Identification of hepatoblastoma susceptibility loci in the TRMT6 gene from a seven-center case-control study.

Hepatoblastoma, the most frequently diagnosed primary paediatric liver tumour, bears the lowest somatic mutation burden among paediatric neoplasms. Therefore, it is essential to identify pathogenic germline genetic variants, especially those in oncogenic genes, for this disease. The tRNA methyltransferase 6 noncatalytic subunit (TRMT6) forms a tRNA methyltransferase complex with TRMT61A to catalyse adenosine methylation at position N1 of RNAs. TRMT6 has displayed tumour-promoting functions in several cancer types. However, the contribution of its genetic variants to hepatoblastoma remains unclear. In this study, we investigated the association between four TRMT6 polymorphisms (rs236170 A > G, rs451571 T > C, rs236188 G > A and rs236110 C > A) and the risk of hepatoblastoma in a cohort of 313 cases and 1446 healthy controls. Germline DNA was subjected to polymorphism genotyping via the TaqMan qPCR method. Odds ratio (OR) and 95% confidence interval (CI) were used to determine hepatoblastoma susceptibility variants. The rs236170 A > G, rs236188 G > A and rs236110 C > A polymorphisms were significantly associated with hepatoblastoma risk. Combination analysis of the four polymorphisms revealed that children bearing 1-4 risk genotypes were at significantly enhanced hepatoblastoma risk compared to those without risk genotype (adjusted OR = 1.52, 95% CI = 1.19-1.95, p = 0.0008). We also conducted stratification analyses by age, sex and clinical stage. Ultimately, we found that the rs236110 C > A was significantly associated with the downregulation of MCM8, a neighbouring gene of TRMT6. In conclusion, we identified three susceptibility loci in the TRMT6 gene for hepatoblastoma. Our findings warrant further validation by extensive case-control studies across different ethnicities.

LMO family gene polymorphisms and Wilms tumor susceptibility in Chinese children: a five-center case-control study.

BACKGROUND: Wilms tumor is the most prevalent embryonal kidney malignancy in children worldwide. Previous genome-wide association study (GWAS) identified that LIM domain only 1 (LMO1) gene polymorphisms affected the susceptibility to develop certain tumor types. Apart from LMO1, the LMO gene family members also include LMO2-4, each of which has oncogenic potential. METHODS: We conducted this five-center case‒control study to assess the correlations between single nucleotide polymorphisms in LMO family genes and Wilms tumor susceptibility. Odds ratios and 95% confidence intervals were calculated to evaluate the strength of the association. RESULTS: We found LMO1 rs2168101 G > T and rs11603024 C > T as well as LMO2 rs7933499 G > A were significantly associated with Wilms tumor risk. Stratified analysis demonstrated a protective role of rs2168101 GT/TT genotypes against Wilms tumor in the subgroups of age ≤ 18 months, males and clinical stages I/II compared to the rs2168101 GG genotype. Nevertheless, carriers with the rs11603024 TT genotype were more likely to have an increased risk of Wilms tumor than those with rs11603024 CC/CT genotypes in age > 18 months. And the rs11603024 was identified as a protective polymorphism for reducing the risk of Wilms tumor in the sex- and gender- subgroup. Likewise, carriers with the rs7933499 GA/AA genotypes were at significantly elevated risk of Wilms tumor in age ≤ 18 months and clinical stages I/II. CONCLUSION: Overall, our study identified the importance of LMO family gene polymorphisms on Wilms tumor susceptibility in Chinese children. Further investigations are needed to validate our conclusions.

Neuroblastoma susceptibility and association of N7-methylguanosine modification gene polymorphisms: multi-center case-control study.

