Identification and expression analysis of XIP gene family members in rice.

Xylanase inhibitor proteins (XIP) are widely distributed in the plant kingdom, and also exist in rice. However, a systematic bioinformatics analysis of this gene family in rice (OsXIP) has not been conducted to date. In this study, we identified 32 members of the OsXIP gene family and analyzed their physicochemical properties, chromosomal localization, gene structure, protein structure, expression profiles, and interaction networks. Our results indicated that OsXIP genes exhibit an uneven distribution across eight rice chromosomes. These genes generally feature a low number of introns or are intronless, all family members, except for OsXIP20, contain two highly conserved motifs, namely Motif 8 and Motif 9. In addition, it is worth noting that the promoter regions of OsXIP gene family members feature a widespread presence of abscisic acid response elements (ABRE) and gibberellin response elements (GARE-motif and TATC-box). Quantitative Real-time PCR (qRT-PCR) analysis unveiled that the expression of OsXIP genes exhibited higher levels in leaves and roots, with considerable variation in the expression of each gene in these tissues both prior to and following treatments with abscisic acid (ABA) and gibberellin (GA3). Protein interaction studies and microRNA (miRNA) target prediction showed that OsXIP engages with key elements within the hormone-responsive and drought signaling pathways. The qRT-PCR suggested osa-miR2927 as a potential key regulator in the rice responding to drought stress, functioning as tissue-specific and temporally regulation. This study provides a theoretical foundation for further analysis of the functions within the OsXIP gene family.

Enhancement of pyranoanthocyanin formation in blueberry wine with non-Saccharomyces yeasts.

The development of blueberry wine provides an alternative method for maintaining the nutritional value and extending the shelf life of blueberries. However, anthocyanin loss and off-flavor compound generation during fermentation impair blueberry wine color and quality. Hydroxycinnamate decarboxylase from yeast can catalyze the conversion of hydroxycinnamic acids to vinylphenols, which later may condense with anthocyanins to form more stable vinylphenolic pyranoanthocyanins. In this study, 10 non-Saccharomyces yeasts from Daqu that showed hydroxycinnamate decarboxylase activity were screened. Among the 10 strains, Wickerhamomyces anomalus Y5 showed the highest consumption (34.59%) of the total tested phenolic acids and almost no H2S production. Furthermore, Y5 seemed to produce four vinylphenol pyranoanthocyanins (cyanidin-3-O-galactoside/glucoside-4-vinylcatechol, cyanidin-3-O-galactoside/glucoside-4-vinylsyringol, malvidin-4-vinylguaiacol, and malvidin-4-vinylcatechol) during blueberry wine fermentation, which may improve the color stability of blueberry wine. These findings provide new insights for improving the quality of blueberry wine using non-Saccharomyces yeasts.

Anti-Obesity Effects of Dietary Fibers Extracted from Flaxseed Cake in Diet-Induced Obese Mice.

Although many efforts have been made to characterize the functional properties of flaxseed, knowledge concerning the properties of insoluble and soluble dietary fibers in flaxseed is still limited. Here, insoluble and soluble dietary fibers were extracted from flaxseed cake-a valuable resource that has not been fully exploited. Subsequently, their monosaccharide compositions, structural properties, and anti-obesity effects in male mice were characterized. The anti-obesity effects of flaxseed cake insoluble dietary fiber (FIDF), flaxseed cake soluble dietary fiber (FSDF), and FIDF combined with FSDF in diet-induced obese mice were investigated in our study. Supplementation with FSDF alone or FIDF and FSDF together lowered the fat accumulation, improved the serum lipid profile, increased the basal metabolism, and improved the gut microbiota of obese mice. Supplementation with FIDF and FSDF together significantly enriched the abundance of g_Akkermansia and g_Bifidobacterium, which are negatively associated with obesity. Supplementation with FIDF alone improved the liver lipid profile, raised the basal metabolism, and enhanced the short-chain fatty acid levels in the guts of the mice. In conclusion, our results collectively support the therapeutic potential of FIDF and FSDF in obesity treatment and indicate that FIDF and FSDF play different roles in the process of obesity treatment. Furthermore, our results provide critical information for flaxseed cake resource exploitation.

Honokiol attenuates mitochondrial fission and cell apoptosis by activating Sirt3 in intracerebral hemorrhage.

