A novel remnant liver-first strategy for liver autotransplantation in patients with end-stage hepatic alveolar echinococcosis: a retrospective case series.

BACKGROUND: Ex vivo liver resection combined with autotransplantation is an effective therapeutic strategy for unresectable end-stage hepatic alveolar echinococcosis (HAE). However, ex vivo liver resection combined with autotransplantation is a technically demanding and time-consuming procedure associated with significant morbidity and mortality. The authors aimed to present our novel remnant liver-first strategy of in vivo liver resection combined with autotransplantation (IRAT) technique for treating patients with end-stage HAE. METHODS: This retrospective study included patients who underwent IRAT between January 2014 and December 2020 at two institutions. Patients with end-stage HAE were carefully assessed for IRAT by a multidisciplinary team. The safety, feasibility, and outcomes of this novel technique were analyzed. RESULTS: IRAT was successfully performed in six patients, with no perioperative deaths. The median operative time was 537.5 min (range, 501.3-580.0), the median anhepatic time was 59.0 min (range, 54.0-65.5), and the median cold ischemia time was 165.0 min (range, 153.8-201.5). The median intraoperative blood loss was 700.0 ml (range, 475.0-950.0). In-hospital complications occurred in two patients. No Clavien-Dindo grade III or higher complications were observed. At a median follow-up of 18.6 months (range, 15.4-76.0) , all patients were alive. No recurrence of HAE was observed. CONCLUSION: The remnant liver-first strategy of IRAT is feasible and safe for selected patients with end-stage HAE. The widespread adoption of this novel technique requires further studies to standardize the operative procedure and identify patients who are most likely to benefit from it.

Differences in Non-suicidal Self-injury Behaviors between Unipolar Depression and Bipolar Depression in Adolescent Outpatients.

OBJECTIVE: Non-suicidal self-injury (NSSI) has a higher prevalence in adolescents with depressive disorders than in community adolescents. This study examined the differences in NSSI behaviors between adolescents with unipolar depression (UD) and those with bipolar depression (BD). METHODS: Adolescents with UD or BD were recruited from 20 general or psychiatric hospitals across China. The methods, frequency, and function of NSSI were assessed by Functional Assessment of Self-Mutilation. The Beck Suicide Ideation Scale was used to evaluate adolescents' suicidal ideation, and the 10-item Kessler Psychological Distress Scale to estimate the anxiety and depression symptoms. RESULTS: The UD group had higher levels of depression (19.16 vs.17.37, F=15.23, P<0.001) and anxiety symptoms (17.73 vs.16.70, F=5.00, P=0.026) than the BD group. Adolescents with BD had a longer course of NSSI than those with UD (2.00 vs.1.00 year, Z=-3.39, P=0.001). There were no statistical differences in the frequency and the number of methods of NSSI between the UD and BD groups. Depression (r=0.408, P<0.01) and anxiety (r=0.391, P<0.01) were significantly and positively related to NSSI frequency. CONCLUSION: Adolescents with BD had a longer course of NSSI than those with UD. More importantly, NSSI frequency were positively and strongly correlated with depression and anxiety symptoms, indicating the importance of adequate treatment of depression and anxiety in preventing and intervening adolescents' NSSI behaviors.

Exosomes derived from human umbilical cord mesenchymal stem cells alleviate Parkinson's disease and neuronal damage through inhibition of microglia.

Microglia-mediated inflammatory responses have been shown to play a crucial role in Parkinson's disease. In addition, exosomes derived from mesenchymal stem cells have shown anti-inflammatory effects in the treatment of a variety of diseases. However, whether they can protect neurons in Parkinson's disease by inhibiting microglia-mediated inflammatory responses is not yet known. In this study, exosomes were isolated from human umbilical cord mesenchymal stem cells and injected into a 6-hydroxydopamine-induced rat model of Parkinson's disease. We found that the exosomes injected through the tail vein and lateral ventricle were absorbed by dopaminergic neurons and microglia on the affected side of the brain, where they repaired nigral-striatal dopamine system damage and inhibited microglial activation. Furthermore, in an in vitro cell model, pretreating lipopolysaccharide-stimulated BV2 cells with exosomes reduced interleukin-1ß and interleukin-18 secretion, prevented the adoption of pyroptosis-associated morphology by BV2 cells, and increased the survival rate of SH-SY5Y cells. Potential targets for treatment with human umbilical cord mesenchymal stem cells and exosomes were further identified by high-throughput microRNA sequencing and protein spectrum sequencing. Our findings suggest that human umbilical cord mesenchymal stem cells and exosomes are a potential treatment for Parkinson's disease, and that their neuroprotective effects may be mediated by inhibition of excessive microglial proliferation.