BACKGROUND: Neuroblastoma (NB) is a common extracranial solid malignancy in children. The N7-methylguanosine (m7G) modification gene METTL1/WDR4 polymorphisms may serve as promising molecular markers for identifying populations susceptible to NB. METHODS: TaqMan probes was usded to genotype METTL1/WDR4 single nucleotide polymorphisms (SNPs) in 898 NB patients and 1734 healthy controls. A logistic regression model was utilized to calculate the odds ratio (OR) and 95% confidence interval (CI), evaluating the association between genotype polymorphisms and NB susceptibility. The analysis was also stratified by age, sex, tumor origin site, and clinical stage. RESULTS: Individual polymorphism of the METTL1/WDR4 gene investigated in this study did not show significant associations with NB susceptibility. However, combined genotype analysis revealed that carrying all 5 WDR4 protective genotypes was associated with a significantly lower NB risk compared to having 0-4 protective genotypes (AOR = 0.82, 95% CI = 0.69-0.96, P = 0.014). Further stratified analyses revealed that carrying 1-3 METTL1 risk genotypes, the WDR4 rs2156316 CG/GG genotype, the WDR4 rs2248490 CG/GG genotype, and having all five WDR4 protective genotypes were all significantly correlated with NB susceptibility in distinct subpopulations. CONCLUSIONS: In conclusion, our findings suggest significant associations between m7G modification gene METTL1/WDR4 SNPs and NB susceptibility in specific populations. IMPACT: Genetic variation in m7G modification gene is associated with susceptibility to NB. Single nucleotide polymorphisms in METTL1/WDR4 are associated with susceptibility to NB. Single nucleotide polymorphisms of METTL1/WDR4 can be used as a biomarker for screening NB susceptible populations.

RNF113A targeted by miR-197 promotes proliferation and inhibits autophagy via CXCR4/CXCL12/AKT/ERK/Beclin1 axis in cervical cancer.

Ring Finger Protein 113 (RNF113A), an ubiquitin E3 ligase, is genetically associated with many biological processes, including proliferation, differentiation, cell death, and neurogenesis. Recently, RNF113A has been found to be an abnormal expression in many diseases, such as X-linked trichothiodystrophy syndrome and esophageal cancer. Here, we explore the potential mechanism of RNF113A in the progression of cervical cancer (CC). In this study, we evaluated the expression level and biological function of RNF113A in CC both in vitro and in vivo by bioinformatic prediction, DIA proteomic analysis, compensation experiment, Co-IP, dual-luciferase reporter assay and nude mouse xenograft to identify the RNF113A-associated autophagy pathways involved with tumorigenesis. Consistent with the prediction from biological information analysis, we found that RNF113A was highly expressed in human CC tissues and cells. In addition, this study illustrated that the high expression of RNF113A dramatically promoted proliferation and suppressed autophagy both in vitro and in vivo. In contrast, low expression of RNF113A enhanced autophagy activities and inhibited tumor growth in CC. We also found that miRNA-197, the level of which (negative correlation with RNF113A) declined in human CC, directly restrained the expression of RNF113A. Mechanistically, proteomic and mechanistic assays uncovered that RNF113A confirmed as the direct downstream target of miR-197, promoted proliferation and restrained autophagy in CC not through direct ubiquitination degradation of autophagy marker Beclin1 but via CXCR4/CXCL12/AKT/ERK/Beclin1 signal transduction axis. In summary, we found a new miR-197/RNF113 A/CXCR4/CXCL12/AKT/ERK/Beclin1 regulation pathway that plays an important part in the survival and progression of CC.

Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression.

Objective: AlkB homolog 5 (ALKBH5) has been proven to be closely related to tumors. However, the role and molecular mechanism of ALKBH5 in neuroblastomas have rarely been reported. Methods: The potential functional single-nucleotide polymorphisms (SNPs) in ALKBH5 were identified by National Center for Biotechnology Information (NCBI) dbSNP screening and SNPinfo software. TaqMan probes were used for genotyping. A multiple logistic regression model was used to evaluate the effects of different SNP loci on the risk of neuroblastoma. The expression of ALKBH5 in neuroblastoma was evaluated by Western blotting and immunohistochemistry (IHC). Cell counting kit-8 (CCK-8), plate colony formation and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays were used to evaluate cell proliferation. Wound healing and Transwell assays were used to compare cell migration and invasion. Thermodynamic modelling was performed to predict the ability of miRNAs to bind to ALKBH5 with the rs8400 G/A polymorphism. RNA sequencing, N6-methyladenosine (m6A) sequencing, m6A methylated RNA immunoprecipitation (MeRIP) and a luciferase assay were used to identify the targeting effect of ALKBH5 on SPP1. Results: ALKBH5 was highly expressed in neuroblastoma. Knocking down ALKBH5 inhibited the proliferation, migration and invasion of cancer cells. miR-186-3p negatively regulates the expression of ALKBH5, and this ability is affected by the rs8400 polymorphism. When the G nucleotide was mutated to A, the ability of miR-186-3p to bind to the 3'-UTR of ALKBH5 decreased, resulting in upregulation of ALKBH5. SPP1 is the downstream target gene of the ALKBH5 oncogene. Knocking down SPP1 partially restored the inhibitory effect of ALKBH5 downregulation on neuroblastoma. Downregulation of ALKBH5 can improve the therapeutic efficacy of carboplatin and etoposide in neuroblastoma. Conclusions: We first found that the rs8400 G>A polymorphism in the m6A demethylase-encoding gene ALKBH5 increases neuroblastoma susceptibility and determines the related mechanisms. The aberrant regulation of ALKBH5 by miR-186-3p caused by this genetic variation in ALKBH5 promotes the occurrence and development of neuroblastoma through the ALKBH5-SPP1 axis.