BACKGROUND: Sirtuin-3 (Sirt3) has been documented to protect against mitochondrial dysfunction and apoptosis. Honokiol (HKL) is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurological disorders. The present study aimed to explore the neuroprotective effects of HKL and the role of Sirt3 following intracerebral hemorrhage (ICH). METHODS: An in vivo ICH model in rats was established by injecting autologous blood into the right basal ganglia. PC12 cells were stimulated with hemin. For the in vivo investigation, the modified Neurological Severity Scores and the Morris water maze test were performed to assess neurological deficits. Hematoxylin-Eosin and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to evaluate the histopathology and apoptosis. Immunohistochemical staining was used to investigate the expression of Sirt3. Adenosine triphosphate (ATP) levels were quantified to assess mitochondrial dysfunction. Cell counting kit-8, lactate dehydrogenase assay, and flow cytometry were used to analyze cell vitality and apoptosis in vitro. Immunofluorescence staining was performed to observe mitochondrial morphology and dynamin-related protein 1 (Drp1) localization to mitochondria. Western blot was applied to quantify the expression of Sirt3, Bax, Bcl-2, cleaved-caspase-3, Drp1, phosphorylation of Drp1 at serine-616, and phosphorylation of Drp1 at serine-637 in vivo and in vitro. RESULTS: HKL treatment alleviated neurological deficits, attenuated the histopathological damage and cell apoptosis, and restored the decreased ATP levels in ICH rats. HKL improved cell survival rate, reduced cell apoptosis, and inhibited mitochondrial fission in PC12 cells. Moreover, both in vivo and in vitro models showed increased phosphorylation of Drp1 at Ser616, and reduced phosphorylation of Drp1 at Ser637. Meanwhile, immunofluorescence co-localization analysis revealed that hemin increased the overlap of Drp1 and mitochondria in PC12 cells. The phosphorylation and mitochondrial translocation of Drp1 were effectively reversed by HKL treatment. Importantly, the selective Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine suppressed these effects. CONCLUSION: Our findings demonstrated that HKL ameliorated ICH-induced apoptosis and mitochondrial fission by Sirt3, suggesting that HKL has immense prospects for the treatment of ICH.

Associations between body mass index and pubertal development based on the outcomes of girls with early breast development.

Objective: To investigate the associations between physical and pubertal development based on the breast development outcomes in girls. Methods: This was a retrospective study. A total of 452 girls aged 6~8 years were included. Based on their breast development outcomes, the patients were divided into an idiopathic central precocious puberty (ICPP) group and a premature thelarche (PT) group. Anthropometry included measurements of height, weight, and BMI. ICPP was diagnosed when five diagnostic criteria from the current guidelines were met. Results: The girls with breast development at initial evaluation had a median age of 6.9 years. In total, 31.4% of patients were diagnosed with ICPP, and ICPP was rare in girls <7 years old (19%). Patients who presented with recurrence of breast development in the PT group accounted for 38.4%. At initial evaluation, the height, weight, BMI and bone age (BA) of the girls in the PT group corresponded to those of a normally developing girl at ages 7.8 years, 8.2 years, 8.6 years and 7.6 years, respectively. The girls in the ICPP group had a mean age of 7.3 years, and their mean height, weight, and BMI were 129.6 cm, 28.4 kg, and 17.0 kg/m2, which corresponded to the mean of a normally developing girl at ages 8.5 years, 9.1 years, and 10.5 years, respectively; these patients had BA of 9.2 years. Additionally, based on receiver operating characteristic (ROC) curve analysis, when the basal luteinizing hormone (LH) level was 0.32 IU/L and BMI reached 16.4 kg/m2, CPP was diagnosed in patients meeting all five diagnostic criteria for CPP, and the specificity and sensitivity were 71.9% and 88.2%, respectively. Conclusions: Girls with breast development before 8 years old had a high proportion of recurrence of breast development. The physical development of these girls at the time of breast development preceded that of normally developing girls by 1-2 years. BMI is an independent risk factor for early pubertal development, and is a simple and clear predictor of ICPP. In addition to the five classic diagnostic criteria, CPP is diagnosed when physical development corresponds to the mean for a 10.5 years old girl.