Analysis of the expression and prognostic significance of DDK complex in Hepatocarcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common and lethal malignancies worldwide. Although DBF4-dependent kinase (DDK) complex composed of CDC7 kinase and its regulatory subunit DBF4 has been shown to be overexpressed in primary tumors and promotes tumor development, while its role and prognostic value in HCC remain largely unknown. In the present study, the expression of DBF4 and CDC7 and their relationship with clinical characteristics were comprehensively analyzed. METHODS: The mRNA expression profiles of HCC and the corresponding clinical data of HCC patients were downloaded from TCGA and GEO databases, respectively. The differences in DBF4 and CDC7 expression in tumor tissues and adjacent normal tissues were analyzed. HCC-derived tissue microarray (TMA) was used to evaluate and score the expression of CDC7 by immunohistochemistry (IHC) staining. The Kaplan-Meier method and the Cox regression method were used to analyze the relationship between overall survival and clinical characteristics of the patients. Gene set enrichment analysis (GSEA) was used to analyze the pathway enrichment of DBF4 and CDC7. RESULTS: DBF4 and CDC7 had similar expression patterns in HCC patients. Detailly, compared with adjacent tissues, both mRNA and protein of DBF4 and CDC7 were significantly higher in HCC, and their expression was positively correlated with AJCC_T stage, clinical stage and G stage (grade) of liver cancer patients, and higher DBF4 or CDC7 expression predicted a worse prognosis in HCC patients with shorter overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS) and progress-free survival (PFS). Cox regression analysis suggested that both DBF4 and CDC7 were independent risk factors for the prognosis of HCC patients in TCGA dataset. GSEA suggested that both DBF4 and CDC7 were positively correlated with cell cycle and DNA replication. Finally, the prognostic value of CDC7 was furtherly confirmed by TMA-based IHC staining results. CONCLUSIONS: Our study showed that DDK complex was significantly increased in HCC. Both DBF4 and CDC7 may be potential diagnostic and prognostic markers for HCC, and high expression of DDK members predicts a worse prognosis in patients with HCC, which may be associated with high tumor cell proliferation rate.

Expression of recombinant human Apolipoprotein A-IMilano in Nicotiana tabacum.

Apolipoprotein A-IMilano (Apo A-IMilano) is a natural mutant of Apolipoprotein. It is currently the only protein that can clear arterial wall thrombus deposits and promptly alleviate acute myocardial ischemia. Apo A-IMilano is considered as the most promising therapeutic protein for treating atherosclerotic diseases without obvious toxic or side effects. However, the current biopharmaceutical platforms are not efficient for developing Apo A-IMilano. The objectives of this research were to express Apo A-IMilano using the genetic transformation ability of N. tabacum. The method is to clone the coding sequence of Apo A-IMilano into the plant binary expression vector pCHF3 with a Flag/His6/GFP tag. The constructed plasmid was transformed into N. tabacum by a modified agrobacterium-mediated method, and transformants were selected under antibiotic stress. PCR, RT-qPCR, western blot and co-localization analysis was used to further verify the resistant N. tabacum. The stable expression and transient expression of N. tabacum were established, and the pure product of Apo A-IMilano was obtained through protein A/G agarose. The results showed that Apo A-IMilano was expressed in N. tabacum with a yield of 0.05 mg/g leaf weight and the purity was 90.58% ± 1.65. The obtained Apo A-IMilano protein was subjected to amino acid sequencing. Compared with the theoretical sequence of Apo A-IMilano, the amino acid coverage was 86%, it is also found that Cysteine replaces Arginine at position 173, which indicates that Apo A-IMilano, a mutant of Apo A-I, is accurately expressed in N. tabacum. The purified Apo A-IMilano protein had a lipid binding activity. The established genetic modification N. tabacum will provide a cost-effective system for the production of Apo A-IMilano. Regarding the rapid propagation of N. tabacum, this system provides the possibility of large-scale production and accelerated clinical translation of Apo A-IMilano.

