Association between MAP3K4 gene polymorphisms and the risk of schizophrenia susceptibility in a Northeast Chinese Han population.

Schizophrenia stands out as one of the most devastating psychiatric disorders. Previous findings have shown that schizophrenia is a polygenic genetic disorder. Thus, abnormal neurodevelopment and neurogenesis may be associated with the etiology of schizophrenia, so genes which affect these processes may be potential candidate genes of schizophrenia. Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) gene is a member of the mitogen-activated protein kinase family. Taking into account previous findings, MAP3K4 plays a crucial role in the fundamental pathology of various nervous system diseases. In the present study, we aim to explore the association of MAP3K4 and schizophrenia in an independent case-control sample including 627 schizophrenic patients and 1175 healthy controls from a Northeast Chinese Han population. Both the allelic and genotypic association analyses showed that 6 SNPs in MAP3K4 were significantly associated with schizophrenia (rs590988, rs625977, rs9295134, rs12110787, rs1001808 and rs9355870). After rigorous Bonferroni correction, 4 SNPs (rs9295134, rs12110787, rs1001808 and rs9355870) were still significantly associated with the disease. The haplotype composed of these four SNPs also showed significantly global and individual association with schizophrenia. These results suggest that MAP3K4 is a susceptibility gene for schizophrenia in the Northeast Chinese Han population.

Laparoscopic versus open pancreatic resection for ductal adenocarcinoma: separate propensity score matching analyses of distal pancreatectomy and pancreaticoduodenectomy.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading causes of cancer mortality worldwide. Currently, laparoscopic pancreatic resection (LPR) is extensively applied to treat benign and low-grade diseases related to the pancreas. The viability and safety of LPR for PDAC needs to be understood better. Laparoscopic distal pancreatectomy (LDP) and pancreaticoduodenectomy (LPD) are the two main surgical approaches for PDAC. We performed separate propensity score matching (PSM) analyses to assess the surgical and oncological outcomes of LPR for PDAC by comparing LDP with open distal pancreatectomy (ODP) as well as LPD with open pancreaticoduodenectomy (OPD). METHODS: We assessed the data of patients who underwent distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) for PDAC between January 2004 and February 2020 at our hospital. A one-to-one PSM was applied to prevent selection bias by accounting for factors such as age, sex, body mass index, and tumour size. The DP group included 86 LDP patients and 86 ODP patients, whereas the PD group included 101 LPD patients and 101 OPD patients. Baseline characteristics, intraoperative effects, postoperative recovery, and survival outcomes were compared. RESULTS: Compared to ODP, LDP was associated with shorter operative time, lesser blood loss, and similar overall morbidity. Of the 101 patients who underwent LPD, 10 patients (9.9%) required conversion to laparotomy. The short-term surgical advantage of LPD is not as apparent as that of LDP due to conversions. Compared with OPD, LPD was associated with longer operative time, lesser blood loss, and similar overall morbidity. For oncological and survival outcomes, there were no significant differences in tumour size, R0 resection rate, and tumour stage in both the DP and PD subgroups. However, laparoscopic procedures appear to have an advantage over open surgery in terms of retrieved lymph nodes (DP subgroup: 14.4 ± 5.2 vs. 11.7 ± 5.1, p = 0.03; PD subgroup 21.9 ± 6.6 vs. 18.9 ± 5.4, p = 0.07). These two groups did not show a significant difference in the pattern of recurrence and overall survival rate. CONCLUSIONS: Laparoscopic DP and PD are feasible and oncologically safe procedures for PDAC, with similar postoperative outcomes and long-term survival among patients who underwent open surgery.

Imperfect-interaction-free entanglement purification on stationary systems for solid quantum repeaters.