The Mycotoxin Beauvericin Exhibits Immunostimulatory Effects on Dendritic Cells via Activating the TLR4 Signaling Pathway.

Beauvericin (BEA), a mycotoxin of the enniatin family produced by various toxigenic fungi, has been attributed multiple biological activities such as anti-cancer, anti-inflammatory, and anti-microbial functions. However, effects of BEA on dendritic cells remain unknown so far. Here, we identified effects of BEA on murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-cultured bone marrow derived dendritic cells (BMDCs) and the underlying molecular mechanisms. BEA potently activates BMDCs as signified by elevated IL-12 and CD86 expression. Multiplex immunoassays performed on myeloid differentiation primary response 88 (MyD88) and toll/interleukin-1 receptor (TIR) domain containing adaptor inducing interferon beta (TRIF) single or double deficient BMDCs indicate that BEA induces inflammatory cytokine and chemokine production in a MyD88/TRIF dependent manner. Furthermore, we found that BEA was not able to induce IL-12 or IFNß production in Toll-like receptor 4 (Tlr4)-deficient BMDCs, whereas induction of these cytokines was not compromised in Tlr3/7/9 deficient BMDCs. This suggests that TLR4 might be the functional target of BEA on BMDCs. Consistently, in luciferase reporter assays BEA stimulation significantly promotes NF-κB activation in mTLR4/CD14/MD2 overexpressing but not control HEK-293 cells. RNA-sequencing analyses further confirmed that BEA induces transcriptional changes associated with the TLR4 signaling pathway. Together, these results identify TLR4 as a cellular BEA sensor and define BEA as a potent activator of BMDCs, implying that this compound can be exploited as a promising candidate structure for vaccine adjuvants or cancer immunotherapies.

Orexin-A exerts neuroprotective effect in experimental intracerebral hemorrhage by suppressing autophagy via OXR1-mediated ERK/mTOR signaling pathway.

Background: Orexin-A (OXA) is a polypeptide produced in the hypothalamus, which binds to specific receptors and exerts multiple physiological effects. Autophagy plays a vital role in early brain injury (EBI) after intracerebral hemorrhage (ICH). However, the relationship between OXA and autophagy after ICH has not been confirmed. Methods: In this study, the protective role of OXA was investigated in a model of hemin-induced injury in PC12 cells and blood-injection ICH model in rats, and its potential molecular mechanism was clarified. Neurobehavioral tests, brain water content, and pathologic morphology were assessed after ICH. Cell survival rate was determined using Cell Counting Kit-8 (CCK-8), while apoptosis was detected using flow cytometry. The autophagy protein LC3 that was originally identified as microtubule-associated protein 1 light 3 was evaluated by immunohistochemistry. The ultrastructural changes of cells following ICH were observed by transmission electron microscopy. Western blotting was performed to determine the expression levels of LC3, p62/SQSTM1 (p62), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), total extracellular signal-regulated kinase 1/2 (t-ERK1/2), mammalian target of rapamycin (mTOR), and phosphorylated mammalian target of rapamycin (p-mTOR). Results: OXA treatment significantly improved neurofunctional outcomes, reduced brain edema, and alleviated neuronal apoptosis. OXA administration upregulated p-mTOR and p62, while it downregulated p-ERK1/2 and LC3; this effect was reversed by the orexin receptor 1 (OXR1) antagonist SB-334867. Conclusions: This study demonstrates that OXA suppresses autophagy via the OXR1-mediated ERK/mTOR signaling pathway to exert neuroprotective effects, and it might provide a novel therapeutic approach in patients suffering from ICH.

Rapid Body-Wide Transcriptomic Turnover During Rhesus Macaque Perinatal Development.

An hourglass cup-shape pattern of regulation at the molecular level was detected during the development of the primate brain. Specifically, a peak of temporally differentially expressed genes around the time of birth has been observed in the human brain. However, to what extend this peak of regulation exists among species has not been investigated in great detail. Here, by integrating multiple large-scale transcriptome data from rhesus macaques, we confirmed that a similar differential expression peak exists during the development of the macaque brain. We also found that a similar peak exists during the development of other organs, such as liver, testis, kidney and heart. Furthermore, we found that distinct pathways are regulated in the peak period of those organs. Our results highlight the importance of co-evolution of diverse organs during critical periods of perinatal development in primates.