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OBJECTIVES: To investigate the differences in non-suicidal self-injury (NSSI) behaviors between only-child and non-only-child adolescents with mood disorders. METHODS: A three-stage sampling method was used to perform a cross-sectional survey of 529 adolescents, aged 12-18 years, who had mood disorders and NSSI behaviors. These adolescents were sampled from the outpatient service of 20 mental hospitals in 9 provinces of China from August to November 2020. A self-made questionnaire was used to collect general demographic data. The Functional Assessment of Self-Mutilation, Beck Scale for Suicide Ideation, Kessler Psychological Distress Scale, Stress Mindset Measure-General, Multidimensional Scale of Perceived Social Support, Multidimensional Students' Life Satisfaction Scales, and Rosenberg Self-Esteem Scale were used to collect the information on self-injury behaviors and psychological factors in these adolescents. RESULTS: A total of 529 adolescents with mood disorders and NSSI behaviors were surveyed, among whom 375 were only-child adolescents and 154 were non-only-child adolescents. Compared with the non-only-child group, the only-child group had a significantly higher total score of Functional Assessment of Self-Mutilation (P<0.05) .The type and frequency of self-injury in the only-child group were significantly higher than those in the non-only-child group (P<0.05). Psychological analysis showed that compared with the non-only-child group, the only-child group had a significantly lower score of self-esteem (P<0.05) and significantly higher scores of psychological distress and depressive symptoms (P<0.05). The multiple linear regression analysis showed that the score of suicidal ideation was positively correlated with the frequency of NSSI behaviors in both only-child and non-only-child adolescents with mood disorders (P<0.05); in the only-child adolescents, the level of self-esteem was negatively correlated with the frequency of NSSI behaviors (P<0.05), and the score of stress perception was positively correlated with the frequency of NSSI behaviors (P<0.05); in the non-only-child adolescents, the score of anxious emotion was positively correlated with the frequency of NSSI behaviors (P<0.05). CONCLUSIONS: Among the adolescents with mood disorders and NSSI behaviors, the only-child adolescents tend to have a higher frequency of self-injury and poorer mental health, and therefore, the only-child adolescents with mood disorders and NSSI behaviors need more attention.

Prevalence and clinical characteristics of COVID-19 in inpatients with schizophrenia in Wuhan, China.

BACKGROUND: In contrast to many Western countries, China has maintained its large psychiatric hospitals. The prevalence and clinical characteristics of coronavirus disease 2019 (COVID-19) in inpatients with schizophrenia (SCZ) are unclear. AIM: To assess the prevalence of COVID-19 among inpatients with SCZ and compare the infected to uninfected SCZ patients in a Wuhan psychiatric hospital. METHODS: We retrospectively collected demographic characteristics and clinical profiles of all SCZ patients with COVID-19 at Wuhan's Youfu Hospital. RESULTS: Among the 504 SCZ patients, 84 had COVID-19, and we randomly sampled 174 who were uninfected as a comparison group. The overall prevalence of COVID-19 in SCZ patients was 16.7%. Among the 84 SCZ patients with confirmed COVID-19, the median age was 54 years and 76.2% were male. The most common symptom was fever (82%), and less common symptoms were cough (31%), poor appetite (20%), and fatigue (16%). Compared with SCZ patients without COVID-19, those with COVID-19 were older (P = 0.006) and significantly lighter (P = 0.002), and had more comorbid physical diseases (P = 0.001). Surprisingly, those infected were less likely to be smokers (< 0.001) or to be treated with clozapine (P = 0.03). Further logistic regression showed that smoking [odds ratio (OR) = 5.61], clozapine treated (OR = 2.95), and male (OR = 3.48) patients with relatively fewer comorbid physical diseases (OR = 0.098) were at a lower risk for COVID-19. SCZ patients with COVID-19 presented primarily with fever, but only one-third had a cough, which might otherwise be the most common mode of transmission between individuals. CONCLUSION: Two unexpected protective factors for COVID-19 among SCZ inpatients are smoking and clozapine treatment.

Overexpression of transcription factor 3 drives hepatocarcinoma development by enhancing cell proliferation via activating Wnt signaling pathway.