Solid quantum repeater is a core part in a large-scale quantum network. Entanglement purification, the key technique in a quantum repeater, is used to distill high-quality nonlocal entanglement from an ensemble in a mixed entangled state and to depress the vicious influence on quantum information carriers caused by noise. Here, we present an imperfect-interaction-free entanglement purification on nonlocal electron spins in quantum dots for solid quantum repeaters, using faithful parity check on electron spins. The faithful parity check can make correct judgement on the parity mode without destructing the nonlocal solid entanglement even with the imperfect interaction between a QD embedded inside a microcavity and a circularly polarized photon in the nearly realistic condition. Therefore, the imperfect-interaction-free entanglement purification can prevent the maximally entangled states from being changed into partially entangled ones and guarantee the fidelity of the nonlocal mixed state to a desired one after purification. As this scheme is feasible in the nearly realistic condition with imperfect interaction, the requirements for experimental implementation will be relaxed. These distinctive features make this imperfect-interaction-free entanglement purification have more practical applications in solid quantum repeaters for a large-scale quantum network.

Complete analysis of hyperentangled Bell states assisted with auxiliary hyperentanglement.

We present a simple protocol for complete analysis of 16 hyperentangled Bell states of two-photon system in the polarization and the first longitudinal momentum degrees of freedom (DOFs). This complete analysis protocol is accomplished with the auxiliary hyperentangled Bell state in the frequency and the second longitudinal momentum DOFs utilizing the experimentally available optical elements including linear optical elements which manipulate the polarizations and the longitudinal momentums and the optical devices which manipulate frequencies of photons. This complete analysis protocol allows the transmission of log216=4 bits of classical information via quantum hyperdense coding scheme, which is the upper bound of the transmission capacity of the quantum hyperdense coding scheme based on 16 orthogonal hyperentangled Bell states. This complete analysis protocol has a potential to be experimentally realized and is useful for high-capacity quantum communication based on hyperentangled states.

Self-error-corrected hyperparallel photonic quantum computation working with both the polarization and the spatial-mode degrees of freedom.

Usually, the hyperparallel quantum computation can speed up quantum computing, reduce the quantum resource consumed largely, resist to noise, and simplify the storage of quantum information. Here, we present the first scheme for the self-error-corrected hyperparallel photonic quantum computation working with both the polarization and the spatial-mode degrees of freedom of photon systems simultaneously. It can prevent bit-flip errors from happening with an imperfect nonlinear interaction in the nearly realistic condition. We give the way to design the universal hyperparallel photonic quantum controlled-NOT (CNOT) gate on a two-photon system, resorting to the nonlinear interaction between the circularly polarized photon and the electron spin in the quantum dot in a double-sided microcavity system, by taking the imperfect interaction in the nearly realistic condition into account. Its self-error-corrected pattern prevents the bit-flip errors from happening in the hyperparallel quantum CNOT gate, guarantees the robust fidelity, and relaxes the requirement for its experiment. Meanwhile, this scheme works in a failure-heralded way. Also, we generalize this approach to achieve the self-error-corrected hyperparallel quantum CNOTN gate working on a multiple-photon system. These good features make this scheme more useful in the photonic quantum computation and quantum communication in the future.

Error-detected generation and complete analysis of hyperentangled Bell states for photons assisted by quantum-dot spins in double-sided optical microcavities.

We construct an error-detected block, assisted by the quantum-dot spins in double-sided optical microcavities. With this block, we propose three error-detected schemes for the deterministic generation, the complete analysis, and the complete nondestructive analysis of hyperentangled Bell states in both the polarization and spatial-mode degrees of freedom of two-photon systems. In these schemes, the errors can be detected, which can improve their fidelities largely, far different from other previous schemes assisted by the interaction between the photon and the QD-cavity system. Our scheme for the deterministic generation of hyperentangled two-photon systems can be performed by repeat until success. These features make our schemes more useful in high-capacity quantum communication with hyperentanglement in the future.

Diffuse filiform polyposis of the small intestine without inflammatory bowel disease.

