Long non-coding RNA LOXL1-AS1: a potential biomarker and therapeutic target in human malignant tumors.

Long non-coding RNAs (lncRNAs) are transcripts that contain more than 200 nucleotides. Despite their inability to code proteins, multiple studies have identified their important role in human cancer through different mechanisms. LncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1), a newly discovered lncRNA located on human chromosome 15q24.1, has recently been shown to be involved in the occurrence and progression of various malignancies, such as colorectal cancer, gastric cancer, hepatocellular carcinoma, prostate cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, breast cancer, glioma, thymic carcinoma, pancreatic carcinoma. LOXL1-AS1 acts as competitive endogenous RNA (ceRNA) and via sponging various miRNAs, including miR-374b-5p, miR-21, miR-423-5p, miR-589-5p, miR-28-5p, miR-324-3p, miR-708-5p, miR-143-3p, miR-18b-5p, miR-761, miR-525-5p, miR-541-3p, miR-let-7a-5p, miR-3128, miR-3614-5p, miR-377-3p and miR-1224-5p to promote tumor cell proliferation, invasion, migration, apoptosis, cell cycle, and epithelial-mesenchymal transformation (EMT). In addition, LOXL1-AS1 is involved in the regulation of P13K/AKT and MAPK signaling pathways. This article reviews the current understanding of the biological function and clinical significance of LOXL1-AS1 in human cancers. These findings suggest that LOXL1-AS1 may be both a reliable biomarker and a potential therapeutic target for cancers.

The association of stress perception on anxiety, depression and sleep quality in parents of children with burns: The moderating effect of social support.

OBJECTIVE: Few studies have explored the mental health status of parents of children with burns and the moderating effect of social support on them. METHODS: A survey was performed with parents of 112 burn-injured children at a burn center in China. Their perceived stress, anxiety, depression, sleep quality, and social support were measured by the Chinese Perceived Stress Scale, Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, and Perceived Social Support Scale. RESULTS: ➀ The prevalence of anxiety (46.43%), depression (52.67%) and poor sleep quality (43.75%) of parents indicated that they experienced emotional and sleep disorders;➁ The perceived stress was positively correlated with sleep quality, anxiety and depression（P＜0.01), and negatively correlated with perceived social support (p＜0.05); ➂ Social support had a significant moderating effect on their perceived stress and anxiety, depression, but not on their sleep quality. With high social support, parental perceived stress had a significant positive association on anxiety and depression, while with low perceived social support, parental perceived stress had no significant association on anxiety and depression. CONCLUSION: Parents of burned children had increased stress, obvious symptoms of anxiety and depression, and poor sleep quality. Social support had a significant buffering effect on them under low pressure, and high pressure will hinder the buffering effect of social support on stress. Therefore, the ideal services to improve mental health should be provided for them to face different levels of stress.

Simultaneous determination of subspecies and geographic origins of 110 rice cultivars by microsatellite markers.

Rice varieties of different subspecies types (indica rice and japonica rice) across various geographical origins (Hunan, Jiangsu, and Northeast China) were monitored using microsatellite markers (simple sequence repeats, SSR). 110 representative rice cultivars were collected from the main crop areas. Multiple methods including clustering analysis (neighbor-joining (NJ) method, unweighted pair-group method with arithmetic mean (UPGMA) method), principal component analysis (PCA) and model-based grouping were applied. The study revealed that 25 pairs of SSR markers exhibited a broad range of polymorphism information content (PIC) values, ranging from 0.240 to 0.830. Furthermore, our study successfully achieved a higher overall mean correct rate of 99.09% in determining the geographical origin of rice. Simultaneously, it accurately classified indica rice and japonica rice. These findings are significant as they provide an SSR fingerprint of 110 high-quality rice cultivars, serving as a valuable scientific resource for the detection of rice adulteration and traceability of its origin.

Biological role of long non-coding RNA KCNQ1OT1 in cancer progression.

Long non-coding RNAs (lncRNAs) are a type of RNAs that are more than 200 nucleotides without protein-coding potential. In recent years, more and more attention has been paid to the role of lncRNAs in cancer pathogenesis. LncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) is located on chromosome 11p15.5 with a total length of 91 kb and is highly expressed in various malignancies, which is closely related to tumor growth, lymph node metastasis, survival cycle and recurrence rate. In addition, KCNQ1OT1 is involved in the regulation of PI3K/AKT and Wnt/ß-catenin signaling pathways. In this review, the mechanism and related progress of KCNQ1OT1 in different cancers were reviewed. It was found that KCNQ1OT1 can stabilize mRNA expression through sponging miRNA, which not only induced tumor cell proliferation, migration, invasion, drug resistance, epithelial-mesenchymal transition (EMT) and inhibited cell apoptosis in vitro, but also promoted tumor growth and metastasis in vivo. Therefore, as a new biomarker and therapeutic target, KCNQ1OT1 has broad prospects for the diagnosis and treatment of different cancers.

