Search

Gut microbial disturbance has been established as potential pathogenesis of mental disorders. However, the signatures and differences regarding patients with schizophrenia (SCH) or bipolar disorder (BD) in emerging adulthood as well as their subtypes have been poorly addressed.In the present study, stool samples obtained from 63 emerging adult patients with schizophrenia (SCH), 50 with bipolar disorder (BD), and 40 healthy controls (HC) were analyzed by 16 S rRNA gene sequencing; psychiatric symptoms and psychological, social, and professional functioning were also assessed.We found that gut microbiota composition was remarkably changed in the patients with SCH and BD. Moreover, the distinct gut microbiome signatures and their potential function in bipolar depression (BP-D) and SCH with predominantly negative symptoms (SCH-N) as well as bipolar mania (BP-M) and SCH with predominantly positive symptoms (SCH-P) were also observed. Furthermore, we identified diagnostic potential biomarkers that can distinguish BD from HC (38 genera, AUC = 0.961), SCH from HC (32 genera, AUC = 0.962), and BD from Scheme (13 genera, AUC = 0.823). Potential diagnostic biomarkers that can distinguish BD-D from SCH-N (16 genera, AUC = 0.969) and BD-M from SCH-P (31 genera, AUC = 0.938) were also identified.This study provides further understanding of abnormal gut microbiome in emerging adulthood patients with SCH and BD and lay the potential foundation for the development of microbe-based clinical diagnosis for BD and SCH.

To improve the clinical outcome of tumor chemotherapy, more effective combination treatments against tumor metastasis and recurrence are required. Licochalcone A (LicA) is the root of Glycyrrhiza inflata and has been reported to possess anti-inflammatory, antimicrobial, and antitumor effects. Sorafenib (Sor), a multikinase inhibitor, is used to treat patients with solid tumors such as advanced hepatocellular carcinoma (HCC). However, the synergistic effects of LicA and Sor on the metastasis of human HCC cells have not been reported. We found that LicA and Sor did not have cytotoxic effects or arrest growth in human SK-Hep-1 and Huh-7 cells. In addition, treatment with LicA or Sor alone inhibited migration and invasion in human SK-Hep-1 and Huh-7 HCC cells. Furthermore, cotreatment with LicA and Sor synergistically inhibited the migration and invasion of HCC cells and significantly inhibited uPA protein expression. Notably, cotreatment of LicA and Sor synergistically and significantly downregulated MKK4-JNK expression. Through tail vein injection in nude mice, the aforementioned cotreatment synergistically suppressed SK-Hep-1 cell-mediated lung metastasis. These findings first revealed the synergistic effects of LicA and Sor cotreatment against human HCC cells, further suggesting that beneficial effects on tumor regression could be confirmed through prospective clinical trials.

β-catenin is important in development of lung cancer. In our previous study, GMI, a fungal immunomodulatory protein, inhibits lung cancer cell survival. The aim of this study is to evaluate the effect of GMI on β-catenin inhibition and apoptosis induction. GMI induced apoptosis in lung cancer cells bearing wild-type and mutated EGFR. GMI did not reduce the β-catenin mRNA expression but suppressed the protein expressions of β-catenin that resulted in the transcriptional downregulation of its target genes: survivin and cyclin-D1. The transcriptional activation activity of β-catenin was demonstrated by TOPFLASH/FOPFLASH luciferase reporter assay. Inhibition of GSK-3β and proteasome blocked the inhibiting effect of GMI on β-catenin and its target genes. β-catenin silencing increased activation of apoptosis in GMI-treated H1355 cells. This is the first study to reveal the novel function of GMI in inducing apoptosis via β-catenin inhibition. These results provide a new potential of GMI in against lung cancer.

“Physical restraint” formerly used as a measure of protection for psychiatric patients is now widely used. However, existing studies showed that physical restraint not only has inadequate effect of protection but also has negative effects on residents. To analyzes the impact of educational program on the physical restraint use in long-term care facilities. Design: A systematic review with meta-analysis and meta-regression. Eight databases, including Cochrane Library, ProQuest, PubMed, EMBASE, EBSCO, Web of Science, Ovid Medline and Physiotherapy Evidence Database (PEDro), were searched up to January 2017. Eligible studies were classified by intervention and accessed for quality using the Quality Assessment Tool for quantitative studies. Sixteen research articles were eligible in the final review; 10 randomize control trail studies were included in the analysis. The meta-analysis revealed that the use of physical restraint was significantly less often in the experimental (education) group (OR = 0.55, 95% CI: 0.39 to 0.78, p < 0.001) compared to the control group. Meta-regression revealed the period of post education would have decreased the effect of the restraint educational program (β: 0.08, p = 0.002); instead, the longer education period and more times of education would have a stronger effect of reducing the use of physical restraint (β: −0.07, p < 0.001; β: −0.04, p = 0.056). The educational program had an effect on the reduced use of physical restraint. The results of meta-regression suggest that long-term care facilities should provide a continuous education program of physical restraint for caregivers.

The origins of Kam-Sui speaking Chadong and Mulam people have been controversial subjects in ethnic history studies and other related fields. Here, we studied Y chromosome (40 informative single nucleotide polymorphisms and 17 short tandem repeats in a non-recombining region) and mtDNA (hypervariable segment I and coding region single nucleotide polymorphisms) diversities in 50 Chadong and 93 Mulam individuals. The Y chromosome and mtDNA haplogroup components and network analyses indicated that both Chadong and Mulam originated from the admixture between surrounding populations and the indigenous Kam-Sui populations. The newly found Chadong is more closely related to Mulam than to Maonan, especially in the maternal lineages.