Inhibition of PTEN Ameliorates Secondary Hippocampal Injury and Cognitive Deficits after Intracerebral Hemorrhage: Involvement of AKT/FoxO3a/ATG-Mediated Autophagy.

Spontaneous intracerebral hemorrhage (ICH) commonly causes secondary hippocampal damage and delayed cognitive impairments, but the mechanisms remain elusive. Here, we sought to identify the molecular mechanisms underlying these hemorrhagic outcomes in a rat autologous blood model of ICH. First, a significant increase in phosphatase and tensin homolog (PTEN) expression was observed in nonhemorrhagic ipsilateral hippocampus. However, systemic administration of PTEN inhibitor BPV or hippocampal injection of PTEN siRNA could prevent hippocampal neuronal injury and cognitive dysfunctions after ICH. Furthermore, we also found that ICH robustly triggered autophagic neuronal death in the ipsilateral hippocampus, but which were strongly reduced by PTEN knockdown. Notably, suppression of autophagy effectively attenuated poststroke hippocampal inflammation, neuronal damage, and cognitive decline, suggesting the beneficial effects of PTEN deletion was associated with autophagy inactivation. Specifically, PTEN antagonized the PI3K/AKT signaling and downstream effector FoxO3a phosphorylation and subsequently enhanced nuclear translocation of FoxO3a to drive proautophagy gene program, but these changes were diminished upon PTEN inhibition. More importantly, lentivirus-mediated FoxO3a overexpression apparently abrogated the antiauotphagy effect of PTEN deletion via enhancing autophagy-related gene (ATG) transcription. Collectively, these results suggest that knockdown of PTEN alleviated progressive hippocampal injury and cognitive deficits by suppression of autophagy induction involving the AKT/FoxO3a/ATG axis after ICH. Thus, this study provides a novel and promising therapeutic target for the treatment of hemorrhagic stroke.

The Association of Polymorphisms in Base Excision Repair Genes with Ovarian Cancer Susceptibility in Chinese Women: A Two-Center Case-Control Study.

Base excision repair (BER) acts upon the most important mechanism of the DNA repair system, protecting DNA stability and integrity from the mutagenic and cytotoxic effects. Multiple researches have indicated that single-nucleotide polymorphisms (SNPs) in the BER-related gene may be associated with the susceptibility of ovarian cancer. However, the results are controversial. In this two-center case-control study, 19 potentially functional SNPs in six BER-related genes (hOGG1, APE1, PARP1, FEN1, LIG3 and XRCC1) was genotyped in 196 ovarian cancer cases and 272 cancer-free controls. And, their associations with ovarian cancer risk were assessed by unconditional logistic regression analyses. We found that PARP1 rs8679 and hOGG1 rs293795 polymorphisms were associated with a decreased risk of ovarian cancer under dominant model (adjusted OR=0.39, 95% CI=0.17-0.90, P=0.026; and adjusted OR=0.36, 95% CI=0.13-0.99, P=0.049, respectively). Stratification analysis demonstrated that this association was more pronounced in the subgroups of lower BMI and patients with early menarche and serous carcinoma. Moreover, LIG3 rs4796030 AA/AC variant genotypes performed an increased risk of ovarian cancer under recessive model (adjusted OR=1.54, 95% CI=1.01-2.35, P=0.046), especially in the subgroups of higher BMI, early clinic stage and the carcinoma at the left. These results suggested that PARP1, hOGG1 and LIG3 polymorphisms might impact on the risk of ovarian cancer. However, more researches with larger and different ethnic populations are warranted to support our findings.

Elevated miR-29a Contributes to Axonal Outgrowth and Neurological Recovery After Intracerebral Hemorrhage via Targeting PTEN/PI3K/Akt Pathway.