BACKGROUND: Transcription factor 3 (TCF3) plays pivotal roles in embryonic development, stem cell maintenance and carcinogenesis. However, its role in hepatocellular carcinoma (HCC) remains largely unknown. This study aimed to analyze the correlation between TCF3 expression and clinicopathological features of HCC, and further explore the underlying mechanism in HCC progression. METHODS: The expression of TCF3 was collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) HCC datasets, and further confirmed by immunostaining and Western blotting assays. The correlation between TCF3 expression and the clinicopathological features was evaluated. Bioinformatical analysis and in vitro experiments were conducted to explore the potential role of TCF3 in HCC development. RESULTS: Both the mRNA and protein levels of TCF3 were significantly higher in HCC tumor tissues compared to tumor adjacent tissues (P < 0.001 and P < 0.01). Analysis based on TCGA datasets showed that TCF3 was positively correlated with tumor clinical stage and grade, and patients with high TCF3 expression had shorter overall survival (P = 0.012), disease-specific survival (P = 0.022) and progression-free survival (P = 0.013). Similarly, the immunostaining results revealed that the high expression of TCF3 was closely correlated with tumor size (P = 0.001) and TNM stage (P = 0.002), and TCF3 was an independent risk factor of HCC. In vitro study exhibited that TCF3 knockdown dramatically suppressed cancer cell proliferation, and the underlying mechanism might be that the silencing of TCF3 reduced the expression of critical regulating proteins towards cell cycle and proteins involved in Wnt signaling pathways. CONCLUSIONS: TCF3 expression is significantly elevated in HCC and positively associated with the tumor size and TNM stage, as well as poor prognosis of HCC patients. The mechanism might be that TCF3 promotes cancer cell proliferation via activating Wnt signaling pathway.

Role of perceived family support in psychological distress for pregnant women during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused major public panic in China. Pregnant women may be more vulnerable to stress, which may cause them to have psychological problems. AIM: To explore the effects of perceived family support on psychological distress in pregnant women during the COVID-19 pandemic. METHODS: A total of 2232 subjects were recruited from three cities in China. Through the online surveys, information on demographic data and health status during pregnancy were collected. Insomnia severity index, generalized anxiety disorder 7-item scale, patient health questionnaire-9, somatization subscale of the symptom check list 90 scale, and posttraumatic stress disorder checklist were used to assess the psychological distress. RESULTS: A total of 1015 (45.4%) women reported having at least one psychological distress. The women who reported having inadequate family support were more likely to suffer from multiple psychological distress (≥ 2 psychological distress) than women who received adequate family support. Among the women who reported less family support, 41.8% reported depression, 31.1% reported anxiety, 8.2% reported insomnia, 13.3% reported somatization and 8.9% reported posttraumatic stress disorder (PTSD), which were significantly higher than those who received strong family support. Perceived family support level was negatively correlated with depressive symptoms (r = -0.118, P < 0.001), anxiety symptoms (r = -0.111, P < 0.001), and PTSD symptoms (r = -0.155, P < 0.001). CONCLUSION: Family support plays an important part on pregnant women's mental health during the COVID-19 pandemic. Better family support can help improve the mental health of pregnant women.

Association of Lipid Profile and Suicide Attempts in a Large Sample of First Episode Drug-Naive Patients With Major Depressive Disorder.

Several studies have reported a link between lipid disorders and suicidality. However, few studies have investigated the relationship between suicidal behavior and blood lipid profiles in patients with first-episode and drug-naive (FEDN) major depressive disorder (MDD). The main purpose of this study was to examine the relationship between plasma lipid profiles and suicide attempts in a large sample of FEDN MDD patients in the Chinese Han population, which has not been reported. A total of 1,718 MDD outpatients were recruited. Their clinical and demographic data as well as plasma lipid parameters were collected. We obtained suicide attempt data through interviews with patients and their family members. We rated the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) for all patients. The suicide attempt rate of MDD patients was 20.14%, of which 13.68% in the last month and 6.46% in the past. Further, compared with non-attempters, suicide attempters had significantly higher total levels of cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c), higher HAMA and HAMD scores, but significantly lower high-density lipoprotein cholesterol (HDL-c) levels. Logistic regression analysis showed that suicide attempts were correlated with higher TC, lower HDL-c, and higher HAMA and HAMD scores with the adjusted odds ratio (OR) of 1.35, 0.52,1.28, and 1.08, respectively (all p < 0.05). Our findings suggest that FEDN patients with MDD have a high rate of attempted suicide. In the early stage of MDD patients, certain blood lipid parameters and more severe symptoms of anxiety and depression are correlated with suicide attempts. However, due to the cross-sectional design of this study, it is impossible to draw a causal relationship between lipid profiles and suicide attempts. Moreover, an inverse correlation can also be considered, that is, high cholesterol may be the consequence of suicide attempts and depression.