Association between lncRNA-H19 polymorphisms and hepatoblastoma risk in an ethic Chinese population.

H19 polymorphisms are associated with increased susceptibility to several cancers; however, their role in hepatoblastoma remains unclear. In this study, we investigated the association between three H19 polymorphisms (rs2839698 G>A, rs3024270 C>G, rs217727 G>A) and hepatoblastoma susceptibility in 213 hepatoblastoma patients. The rs2839698 and rs3024270 polymorphisms were associated with significantly increased hepatoblastoma risk, with the GG genotype associated with a higher risk of hepatoblastoma than the CC genotype at the rs3024270 locus. The rs217727 polymorphism was associated with significantly decreased hepatoblastoma risk, with the AG genotype associated with a lower risk of hepatoblastoma than the GG genotype. These findings were confirmed by combined analysis, and stratification analysis revealed that age, gender and clinical stage were associated with increased hepatoblastoma susceptibility. The GGG and AGG haplotypes were significantly associated with increased hepatoblastoma risk compared with the GCA reference (rs2839698, rs3024270, rs217727). The rs2839698 and rs3024270 polymorphisms correlated with decreased MRPL23-AS1 expression, whereas the rs217727 polymorphism was associated with increased MRPL23-AS1 expression. Overall, the H19 rs2839698, rs3024270 and rs217727 polymorphisms were associated with hepatoblastoma susceptibility in a Chinese Han population.

Genetic variations in nucleotide excision repair pathway genes and hepatoblastoma susceptibility.

The etiology of hepatoblastoma is largely unknown due to the rarity of this disease. Nucleotide excision repair (NER), a versatile system in repairing DNA damage, is highly implicated in carcinogenesis. However, it remains unclear whether single nucleotide polymorphisms (SNPs) of genes in the NER pathway are related to hepatoblastoma risk. A total of 313 Chinese children diagnosed with hepatoblastoma and 1446 controls were recruited from seven hospitals across China. TaqMan assay was adopted to genotype 19 SNPs in NER pathway genes including ERCC1, XPA, XPC, XPD, XPF and XPG. Of them, only two SNPs in XPC gene predisposed to hepatoblastoma risk. The XPC rs2607775 polymorphism significantly contributed to hepatoblastoma risk (dominant model: adjusted OR = 1.44, 95% CI = 1.01-2.05, P = .046). However, XPC rs1870134 conferred a significantly decreased risk of hepatoblastoma in recessive model (adjusted OR = 0.50, 95% CI = 0.26-0.98, P = .042). Stratified analysis revealed that rs2607775 CG/GG genotype, rs1870134 CC genotype and four to five risk genotypes were associated with the risk of hepatoblastoma under certain subgroups. The significant relationships were confirmed by haplotype analyses and false-positive report probability analyses. In addition, expression quantitative trait locus analysis suggested that rs2607775 G increased expression of XPC mRNA. Collectively, our discover a promising candidate XPC gene as a biomarker for the risk of hepatoblastoma.

Role of FTO gene polymorphisms in Wilms tumor predisposition: A five-center case-control study.

