The identification and classification of candidate genes during the zygotic genome activation in the mammals.

Zygotic genome activation (ZGA) is a critical event in early embryonic development, and thousands of genes are involved in this delicate and sophisticated biological process. To date, however, only a handful of these genes have revealed their core functions in this special process, and therefore the roles of other genes still remain unclear. In the present study, we used previously published transcriptome profiling to identify potential key genes (candidate genes) in minor ZGA and major ZGA in both human and mouse specimens, and further identified the conserved genes across species. Our results showed that 887 and 760 genes, respectively, were thought to be specific to human and mouse in major ZGA, and the other 135 genes were considered to be orthologous genes. Moreover, the conserved genes were most enriched in rRNA processing in the nucleus and cytosol, ribonucleoprotein complex biogenesis, ribonucleoprotein complex assembly and ribosome large subunit biogenesis. The findings of this first comprehensive identification and characterization of candidate genes in minor and major ZGA provide relevant insights for future studies on ZGA.

The effect of female body mass index on cumulative live birth rate in women undergoing in vitro fertilization according to age.

The aim of this study was to explore the impact of female body mass index (BMI) on cumulative live birth rates (CLBR) in patients treated with in vitro fertilization (IVF) and embryo transfer. A total of 2377 patients who visited the Reproductive Medical Center, Luoyang Maternal and Child Health Hospital from January 2015 to December 2021. The patients underwent the first IVF cycles. According to female BMI, patients were divided into 3 groups, group A: BMI ≤ 18.5 kg/m2 (underweight), group B: BMI: 18.5 to 24.0 kg/m2 (normal), group C: BMI ≥ 24.0 kg/m2 (overweight/obesity). Patient basic parameters and clinical outcomes were compared among these 3 groups. Multivariate logistic regression analysis was used to explore the impact of BMI on CLBR. In all treatment cycles, patients' basic parameters were significantly different among 3 BMI groups. Age of underweight patient was younger than patients in the other 2 groups (28.45 ±â€…5.32 vs 29.89 ±â€…5.00 vs 30.74 ±â€…5.40; P = .000). In addition, number of oocytes retrieved was also significantly higher in group A (11.25 ±â€…5.97 vs 11.07 ±â€…5.49 vs 10.52 ±â€…5.02; P = .000). CLBR in these 3 groups were 66.40%, 65.98%, and 59.14%, respectively. In logistic analysis, overweight/obesity was associated with CLBR in young patients (aOR = 0.822, 95% CI: 0.817-0.957, P = .000). However, in the cycles of older patients, the effect of overweight/obesity on the CLBR was not significant (aOR = 0.986, 95% CI: 0.903-1.027, P > .05). Overweight/obesity is a predictor for CLBR in younger patients (<35 years old), but not in advanced age patients undergoing their first IVF/intracytoplasmic sperm injection treatment cycles.

EGR1/LINC00839/SOX5 axis modulates migration, invasion and Gemcitabine resistance of bladder cancer cells.

BACKGROUND: Bladder cancer is one of the most common malignant tumors of the urinary system, and its incidence is increasing worldwide. However, the underlying mechanisms that trigger migration, invasion and chemotherapy resistance are unclear. RESULTS: Bioinformatics analysis of bladder cancer cohort indicated that LINC00839 is deregulated in bladder cancer. LINC00839 was validated and highly expressed in bladder cancer patients and cell lines. In addition, LINC00839 induced the migration, invasion and Gemcitabine resistance of bladder cancer cells. We identified that the transcription factor EGR1 directly repressed LINC00839 and thereby suppressed the migration and invasion of bladder cancer cells. Furthermore, LINC00839 interacted with miR-142, which subsequently regulated the expression of SOX5, a well-studied oncogene and targeted by miR-142. In addition, EGR1 served as a suppressive transcription factor of SOX5. Therefore, EGR1 directly or indirectly regulates SOX5 via LINC00839/miR-142 axis. LINC00839 induced Gemcitabine resistance by promoting autophagy. CONCLUSIONS: EGR1, LINC00839/miR-142 and SOX5 form a coherent feed-forward loop that modulates the migration, invasion and Gemcitabine resistance of bladder cancer.

Pediatric hypereosinophilic syndrome associated with liver damage, portal vein, splenic vein and superior mesenteric vein thromboses: a case report.