Integrated transcriptomics and metabolomics analysis of catechins, caffeine and theanine biosynthesis in tea plant (Camellia sinensis) over the course of seasons.

BACKGROUND: Catechins, caffeine, and theanine as three important metabolites in the tea leaves play essential roles in the formation of specific taste and shows potential health benefits to humans. However, the knowledge on the dynamic changes of these metabolites content over seasons, as well as the candidate regulatory factors, remains largely undetermined. RESULTS: An integrated transcriptomic and metabolomic approach was used to analyze the dynamic changes of three mainly metabolites including catechins, caffeine, and theanine, and to explore the potential influencing factors associated with these dynamic changes over the course of seasons. We found that the catechins abundance was higher in Summer than that in Spring and Autumn, and the theanine abundance was significantly higher in Spring than that in Summer and Autumn, whereas caffeine exhibited no significant changes over three seasons. Transcriptomics analysis suggested that genes in photosynthesis pathway were significantly down-regulated which might in linkage to the formation of different phenotypes and metabolites content in the tea leaves of varied seasons. Fifty-six copies of nine genes in catechins biosynthesis, 30 copies of 10 genes in caffeine biosynthesis, and 12 copies of six genes in theanine biosynthesis were detected. The correlative analysis further presented that eight genes can be regulated by transcription factors, and highly correlated with the changes of metabolites abundance in tea-leaves. CONCLUSION: Sunshine intensity as a key factor can affect photosynthesis of tea plants, further affect the expression of major Transcription factors (TFs) and structural genes in, and finally resulted in the various amounts of catechins, caffeine and theaine in tea-leaves over three seasons. These findings provide new insights into abundance and influencing factors of metabolites of tea in different seasons, and further our understanding in the formation of flavor, nutrition and medicinal function.

Reliability and validity of the Chinese version of the Childhood Trauma Questionnaire-Short Form for inpatients with schizophrenia.

BACKGROUND: The evaluation of childhood trauma is essential for the treatment of schizophrenia. The short form of Childhood Trauma Questionnaire (CTQ-SF) is a widely used measure of the experience of childhood trauma in the general population. Nevertheless, data regarding the psychometric property of CTQ-SF for assessing childhood trauma of patients with schizophrenia are very limited. METHODS: Two hundred Chinese inpatients with schizophrenia completed the Chinese CTQ-SF, the Child Psychological Maltreatment Scale (CPMS), the Impact of Events Scale-Revised (IES-R), and the Dissociative Experiences Scale-II (DES-II). To assess test-retest reliability of the CTQ-SF, all patients completed the CTQ-SF again two weeks later. Concurrent and convergent validity was assessed by analyzing Pearson bivariate correlation coefficients between CTQ-SF and CPMS, IES-R, and DES-II. RESULTS: The Cronbach's α coefficient of the Chinese CTQ-SF was 0.81, and the two-week re-test reliability was 0.81 (P<0.01). The criterion-related validity coefficients of CTQ-SF with the CMPS, IES-R and DES-II were 0.61, 0.41, and 0.51, respectively. CONCLUSION: The Chinese CTQ-SF has satisfactory psychometric properties to measure childhood abuse or neglect in Chinese inpatients with schizophrenia.

Histone deacetylase 3 promotes liver regeneration and liver cancer cells proliferation through signal transducer and activator of transcription 3 signaling pathway.