BACKGROUND: Wilms tumor is the most frequently occurring renal malignancy in pediatrics. The FTO gene exhibits a featured genetic contribution to cancer development. Nonetheless, its single nucleotide polymorphism (SNP) contribution to Wilms tumor remains unknown. METHODS: In the present study, 402 Wilms tumor patients and 1198 healthy controls were successfully genotyped for FTO gene SNPs (rs1477196 G>A, rs9939609 T>A, rs7206790 C>G and rs8047395 A>G) using TaqMan SNP genotyping assays. Odds ratios (ORs) and 95% confidence intervals (CIs), generated from unconditional logistic regression, were applied to quantify the effects of FTO gene SNPs on Wilms tumor risk. RESULTS: We found that the rs8047395 A>G polymorphism was significantly correlated with an increased risk for Wilms tumor (GG versus AA/AG: adjusted OR = 1.38, 95% CI = 1.04-1.85, p = 0.027). Carriers with 1 and 1-2 risk genotypes are more susceptible of developing Wilms tumor than those without risk genotypes. Stratified analysis of rs8047395 and risk genotypes revealed more significant relationships with Wilms tumor risk in certain subgroups. Preliminary functional annotations revealed that the rs8047395 A allele increases expression levels of the FTO gene as determined by expression quantitative trait locus analysis. CONCLUSIONS: The present study provides evidence that rs8047395 may regulate FTO gene expression and thus confer susceptibility to Wilms tumor. The candidate FTO gene rs8047395 A>G polymorphism identified in this study warrants independent investigation.

METTL14 gene polymorphisms decrease Wilms tumor susceptibility in Chinese children.

BACKGROUND: Wilms tumor is a highly heritable malignancy. Aberrant METTL14, a critical component of N6-methyladenosine (m6A) methyltransferase, is involved in carcinogenesis. The association between genetic variants in the METTL14 gene and Wilms tumor susceptibility remains to be fully elucidated. We aimed to assess whether variants within this gene are implicated in Wilms tumor susceptibility. METHODS: A total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay. RESULT: Among the five SNPs analyzed, rs1064034 T > A and rs298982 G > A exhibited a significant association with decreased susceptibility to Wilms tumor. Moreover, the joint analysis revealed that the combination of five protective genotypes exerted significantly more protective effects against Wilms tumor than 0-4 protective genotypes with an OR of 0.69. The stratified analysis further identified the protective effect of rs1064034 T > A, rs298982 G > A, and combined five protective genotypes in specific subgroups. The above significant associations were further validated by haplotype analysis and false-positive report probability analysis. Preliminary mechanism exploration indicated that rs1064034 T > A and rs298982 G > A are correlated with the expression and splicing event of their surrounding genes. CONCLUSIONS: Collectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.

Impact of YTHDF1 gene polymorphisms on Wilms tumor susceptibility: A five-center case-control study.

BACKGROUND: Wilms tumor is the most frequent renal malignancy in children. YTHDF1 is associated with the development of several kinds of cancers, yet whether common variants of the YTHDF1 gene influence Wilms tumor risk is unknown. We present, here, a hospital-based case-control study specifically designed to investigate the role of YTHDF1 genetic variants on Wilms tumor. METHODS: We successfully genotyped samples of 408 Wilms tumor cases and 1198 controls which were collected from five hospitals across China. The unconditional logistic regression was adopted to analyze the contributions of YTHDF1 gene single nucleotide polymorphisms (SNPs) to the risk of Wilms tumor. The odds ratio (OR) and 95% confidence interval (CI) were generated to evaluate the conferring risk of YTHDF1 gene SNPs (rs6011668 C>T, rs6090311 A>G). RESULTS: Neither of the two SNPs could contribute to the risk of Wilms tumor. A negative association was also detected in the combined effects of protective genotypes on Wilms tumor risk. The stratification analysis revealed that compared with those with CC genotype, rs6011668 CT/TT genotype was associated with increased Wilms tumor risk in those ≤18 months (OR = 1.54, 95% CI = 1.02-2.30, p = 0.038), and with decreased Wilms tumor risk in those >18 months (OR = 0.70, 95% CI = 0.50-0.97, p = 0.034). CONCLUSION: Our present work sheds some light on the potential role of YTHDF1 gene polymorphisms on Wilms tumor risk.

In vitro and in vivo antioxidant activities of soy protein isolate fermented with Bacillus subtilis natto.

The Bacillus subtilis natto fermented soy protein isolate (FSPI) exhibited concentration-dependent scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS+·) and hydroxyl (·OH) free-radicals. In addition, FSPI administration significantly increased superoxide dismutase activity in mice liver and serum by 20.2% and 86.2%, and suppressed the production of malondialdehyde by 51.3% and 35.1%, respectively, compared to high-fat control (HFC) group. Notably, the movement of mice treated with FSPI was livelier and more active, and its weight gain was significantly lower than that of both NC and HFC groups. The production and accumulation of perirenal fat was also significantly inhibited by FSPI, however, no significant difference in TG and TC levels were observed between FSPI and HFC groups. The results revealed the great potential of FSPI applying in the development of health food or sports food.