BACKGROUND: The hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent eosinophilia and damage to multiple organs. HES can be either primary, secondary or idiopathic. Secondary HES are commonly caused by parasitic infections, allergic reactions or cancer. We described a pediatric case of HES associated with liver damage and multiple thrombi. A 12-year-old boy with eosinophilia was complicated with severe thrombocytopenia, liver damage, portal vein, splenic vein, and superior mesenteric vein thromboses. The thrombi recanalized after treatment with methylprednisolone succinate and low molecular weight heparin. No side effects appeared after 1-month. CONCLUSIONS: Corticosteroids should be used at an early stage of HES to prevent further damage to vital organs. Anticoagulants should be recommended only in cases with thrombosis which should be actively screened as a part of evaluation of end organ damage.

hsa_circ_0139402 Promotes Bladder Cancer Progression by Regulating hsa-miR-326/PAX8 Signaling.

BACKGROUND: Bladder cancer (BC) is a malignant and common malignant tumors. However, the prognosis of most patients with bladder cancer is still poor, and it is particularly important to identify early tumor diagnostic and treatment targets. MATERIALS AND METHODS: High-throughput sequencing was used to evaluate the expression level of circRNA in bladder cancer tissue. MTT assay, wound healing assay, and transwell assay were used to detect the cancer cells' proliferation, migration, and invasion affected by hsa_circ_0139402. The possible miRNA targets of hsa_circ_0139402 and downstream genes were detected by bioinformatics methods and dual-luciferase reporting experiment. FISH was used to observe their interaction. RESULTS: High-throughput sequencing result showed that the expression of hsa_circ_0139402 was highest in BC tissues and increased in metastatic tissues compared to that of nonmetastatic tissues. MTT assay, wound healing assay, and transwell assay revealed that sh-hsa_circ_0139402 could suppress BC cells' proliferation, invasion, and migration. Bioinformatics analysis, dual-luciferase reporter, and RIP assay showed that hsa_circ_0139402 can bind to hsa-miR-326, and PAX8 is a direct target of hsa-miR-326 in BC cell. Further, cytological studies found that hsa_circ_0139402 enhances BC cells' proliferation, migration, and invasion by targeting PAX8 via hsa-miR-326. CONCLUSION: hsa_circ_0139402 plays a oncogene in BC and that can effectively promote cell proliferation, migration, invasion, and EMT by targeting Paired Box Protein Pax-8 (PAX8) via hsa-miR-326 and provides a potential therapeutic target for BC patients.

Hydroalcoholic extract from Abelmoschus manihot (Linn.) Medicus flower reverses sleep deprivation-evoked learning and memory deficit.

Previous researches have indicated that sleep plays a vital role in cognitive functions. Sleep deprivation (SD) causes learning and memory damage, which is associated with oxidative stress. This study was performed to investigate the neuroprotective effects of an extract of Abelmoschus manihot flower (EAM) against memory deficit induced by SD in mice. The SD model was evoked by multiple platform method for 5 days, successively. The learning and memory-improving effects of EAM were assessed by behavioral trials and the underlying mechanism was investigated by measuring the oxidative stress alteration. Our findings indicated that the SD-induced memory deficit and the EAM treatment improved the cognitive functions of mice in the object location recognition test and passive avoidance task. In addition, EAM effectively improved the activities of the antioxidant enzyme, decreased the content of malondialdehyde (MDA), and restored the protein expression of the brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB) and glutamate receptor 1 (GluR1) in brain tissues. In conclusion, EAM could improve the SD-evoked learning and memory impairments. The possible underlying mechanisms of EAM may be related to its antioxidant capacity and enhanced BDNF/TrkB/GluR1 levels in the hippocampal memory.

The biologically functional identification of a novel TIM3-binding peptide P26 in vitro and in vivo.

PURPOSE: Recent studies have shown that TIM3 plays an important role in T-cell failure, which is closely related to the resistance to anti-programmed cell death protein 1 (PD-1) treatment. However, there have been no reports on the application of peptide blockers to TIM3. In this study, we endeavored to identify the in vitro and in vivo anti-tumor activities of a TIM3-targeting peptide screened from the phage peptide library. METHODS: Phage display peptide library technology, surface plasmon resonance, flow cytometry, and mixed lymphocyte reaction were utilized to screen and demonstrate the bioactivities of P26, a TIM3-targeting peptide. Meanwhile, tumor growth assay was performed to evaluate the anti-tumor effect of P26. RESULTS: In terms of affinity, we demonstrated that P26 specifically binds to TIM3 at the cellular and molecular levels, which therefore blocks the interaction between TIM3 and Galectin-9 (Gal-9) and competes with Gal-9 to bind TIM3. Additionally, P26 significantly increases T-cell activity and elevates IFN-γ and IL-2 levels in a dose-dependent manner. Notably, P26 also counteracts Gal-9-mediated T-cell suppression. More importantly, P26 can inhibit growth of MC38-hPD-L1 tumor in mice. CONCLUSIONS: P26, as a novel TIM3-binding peptide, has the ideal bioactivity connecting to TIM3 and the potential prospect of application in immunotherapy as an alternative or adjuvant to existing agents.