Spontaneous intracerebral hemorrhage (ICH) is a clinical challenge with high disability and lacks an effective treatment. miR-29a strongly expressed in the brain has been implicated in various neurological disorders. In this study, we investigated the biological roles of miR-29a in axonal outgrowth and neurological outcomes after ICH and relevant molecular mechanism. The rat model of ICH was established by injection of autologous whole blood into the right basal ganglia. First, a significant decrease in miR-29a level was found in perihematomal brain tissues and cerebrospinal fluid (CSF) after ICH in vivo and hemin-treated neurons in vitro. Further study documented that lentivirus-mediated miR-29a overexpression could remarkably attenuate hemorrhagic brain injury, promoted regenerative outgrowth of injured axons and improved neurobehavioral and cognitive impairments after ICH in rats. In addition, we also identified that overexpression of miR-29a obviously alleviated neuronal damage and mitochondrial dysfunctions, and facilitated neurite outgrowth in cultured neurons exposed to hemin in vitro. Furthermore, luciferase reporter assay showed that miR-29a directly targeted the 3'-UTR region of phosphatase and tensin homolog (PTEN) mRNA and negatively regulated its expression. More importantly, pharmacological inhibition of PTEN has similar neuroprotective effects as miR-29a overexpression involving activation of the PI3K/Akt pathway after hemorrhagic stroke. Collectively, these results suggested that elevated miR-29a could contribute to axonal outgrowth and neurological recovery through targeting PTEN/PI3K/Akt pathway after ICH, thereby providing a potential therapeutic target for patients with ICH.

Insights into the metabolic characteristics of aminopropanediol analogues of SYLs as S1P1 modulators: from structure to metabolism.

SYL927 and SYL930, two aminopropanediol analogues, are novel Sphingosine-1-phosphate receptor 1 (S1P1) modulators with higher selectivity and pharmacological activity compared with FTY720. Although the immunosuppressive activity of SYLs has been well demonstrated, information regarding the metabolic fates of the two chemicals is limited except for the CYP-catalyzed hydroxylation of SYL930. In this study, the biotransformation schemes of the two promising chemicals were investigated and compared using liver microsomes, S9 fractions and recombinant enzymes, and relevant molecular mechanism was primarily demonstrated by ligand-enzyme docking analysis (CDOCKER). As a result, the hydroxylation at alkyl chain on oxazole ring by the action of CYPs was found for both SYLs in vivo. The SULT-catalyzed sulfonation of the hydroxide was observed for SYL927 while the ADH/ALDH-catalyzed oxidation was only discovered for SYL930. The docking analysis suggested that specific non-covalent forces and/or bonding conformations of the hydroxides with biomacromolecules might be involved in the disparate metabolism of SYLs. Exploring the metabolic characteristics will help clarify the substance base for efficacy and safety of the two drugs. The uncovered structure-metabolism relationship in this study may provide an implication for the design and optimization for other S1P modulators.

Effect of nanoliposomal entrapment on antioxidative hydrolysates from goose blood protein.

In this study, the encapsulation of goose blood hydrolysate (GBH) was performed within nanoliposomes. We investigated the physicochemical properties, stability, antioxidant indices, the morphology of nanoparticles, the digestion stability in simulated gastrointestinal fluid, differential scanning calorimetry (DSC) analysis, and Fourier transform infrared (FTIR) spectroscopy. GBH was successfully encapsulated into nanoliposomes using reverse-phase evaporation method. The entrapment efficiency of GBH-loaded nanoliposomes was about 70.99 ± 2.85%, the average particle size was 93.3 ± 2.45 nm, the zeta-potential of GBH-loaded nanoliposomes was -30 mV, and the morphology of GBH-loaded nanoliposomes was characterized by transmission electron microscope. Moreover, the results of DSC and FTIR showed that the GBH nanoliposome was more stable than the empty liposomes due to hydrogen bond complexation between liposome and GBH. The release of GBH from nanoliposomes could be significantly controlled, and the release ratios were 48.9 ± 2.96% in simulated gastric fluid and 59.9 ± 5.30% in simulated intestinal fluid, respectively, proving that degradation rate of antioxidant activities of GBH encapsulated in nanoliposomes was decreased. In conclusion, nanoliposomes embedding is a promising and effective way to increase the stability of hydrolysates from GBH and produce various types of functional food.

Association of polymorphisms in MALAT1 with the risk of endometriosis in Southern Chinese women.