Filiform polyposis is a rare disease, which typically occurs in patients with inflammatory bowel disease. We report a case of filiform polyposis occurring in a 56-year-old man with no history or evidence of inflammatory bowel disease. The patient's main symptoms were melena and anemia. We performed an emergency exploratory laparotomy, in which we observed worm-like polyps spread almost along the entire small intestine, and a partial resection of the small intestine to treat bleeding in the bowel was carried out. Two days later, the patient was noted to have melena again, and we performed an abdominal angiographic embolization, successfully stopping the bleeding. Histologic evaluation of the excised specimen revealed chronic inflammatory cells within the lamina propria without hyperplastic or adenomatous epithelial changes. Although the surgery was very successful, careful management of the patient was required, owing to the great risk of re-bleeding.

[Hydrochemical and Stable Isotopic Characteristics and Transformation Relationship of Water Bodies in the Guohe River Basin, Anhui Province].

The Guohe River Basin in Anhui Province was selected as the research area for this study. By collecting surface water, shallow groundwater, and middle-deep groundwater samples, various hydrochemical parameters and stable isotopes of water in different water bodies were analyzed using methods such as the Gibbs diagram, ion ratios, and MixSIAR model to reveal and quantify the transformation relationships between these water bodies. The results indicated that both surface water and groundwater in the study area were predominantly neutral to weakly alkaline. The hydrochemical types of surface water were mainly characterized by Cl·SO4·HCO3-Na and Cl·SO4-Na types, whereas the shallow groundwater exhibited HCO3-Ca·Mg and HCO3-Mg·Na types, and the middle-deep groundwater was of the Cl·HCO3-Na type. The hydrochemical characteristics of various water bodies were influenced by multiple factors such as rock weathering, evaporation concentration, and positive cation exchange. The distribution characteristics of δ18O and δ2H values in surface water and groundwater indicated that atmospheric precipitation was the main water source. The δ18O and δ2H in groundwater were significantly correlated with K+, Na+, Cl-, SO42-, and NO3-. According to the analysis using the MixSIAR model, the contribution of atmospheric precipitation to surface water was 46.5 %, whereas the contribution from shallow groundwater was 53.5 %. The sources of shallow groundwater were identified as atmospheric precipitation (57.4 %) and surface water (42.6 %), and the main source of supply for middle-deep groundwater was lateral flow from upstream groundwater.

Protective effect of rosmarinic acid-rich extract from Trichodesma khasianum Clarke against microbiota dysbiosis in high-fat diet-fed obese mice.

Hypertrophy of adipose tissues and dysbiosis are hallmarks of obesity. Although drugs are applied for obesity treatment, side effects limit their use. The anti-obesity capacity of rosmarinic acid (RA) has been documented. Trichodesma khasianum Clarke is an edible RA-rich plant grown in Taiwan. Our previous study found that an 80 % ethanol extract of T. khasianum Clarke leaves (80EETC) ameliorates gastric mucosal damage through its anti-inflammatory, antioxidant, and microbiota modulation abilities. However, the anti-obesity effect of 80EETC remains unclear. Therefore, the objective of this study was to explore the protective effects of low-dose 80EETC (125 mg/kg b.w., 80EETCL) or high-dose 80EETC (250 mg/kg b.w., 80EETCH) on obesity development through gut microbiota modulation in high-fat diet (HFD)-induced C57BL/6 mice. The results showed a high RA content (89.2 ± 7.4 mg/g) in 80EETC. 80EETC administration significantly decreased body weight, body fat ratio, serum lipid levels (TC, TG, and LDL-C), adipose tissue accumulation, malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) in HFD-fed mice. Furthermore, supplementation with 80EETC reduced the Firmicutes/Bacteroidetes ratio and enhanced the relative abundance of gut microbiota (p_Bacteroidetes, f_Lactobacillus, f_Muribaculaceae, f_Prevotellaceae, g_Lactobacillus, g_Prevotellaceae_NK3B31_group, g_Ruminococcaceae_UCG-013, and g_Ruminococcaceae_UCG-014), which negatively correlated with obesity-related factors such as body weight, energy intake, fat accumulation in adipose tissue, TC, TG, LDL, and MDA. In conclusion, RA-rich 80EETC had a protective effect against obesity development and it has potential in healthy food applications.

BMI-1 activates hepatic stellate cells to promote the epithelial-mesenchymal transition of colorectal cancer cells.