A retrospective study of probiotics for the treatment of children with antibiotic-associated diarrhea.

This retrospective study aimed to explore the benefits and safety of probiotics (live combined Bacillus subtilis and Enterococcus faecium granules with multivitamines) for the treatment of children with antibiotic-associated diarrhea (AAD).A total of 72 children with AAD were analyzed in this study. Of these, 36 children received routine treatment plus probiotics, and were assigned to a treatment group. The other 36 children underwent routine treatment alone, and were assigned to a control group. Patients in both groups were treated for a total of 7 days. The efficacy and safety were evaluated by duration of diarrhea (days), number of dressings needed daily, abdominal pain intensity, stool consistency (as assessed by Bristol Stool Scale (BSS)), and any adverse events.After treatment, probiotics showed encouraging benefits in decreasing duration of diarrhea (days) (P < .01), number of dressings needed every day (P < .01), abdominal pain intensity (P < .01), and stool consistency (BSS (3-5), P < .01; BSS (6-7), P < .01). In addition, no adverse events were documented in this study.The findings of this study demonstrated that probiotics may provide promising benefit for children with AAD. Further studies are still needed to warrant theses findings.

Effect of nano yam polysaccharide on the blood glucose and blood lipid in rats.

Chinese yam is the dry rhizome of dioscoreaceae plant. Polysaccharide in yam is one of significant functional components, its pharmacological effects include glucose-lowering, lipid-lowering, anti-tumor, anti-oxidation and enhancing the immune. The effects of nano yam polysaccharide on the metabolism of blood glucose and blood lipid in model rats were systematically investigated in this study. The results showed that the diabetic rat model can been successfully induced by the peritoneal injection of 200mg/kg alloxan. The rats were fed with the high-fat diet for 30d, which could induce a model of hyperlipidemia rat successfully. After the model rats were fed with nano yam polysaccharide of 50mg/ml and 100mg/ml per day for 12d and 30d, respectively. For each nano yam polysaccharide group, the blood glucose level was significantly reduced, the glucose tolerance, glycogen and the content of C-peptide were improved in alloxan rats. Moreover, the symptom of one little and three more in diabetic rats was ameliorated and the contents of TC, TG and LDL-C in the serum for the high fat rats were significantly decreased.

Randomized controlled clinical trial comparing the efficacy and tolerability of aripiprazole and sodium valproate in the treatment of Tourette syndrome.

OBJECTIVE: This study compared the efficacy and tolerability of sodium valproate and aripiprazole in the treatment of Tourette syndrome (TS). METHOD: 24 children and adolescents with a diagnosis of TS from the Jiamusi Central Hospital between January 2014 and August 2017 were randomly divided into sodium valproate group and aripiprazole group according to the order of clinic visits and treated for 10 days. Tic severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impressions Scale for tics (CGI-Tics) and the adverse reactions were valued using the Treatment Emergent Symptom Scale (TESS) at baseline and at each follow-up visit. RESULTS: The TTS score in the YGTSS scale decreased over time in both groups while the aripiprazole group was significantly higher on the 5th day (p < 0.05) and 10th day (p < 0.05) than the sodium valproate group. There was no significant difference in TESS score between the two groups. CONCLUSIONS: The study indicates that the patients treated with sodium valproate injection have a faster onset time than the patients treated with oral aripiprazole in controlling tics.

CXCL5, the upregulated chemokine in patients with uterine cervix cancer, in vivo and in vitro contributes to oncogenic potential of Hela uterine cervix cancer cells.

CXCL5 is showed a surprisingly elevated profile and implicated in tumorigenesis in several tumors. However, the expression and function of CXCL5 in uterine cervix cancer (UCC) remain largely unknown. The current study aimed to elucidate the expression pattern of CXCL5 in human UCC tissues and Hela cervix cancer cell, as well as its functions in Hela cells. Our data showed that CXCL5 and its receptor CXCR2 were expressed by Hela uterine cervix cancer cells. CXCL5 was upregulated in UCC tissues, and its overexpression was positively correlated with age, but did not correlate with clinical stages and tumor infiltration. Exogenous administration of CXCL5 and CXCL5 overexpression contributed to proliferation and migration activities of Hela cells in vitro, consistent with this, CXCL5 overexpression also promoted growth of Hela cells in a nude mouse xenograft model. At the gene level, CXCL5 overexpression regulated the expression of tumor-related genes including ERK, p-ERK, AKT, p-AKT, DIABOL, NUMB, NDRG3 and CXCR2. Taken together, CXCL5 may contribute to a dominant role in UCC progression and sever as a potential molecular therapeutic target for UCC.

