Response rate and safety of antidepressants combined with electroconvulsive therapy in adolescent depression: Real-world clinical application.

BACKGROUND: METHODS: This study included 210 depression patients receiving antidepressants and ECT. The symptoms of depression were examined with the Hamilton Depression Scale (HAMD) and Clinical Global Impressions Scale (CGI) at baseline and the end of treatment. Response and safety were compared among adolescent and adult patients. RESULTS: For adolescents, the response rate (much improved or very much improved) was 80.9 %, and CGI-Severity (CGI-S), HAMD, and suicide factor scores were significantly changed as compared to baseline (P < 0.001), results of which were similar to the adult group. There were no significant differences in HAMD, CGI scores between adolescent and adult depression before or after treatment (P > 0.05). Notably, adolescents expressed stronger suicidal intent than adults, and ECT observably relieved it. Side effects (memory problems, headache, nausea/vomiting, muscle soreness) in adolescents were not statistically different from those in adults (P > 0.05). LIMITATIONS: As data were derived from a single center, the generalizability of results may be limited, and the potential factors affecting the efficacy of ECT were not further explored. CONCLUSION: Antidepressants combined with ECT are associated with high response rate and safety for treating depression, regardless of age. A stronger expression of suicide ideation was observed in depressed adolescents, and side effects of ECT were similar to the adults.

Long Non-Coding RNA AC008972.1 as a Novel Therapeutic Target for Prostate Cancer.

Background: Prostate cancer is a common male malignancy and the leading cause of cancer death in men. Long non-coding RNAs (lncRNAs), microRNA (miRNAs) and mRNAs networks mediate prostate cancer progression. Here, we aim to investigate the functions of lncRNA AC008972.1 and its regulatory mechanism in prostate cancer. Materials and Methods: The expression levels of lncRNA AC008972.1, miR-143-3p, and TAOK2 were detected in prostate cancer tissues and cell lines by reverse transcription-quantitative polymerase chain reaction. PC3 and LNCaP cells were used to establish lncRNA AC008972.1-knockdown, miR-143-3p-overexpressing, and thousand-and-one-amino acid 2 kinase (TAOK2)-downregulated cells. Cell viability was examined by MTT assays and cell proliferation was detected by clone formation assay. Cell migration and invasion were detected by wound scratch assay and transwell chamber assay. The apoptosis rate was analyzed by flow cytometry. The protein expression was detected by Western blot assay. The RNA interaction was explored and validated by RNA binding protein immunoprecipitation (RIP) assay and dual luciferase activity assay. A mouse xenograft model was established to investigate the effect of lncRNA AC008972.1 on prostate cancer progression. Results: High expression of lncRNA AC008972.1 was associated with low overall survival in prostate cancer patients. Downregulation of lncRNA AC008972.1 suppressed prostate cancer progression by inhibiting cell viability, proliferation, migration, and invasion, in addition to the EMT process, whereas cell apoptosis was significantly promoted. LncRNA AC008972.1 bound with miR-143-3p and negatively regulated miR-143-3p expression. MiR-143-3p overexpression suppressed prostate cancer malignant behaviors in vitro. TAOK2 expression was decreased by miR-143-3p through the complementary targeting of TAOK2 mRNA. Downregulation of lncRNA AC008972.1 mitigated prostate cancer malignant behaviors in vitro based on miR-143-3p/TAOK2 node. Furthermore, the data of xenograft model experiment showed that inhibition of lncRNA AC008972.1 suppressed tumor growth in vivo. Conclusions: Knockdown of lncRNA AC008972.1 inhibits prostate cancer cell growth via downregulation of TAOK2 induced by miR-143-3p. LncRNA AC008972.1 acts as an oncogene in the progression of prostate cancer and may provide a novel therapeutic target for prostate cancer.

Schistosoma japonicum proteins that interact with the gynecophoral canal protein identified using a yeast two-hybrid system.