BACKGROUND: Activated hepatic stellate cells (aHSCs) are the major source of cancer-associated fibroblasts in the liver. Although the crosstalk between aHSCs and colorectal cancer (CRC) cells supports liver metastasis (LM), the mechanisms are largely unknown. AIM: To explore the role of BMI-1, a polycomb group protein family member, which is highly expressed in LM, and the interaction between aHSCs and CRC cells in promoting CRC liver metastasis (CRLM). METHODS: Immunohistochemistry was carried out to examine BMI-1 expression in LM and matched liver specimens of CRC. The expression levels of BMI-1 in mouse liver during CRLM (0, 7, 14, 21, and 28 d) were detected by Western blotting (WB) and the quantitative polymerase chain reaction (qPCR) assay. We overexpressed BMI-1 in HSCs (LX2) by lentivirus infection and tested the molecular markers of aHSCs by WB, qPCR, and the immunofluorescence assay. CRC cells (HCT116 and DLD1) were cultured in HSC-conditioned medium (LX2 NC CM or LX2 BMI-1 CM). CM-induced CRC cell proliferation, migration, epithelial-mesenchymal transition (EMT) phenotype, and transforming growth factor beta (TGF-ß)/SMAD pathway changes were investigated in vitro. A mouse subcutaneous xenotransplantation tumor model was established by co-implantation of HSCs (LX2 NC or LX2 BMI-1) and CRC cells to investigate the effects of HSCs on tumor growth and the EMT phenotype in vivo. RESULTS: Positive of BMI-1 expression in the liver of CRLM patients was 77.8%. The expression level of BMI-1 continued to increase during CRLM in mouse liver cells. LX2 overexpressed BMI-1 was activated, accompanied by increased expression level of alpha smooth muscle actin, fibronectin, TGF-ß1, matrix metalloproteinases, and interleukin 6. CRC cells cultured in BMI-1 CM exhibited enhanced proliferation and migration ability, EMT phenotype and activation of the TGF-ß/SMAD pathway. In addition, the TGF-ßR inhibitor SB-505124 diminished the effect of BMI-1 CM on SMAD2/3 phosphorylation in CRC cells. Furthermore, BMI-1 overexpressed LX2 HSCs promoted tumor growth and the EMT phenotype in vivo. CONCLUSION: High expression of BMI-1 in liver cells is associated with CRLM progression. BMI-1 activates HSCs to secrete factors to form a prometastatic environment in the liver, and aHSCs promote proliferation, migration, and the EMT in CRC cells partially through the TGF-ß/SMAD pathway.

Active Ingredients of Reduning Injection Maintain High Potency against SARS-CoV-2 Variants.

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC50) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC50 lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS: The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.

Spatial distribution characteristics and prediction of fluorine concentration in groundwater based on driving factors analysis.

Excess fluoride (F-) in groundwater can be hazardous to human health. A total of 360 ground water samples was collected from northern Anhui, China, to study the levels, distribution, and source of F-. And on this basis, predicting the spatial distribution of F- in a wider scale space. The range of F- was 0.1-5.8 mg/L, with a mean value of 1.2 mg/L, and 26.4 % of the samples exceeded the acceptable level of 1.5 mg/L. Moreover, the water-rock interaction (fluorite dissolution) and cation alternate adsorption were considered to be two main driving factors of high F- in groundwater. To further illustrate the spatial effects, the BME-RF model was established by combining the main environmental factors. The spatial distribution of F- was quantitatively predicted, and the response to environmental variables was analyzed. The R2 of BME-RF model reached 0.93, the prediction results showed that the region with 1.0-1.5 mg/L of F- accounts for 47.2 % of the total area. The predicted F- content of nearly 70 % of groundwater in this area has exceeded 1.0 mg/L, which was dominated by Na+ and HCO3- type. The spatial variability of F- in the study area was mainly affected by hydrogeological conditions, and the vertical distribution characteristics were related to the spatial variation of slope, distance from runoff, and hydrochemical types. The results of the study provide new insights into the F- concentration prediction in underground environment, especially in the borehole gap area.

