Chronic ghrelin administration suppresses IKK/NF-κB/BACE1 mediated Aß production in primary neurons and improves cognitive function via upregulation of PP1 in STZ-diabetic rats.

Diabetic rats display cognition impairments accompanied by activation of NF-κB signalling and increased Aß expression. Ghrelin has been suggested to improve cognition in diabetic rats. In this study, we investigated the role of ghrelin on cognition and NF-κB mediated Aß production in diabetic rats. A diabetic rat model was established with streptozotocin (STZ) injection, and diabetic rats were intracerebroventricularly administered with ghrelin or (D-lys3)-GHRP-6 (DG). Our results showed that diabetic rats had cognition impairment in the Morris water maze test, accompanied by the higher expression of Aß in the hippocampus. Western blot analysis showed that diabetic rats exhibited significantly decreased levels of GHSR-1a and protein phosphatase 1 (PP1) in the hippocampus and increased activation of the IKK/NF-κB/BACE1 pathway. Chronic ghrelin administration upregulated hippocampal PP1 expression, suppressed IKK/NF-κB/BACE1 mediated Aß production, and improved cognition in STZ-induced diabetic rats. These effects were reversed by DG. Then, primary rat hippocampal neurons were isolated and treated with high glucose, followed by Ghrelin and DG, PP1 or IKK. Similar to the in vivo results, high glucose suppressed the expression levels of GHSR-1a and PP1, activated the IKK/NF-κB/BACE1 pathway, increased Aß production. Ghrelin suppressed IKK/NF-κB/BACE1 induced Aß production. This improvement was reversed by DG and a PP1 antagonist and was enhanced by the IKK antagonist. Our findings indicated that chronic ghrelin administration can suppress IKK/NF-κB/BACE1 mediated Aß production in primary neurons with high glucose treatment and improve the cognition via PP1 upregulation in diabetic rats.

Vitamin D supplementation rescues simvastatin induced myopathy in mice via improving mitochondrial cristae shape.

Statin induced myopathy (SIM) is a main deleterious effect leading to the poor treatment compliance, while the preventive or therapeutic treatments are absent. Mounting evidences demonstrated that vitamin D plays a vital role in muscle as a direct modulator. The deficiency of vitamin D was considered as a cause of muscle dysfunction, whereas the supplementation resulted in a remission. However, there is no causal proof that vitamin D supplementation rescues SIM. Here, using the mice model of simvastatin-induced myopathy, we investigated the role of vitamin D supplementation and the mechanisms associated with mitochondria. Results indicated that simvastatin administration (80 mg/kg) impaired skeletal muscle with the increased serum creatine kinase (CK) level and the declined grip strength, which were alleviated by vitamin D supplementation. Moreover, vitamin D supplementation rescued the energy metabolism dysfunction in simvastatin-treated mice gastrocnemius by reducing the abnormal aggregation of muscular glycogen and lactic acid. Mitochondrial homeostasis plays a key role in the process of energy metabolism. Thus, the mitochondrial dysfunction is a mortal damage for the highly energy-requiring tissue. In our study, the mitochondrial cristae observed under transmission electron microscope (TEM) were lytic in simvastatin-treated gastrocnemius. Interestingly, vitamin D supplementation improved the mitochondrial cristae shape by regulating the expression of mitofusin-1/2 (MFN1/2), optic atrophy 1 (OPA1) and dynamin-related protein 1 (Drp1). As expected, the mitochondrial dysfunction and oxidative stress was mitigated by vitamin D supplementation. In conclusion, these findings suggested that moderate vitamin D supplementation rescued simvastatin induced myopathy via improving the mitochondrial cristae shape and function.

Cytomegalovirus Infection Is a Risk Factor in Gastrointestinal Cancer: A Cross-Sectional and Meta-Analysis Study.

