreased in ovarian cancer patients (P < 0.0001), while no significant relationship was found between IL-27p28 mRNA expression and polymorphism of rs153109 and rs17855750 (P = 0.193 and P = 0.146, respectively). Our study suggests that IL-27 gene polymorphisms may be involved in the susceptibility to epithelial ovarian cancer, but not in survival in a clinic-based Chinese population. Haplotype analysis of these two SNPs seems to be an important mark to predict the disease susceptibility. Advanced FIGO stage, as the only significant, independent risk factor, predicts poor clinical outcomes for patients diagnosed with epithelial ovarian cancer. The decreased expression of IL-27p28 mRNA in ovarian cancer might indicate the antitumor activities of this novel cytokine.

Genetic variants in NAMPT predict bladder cancer risk and prognosis in individuals from southwest Chinese Han group.

Nicotinamide phosphoribosyltransferase (Nampt) was served as a useful biomarker for tumorigenesis and for the prediction of cancer survival. In the present study, we analyzed the SNPs of the NAMPT gene and their impact on the susceptibility and prognosis for patients with bladder cancer (BC). The rs61330082, rs2505568 and rs9034 were selected and genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method in 407 patients with bladder cancer and 316 ethnicity-matched healthy control subjects. The genotyping method was confirmed by the DNA sequencing analysis. Statistically significant increased bladder cancer risk was found to be associated with the C allele and CC genotype of rs61330082; nevertheless, decreased bladder cancer risk was revealed to be associated with A allele and AT genotype of rs2505568. Stratified analyses revealed the rs61330082 to be statistically associated with increased bladder cancer risk in smokers and increased invasiveness of bladder cancer. The AT heterozygote of rs2505568 may prevent the recurrence of bladder cancer. Kaplan-Meier curves revealed a statistically significant association of rs2505568 with recurrence-free survival for total bladder cancer patients and non-muscle-invasive bladder cancer patients, and a statistically significant association of rs9034 with recurrence-free survival for muscle-invasive bladder cancer patients. Multiple Cox regression analysis identified the rs2505568 as a possible independent prognostic factor for recurrence-free survival in total bladder cancer patients. Our results suggested an important role for NAMPT in the pathogenesis of bladder cancer and SNPs of NAMPT gene might be a novel genetic biomarker for the prognosis of bladder cancer.

Prognostic value of PDCD6 polymorphisms and the susceptibility to bladder cancer.

Programmed cell death 6 (PDCD6) has recently been found dysregulated in tumors of various origin. The aim of this study is to explore the association between PDCD6 genetic polymorphisms and susceptibility to bladder cancer and survival of patients with bladder cancer. Two tag SNPs of PDCD6, rs3756712 and rs4957014, were genotyped in 332 patients with bladder cancer and 509 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and correlated with patients' survival. The frequencies of G allele and GG genotype of rs3756712 in patients were significantly lower than that of controls (P = 0.001, odds ratio [OR] = 0.68 for G allele; P = 0.024, OR = 0.53 for GG genotype in the recessive genetic model, respectively). The GT genotype of rs4957014 was associated with decreased susceptibility to bladder cancer in the overdominant genetic model (P = 0.023, OR = 0.72). Kaplan-Meier curves revealed a significant higher risk for death in superficial bladder cancer patients harboring GG homozygous of rs3756712 (P < 0.001), and an increased risk for recurrence in invasive bladder cancer patients carrying GT heterozygous of rs4957014 (P = 0.04). Multiple Cox regression analysis identified rs3756712 GG genotype as an independent prognostic factor for death in superficial bladder cancer patients (hazard ratio [HR] = 5.11, P = 0.01), and rs4957014 GT genotype as an independent prognostic factor for recurrence in invasive bladder cancer patients (HR = 1.93, P = 0.03). PDCD6 may represent a biomarker candidate gene that could help to identify a group of patients at high risk for recurrence and death.