Positive Association of TEAD1 With Schizophrenia in a Northeast Chinese Han Population.

OBJECTIVE: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case-control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. METHODS: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. RESULTS: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. CONCLUSION: The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.

Pregnane X receptor (PXR) deficiency protects against spinal cord injury by activating NRF2/HO-1 pathway.

INTRODUCTION: As a devastating neurological disease, spinal cord injury (SCI) results in severe tissue loss and neurological dysfunction. Pregnane X receptor (PXR) is a ligand-activated nuclear receptor with a major regulatory role in xenobiotic and endobiotic metabolism and recently has been implicated in the central nervous system. In the present study, we aimed to investigate the role and mechanism of PXR in SCI. METHODS: The clip-compressive SCI model was performed in male wild-type C57BL/6 (PXR+/+ ) and PXR-knockout (PXR-/- ) mice. The N2a H2 O2 -induced injury model mimicked the pathological process of SCI in vitro. Pregnenolone 16α-carbonitrile (PCN), a mouse-specific PXR agonist, was used to activate PXR in vivo and in vitro. The siRNA was applied to knock down the PXR expression in vitro. Transcriptome sequencing analysis was performed to discover the relevant mechanism, and the NRF2 inhibitor ML385 was used to validate the involvement of PXR in influencing the NRF2/HO-1 pathway in the SCI process. RESULTS: The expression of PXR decreased after SCI and reached a minimum on the third day. In vivo, PXR knockout significantly improved the motor function of mice after SCI, meanwhile, inhibited apoptosis, inflammation, and oxidative stress induced by SCI. On the contrary, activation of PXR by PCN negatively influenced the recovery of SCI. Mechanistically, transcriptome sequencing analysis revealed that PXR activation downregulated the mRNA level of heme oxygenase-1 (HO-1) after SCI. We further verified that PXR deficiency activated the NRF2/HO-1 pathway and PXR activation inhibited this pathway in vitro. CONCLUSION: PXR is involved in the recovery of motor function after SCI by regulating NRF2/HO-1 pathway.

Protective effects of camellia and olive oils against cognitive impairment via gut microbiota-brain communication in rats.

Food intake influences neurofunction via the gut microbiota-brain axis. Monounsaturated fatty acid (MUFA) consumption is highly associated with neuroprotection; the mechanism behind the effects of olive oil and camellia oil on gut microbiota remains unclear. In this study, the objective was to compare the neuroprotective role of oleic acid-rich camellia oil and olive oil against AlCl3-induced mild cognitive impairment (MCI) in rats. Morris water maze tests revealed that learning and memory capacities improved in AlCl3-induced rats subjected to camellia oil administration better than olive oil treatment. Moreover, the results showed that the camellia oil- and olive oil-treated AlCl3-induced rat groups had significantly reduced oxidative stress and inflammatory cytokines. Notably, Spearman correlation analysis indicated that the inflammatory cytokines negatively correlated with the microbial strains (Bacteroides pectinophilus_group and Blautia) in response to camellia oil administration. Furthermore, Ruminococcaceae_UCG014 abundance was significantly enhanced by camellia oil intake, which was highly positively associated with antioxidant activity expression. In conclusion, the novel data suggest that the outcomes of camellia oil consumption were superior to those of olive oil intake as camellia oil may have a beneficial effect on MCI protection and improvement through the gut microbiota-brain communication.

Current knowledge about the outbreak of acute severe hepatitis of unknown origin among children.