Recent developments in Salvia miltiorrhiza polysaccharides: Isolation, purification, structural characteristics and biological activities.

In recent years, natural polysaccharides have attracted more and more attention and research because of their value in the medicine, beauty and food fields. Salvia miltiorrhiza is a traditional Chinese herb that has been used for thousands of years and has antidiabetic, antifibrotic, neuroprotective, antioxidation, anti-inflammatory and other effects. It mainly includes rosmarinic acid, tanshinone I, tanshinone IIA, tanshinone IIB, procatechualdehyde, polysaccharide and salvianolic acids. Salvia miltiorrhiza polysaccharide is a polysaccharide extracted and isolated from Salvia miltiorrhiza and has diverse biological functions, including antioxidation, anti-tumor, hepatoprotective, anti-inflammatory, immune regulatory and cardioprotective effect. In this review, the extraction, purification, structural characterization and biological activity of SMPs are summarized and new perspectives for the future work of SMPs were also proposed, we hope our research can provide a reference for further research on SMPs.

First report of Pectobacterium carotovorum and Pectobacterium brasiliense causing bacterial soft rot of bok choy in Taiwan.

Bok choy (Brassica rapa var. chinensis) is one of the most popular leafy green vegetables in Asia (Wang et al. 2019; Zhang et al. 2014). In May 2022, disease resembling bacterial soft rot was observed in a commercial greenhouse located in Xiluo, Yunlin County, Taiwan. Affected plants exhibited maceration, primarily close to the base of the plants (Fig. S1). Almost all bok choy plants (about 1,800 plants in total) on site were symptomatic. Macerated tissues were collected from six plants. The samples were homogenized in 10 mM MgCl2 and bacteria were isolated on nutrient agar (NA) by streak plating. After 1 day of culturing at 28°C, creamy-white, round colonies were consistently grown on all the plates, and six strains (Br1 to Br6) were obtained; each isolated from a different plant. The strains were able to ferment glucose and induced maceration on potato tuber slices (Schaad et al. 2001) but could not produce indigoidine on NGM medium (NA added with glycerol and MnCl2; Lee and Yu 2006). The DNA samples of these strains were tested with Pectobacterium-specific primers Y1 and Y2 (Darrasse et al. 1994) and all samples produced the expected amplicon. To identify the isolated pathogens, 1,592-bp sequences concatenated from fragments of the leuS (452 bp), dnaX (492 bp), and recA (648 bp) genes (GenBank accession nos. OP360013-OP360021) were obtained for each strain as previously described (Portier et al. 2019). Three genotypes were detected, the sequences of strains Br1, Br2, Br4, and Br5 were identical, while strains Br3 and Br6 each belong to a different genotype. The sequence identity between Br3 and Br6 was 98.2%. The concatenated sequences (dnaX-leuS-recA), along with those of type strains from known Pectobacterium species, were subjected to maximum likelihood analysis. The reconstructed trees showed that strains Br1, Br2, Br4, and Br5 grouped with P. carotovorum CFBP2046T (Fig. S2); the sequence identity between the isolated strains and the type strain was 98.7%. Strains Br3 and Br6 clustered with P. brasiliense CFBP6617T (Fig S2); the sequence identity between CFBP6617T and Br3 and Br6 were 97.5% and 98.4%, respectively. The six strains were inoculated onto 55-day-old bok choy plants using previously described prick inoculation methods (Wei et al. 2019). Autoclaved toothpicks, each carrying 9.3 x 106- 5.6 x 107 cfu of bacteria, were used to inoculate the base of plant leaves. All six strains were tested, and each strain had three replicates. Plants in the control group were stabbed with bacteria-free toothpicks. The plants were enclosed in clear plastic bags during the assay to maintain humidity and kept in a growth chamber (27/25°C day/night; 14-h photoperiod). After 1 d, all inoculated plants produced soft rot symptoms resembling those observed in the sampling site. No noticeable differences were observed among symptoms produced by different strains. The controls were symptomless. One strain was re-isolated from each treatment group and their identity were confirmed by sequencing the dnaX gene. All re-isolated strains shared the same sequences with those of the original strains tested. This is the first report of P. brasiliense and P. carotovorum causing bacterial soft rot of bok choy in Taiwan. Importantly, the findings showed that different Pectobacterium species and genotypes could induce symptoms on a crop in the same facility at the same time, highlighting the potential complexity of interactions among different soft rot bacteria in the environment.

Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic-pituitary-adrenal axis.

Elucidating the molecular mechanism underlying the hyperactivity of the hypothalamic-pituitary-adrenal axis during chronic stress is critical for understanding depression and treating depression. The secretion of corticotropin-releasing hormone (CRH) from neurons in the paraventricular nucleus (PVN) of the hypothalamus is controlled by salt-inducible kinases (SIKs) and CREB-regulated transcription co-activators (CRTCs). We hypothesised that the SIK-CRTC system in the PVN might contribute to the pathogenesis of depression. Thus, the present study employed chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioural tests, virus-mediated gene transfer, enzyme-linked immunosorbent assay, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription polymerase chain reaction, and immunofluorescence to investigate this connection. Our results revealed that both CSDS and CUMS induced significant changes in SIK1-CRTC1 signalling in PVN neurons. Both genetic knockdown of SIK1 and genetic overexpression of CRTC1 in the PVN simulated chronic stress, producing a depression-like phenotype in naive mice, and the CRTC1-CREB-CRH pathway mediates the pro-depressant actions induced by SIK1 knockdown in the PVN. In contrast, both genetic overexpression of SIK1 and genetic knockdown of CRTC1 in the PVN protected against CSDS and CUMS, leading to antidepressant-like effects in mice. Moreover, stereotactic infusion of TAT-SIK1 into the PVN also produced beneficial effects against chronic stress. Furthermore, the SIK1-CRTC1 system in the PVN played a role in the antidepressant actions of fluoxetine, paroxetine, venlafaxine, and duloxetine. Collectively, SIK1 and CRTC1 in PVN neurons are closely involved in depression neurobiology, and they could be viable targets for novel antidepressants.

Polysaccharides from Rhizoma Atractylodis Macrocephalae: A Review on Their Extraction, Purification, Structure, and Bioactivities.

Rhizoma Atractylodes macrocephala polysaccharide (RAMP), the main bioactive compound extracted from Rhizoma Atractylodes macrocephala (RAM), exhibits various biological activities in in vivo and in vitro methods, such as anti-inflammatory, antioxidant, antitumor, immunomodulatory, hepatoprotective effects, and other functions. This review systematically summarizes the recent research progress on the extraction, purification, structural characteristics, and biological activities of RAMP. We hope to provide a theoretical basis for further research on the application of RAMP in the fields of biomedicine and food.

Ginsenoside Rh2 administration produces crucial antidepressant-like effects in a CUMS-induced mice model of depression.

INTRODUCTION: The most striking feature of depression is sadness and a loss of interest in activities, which represents a major cause of disability globally. Therefore, it is necessary to identify novel antidepressants for clinical practice. Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides that can be extracted from Panax ginseng and has been demonstrated to improve both memory and learning. The purpose of this study was to provide broad insight into the mechanisms underlying depression and gain greater insights into antidepressant therapy. METHODS: In this study, we first established an effective and feasible depression animal model of chronic unpredictable mild stress (CUMS) and behavioral testing was evaluated by the forced swim test (FST), the tail suspension test (TST) and the sucrose preference test. Following pretreatment with Rh2 (10 and 20 mg/kg), the immobility time of mice was reduced without affecting locomotor activity in both the FST and TST. Western blotting and immunofluorescence were used to investigate the activation of the hippocampal BDNF signaling pathway and hippocampal neurogenesis. RESULTS: Different concentrations of Rh2 significantly reduced depressive-like symptoms in CUMS-induced mice and downregulated the effects of the BDNF signaling cascade and neurogenesis in the hippocampus. Furthermore, the administration of K252a completely prevented the antidepressant-like activity of Rh2 in mice. CONCLUSION: The results indicated that Rh2 possesses the antidepression action via the positive regulation of the BDNF-TrkB pathway.

Hippocampal miR-124 Participates in the Pathogenesis of Depression via Regulating the Expression of BDNF in a Chronic Social Defeat Stress Model of Depression.