Histone deacetylase 3 (HDAC3) plays pivotal roles in cell cycle regulation and is often aberrantly expressed in various cancers including hepatocellular carcinoma (HCC), but little is known about its role in liver regeneration and liver cancer cells proliferation. Using an inducible hepatocyte-selective HDAC3 knockout mouse, we find that lack of HDAC3 dramatically impaired liver regeneration and blocked hepatocyte proliferation in the G1 phase entry. HDAC3 inactivation robustly disrupted the signal transducer and activator of transcription 3 (STAT3) cascade. HDAC3 silencing impaired the ac-STAT3-to-p-STAT3 transition in the cytoplasm, leading to the subsequent breakdown of STAT3 signaling. Furthermore, overexpressed HDAC3 was further associated with increased tumor growth and a poor prognosis in HCC patients. Inhibition of HDAC3 expression reduced liver cancer cells growth and inhibited xenograft tumor growth. Our results suggest that HDAC3 is an important regulator of STAT3-dependent cell proliferation in liver regeneration and cancer. These findings provide novel insights into the HDAC3-STAT3 pathway in liver pathophysiological processes.

ω-3PUFAs prevent MK-801-induced cognitive impairment in schizophrenic rats via the CREB/BDNF/TrkB pathway.

This study was to determine the protective effect of ω-3 polyunsaturated fatty acids (ω-3PUFAs) on MK-801-induced cognitive impairment in schizophrenia (SZ) rats and the underlying mechanism. A rat model of schizophrenia was induced by MK-801. The cognitive function of rats was assessed using a Morris water maze. The number of hippocampal neurons was measured by Nissl staining. The expression of CREB, p-CREB, BDNF, TrkB, p-TrkB, AKT, p-AKT, ERK, and p-ERK in the hippocampus of rats was detected by Western blotting. The results showed that ω-3PUFAs attenuated MK-801-induced cognitive impairment and hippocampal neurons loss, reversed the injury of the CREB/BDNF/TrkB pathway induced by MK-801, and antagonized MK-801-induced down-regulation of p-AKT and p-ERK in the hippocampus of rats. In conclusion, ω-3PUFAs enhances the CREB/BDNF/TrkB pathway by activating ERK and AKT, thereby increasing the synaptic plasticity and decreasing neuron loss, and antagonizing MK-801-induced cognitive impairment in schizophrenic rats.

Elevated expression of Gsα in intrahepatic cholangiocarcinoma associates with poor prognosis.

BACKGROUND: The stimulatory G protein a subunit (Gsα) plays important roles in diverse cell processes including tumorigenesis. Activating mutations in Gsα gene (GNAS) have been reported to be associated with poor prognosis in various human carcinomas. Furthermore, Gsα signaling is crucial in promoting liver regeneration by interacting with growth factor signaling, indicating that Gsα might play a promoting role in cancer development. However, little is known about the correlation between Gsα levels and clinicopathological parameters in intrahepatic cholangiocarcinoma (ICC). METHODS: We performed immunoblotting to examine the expression levels of Gsα and Ki67 proteins in tumor tissues and the corresponding adjacent tissues. A total of 74 pair of specimens resected from 74 ICC patients were examined. The association between Gsα levels and clinicopathological findings and prognosis of the patients was evaluated. RESULTS: Western blotting demonstrated that the expression of Gsα was significantly higher in ICC tissues compared with that in their corresponding adjacent tissues. Gsα protein was highly expressed in about half of ICC tissues (48.6%, 36/74) while only 28.4% (21/74) of tumor adjacent tissues showed Gsα high expression (P=0.011). High Gsα expression in ICC was significantly associated with the numbers of tumor nodules (P=0.037) and lymph node metastases (P=0.010). Moreover, the level of Gsα was significantly and positively correlated with Ki67 expression (P<0.001). In addition, the recurrence-free survival rate and overall survival rate in the Gsα high group were significantly lower than those in the Gsα low group (P=0.004 and P=0.005, respectively). CONCLUSIONS: High Gsα expression is correlated with poor prognosis in ICC patients. Gsα might serve as a potential prognostic indicator of ICC.