Background and Aim: A recent outbreak of acute severe hepatitis of unknown etiology (ASHep-UA) among children 16 years old and younger has aroused global concern. Initially reported in central Scotland, the disease has been notified in 35 countries and linked to 22 deaths as of 25 September 2022. This review aimed to provide current knowledge about the outbreak of ASHep-UA. Methods and Results: The websites of the World Health Organization, the UK Health Security Agency, the European Center for Disease Prevention and Control, the Centers for Disease Control and Prevention, and the PubMed database were searched, based on the search term "acute severe hepatitis of unknown etiology." The corresponding reports or literature previously released by the mentioned websites and database were integrated to obtain current information about ASHep-UA. Conclusion: Even though the potential relevance between ASHep-UA and adenovirus, adeno-associated virus 2, and human herpes viruses was revealed, the etiology of ASHep-UA is still unknown. More effort should be made to explore whether ASHep-UA is caused by a novel virus or other environmental factors, to generate appropriate treatment strategies. Relevance to Patients: ASHep-UA has aroused global concern recently, which may lead to adverse outcomes such as liver transplants and death. The present review shares current development and information about the outbreak of acute severe hepatitis of unknown origin among children.

Qingyi decoction attenuates intestinal epithelial cell injury via the calcineurin/nuclear factor of activated T-cells pathway.

BACKGROUND: Recent studies have demonstrated that dysfunction of the intestinal barrier is a significant contributing factor to the development of severe acute pancreatitis (SAP). A stable intestinal mucosa barrier functions as a major anatomic and functional barrier, owing to the balance between intestinal epithelial cell (IEC) proliferation and apoptosis. There is some evidence that calcium overload may trigger IEC apoptosis and that calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) signaling might play an important role in calcium-mediated apoptosis. AIM: To investigate the potential mechanisms underlying the therapeutic effect of Qingyi decoction (QYD) in SAP. METHODS: A rat model of SAP was created via retrograde infusion of sodium deoxycholate. Serum levels of amylase, tumor necrosis factor (TNF-α), interleukin (IL)-6, D-lactic acid, and diamine oxidase (DAO); histological changes; and apoptosis of IECs were examined in rats with or without QYD treatment. The expression of the two subunits of CaN and NFAT in intestinal tissue was measured via quantitative real-time polymerase chain reaction and western blotting. For in vitro studies, Caco-2 cells were treated with lipopolysaccharide (LPS) and QYD serum, and then cell viability and intracellular calcium levels were detected. RESULTS: Retrograde infusion of sodium deoxycholate increased the severity of pancreatic and intestinal pathology and the levels of serum amylase, TNF-α, and IL-6. Both the indicators of intestinal mucosa damage (D-lactic acid and DAO) and the levels of IEC apoptosis were elevated in the SAP group. QYD treatment reduced the serum levels of amylase, TNF-α, IL-6, D-lactic acid, and DAO and attenuated the histological findings. IEC apoptosis associated with SAP was ameliorated under QYD treatment. In addition, the protein expression levels of the two subunits of CaN were remarkably elevated in the SAP group, and the NFATc3 gene was significantly upregulated at both the transcript and protein levels in the SAP group compared with the control group. QYD significantly restrained CaN and NFATc3 gene expression in the intestine, which was upregulated in the SAP group. Furthermore, QYD serum significantly decreased the LPS-induced elevation in intracellular free Ca2+ levels and inhibited cell death. CONCLUSION: QYD can exert protective effects against intestinal mucosa damage caused by SAP and the protective effects are mediated, at least partially, by restraining IEC apoptosis via the CaN/NFATc3 pathway.

Inhibition of microRNA-129-2-3p protects against refractory temporal lobe epilepsy by regulating GABRA1.