BACKGROUND: This study was planned to investigate the association betweenhuman cytomegalovirus (HCMV) infection and gastrointestinal cancer (GIC) risk, by undertaking a meta-analysis and case-control cross-sectional study. SUMMARY: A cross-sectional study analysis of 160 GIC patients and 100 control subjects indicated significantly higher HCMV prevalence in GIC patients based on the HCMV IgM test. However, a similar analysis based on an IgG test revealed no significant relationship. Further meta-analysis of 11 studies, including 1,044 patients and 991 healthy subjects, displayed HCMV infection as an important risk factor for not only colorectal cancer occurrence and development based on a HCMV DNA test, but also for GIC based on a HCMV IgM test. However, the IgG test again displayed no significant relationship between HCMV infection and GIC occurrence. Key Message: Overall, our study revealed that HCMV infection is associated with an increased GIC risk. However, additional studies are warranted to elucidate the molecular mechanism underlying this association.

Ceramide induces MMP-9 expression through JAK2/STAT3 pathway in airway epithelium.

BACKGROUND: Ceramide, a bioactive lipid, plays an essential role in the development of several pulmonary inflammatory diseases. Matrix metallopeptidase 9 (MMP-9) regulates the synthesis and degradation of extracellular matrix, and is associated with airway remodeling and tissue injury. This study was conducted to investigate the effects and underlying mechanisms of ceramide on MMP-9 expression in airway epithelium. METHODS: BEAS-2B cells, normal human bronchial epithelium cell lines, were pretreated with AG490, a selective janus tyrosine kinase 2 (JAK2) inhibitor, or Stattic, a selective signal transducer and activator of transcription 3 (STAT3) inhibitor. The cells were then stimulated with C6-ceramide. The levels of MMP-9 were determined by ELISA and real-time quantitative PCR (RT-qPCR). JAK2, phosphorylated JAK2 (p-JAK2), STAT3, and phosphorylated STAT3 (p-STAT3) expression was examined by Western blotting. BALB/c mice were pretreated with AG490 or Stattic before intratracheally instillated with C6-ceramide. Pathological changes in lung tissues were examined by Hematoxylin and Eosin staining, Periodic-acid Schiff staining, and Masson's trichrome staining. MMP-9, JAK2, p-JAK2, STAT3, and p-STAT3 expression in the lung tissues was examined by Western blotting. RESULTS: The expression of MMP-9, p-JAK2 and p-STAT3 in BEAS-2B cells was significantly increased after the treatment of C6-ceramide. Furthermore, the increased expression of MMP-9 induced by C6-ceramide was inhibited by AG490 and Stattic. Similar results were obtained in the lung tissues of C6-ceramide-exposed mice which were treated with AG490 or Stattic. CONCLUSIONS: Ceramide could up-regulate MMP-9 expression through the activation of the JAK2/STAT3 pathway in airway epithelium. Targeted modulation of the ceramide signaling pathway may offer a potential therapeutic approach for inhibiting MMP-9 expression. This study points to a potentially novel approach to alleviating airway remodeling in inflammatory airway diseases.

Akebia saponin D alleviates hepatic steatosis through BNip3 induced mitophagy.

Akebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this paper was to explore the mechanisms through which ASD alleviates hepatic steatosis. ASD significantly reduced lipid accumulation in BRL cells. Furthermore, ASD significantly increased the mitophagy acting as increase the colocalization between mitochondria and punctate EGFP-LC3. ASD treatment increased the expression of BNip3, phospho-AMPK, prevented oleic acid (OA) induced LC3-II and phospho-mTOR expression. These effects were similar to the effects cotreatment with rapamycin. ASD treatment could not attenuate the expression of BNip3 blocked by chloroquine (CQ) or siRNA-mediated knockdown of BNip3. These results suggest that Akebia saponin D alleviates hepatic steatosis targeted at BNip3 mediated mitophagy. Activation of BNip3 via ASD may offer a new strategy for treating NAFLD.

Association between chronic obstructive pulmonary disease and serum lipid levels: a meta-analysis.