Association between METTL3 gene polymorphisms and neuroblastoma susceptibility: A nine-centre case-control study.

Neuroblastoma ranks as the most commonly seen and deadly solid tumour in infancy. The aberrant activity of m6 A-RNA methyltransferase METTL3 is involved in human cancers. Therefore, functional genetic variants in the METTL3 gene may contribute to neuroblastoma risk. In the current nine-centre case-control study, we aimed to analyse the association between the METTL3 gene single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility. We genotyped four METTL3 gene SNPs (rs1061026 T>G, rs1061027 C>A, rs1139130 A>G, and rs1263801 G>C) in 968 neuroblastoma patients and 1814 controls in China. We found significant associations between these SNPs and neuroblastoma risk in neither single-locus nor combined analyses. Interestingly, in the stratified analysis, we observed a significant risk association with rs1061027 AA in subgroups of children ≤ 18 months of age (adjusted OR = 1.87, 95% CI = 1.03-3.41, P = .040) and females (adjusted OR = 1.86, 95% CI = 1.07-3.24, P = .028). Overall, we identified a significant association between METTL3 gene rs1061027 C>A polymorphism and neuroblastoma risk in children ≤18 months of age and females. Our findings provide novel insights into the genetic determinants of neuroblastoma.

YTHDC1 gene polymorphisms and hepatoblastoma susceptibility in Chinese children: A seven-center case-control study.

BACKGROUND: Hepatoblastoma is a commonly occurring embryonal tumors in children. N6-methyladenosine (m6 A) plays a critical role in gene expression, thus contributing to the occurrence and progression of cancer. RNA splicing is regulated by the nuclear m6 A reader YTHDC1, yet the roles of YTHDC1 polymorphisms in hepatoblastoma remain unclear. METHODS: We conducted a seven-center case-control study to determine the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C and rs3813832 T>C) and hepatoblastoma susceptibility. We recruited 313 hepatoblastoma patients and 1446 healthy controls. RESULTS: There was no significant association between all of these polymorphisms and hepatoblastoma susceptibility in single locus or combined analysis. Stratification analysis revealed that rs2293596 TC/CC genotype carriers had a higher risk of developing hepatoblastoma in the subgroup of clinical stages III + IV [adjusted odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.18-2.76, p = 0.007]. In addition, 3 risk genotype carriers are more likely to develop hepatoblastoma in the subgroup of clinical stages III + IV (adjusted OR = 1.80, 95% CI = 1.18-2.76, p = 0.007). Furthermore, false-positive probability analysis was used to notarize our findings. Haplotype analysis indicated that there was no significant association between inferred haplotypes of YTHDC1 gene based on observed genotypes and hepatoblastoma risk. CONCLUSIONS: In conclusion, our findings suggest that the rs2293596 T>C polymorphism may contribute to hepatoblastoma susceptibly and YTHDC1 gene polymorphisms may have a cumulative effect on hepatoblastoma risk.

METTL3 polymorphisms and Wilms tumor susceptibility in Chinese children: A five-center case-control study.

BACKGROUND: Wilms tumor is a common pediatric tumor worldwide. Methyltransferase like 3 (METTL3) is a core gene of the N6 -methyladenosine (m6 A) modification that widely affects the transcription of tumor-related genes in eukaryotes. METTL3 has been extensively investigated in various tumors but not Wilms tumor. METHODS: We describe a five-center case-control study with 414 patients and 1199 controls aiming to explore the associations between METTL3 polymorphisms (rs1061026 T>G, rs1061027 C>A, rs1139130 A>G and rs1263801 G>C) and Wilms tumor susceptibility. A TaqMan real-time polymerase chain reaction was performed for genotyping. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported as evaluation indicators to determine any associations. RESULTS: Referring to the preliminary analysis results, protective genotypes were identified as rs1061026 TG/GG, rs1061027 CA/AA, rs1139130 GG and rs1263801 GC/CC. The children with three protective genotypes were less likely to develop Wilms tumor than children without protective genotypes (adjusted OR = 0.68, 95% CI = 0.46-0.999, p = 0.0496). Similarly, stratified analysis of the subgroup aged > 18 months, carrying 3 or 4 protective genotypes, was a protective factor for Wilms tumor compared to carrying 0-2 protective genotypes (adjusted OR = 0.59 95% CI = 0.39-0.91, p = 0.016). However, we did not observe any other significant results. CONCLUSIONS: The combined effect of METTL3 polymorphisms reduce Wilms tumor susceptibility in Chinese children. This conclusion requires further verification.