BACKGROUND: Accumulating evidence demonstrates that certain microRNAs play critical roles in epileptogenesis. Our previous studies found microRNA (miR)-129-2-3p was induced in patients with refractory temporal lobe epilepsy (TLE). In this study, we aimed to explore the role of miR-129-2-3p in TLE pathogenesis. METHOD: By bioinformatics, we predicted miR-129-2-3p may target the gene GABRA1 encoding the GABA type A receptor subunit alpha 1. Luciferase assay was used to investigate the regulation of miR-129-2-3p on GABRA1 3'UTR. The dynamic expression of miR-129-2-3p and GABRA1 mRNA and protein levels were measured in primary hippocampal neurons and a rat kainic acid (KA)-induced seizure model by quantitative reverse transcription-polymerase chain reaction (qPCR), Western blotting, and immunostaining. MiR-129-2-3p agomir and antagomir were utilized to explore their role in determining GABRA1 expression. The effects of targeting miR-129-2-3p and GABRA1 on epilepsy were assessed by electroencephalography (EEG) and immunostaining. RESULTS: Luciferase assay, qPCR, and Western blot results suggested GABRA1 as a direct target of miR-129-2-3p. MiR-129-2-3p level was significantly upregulated, whereas GABRA1 expression downregulated in KA-treated rat primary hippocampal neurons and KA-induced seizure model. In vivo knockdown of miR-129-2-3p by antagomir alleviated the seizure-like EEG findings in accordance with the upregulation of GABRA1. Furthermore, the seizure-suppressing effect of the antagomir was partly GABRA1 dependent. CONCLUSIONS: The results suggested GABRA1 as a target of miR-129-2-3p in rat primary hippocampal neurons and a rat kainic acid (KA) seizure model. Silencing of miR-129-2-3p exerted a seizure-suppressing effect in rats. MiR-129-2-3p/GABRA1 pathway may represent a potential target for the prevention and treatment of refractory epilepsy.

Protective effect of rosmarinic acid-rich trichodesma khasianum clarke leaves against ethanol-induced gastric mucosal injury in vitro and in vivo.

BACKGROUND: Although gastroprotective drugs have been used for peptic ulcer disease prevention and treatment, side effects have been observed. Finding a safe and effective treatment strategy is important. PURPOSE: Edible Trichodesma khasianum (T. khasianum) Clarke leaves are considered to protect against peptic ulcers. However, scientific evidence of this effect of T. khasianum Clarke leaves remains limited. STUDY DESIGN/METHODS: In this study, we aimed to evaluate the effect of T. khasianum Clarke leaves on ethanol-induced gastric injury and gut microbiota using RAW 264.7 cells, RGM-1 cells, and BALB/c mice, respectively. RESULT: The rosmarinic acid was identified as the major component of T. khasianum Clarke leaves extracted by 80% ethanol (80EETC). The results showed that 80EETC suppressed inflammatory mediator protein levels in LPS-induced RAW 264.7 cells. Additionally, heat shock protein expression, antiapoptotic ability, and wound healing migration capability were increased by 80EETC pretreatment in RGM-1 cells with the ethanol-induced injury. Remarkably, pretreatment with 80EETC (150 mg/kg b.w.) promoted gastric mucosal healing by decreasing oxidative stress, inflammatory response, proapoptotic protein expression, and gastric mucosa damage in ethanol-induced gastric injury in mice. Crucially, no liver or kidney toxicities were observed by 80EETC oral gavage. Moreover, 80EETC increased gut microbiota diversity and short-chain fatty acid production. CONCLUSION: Our results illustrated the remarkable gastroprotective effect by 80EETC treatment in vitro and in vivo. These findings are the first to demonstrate the powerful protective effect of T. khasianum Clarke leaves against gastric mucosal injury development.

Positive Association of Human SHC3 Gene with Schizophrenia in a Northeast Chinese Han Population.

OBJECTIVE: Schizophrenia is one of the most devastating neuropsychiatric disorders. Genetic epidemiological studies have confirmed that schizophrenia is a genetic disease. Genes promoting neurodevelopment may be potential candidates for schizophrenia. As an adaptor linking a number of tyrosine kinase receptors in multiple intracellular signaling cascades, Src homology 2 domain containing transforming protein 3 (SHC3) is a member of the Shc-like adaptor protein family, and expressed predominantly in the mature neurons of the central nervous system (CNS). In the present study, we aimed to investigate the association of SHC3 and schizophrenia. METHODS: An independent case-control association study was performed in a sample including 710 schizophrenia patients and 1314 healthy controls from a Northeast Chinese Han population. RESULTS: The allelic and genotypic association analyses showed that four SNPs in SHC3 significantly associated with schizophrenia (rs2316280, rs4877041, rs944485 and rs7021743). The haplotype composing of these four SNPs also showed significantly individual and global association with schizophrenia. CONCLUSION: Our present results suggest SHC3 as a susceptibility gene for schizophrenia.