Chinese bittersweet, Celastrus angulatus Max., is a widely distributed plant and is used as a traditional insecticide in China. Celangulin V (CA-V), one of the main insecticidal ingredients from the plant, has special insecticidal mechanism. A synthesized compound, 6β-propoxycelangulin V, exhibits more remarkable insecticidal activity against insect pests. In this study, the synthesis of a labeled version of a CA-V analog, 6β-([1-14C]propoxy)celangulin V, was accomplished from 1-[1-14C]propanol and CA-V in two steps with the chemical and radiochemical purities of 98.7 and 99.9%, respectively. The labeled compound can be used as a radiotracer to study the mechanism of action of CA-V analogs. Copyright © 2008 John Wiley & Sons, Ltd.

The lack of a human papillomavirus (HPV)-infected skin cancer cell line has hampered the investigation of the interaction of UV and HPV in skin carcinogenesis. We identified a human basal cell carcinoma (BCC-1/KMC) cell line integrated with E6 and E7 genes of high-risk HPV type 18 and demonstrated that repression of E6 and E7 results in proliferation inhibition. Sublethal ultraviolet-B (UVB) irradiation induced the expressions of interleukin-6 (IL-6) and interleukin-8 (IL-8), as well as viral E6 and E7 genes, in BCC-1/KMC cells. When E6 and E7 expressions were inhibited, IL-6/IL-8 expressions were repressed. Furthermore, IL-6/IL-8 remained inducible by UVB irradiation when E6 and E7 were inhibited. These results indicated that IL-6 and IL-8 can be upregulated by viral E6 and E7 proteins without UVB irradiation. Moreover, chronic exposure to UVB upregulates IL-6 and IL-8 when E6/E7 is induced by UVB.

Background: Acute administration of EtOH suppresses basal NK cell lytic function in mice, and this suppression is caused, in part, by neuroendocrine mediators induced by EtOH. There is also evidence that a smaller part of the suppression is caused by direct action of EtOH. However, activation of NK cells to higher levels of lytic activity may be more important than basal NK cell lytic function in resistance to cancer or infectious agents. Therefore, the study described here examined the effects of acute EtOH exposure on activation of NK cells by polyinosinic-polycytidilic acid (poly I:C). Methods: Ethanol was administered by gavage as a 32% solution in water, and poly I:C was administered to activate NK cells. NK cell activity was measured using a standard 4 hr 51 Cr release assay with YAC-1 tumor cells. The effects of corticosterone were evaluated by administration of a glucocorticoid antagonist (RU 486) or a dosage of corticosterone previously shown to induce similar blood levels as treatment with EtOH. Results: EtOH at 5-7 g/kg suppressed poly I:C-induced increases in NK cell lytic activity, and at least the lower end of this dosage range yields blood EtOH levels that are relevant for humans (0.25-0.3%). This suppression was partially blocked in mice that were pretreated with a glucocorticoid antagonist, and administration of exogenous corticosterone also suppressed NK cell activation. Conclusions: EtOH-induced increases in corticosterone are apparently involved in the suppression of NK cell activation. This conclusion was supported by the lack of a direct effect of EtOH or its major metabolites (acetaldehyde and acetate) on NK cell activation by poly I:C in vitro.

The present study was done to delineate cause-effect relationships between the ethanol (EtOH)-induced stress response, natural-killer (NK)-cell activity, and resistance to experimental metastases of B16F10 melanoma cells in mice. Increased numbers of metastatic nodules were noted in the lungs of mice treated with dosages of EtOH that produce peak blood levels of 0.25-0.4%. EtOH caused only a minor depletion of NK cells or NK-cell activity from the spleen or lungs of normal or B16F10-challenged mice. However, in earlier studies we have shown consistent, significant decreases in NK-cell activity (approx. 50%) in spleen preparations from EtOH-treated mice. Depletion of NK cells by a monoclonal antibody increased the number of B16F10 nodules in the lungs, confirming an important role for NK cells for resistance to B16F10 metastases. Treatment of NK-cell-depleted mice with EtOH caused no further decrease in resistance to B16F10 cells, indicating that suppression of NK-cell activity is the major mechanism by which EtOH suppresses resistance to B16F10 metastases. Adrenalectomy or a glucocorticoid antagonist partially prevented EtOH-induced increases in the number of metastatic nodules in the lungs. Administration of exogenous corticosterone increased the number of B16F10 nodules to an extent similar to that caused by EtOH. These results indicate a role for the EtOH-induced stress response in decreasing resistance to B16F10 metastases. EtOH-induced decreases in resistance to cancer have also been reported in rats. The findings of the present study support the possibility that this is a generalized phenomenon, which could occur in humans.

Ethanol (EtOH) suppresses splenic natural killer (NK) cell activity in a mouse binge drinking model. Direct effects of EtOH and its metabolites are not the major cause of this suppression. Also, catecholamines do not completely explain this suppression. This implicates the involvement of other neuroendocrine mediators in this suppression. Previous studies in this laboratory have shown that RU 486 at a dosage of 100 mg/kg did not affect EtOH-induced suppression of NK cell activity. However, in the present study, RU 486 at a dosage of 200 mg/kg partially blocked the suppression of NK cell activity induced by EtOH. Moreover, corticosterone at levels expected in the free (unbound) form in EtOH-treated mice decreased NK cell activity in vitro. Nadolol in combination with RU 486 blocked the suppression of NK cell activity in EtOH-treated mice. Although there were reasons to suspect that EtOH-induced changes in the levels of growth hormone or prolactin might also contribute to the suppression of NK cell activity; evidence obtained herein did not indicate such involvement. Thus, glucocorticoids and catecholamines seem to be involved in EtOH-induced suppression of NK cell activity. Together, with the direct effects of EtOH, these neuroendocrine mediators seem to be sufficient to explain all of the suppression of NK cell activity caused by EtOH.