BACKGROUND: Metabolic syndrome is a common extrapulmonary comorbidity in patients with chronic obstructive pulmonary disease (COPD). However, the reported relationship of COPD with dyslipidemia, an important component of metabolic syndrome, is ambiguous. The aim of this meta-analysis is to investigate the association between COPD and the serum levels of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), and triglyceride (TG). METHODS: The PubMed and Embase databases were searched to find potential studies using the search terms of ("dyslipidemia" or "HDL" or "LDL" or "cholesterol" or "triglyceride") and COPD. We also performed subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia. Mean differences (MD) with 95% confidence intervals (CI) were estimated with random effects models. RESULTS: A total of 11 studies comprising 615 cases and 471 controls were included in the study. No significant differences were found in the HDL (MD = -2.55, 95% CI [-6.03, 0.93], P = 0.15), LDL (MD = -2.25, 95% CI [-13.36, 8.86], P = 0.69), TC (MD = -2.69, 95% CI [-13.30, 7.92], P = 0.62), and TG (MD = 6.90, 95% CI [-2.81, 16.60], P = 0.16) levels of the 2 groups. However, subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia showed that TG levels were higher in patients with stable COPD than in healthy individuals (MD = 16.35, 95% CI [5.90, 26.80], P = 0.002). CONCLUSIONS: Excluding the impact of hypolipidemic treatment on serum lipid profile, TG levels were higher in patients with COPD than in healthy individuals. This meta-analysis suggested that physicians should screen COPD patients for elevated TG levels to reduce the risk of cardiovascular morbidity and mortality.

Cytomegalovirus infection and atherosclerosis risk: A meta-analysis.

Human cytomegalovirus (HCMV) infection is an important risk factor for atherosclerosis (AS). Numerous studies have been conducted to analyze the association between HCMV infection and risk of AS, but no clear consensus has been reached. So the objective of this paper was aimed to demonstrate the relationship between HCMV and AS by doing a meta-analysis. Relative literature was searched through the electronic databases PubMed, Embase, and CNKI. Data were accurately assessed and analyzed independently by two investigators. Ultimately, the 30 studies, involving 3328 cases and 2090 controls were included in our meta-analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively, 63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were, respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26% (28/229) in control subjects. The positive ratio of HCMV infection was higher in atherosclerosis group than that in non-atherosclerosis group. Especially in Asian group, calculated odds ratios for the presence of HCMV infection in IgG-based HCMV tests, IgM-based tests, PCR-based tests, and pp65-based tests, expressed as OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09-4.51), 8.92(95%CI 3.17-25.11), 6.75 (95%CI 3.50-13.02), and 5.72(95%CI 1.51-21.58), respectively. The meta-analysis results showed that HCMV infection is significant connected with an increased risk for AS.

VDR Gene variation and insulin resistance related diseases.

BACKGROUND: Vitamin D status may influence the risk of Insulin resistance related diseases such as Type 2 diabetes (T2DM), metabolic syndrome (MetS), and polycystic ovarian syndrome (PCOS). Several studies have assessed vitamin D receptor (VDR) gene polymorphism in relationship with these diseases; however, results remain inconsistent. Our study was conducted to elucidate whether VDR Gene polymorphisms could predict insulin resistance on a large scale. METHODS: A meta-analysis using MEDLINE and EMBASE, was performed up to December 16th, 2016. Studies reporting association of vitamin D gene polymorphism with incident T2DM, MetS and PCOS outcomes were included and sub-group analysis by pigment of skin and latitude were performed. RESULTS: A total of 28 articles based on four gene variation, and comprising 9232 participants with 5193 Insulin resistance related diseases patients were included. No significant associations of the VDR ApaI, BsmI, FokI and TaqI variant with Insulin resistance related diseases were found. However, sub-group analysis analysis showed that PCOS in TaqI (OR = 1.47, 95% CI = 1.03-2.09, P = 0.03) for T allele and MetS for G allele (OR = 1.41, 95% CI = 1.07-1.85, P = 0.01) in BsmI was significant association with VDR gene polymorphism. Simultaneously, sub-group analysis showed VDR ApaI rs7975232(G > T)variant was associated with insulin resistance related diseases in Asians (GG/GT + TT) (OR, 1.62; 95% CI, 1.03-2.53; P = 0.04) and population who lived in middle latitude district (30-60°) (GG/GT + TT) (OR, 1.22; 95% CI, 1.04-1.43; P = 0.02), VDR BsmI rs1544410 (A > G)and VDR Taq1rs731236 (T/C) variant were associated with insulin resistance related diseases in Caucasian (dark-pigmented). CONCLUSION: The results suggested that the association between insulin resistance related diseases and VDR ApaI, BsmI, FokI variant was more obvious in dark-pigmented Caucasians and Asians but not in Caucasian with white skin.