Endometriosis is a common estrogen-dependent inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, which causes infertility and pelvic pain. Polymorphisms in MALAT1 have been demonstrated to play crucial roles in many diseases. However, the roles of MALAT1 polymorphisms in the etiology of endometriosis have not been well documented. We genotyped three MALAT1 polymorphisms in 555 endometriosis patients and 535 female control participants using quantitative polymerase chain reaction with TaqMan probes. To estimate the associations between MALAT1 polymorphisms and endometriosis risk, an unconditional logistic regression model was conducted to calculate an odds ratio (OR) and the 95% confidence interval (CI), adjusting for age, abortion history, number of deliveries, Body Mass Index (BMI), and The International Federation of Gynecology and Obstetrics (FIGO) stage. We found that the MALAT1 rs591291 C > T polymorphism significantly enhanced endometriosis risk (heterogeneous: adjusted OR = 1.36, 95% CI = 1.00-1.85, P = 0.050; homogenous: adjusted OR = 1.55, 95% CI = 1.03-2.33, P = 0.037; dominant: adjusted OR = 1.41, 95% CI = 1.05-1.88, P = 0.021). In stratification analyses, these associations were more predominant in the patients younger than 35 years old, with a relatively high number of deliveries and with a BMI between 25 and 29.9. Compared with wild-type CCG haplotype carriers, individuals with TCC haplotypes had a higher risk of developing endometriosis. The MALAT1 rs591291 C > T polymorphism was associated with a significant increase in endometriosis risk.

Glioma stages prediction based on machine learning algorithm combined with protein-protein interaction networks.

BACKGROUND: Glioma is the most lethal nervous system cancer. Recent studies have made great efforts to study the occurrence and development of glioma, but the molecular mechanisms are still unclear. This study was designed to reveal the molecular mechanisms of glioma based on protein-protein interaction network combined with machine learning methods. Key differentially expressed genes (DEGs) were screened and selected by using the protein-protein interaction (PPI) networks. RESULTS: As a result, 19 genes between grade I and grade II, 21 genes between grade II and grade III, and 20 genes between grade III and grade IV. Then, five machine learning methods were employed to predict the gliomas stages based on the selected key genes. After comparison, Complement Naive Bayes classifier was employed to build the prediction model for grade II-III with accuracy 72.8%. And Random forest was employed to build the prediction model for grade I-II and grade III-VI with accuracy 97.1% and 83.2%, respectively. Finally, the selected genes were analyzed by PPI networks, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the results improve our understanding of the biological functions of select DEGs involved in glioma growth. We expect that the key genes expressed have a guiding significance for the occurrence of gliomas or, at the very least, that they are useful for tumor researchers. CONCLUSION: Machine learning combined with PPI networks, GO and KEGG analyses of selected DEGs improve our understanding of the biological functions involved in glioma growth.

Association of polymorphisms in MALAT1 with the risk of endometrial cancer in Southern Chinese women.

BACKGROUND: Endometrial cancer is the most common gynecologic malignancy worldwide. Polymorphisms in MALAT1 have been demonstrated to play critical roles in cancer. However, the roles of MALAT1 polymorphisms in the etiology of endometrial cancer have not been well documented. METHODS: We genotyped three MALAT1 polymorphisms in 249 endometrial cancer cases and 446 cancer-free female controls using quantitative polymerase chain reaction with TaqMan probes. To estimate the association between MALAT1 polymorphisms (rs591291 C>T, rs664589 C>G, and rs4102217 G>C) and the risk of endometrial cancer, an unconditional logistic regression model was conducted to calculate the odds ratio (OR) and the 95% confidence interval (CI), adjusting for surgery history, menopause, number of deliveries, BMI, and FIGO stage. RESULTS: We found that the MALAT1 rs664589 C>G polymorphism was significantly associated with endometrial cancer risk (heterogeneous: adjusted OR = 0.57, 95% CI = 0.34-0.93, P = .026; homogenous: adjusted OR = 3.74, 95% CI = 1.12-12.45, P = .032; and recessive: adjusted OR = 4.06, 95% CI = 1.22-13.48, P = .022). Stratified analysis further demonstrated that the MALAT1 rs664589 C>G polymorphism significantly increased the risk of endometrial cancer susceptibility in patients with no history of surgery, more deliveries, BMI between 25 and 29.9, and FIGO stages II-III. Compared with the wild-type GCG haplotype carriers, individuals with CGG haplotypes had a higher risk of developing endometrial cancer. CONCLUSION: The MALAT1 rs664589 C>G polymorphism was associated with a significant increase in endometrial cancer risk.