The large amount of schistosome eggs produced by mature female worms not only induce major pathological damage to the host but also lead to the transmission of schistosomiasis. Mature female schistosome worms need constant pairing contact with a male partner as male signaling is indispensable to female growth, development, and reproduction. The gynecophoral canal protein (GCP), a cell-surface glycoprotein, plays a potential role in the interaction between males and females and in stimulating female development and maturation. In this study, a yeast two-hybrid cDNA library of Schistosoma japonicum (Sj) parasites 18 days post-infection (dpi) was constructed; the Sjgcp gene was inserted into a pGBKT7-BD bait plasmid and used as a bait protein to screen for its molecular interactions using a yeast mating procedure. Twenty-four prey proteins that interacted with the SjGCP were selected after excluding false positives; the interactions between S.japonicum lethal giant larvae (SjLGL) and SjGCP, S.japonicum type V collagen (SjColV) and SjGCP, were verified by co-immunoprecipitation. The RNA interference against SjGCP, SjColV and SjGCP + SjColV led to severe underdevelopment of tegument in male worms and vitelline globules in female worms as well as reduced reproductive capacity of the females. Collectively, SjGCP and its interacting proteins may play pivotal roles in growth and development. The findings also suggested that SjGCP and its interacting protein partners might represent new candidate targets for drug development against schistosomiasis.

Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response.

Chronic stress is known to promote inflammatory bowel disease (IBD), but the underlying mechanism remains largely unresolved. Here, we found chronic stress to sensitize mice to dextran sulfate sodium (DSS)-induced colitis; to increase the infiltration of B cells, neutrophils, and proinflammatory ly6Chi macrophages in colonic lamina propria; and to present with decreased thymus and mesenteric lymph node (MLN) coefficients. Circulating total white blood cells were significantly increased after stress, and the proportion of MLN-associated immune cells were largely changed. Results showed a marked activation of IL-6/STAT3 signaling by stress. The detrimental action of stress was not terminated in IL-6-/- mice. Interestingly, the composition of gut microbiota was dramatically changed after stress, with expansion of inflammation-promoting bacteria. Furthermore, results showed stress-induced deficient expression of mucin-2 and lysozyme, which may contribute to the disorder of gut microbiota. Of note is that, in the case of cohousing, the stress-induced immune reaction and decreased body weight were abrogated, and transferred gut microbiota from stressed mice to control mice was sufficient to facilitate DSS-induced colitis. The important role of gut microbiota was further reinforced by broad-spectrum antibiotic treatment. Taken together, our results reveal that chronic stress disturbs gut microbiota, triggering immune system response and facilitating DSS-induced colitis.

Pretreatment with lipopolysaccharide attenuates diethylnitrosamine-caused liver injury in mice via TLR4-dependent induction of Kupffer cell M2 polarization.

In this study, we found that pretreatment with low dose of lipopolysaccharide (LPS), also known as lipoglycans and endotoxin, obviously attenuated liver injury caused by diethylnitrosamine (DEN) in mice. This protective effect was described by decreased ALT, TNF-α, and IL-1ß and increased TGF-ß production. However, Toll-like receptor 4-deficient (TLR4(-/-)) or macrophages depletion abolished this protection in mice, which revealed Kupffer cells (KCs) and TLR4 to be crucial for the prevention of LPS against DEN-induced damage. Further study revealed that LPS pretreatment induced the KCs to M2 polarization and impaired the signaling of MAPKs and NF-κB that mediated the production of inflammatory cytokines. Moreover, T regulatory cells (Tregs) were also recruited to the liver, which may mediate immunosuppression and participate in the prevention of DEN-induced injury. Our results suggested that LPS protected against DEN-induced hepatitis via induction of M2 Kupffer cells and recruitment of Tregs, which contributes to liver tolerance in TLR4-dependent mechanism.

RNAi silencing of calcium-regulated heat-stable protein of 24 kDa in Schistosoma japonicum affects parasite growth.

The calcium-regulated heat-stable protein of 24 kDa (CRHSP-24) is a major calcineurin phosphoprotein that functions in multiple signal transduction pathways in cell metabolism. Schistosomes are multicellular parasites that infect 200 million people worldwide, even though treatment has been available for two decades. To determine the function of schistosome CRHSP-24 (SjCRHSP-24), we successfully knocked down SjCRHSP-24 in Schistosoma japonicum by RNA interference (RNAi). By establishing controls for measuring off-target RNAi effects, we found that different double-stranded (dsRNA) sequences had different levels of effectiveness. While all tested dsRNAs reduced CRHSP-24 transcript levels, the S2 dsRNA consistently reduced CRHSP-24 expression to >95% of the control. Knockdown of the SjCRHSP-24 gene significantly affected the morphology and vitality of S. japonicum.