Publications by authors named "Wanhua Zhang"

Autism spectrum disorders (ASD) are associated with the contribution of many prenatal risk factors; in particular, the sex hormone progestin and vitamin D receptor (VDR) are associated with gastrointestinal (GI) symptoms in ASD development, although the related mechanism remains unclear. We investigated the possible role and mechanism of progestin 17-hydroxyprogesterone caproate (17-OHPC) exposure-induced GI dysfunction and autism-like behaviours (ALB) in mouse offspring. An intestine-specific VDR-deficient mouse model was established for prenatal treatment, while transplantation of haematopoietic stem cells (HSCT) with related gene manipulation was used for postnatal treatment for 17-OHPC exposure-induced GI dysfunction and ALB in mouse offspring.

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A hydroxamic acid based microtubule-destabilizing agent (MDA) SKLB-14b was discovered in this study, which was derived from shortening the linker length of the HDAC6 and microtubule dual-target inhibitor SKLB-23bb. SKLB-14b exhibited low nanomolar IC values on a wide spectrum of human cancer cell lines including both sensitive and multidrug-resistant cell lines. Surprisingly, its anti-proliferative activity relied on the presence of the hydroxamic acid group but lost inhibitory activity against HDACs.

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Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is a high-risk disease subtype with a dismal prognosis. Inhibiting BCR-ABL kinase alone is insufficient to eradicate Ph+ALL clones, and alternative BCR-ABL-dependent and -independent pathways need to be targeted as an effective strategy. Our study revealed that the combination of dasatinib and interferon-α showed synergistic activity against Ph+ALL, inducing mitochondrial dysfunction and causing necrosis-like cell lysis.

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Background: Retinoic acid-related orphan receptor alpha (RORA) has been reported to be suppressed in autistic patients and is associated with autism spectrum disorders (ASD), although the potential role and mechanism of RORA on gastrointestinal (GI) symptoms in ASD patients is still not reported. In this study, we aim to investigate the contribution of RORA to GI symptoms through a maternal diabetes-mediated autism-like mouse model.

Results: Male offspring of diabetic dams were treated with either superoxide dismutase (SOD) mimetic MnTBAP or RORA agonist SR1078, or were crossbred with intestine epithelial cells (IEC)-specific RORA knockout (RORA) mouse.

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In this study, we described a series of 2,8-diazaspiro[4.5]decan-1-one derivatives as selective TYK2/JAK1 inhibitors. Systematic exploration of the structure-activity relationship through the introduction of spirocyclic scaffolds based on the reported selective TYK2 inhibitor led to the discovery of the superior derivative compound .

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Intestinal ischemia-reperfusion (I/R) injury promotes the release of IL-17A, and previous studies have indicated that TGF-β activated kinase 1 (TAK1) is an important signaling molecule in the regulatory function of IL-17A. The present study aimed to explore the potential effects of IL-17A release in intestinal I/R injury, and to investigate the underlying regulatory mechanisms. Initially, the expression levels of TAK1 and JNK in a hypoxia/reoxygenation model were determined, and the effects of TAK1-knockdown on JNK phosphorylation and the viability, inflammation, apoptosis and barrier function of Caco-2 cells were assessed using Cell Counting Kit-8, reverse transcription-quantitative PCR, TUNEL and transepithelial electrical resistance assays, respectively.

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Hydroxamic acid group is one of the characteristic pharmacophores of histone deacetylase (HDAC) inhibitors. But here, we discovered a series of hydroxamic acid-based microtubule destabilizing agents (MDAs), which were derived from shortening the length of the linker in HDAC6 inhibitor SKLB-23bb. Interestingly, the low nanomolar antiproliferative activity of these MDAs depended on the presence of hydroxamic acid groups, but their inhibitory effects on HDAC were lost.

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Minimal residual disease (MRD) appeared to be a potent prognostic indicator in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), with potential value in informing individualized treatment decisions. Hence, we performed herein a systemic literature review and meta-analysis to comprehensively address the prognostic value of MRD in Ph+ ALL. Systematic literature review was conducted in PubMed, Embase, and Cochrane databases with the data access date up to September 23, 2020.

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BCR-ABL1 fusion gene is the driver mutation of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Although the prognostic value of BCR-ABL1 isoforms in Ph+ ALL patients has been investigated in numerous studies in the tyrosine kinase inhibitor (TKI) era, the results were still conflicting. Hence we performed herein the meta-analysis to comprehensively assess the impact of BCR-ABL1 isoforms on the clinical outcomes of Ph+ ALL patients.