Association of TP53 rs1042522 C>G and miR-34b/c rs4938723 T>C polymorphisms with hepatoblastoma susceptibility: A seven-center case-control study.

BACKGROUND: Hepatoblastoma is a rare malignancy originating from pluripotent stem cells with unknown etiology. An understanding of the etiology in pediatric hepatoblastoma has been hampered by the unavailability of sufficient patient samples. To date, only a few epidemiological studies with small sample sizes have been performed investigating risk factors for hepatoblastoma. TP53 and pri-miR-34b/c genes are implicated in the tumorigenesis, yet the role of their polymorphisms in hepatoblastoma susceptibility remains unknown. METHODS: We conducted a seven-center case-control study to explore the genetic variants predisposing to hepatoblastoma susceptibility. In our study, we genotyped two functional polymorphisms, the TP53 rs1042522 C>G (Arg72Pro) and miR-34b/c rs4938723 T>C, in 313 cases and 1446 controls using the TaqMan method. RESULTS: Single loci analysis showed that neither TP53 rs1042522 C>G, nor miR-34b/c rs4938723 T>C significantly modified hepatoblastoma risk. In the stratification analysis, we identified that the miR-34b/c rs4938723 TC/CC genotypes were associated with a decreased risk in patients with clinical stages III + IV hepatoblastoma (adjusted odds ratio = 0.53, 95% confidence interval = 0.33-0.84, P=0.007] compared to the rs4938723 TT genotype. Subsequent analysis further showed that the combination of TP53 and miR-34b/c variant genotypes had no impact on susceptibility hepatoblastoma. CONCLUSIONS: Taken together, TP53 rs1042522 C>G and miR-34b/c rs4938723 T>C may not confer hepatoblastoma susceptibility. These findings may aid in our understanding of the genetic etiology of hepatoblastoma.

Optimization of pH conditions to improve the spore production of Clostridium butyricum NN-2 during fermentation process.

Clostridium butyricum, an anaerobic spore-forming bacillus, is a common human and animal gut commensal bacterium. Spore is an important structure for C. butyricum to tolerate environmental stress. However, it is not easy to form in common fermentation process of C. butyricum. In this study, the parameters for optimizing the spore formation of C. butyricum NN-2 were defined. The results showed that the pH value was a crucial factor that significantly affected the spore formation of C. butyricum NN-2. Down-regulation steps of pH value from 6.5 to 5.5 over time during the cultural process significantly (p < 0.05) promoted spore formation of C. butyricum NN-2, allowing for the sporulation rate of > 90%. In addition, the duration of pH regulation also had significant effects on the spore formation of C. butyricum NN-2. The results revealed a highly effective strategy for enhancing the spore production of C. butyricum.

Optimization of production conditions of rice α-galactosidase II displayed on yeast cell surface.

The yeast surface displayed rice α-galactosidase II (YSD rice α-Gal II) was generated with the pYD1 vector. The expression and cultural conditions for the improvement of production of YSD rice α-Gal II were optimized. The results showed that several induction factors, which were the initial cell density, inoculation ratio, galactose (inducer) concentration, induction time and temperature, determined the activity and expression efficiency of YSD rice α-Gal II. Meanwhile, the medium composition also affected its activity and production. Moreover, the production of YSD rice α-Gal II was further improved by continuous feeding of galactose in the fermenter level. The highest production was obtained at an initial cell density of OD600 = 2.9, 2% inoculation ratio, and 2% galactose, with 0.6 g/L compound nitrogen source ((NH4)2SO4/urea = 2/1, w/w) and 5 g/L sucrose, followed by continuous feeding of galactose (20 g/L with flow rate of 1.5 mL/h). At such conditions, the enzyme activity and productivity reached to 676.2 U/g (DCW) and 1548.5 U/L, respectively, 26.4- and 63.7-fold to that before optimization. The results provided a basic and effective strategy for the industrial production of YSD rice α-Gal II.

ALKBH5 gene polymorphisms and Wilms tumor risk in Chinese children: A five-center case-control study.