Analysis of the status of EGFR, ROS1 and MET genes in non-small cell lung adenocarcinoma.

PURPOSE: To investigate the status and distribution of epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (MET), and receptor tyrosine kinase (ROS1) genes in patients with non-small cell lung (NSCL) adenocarcinoma. METHODS: The copy number of the MET gene was detected using fluorescence in situ hybridization (FISH). The splice mutation in exon 14 gene was detected by Sanger sequencing. The mutations in EGFR and the fusion of the ROS1 gene were detected using the fluorescence real-time quantitative PCR method (RT-qPCR). RESULTS: The gene mutation frequency of EGFR was 46.51%. There were 7 types of mutations; exon 19 deletions and exon 21 L858R mutations were most frequent. There were 3 cases of double mutations. The MET gene had increased copy numbers in 9.88% of the NSCL adenocarcinoma patients; 3.49% of MET mutations in NSCL adenocarcinoma included 3 intron mutations. The ROS1 gene fusion frequency was 1.74%. CONCLUSION: The NSCL adenocarcinoma patients who were females, did not have a smoking history, and had high grade of differentiation, had higher EGFR mutation rates. Although the MET gene amplification and ROS1 gene fusion in NSCL adenocarcinoma were low-probability events, detection of the gene status of EGFR, ROS1, and MET will facilitate screening more NSCL adenocarcinoma patients who might benefit from targeted therapy.

Akebia Saponin D Decreases Hepatic Steatosis through Autophagy Modulation.

Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of the metabolic syndrome, and the incidence of NAFLD is increasing rapidly. However, appropriate drugs for treatment of NAFLD are lacking. This study aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD in ob/ob mice and Buffalo rat liver cells. ASD significantly decreased hepatic steatosis and hepatocyte apoptosis in ob/ob mice. ASD also significantly activated autophagic flux, as assessed by the decreased expression of light chain 3 (LC3)-II and P62 accumulation of autophagosomes. In Buffalo rat liver cells, ASD prevented oleic acid (OA)-induced lipid droplets and increased autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA-induced expression of LC3-II, P62, Beclin, and phospho-mammalian target of rapamycin. These effects were similar to those of cotreatment with rapamycin. ASD treatment could not prevent OA-increased, autophagy-related protein expression after treatment with chloroquine or small interfering RNA-mediated knockdown of atg7. These results suggest that ASD alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, and autophagy modulation via ASD may offer a new strategy for treating NAFLD.

First molecular evidence for the presence of Anaplasma DNA in milk from sheep and goats in China.

Anaplasmosis, a disease caused by bacteria in the genus of Anaplasma, imposes economic constraints on animal breeders and also threatens human health. In the present study, we investigated the presence of Anaplasma spp. DNA in milk collected from sheep and goats in China. A total of 120 milk samples and 414 field-sampled blood specimens from sheep and goats were analyzed by PCR and DNA sequencing. Anaplasma ovis was detected in 12 milk samples (three from sheep and nine from goats). The blood specimens corresponding to the A. ovis DNA-positive milk were analyzed for Anaplasma DNA presence, and A. ovis DNA was identified in 10 out of the 12 blood specimens. One goat's milk sample was Anaplasma bovis DNA-positive, as was the corresponding blood sample. Anaplasma phagocytophilum was found in a milk sample and blood sample from one goat. One milk sample from Xinmi in Henan province was simultaneously positive for A. bovis and A. phagocytophilum; however, the corresponding blood was negative for both species. DNA sequencing of the PCR products and phylogenetic analysis confirmed that the sequences from the milk samples matched those of the corresponding blood samples. This is the first report to detect the Anaplasma DNA in milk samples under natural condition, and represents the first evidence of the presence of A. ovis, A. bovis and A. phagocytophilum DNA in milk from sheep and goats.

Benzophenone C-glucosides and gallotannins from mango tree stem bark with broad-spectrum anti-viral activity.