A Study of the Mechanism of Binding between Neratinib and MAD2L1 Based on Molecular Simulation and Multi-spectroscopy Methods.

BACKGROUND: Nilatinib is an irreversible tyrosine kinase inhibitor, which is used in the treatment of some kinds of cancer. To study the interaction between Neratinib and MAD2L1, a potential tumor target, is of guiding significance for enriching the medicinal value of Neratinib. METHOD: The binding mechanism between Mitotic arrest deficient 2-like protein 1 (MAD2L1) and Neratinib under simulative physiological conditions was investigated by molecule simulation and multi-spectroscopy approaches. RESULTS: Molecular docking showed the most possible binding mode of Neratinib-MAD2L1 and the potential binding sites and interaction forces of the interaction between MAD2L1 and Neratinib. Fluorescence spectroscopy experiments manifested that Neratinib could interact with MAD2L1 and form a complex by hydrogen bond and van der Waals interaction. These results were consistent with the conclusions obtained from molecular docking. In addition, according to Synchronous fluorescence and three-dimensional fluorescence results, Neratinib might lead to the conformational change of MAD2L1, which may affect the biological functions of MAD2L1. CONCLUSION: This study indicated that Neratinib could interact with MAD2L1 and lead to the conformational change of MAD2L1. These works provide helpful insights for the further study of biological function of MAD2L1 and novel pharmacological utility of Neratinib.

Gene expression and phenoloxidase activities of hemocyanin isoforms in response to pathogen infections in abalone Haliotis diversicolor.

Hemocyanins (Hc), the main protein components of hemolymph in invertebrates, are not only involved in oxygen transport but also linked to non-specific immune responses. In this study, we used abalone (Haliotis diversicolor) Hc to study the basis of its diversified functions through gene, protein, peptides, and phenoloxidase (PO) activity levels. Three complete hemocyanin gene (HdH) sequences were cloned for the first time. By comparing the copies and location of HdH between abalone and other mollusks, we propose that Hc gene duplication and linkage is likely to be common during the evolution of mollusk respiratory proteins. We further demonstrate that all three genes could be expressed in abalone, with expression varying based on the developmental stages, tissue types, and different pathogen infections. However, HdH1 and HdH2 appear to be synthesized by the same cells by fluorescence in situ hybridization. Furthermore, the PO activity of HdH can be induced by trypsin, urea, and SDS in vitro. Viral infection can stimulate its PO activity in vivo by cleaving the protein into fragments. Consequently, we present a comprehensive study of abalone hemocyanin, providing important evidence for an in-depth understanding of the physiological and immune functions of Hc in mollusks.

Shear Stress Induces Phenotypic Modulation of Vascular Smooth Muscle Cells via AMPK/mTOR/ULK1-Mediated Autophagy.

Phenotypic modulation of vascular smooth muscle cells (VSMCs) is involved in the pathophysiological processes of the intracranial aneurysms (IAs). Although shear stress has been implicated in the proliferation, migration, and phenotypic conversion of VSMCs, the molecular mechanisms underlying these events are currently unknown. In this study, we investigated whether shear stress(SS)-induced VSMC phenotypic modulation was mediated by autophagy involved in adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) pathway. The results show that shear stress could inhibit the expression of key VSMC contractile genes and induce pro-inflammatory/matrix-remodeling genes levels, contributing to VSMCs phenotypic switching from a contractile to a synthetic phenotype. More importantly, Shear stress also markedly increased the levels of the autophagy marker microtubule-associated protein light chain 3-II (LC3II), Beclin-1, and p62 degradation. The autophagy inhibitor 3-methyladenine (3-MA) significantly blocked shear-induced phenotypic modulation of VSMCs. To further explore the molecular mechanism involved in shear-induced autophagy, we found that shear stress could activate AMPK/mTOR/ULK1 signaling pathway in VSMCs. Compound C, a pharmacological inhibitor of AMPK, significantly reduced the levels of p-AMPK and p-ULK, enhanced p-mTOR level, and finally decreased LC3II and Beclin-1 level, which suggested that activated AMPK/mTOR/ULK1 signaling was related to shear-mediated autophagy. These results indicate that shear stress promotes VSMC phenotypic modulation through the induction of autophagy involved in activating the AMPK/mTOR/ULK1 pathway.