BACKGROUND: Wilms tumor is a frequently diagnosed renal cancer among children with unclear genetic causes. N6-methyladenosine (m6 A) modification genes play critical roles in tumorigenesis. However, whether genetic variations of m6 A modification genes predispose to Wilms tumor remain unclear. ALKBH5 (AlkB homolog 5), a crucial member of m6 A modification genes, encodes a demethylase that functions to reverse m6 A RNA methylation. METHODS: Herein, we evaluated the association of single nucleotide polymorphisms (SNPs) in the m6 A modification gene ALKBH5 and Wilms tumor susceptibility in a large multi-center case-control study. A total of 414 Wilms tumor cases and 1199 healthy controls were genotyped for ALKBH5 rs1378602 and rs8400 polymorphisms by TaqMan. RESULTS: No significant association was detected between these two polymorphisms and Wilms tumor risk. Moreover, 1, 2, and 1-2 protective genotypes (rs1378602 AG/AA or rs8400 GG) did not significantly reduce Wilms tumor risk, compared with risk genotypes only. Stratification analysis revealed a significant relationship between rs1378602 AG/AA genotypes and decreased Wilms tumor risk in children in clinical stage I diseases [adjusted odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.32-0.98, P = .042]. The presence of 1-2 protective genotypes was correlated with decreased Wilms tumor risk in subgroups of age > 18 months, when compared to the absence of protective genotypes (adjusted OR = 0.74, 95% CI = 0.56-0.98, P = .035). CONCLUSION: Collectively, our results demonstrate that ALKBH5 SNPs may exert a weak influence on susceptibility to Wilms tumor. This finding increases the understanding of the role of the m6 A gene in tumorigenesis of Wilms tumor.

LINC00673 rs11655237 C>T and susceptibility to Wilms tumor: A five-center case-control study.

BACKGROUND: Wilms tumor, a frequently occurring pediatric renal cancer worldwide, originated from the embryonal nephric mesenchyme. However, epidemiological data on the association between LINC00673 polymorphisms and Wilms tumor risk are scant. This case-control study was conducted to investigate the potential role of the LINC00673 rs11655237 C>T polymorphism in the susceptibility to Wilms tumor. METHODS: In the present study, we conducted a genotyping analysis of LINC00673 rs11655237 C>T in 414 cases and 1199 controls recruited from five hospitals in China. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple logistic regression models to determine the association of LINC00673 rs11655237 C>T polymorphism and Wilms tumor susceptibility. RESULTS: No significant association between the LINC00673 rs11655237 C>T polymorphism and Wilms tumor risk was observed (CT versus CC: adjusted OR = 0.90, 95% CI = 0.71-1.15; TT versus CC: adjusted OR = 0.86, 95% CI = 0.50-1.49; TT/CT versus CC: adjusted OR = 0.90, 95% CI = 0.71-1.13; and TT versus CC/CT: adjusted OR = 0.89, 95% CI = 0.52-1.53). We also failed to make any remarkable findings for this genotype in the stratification analysis. CONCLUSIONS: In summary, we failed to provide any evidence in favor of the significant susceptibility of rs11655237 C>T polymorphism in LINC00673 to Wilms tumor. These data could be useful for reinforcing our understanding of the potential contribution of LINC00673 rs11655237 C>T to Wilms tumor susceptibility.

Vitexin-rhamnoside encapsulated with zein-pectin nanoparticles relieved high-fat diet induced lipid metabolism disorders in mice by altering the gut microbiota.

This study aimed to investigate the modulatory effects of Vitexin-rhamnoside (VR) and Zein-VR-pectin nanoparticles (VRN) on lipid metabolism disorders induced by high-fat diet (HFD). The ingestion of VR or VRN attenuated dyslipidemia and fat accumulation in HFD mice, and improved intestinal dysbiosis by regulating the relative abundance of dominant bacteria, alleviating chronic inflammation and hepatic injury in HFD mice. The intervention effect of VRN was significantly higher than that of VR. After fecal microbiota transplantation (FMT) treatment, the fecal microbiota of VRN-treated donor mice significantly attenuated the symptoms associated with hyperlipidemia, confirming that VRN ameliorates HFD-induced disorders of lipid metabolism by modulating the gut microbiota, especially increasing the abundance of Rombousia and Faecalibaculum. Overall, VRN can regulate the gut microbiota and thus improve lipid metabolism. The present study provided new evidence that nanoparticles enhance the bioavailability of food bioactive ingredients.