The high mutation rate of RNA viruses has resulted in limitation of vaccine effectiveness and increased emergence of drug-resistant viruses. New effective antivirals are therefore needed to control of the highly mutative RNA viruses. The n-butanol fraction of the stem bark of Mangifera indica exhibited inhibitory activity against influenza neuraminidase (NA) and coxsackie virus 3C protease. Bioassay guided phytochemical study of M. indica stem bark afforded two new compounds including one benzophenone C-glycoside (4) and one xanthone dimer (7), together with eleven known compounds. The structures of these isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Anti-influenza and anti-coxsackie virus activities were evaluated by determining the inhibition of anti-influenza neuraminidase (NA) from pandemic A/RI/5+/1957 H2N2 influenza A virus and inhibition of coxsackie B3 virus 3C protease, respectively. The highest anti-influenza activity was observed for compounds 8 and 9 with IC50 values of 11.9 and 9.2µM, respectively. Compounds 8 and 9 were even more potent against coxsackie B3 virus 3C protease, with IC50 values of 1.1 and 2.0µM, respectively. Compounds 8 and 9 showed weak cytotoxic effect against human hepatocellular carcinoma and human epithelial carcinoma cell lines through MTT assay.

Mechanism of curcumin resistance to human cytomegalovirus in HELF cells.

BACKGROUND: We have previously shown that curcumin exhibited an outstanding anti-HCMV effect in vitro and in vivo. However, the underlying mechanism for the anti-HCMV effect remains unclear. METHODS: Levels of IL-6 and TNF-α cytokine secretions in HELF cells were determined by enzyme-linked immunosorbent assay (ELISA); cell cycles were assessed by flow cytometry; ie and ul83 gene expressions were evaluated using reverse transcriptase real-time quantitative PCR; HCMV IE and UL83 antigen expressions were studied using immunofluorescence staining assay and western blot. RESULTS: Curcumin reduced HCMV immediate early antigen (IEA) and UL83A expressions and IL-6, and TNF-α secretions and recovered cell proliferation to normal level in HCMV infected HELF cells. CONCLUSIONS: Curcumin anti-HCMV effect may possibly be that curcumin concurrently alters host cell microenviroment and inhibits the HCMV antigen expressions. These findings may provide a basic understanding of the curcumin anti-HCMV effect and a novel strategy for further development of curcumin anti-HCMV treatment.

Differences in the severity and mortality risk factors for patients hospitalized for COVID-19 pneumonia between the early wave and the very late stage of the pandemic.

Background: Since China's dynamic zero-COVID policy is cancelled on December 7, 2022, the rapidly growing number of patients has brought a major public health challenge. This study aimed to assess whether there were differences in the severity and mortality risk factors for patients hospitalized for COVID-19 pneumonia between the early wave and the very late stage of the pandemic. Methods: A retrospective cross-sectional study was carried out using data from 223 hospitalized patients diagnosed with COVID-19 pneumonia during the Omicron surge in Xi'an People's Hospital (Xi'an Fourth Hospital) from December 8, 2022, to January 31, 2023. Univariable and multivariable logistic regression analyses were used to identify potential risk factors associated with the severity and mortality of COVID-19 pneumonia during the first wave of the pandemic after the dynamic zero-COVID policy was retracted. Differences in the severity and mortality risk factors were assessed at different stages of the pandemic, mainly from demographic, clinical manifestation, laboratory tests and radiological findings of patients on admission. Results: The mean age of the 223 participants was 71.2 ± 17.4. Compared with the patients in the initial stage of the pandemic, the most common manifestation among patients in this study was cough (90.6%), rather than fever (79.4%). Different from the initial stage of the pandemic, older age, chest tightness, elevated neutrophil-to-lymphocyte ratio (NLR), decreased albumin (ALB) level and ground glass opacification (GGO) in radiological finding were identified as severity risk factors, instead of mortality risk factors for COVID-19 patients in the very late stage of the pandemic. Arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤300 mmHg, cardiovascular disease and laboratory findings including elevated levels of D-dimer, α-hydroxybutyrate dehydrogenase (α-HBDH), total bilirubin (TBIL), alanine aminotransferase (ALT), urea nitrogen (BUN), creatinine (CR), fasting blood glucose (FBG) and decreased platelet count (PLT) were still associated with mortality in the very late stage of the pandemic. Conclusion: Monitoring continuously differences in the severity and mortality risk factors for COVID-19 patients between different stages of the pandemic could provide evidence for exploring uncharted territory in the coming post-pandemic era.