CDKN1C (P57): one of the determinants of human endometrial stromal cell decidualization.

Decidualization is regulated by crosstalk of progesterone and the cAMP pathway. It involves extensive reprogramming of gene expression and includes a wide range of functions. To investigate how cell cycle regulatory genes drive the human endometrial stromal cell (ESC) exit cell cycle and enter differentiation, primary cultured ESC was treated with 8-Br-cAMP and MPA and cell cycle distribution was investigated by flow cytometry. High-throughput cell cycle regulatory gene expression was also studied by microarray. To validate the results of microarray chip, immunohistochemistry and semi-quantitative method of optical density were used to analyze the expression of cell cycle regulator proteins in proliferative phase of endometrium (n = 6) and early pregnancy decidua (n = 6). In addition, we selected cyclin-dependent kinase inhibitor 1c (CDKN1C, also known as P57) and cyclin-dependent kinase inhibitor 2b (CDKN2B, also known as P15) in order to study their role in the process of decidualization by the RNAi method. ESC was arrested at G0/G1 checkpoints during decidualization. Cell cycle regulatory genes P57 and P15 were upregulated, while cyclin D1 (CCND1), cyclin-dependent kinase 2 (CDK2), and cell division cycle protein 2 homolog (CDC2) were downregulated during ESC differentiation both in vitro and vivo. P57 siRNA impaired ESC decidualization and caused different morphological and ultrastructural changes as well as a relatively low secretion of prolactin, but P15 siRNA had no effects. We concluded that P15, CCND1, CDK2, and CDC2 may participate in ESC withdraw from the cell cycle and go into differentiation both in vitro and in vivo. P57 is one of the key determinants of ESC differentiation due to its effect on the cell cycle distribution, but its association with the decidua-specific transcription factor needs further investigation.

Draft Genome Sequence of Staphylococcus succinus subsp. succinus Type Strain DSM 14617, Isolated from Plant and Soil Inclusions within 25- to 35-Million-Year-Old Dominican Amber.

Staphylococcus succinus subsp. succinus type strain DSM 14617 was isolated from plant and soil inclusions within 25- to 35-million-year-old Dominican amber. The complete genome sequence of strain DSM 14617T includes a genome of 2.88 Mb (32.94% G+C content) without any plasmids.

Effect of dopamine receptor 1 on apoptosis of cultured neonatal rat cardiomyocytes in simulated ischaemia/reperfusion.

Dopamine receptors exist in many tissues, including rat cardiac tissue. However, the physiological importance of dopamine receptors in the homeostatic regulation of cardiac function is unclear. In this study, a model of ischaemia/reperfusion was established by culturing primary neonatal rat cardiomyocytes in ischaemia-mimetic solution for 2 hr, followed by incubation in normal culture medium for 24 hr. Lactate dehydrogenase activity, superoxide dismutase activity and malondialdehyde content were determined colorimetrically with a spectrophotometer. Apoptotic cell death was assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling staining and flow cytometry, and morphological alterations were observed with transmission electron microscopy. The intracellular free calcium concentration ([Ca2+]i) was measured by confocal laser scanning microscopy. Finally, the expression of dopamine receptor 1 (DR1), caspase-3, -8 and -9, Fas, Fas ligand and Bcl-2 and the release of cytochrome c were analysed by Western blot. The results showed that DR1 expression was increased markedly during ischaemia/reperfusion. Treatment with 10 microM SKF-38393 (DR1 agonist) significantly increased lactate dehydrogenase activity, decreased superoxide dismutase activity and increased malondialdehyde content in the culture medium. The DR1 agonist promoted the release of cytochrome c, accumulation of [Ca2+]i, and apoptosis induced by ischaemia/reperfusion. Furthermore, SKF-38393 up-regulated the expression of caspase-3, -8 and -9, Fas and Fas ligand, and down-regulated Bcl-2 expression. In contrast, 10 microM SCH-23390 (DR1 antagonist) had no significant effects on the above indicators. In conclusion, DR1 activation is involved in the apoptosis of cultured neonatal rat cardiomyocytes in simulated ischaemia/reperfusion through the mitochondrial and death receptor pathways.