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Through genome-wide association studies (GWAS), multiple inherited predispositions to acute lymphoblastic leukemia (ALL) have been identified in children. Most recently, a novel susceptibility locus at was localized, exhibiting Hispanic-specific manner. In this study, we conducted a replication study to in all-age Chinese patients ( = 451), not only validating the novel locus, but also systematically determining the impact of age on association status of the top GWAS signals.

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In this study, a series of novel HDAC inhibitors, using 1,2,4-oxadiazole-containing as the cap group, were synthesized and evaluated in vitro. Compound 14b, N-hydroxy-2-(methyl((3-(1-(4-methylbenzyl)piperidin-4-yl)-1,2,4-oxadiazol-5-yl)methyl)amino)pyrimidine-5-carboxamide, displayed the most potent histone deacetylase (HDAC) inhibition, especially against HDAC1, 2, and 3 with IC values of 1.8, 3.

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A series of pyrrolo[2,3- d]pyrimidine derivatives were prepared and optimized for cytotoxic activities against FLT3-ITD mutant cancer cells. Among them, compound 9u possessed nanomolar FLT3 inhibitory activities and subnanomolar inhibitory activities against MV4-11 and Molm-13 cells. It also showed excellent inhibitory activities in FLT3-ITD-D835V and FLT3-ITD-F691L cells which were resistant to quizartinib.

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Germline variants of impact susceptibility of acute lymphoblastic leukemia (ALL) through inducing its overexpression. Although limited reports suggested the oncogenic role of in cancers, regulatory network and prognostic effect of this gene remains poorly understood in tumorigenesis and leukemogenesis. In this study, we conducted genome-wide gene expression association analyses in pediatric B-ALL cohorts to discover expression associated genes and pathways, which is followed by the bioinformatics analyses to investigate the prognostic role of and its related genes in multiple cancer types.

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In the present study, a series of novel dual-target histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) inhibitors were designed and synthesized using pyrimidine-pyrazolyl pharmacophore to append HDAC recognition cap and hydroxamic acid as a zinc-binding motif. Among them, 12l was the optimal lead compound with potent inhibition activities against mTOR and HDAC1 with half-maximal inhibitory concentration of 1.2 and 0.

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Background: Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) genes are frequently altered in acute lymphoblastic leukaemia (ALL) patients. The aim of this meta-analysis was to comprehensively assess the prognostic value of CDKN2A/B deletions in ALL patients.

Methods: Systematic literature review was conducted in PubMed, Embase and Cochrane databases up to July 2018.

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We retrospectively analyzed the samples collected from 66 patients with PhALL enrolled on ChiCTR-TNRC-09000309 clinical trial. CR rate was 95.5%, and estimated 2-year OS and DFS were 51.

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The IKAROS family zinc finger 1 (IKZF1) gene is frequently altered in adults with B cell acute lymphoblastic leukemia (ALL). Although many studies have indicated that IKZF1 alterations might be associated with poor outcomes in adults with ALL, the results remain controversial. A previous meta-analysis demonstrated the negative prognostic significance of IKZF1 deletion in ALL.

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The inhibitory effects of recombinant porcine interferon alpha (rPoIFN-α) on the propagation of low-virulence PRRSV (lvPRRSV) in MARC-145 cells, and on the progress and severity of high virulence PRRSV (hvPRRSV)-induced infections in pigs, were determined. Pre-treatment of MARC-145 cells with increasing concentrations of rPoIFN-α prior to infection with lvPRRSV decreased the observed cytopathic effects (CPEs) in a concentration-dependent manner. Viral propagation and antibody response were temporarily delayed in swine treated with rPoIFN-α either at the same time as the hvPRRSV challenge was administered or post-challenge.

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Aim: To determine the relationship between biliary stricture and pigment gallstone formation, and the prevention of pigment gallstones with medicine.

Methods: One hundred and eighteen male guinea pigs were randomly divided into four groups: stricture group (S, n = 30) underwent partial ligation of common bile duct, and fed on regular chow; S plus medicine group (S+M, n = 27) underwent the same operation but fed on medicinal chow (0.3 g chenodeoxycholic acid, 0.

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