Alternations of interhemispheric functional connectivity in patients with optic neuritis using voxel-mirrored homotopic connectivity: A resting state fMRI study.

BACKGROUND AND PURPOSE: We used the voxel-mirrored homotopic connectivity (VMHC) method to investigate brain interhemispheric functional connectivity changes in patients with optic neuritis (ON). METHODS: A total of 22 ON patients and 22 healthy controls (HCs) closely matched in age, sex, and weight were enrolled. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). Functional interaction between the hemispheres was assessed with the VMHC method. Correlation analysis was applied to explore the association between altered VMHC values in different brain areas and cognitive features. Receiver operating characteristic (ROC) curve analysis was applied to distinguish ON patients from HCs. RESULTS: Compared with HCs, ON patients had obviously reduced VMHC values in the right superior temporal gyrus, left margin superior gyrus, right superior motor cortex, and left middle cingulate gyrus. a negative relationship between best-corrected visual acuity and VMHC values in left margin superior gyrus was found, besides, the VMHC values within the right superior motor cortex and the right superior temporal gyrus were also anti-correlated with the Hamilton Depression Scales. The ROC curve displayed high diagnostic values in those altered regions. CONCLUSION: Abnormal VMHC values may reflect the underlying neuropathologic mechanism of ON.

A solid-state synthetic strategy toward nickel-based bimetallic interstitial compounds (MNi3Cx, M = Zn, In, Ga).

Bimetallic interstitial compounds with unique geometric properties have attracted increasing attention in energy-related fields and diverse chemical transformations. Current synthesis of these compounds generally involves at least one wet-chemistry step with the use of various solvents to prepare the bimetallic precursors, and no universal protocols for different compositions are yet available. Herein, a novel synthetic strategy toward a platform of nickel-based bimetallic interstitial compounds with the formula MNi3Cx, M = Zn, In, and Ga, was developed based on a straightforward solid-state transformation, i.e., simply annealing the hydroxides of the respective metals in the presence of different carbon precursors (cyanamide, dicyandiamide, melamine, and urea) in a hydrogen stream. The key process parameters influencing the compositions of the final products are studied and the formation mechanism is discussed based on advanced characterization techniques. Powder X-ray diffraction reveals MNi3Cx as a single phase and electron microscopy shows that the MNi3Cx particles are covered with N-doped carbon shells. Extrapolation to other bimetallic interstitial compounds failed when following the above protocol, and the successful examples are linked to the formation of the corresponding bimetallic alloys in the absence of carbon precursors. When evaluated for the selective hydrogenation of dimethyl oxalate, both InNi3C0.5 and ZnNi3C0.7 show comparable high activity. While ZnNi3C0.7 delivers the highest selectivity for methyl glycolate, tunable methyl glycolate and ethylene glycol are formed on InNi3C0.5. In general, this facile solvent-free strategy affords an interesting scaffold to fabricate more advanced multi-metallic interstitial compounds with broad applications.

Baseline white matter function predicts short-term treatment response in first-episode schizophrenia.

BACKGROUND AND PURPOSE: The detection and characterization of functional activities in the gray matter of schizophrenia (SZ) have been widely explored. However, the relationship between resting-state functional signals in the white matter of first-episode SZ and short-term treatment response remains unclear. METHODS: Thirty-six patients with first-episode SZ and 44 matched healthy controls were recruited in this study. Patients were classified as nonresponders and responders based on response to antipsychotic medication during a single hospitalization. The fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) of white matter were calculated. The relationships between functional changes and clinical features were analyzed. In addition, voxel-based morphometry was performed to analyze the white matter volume. RESULTS: One-way analysis of variance showed significant differences of fALFF and ReHo in the left posterior thalamic radiation and left cingulum (hippocampus) in the patient group, and the areas were regarded as seeds. The FC was calculated between seeds and other white matter networks. Compared with responders, nonresponders showed significantly increased FC between the left cingulum (hippocampus) and left posterior thalamic radiation, splenium of corpus callosum, and left tapetum, and were associated with the changes of clinical assessment. However, there was no difference in white matter volume between groups. CONCLUSION: Our work provides a novel insight that psycho-neuroimaging-based white matter function holds promise for influencing the clinical diagnosis and treatment of SZ.