ω-3PUFAs Prevent MK-801-induced Cognitive Impairment in Schizophrenic Rats via the CREB/BDNF/TrkB Pathway / 华中科技大学学报（医学）（英德文版）

This study was to determine the protective effect of ω-3 polyunsaturated fatty acids (ω-3PUFAs) on MK-801-induced cognitive impairment in schizophrenia (SZ) rats and the underlying mechanism.A rat model of schizophrenia was induced by MK-801.The cognitive function of rats was assessed using a Morris water maze.The number of hippocampal neurons was measured by Nissl staining.The expression of CREB,p-CREB,BDNF,TrkB,p-TrkB,AKT,p-AKT,ERK,and p-ERK in the hippocampus of rats was detected by Western blotting.The results showed that ω-3PUFAs attenuated MK-801-induced cognitive,impairment and hippocampal neurons loss,reversed the injury of the CREB/BDNF/TrtB pathway induced by MK-801,and antagonized MK-801-induced down-regulation of p-AKT and p-ERK in the hippocampus of rats.In conclusion,ω-3PUFAs enhances the CREB/BDNF/TrkB pathway by activating ERK and AKT,thereby increasing the synaptic plasticity and decreashng neuron loss,and antagonizing MK-801-induced cognitive impairment in schizophrenic rats.

Alterations of Thymic Epithelial Cells in Lipopolysaccharide-induced Neonatal Thymus Involution.

BACKGROUND: Vascular endothelial growth factor (VEGF) in the thymus was mainly produced by the thymic epithelial cells (TECs), the predominant component of the thymic microenvironment. The progression of TECs and the roles of VEGF in the neonatal thymus during sepsis have not been reported. This study aimed to explore the alterations of TECs and VEGF level in the neonatal thymus involution and to explore the possible mechanisms at the cellular level. METHODS: By establishing a model of clinical sepsis, the changes of TECs were measured by hematoxylin-eosin staining, confocal microscopy, and flow cytometry. Moreover, the levels of VEGF in serum and thymus were assessed based on enzyme-linked immunosorbent assay and Western blotting. RESULTS: The number of thymocytes and TECs was significantly decreased 24 h after lipopolysaccharide (LPS) challenge, (2.40 ± 0.46)×10 7 vs. (3.93 ± 0.66)×10 7 and (1.16 ± 0.14)×10 5 vs. (2.20 ± 0.19)×10 5 , P < 0.05, respectively. Cortical TECs and medullary TECs in the LPS-treated mice were decreased 1.5-fold and 3.9-fold, P < 0.05, respectively, lower than those in the controls. The number of thymic epithelial progenitors was also decreased. VEGF expression in TECs was down-regulated in a time-dependent manner. CONCLUSION: VEGF in thymic cells subsets might contribute to the development of TECs in neonatal sepsis.

Loss of Dicer1 impairs hepatocyte survival and leads to chronic inflammation and progenitor cell activation.

AIM: To investigate the continuous hepatic histopathological processes which occur in response to the loss of Dicer1. METHODS: We generated a hepatocyte-selective Dicer1 knockout mouse and observed the gradual hepatic histopathological changes in the mutant liver. Immunohistochemistry and Western blotting were performed to detect Dicer1 expression. We performed hematoxylin and eosin staining, Periodic acid-Schiff staining, Oil Red O staining, and Masson's trichrome staining to detect histological changes in Dicer1-deficient livers. Ki67 immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and Western blotting were used to determine hepatocyte proliferation and apoptosis. Serum biochemistry, cytokine assays, and flow cytometric analysis were performed to quantity liver necrosis and inflammation. Fibrogenic markers were determined by Western blotting and qPCR. CK19, CD133, and OV6 immunofluorescence were used to observe liver progenitor cells. Immunofluorescence and qPCR were performed to reveal embryonic gene expression. We also performed histological staining and Western blotting to analyze hepatocellular carcinoma (HCC) development. RESULTS: Dicer1 inactivation resulted in significant architecture disorganization and metabolism disruption in the liver. Dicer1 disruption impaired hepatocyte survival and resulted in profound cell apoptosis and continuous necrosis. In contrast to previous reports, the mutant liver exhibited chronic inflammation and progressive fibrosis, and could not be repopulated by Dicer1-positive cells. In addition, extensive activation of hepatic progenitor cells was observed. Primary HCC was observed as early as 4 mo after birth. CONCLUSION: Hepatic loss of Dicer1 results in complex chronic pathological processes, including hepatocyte death, inflammatory infiltration, chronic fibrosis, compensatory proliferation, progenitor activation, and spontaneous hepatocarcinogenesis.