Diabetes influences the fusion of autophagosomes with lysosomes in SH-SY5Y cells and induces Aß deposition and cognitive dysfunction in STZ-induced diabetic rats.

Diabetes has been regarded as an independent risk factor for Alzheimer's disease (AD). Our previous study found that diabetes activated autophagy, but lysosome function was impaired. Autophagy-lysosome dysfunction may be involved in Aß deposition in diabetic cognitive impairment. In the present study, we used STZ-induced diabetic rats and SH-SY5Y cells to investigate whether diabetes inhibits autophagosome fusion with lysosomes. We found that in the in vivo study, STZ-induced diabetic rats exhibited cognitive dysfunction, and the lysosome function-related factors CTSL, CTSD, and Rab7 were decreased (P < 0.05). In an in vitro study, the mRFP-GFP-LC3 assay showed that the fusion of autophagosomes with lysosomes was partly blocked in SH-SY5Y cells. High glucose treatment downregulated the number of autophagolysosomes, downregulated CTSD, CTSL, and Rab7 expression (P < 0.05), and then influenced the function of ACP2 to partly block the fusion of autophagosomes and lysosomes to inhibit Aß clearance. These findings indicate that high glucose treatment affected lysosome function, interfered with the fusion of autophagosomes with lysosomes, and partly blocked autophagic flux to influence Aß clearance.

Meta-analysis shows strong positive association of the TNF-α gene with tumor stage in bladder cancer.

There is no consensus on the association between the tumor necrosis factor-α (TNF-α) gene promoter -308 A/G single nucleotide polymorphisms and bladder cancer risk. To obtain a more precise estimation of this correlation, we conducted a meta-analysis. The PubMed, MEDLINE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases were searched for relevant published studies. Seven case-control studies with a total of 1,311 cases and 1,436 controls were identified and analyzed. A notable correlation was observed between the TNF-α genotype and bladder cancer grade (AA+GA vs. GG; odds ratio 1.96, 95% confidence interval 1.37-2.80, p = 0.0002). In summary, this meta-analysis demonstrates that the TNF-α -308 AA+GA genotype may be a marker to the tumor-invasive stage of bladder cancer.

Trastuzumab combined with docetaxel-based regimens in previously treated metastatic gastric cancer patients with HER2 over-expression.

BACKGROUND/AIMS: This study evaluates the efficacy and safety of trastuzumab combined with docetaxel-based chemotherapy in previously treated metastatic gastric carcinoma of Chinese patients with HER2 over-expression. METHODOLOGY: Twenty-two meta-static gastric cancer patients with HER2 over-expression (3+ by immunohistochemistry or HER2 amplification by fluorescence in situ hybridization) previously treated with 5-fluorouracil-based chemotherapy were eligible. Trastuzumab was administrated at 8mg/kg as a loading dose followed by 6mg/kg ev-ery 21 days. Docetaxel-based chemotherapy regimens were also given every 21 days. RESULTS: Median age was 56 years. ECOG performance status was 0-2. Thir-teen patients (59.1%) achieved partial response (PR)and 7 patients (31.8%) had stable disease (SD). Median progression free survival was 6.8 months and the median overall survival was 16.0 months. A patient with 3+ HER2 expression and HER2 gene amplification achieved PR after 6 cycles of combined treatment and received operation. Interestingly, his HER2 expression status in tumor tissue turned into negative after operation and he was still alive without progression until now. Trastuzumab combined with docetaxel-based chemotherapy was well tolerated. Grade 3-4 hematological toxicities were leucopenia (31.8%), neutropenia (18.2%) thrombocytopenia (9.1%) and ane-mia (4.5%). No unexpected toxicities, treatment-related deaths and symptomatic congestive heart failure were observed. CONCLUSIONS: Combinations of trastuzumab plus docetaxel-based regimens were well tolerated and effective in previously treated metastatic gastric cancer of Chinese patients with HER2 over-expression or gene amplification.