OBJECTIVE: As one of the most prevalent psychiatric disorders, the exact pathogenesis of depression remains elusive. Therefore, there is an urgent need to identify novel antidepressants for effective treatment. MicroRNA-124 (miR-124), the most abundant miRNA in brain tissue, plays a key effect on adult neurogenesis and neuronal differentiation. However, the mechanism of miR-124 in depression has not been clarified so far. The aim of this study is to provide broad insight into the mechanisms underlying depression. METHODS: In the study, we used the forced swim test (FST), the tail suspension test (TST), and a Chronic Social Defeat Stress (CSDS) mice model of depression. Quantitative real-time reverse transcription PCR (qRT-PCR), western blotting, immunofluorescence and virus-mediated gene transfer were used together. The level of plasma corticosterone in mice was analyzed by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: It was found that CSDS robustly increased the level of miR-124 in the hippocampus. Genetic knockdown of hippocampal miR-124 produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, AAV-siR-124-EGFP treatment increased the level of plasma corticosterone in CSDS-induced mice. Moreover, it was found that the antidepressant-like effects induced by miR-124 inhibition required the hippocampal BDNF-TrkB system. CONCLUSION: Hippocampal miR-124 participated in the pathogenesis of depression by regulating BDNF biosynthesis and was a feasible antidepressant target.

First report of bacterial soft rot on Epipremnum aureum caused by Pectobacterium aroidearum in Taiwan.

Pothos (Epipremnum aureum) is an Araceae foliage plant with great ornamental values, which has long been enjoyed by consumers (Chen et al. 2010). In September 2021, pothos showing soft rot symptoms were found in 2 nurseries in Taichung, Taiwan. The petioles of the infected plants were macerated; some lesions extended to the leaves (Figure S1). The disease incidence was 50% in one nursery and 37.5% in the other; two and three plants were respectively collected from the two sites. Macerated tissues were homogenized in 10 mM MgCl2 and the samples were observed microscopically without dyeing. Motile, rod-shaped bacteria were observed in the samples, and the bacteria were isolated onto nutrient agar (NA) and grown at 28°C for 2 days. Fast-growing, round, creamy colonies were isolated from all 5 plants. One strain was isolated from each plant and the strains were named Ea1 to Ea5. The bacteria could ferment glucose and induce maceration on potato tuber slices (Schaad et al. 2001), but did not produce indigoidine on NGM medium (Lee and Yu 2006) and were tested negative for phosphatase activity (Schaad et al. 2001). The bacteria's DNA samples were tested using primers specific to Pectobacterium (Y1/Y2; Darrasse et al. 1994). The expected 434-bp amplicon was amplified in all five strains. Multilocus sequence analysis was conducted as previously described (Portier et al. 2019). A concatenated sequence (1,592 bp) comprising partial dnaX (492 bp), leuS (452 bp) and recA (648 bp) sequences was obtained for each strain. Two genotypes were detected among the strains; Ea1 and Ea2 belonged to one genotype (i.e., they had identical sequences), while Ea3, Ea4 and Ea5 belonged to the other (GenBank accession nos. OK416015-OK416020). Phylogenetic analysis was conducted using these data and those of representative strains of known Pectobacterium species (Klair et al. 2022). A maximum-likelihood tree showed that Ea1 to Ea5 clustered with P. aroidearum CFBP8168T (Figure S2). Sequence comparison (Table S1) showed that the similarity between the two genotypes' concatenated sequences was 99.1% (Ea1 vs. Ea3; 1,578/1,592 bp); Ea1 and Ea3 shared 99.2% and 99.3% sequence similarity with P. aroidearum CFBP8168T, respectively. The sequences obtained in this work were searched against GenBank and all of their top hits were those of strains belonging to P. aroidearum (supplementary information). Koch's Postulates were fulfilled by stab inoculating cutting-propagated pothos (8-cm tall) using toothpicks carrying bacteria grown on NA. The pathogen loads used were estimated by suspending cells (attached to individual toothpicks) in 10 mM MgCl2 and spread-plating them onto NA (after dilution); the loads were 5.5 x 106 - 2.2 x 107 CFU. Three plants were inoculated for each strain (3 petioles per plant). Control plants were stabbed with sterile toothpicks. Each plant was then bagged and placed in a growth chamber (28°C; 14 h light). After 24 h, all inoculated plants produced symptoms resembling those found in the nurseries, and the controls did not. For every treatment group, a strain was re-isolated onto NA; each of them shared the same recA sequence with the original strain inoculated. This is first report of P. aroidearum causing pothos soft rot in Taiwan. Local nurseries often grow pothos and other Araceae plants together in humid areas. Since other Araceae species are also known to be susceptible to P. aroidearum (Xu et al. 2020), growers should be cautious of the pathogen's spread across hosts.

Hippocampal MSK1 regulates the behavioral and biological responses of mice to chronic social defeat stress: Involving of the BDNF-CREB signaling and neurogenesis.

Depression is one of the most common psychiatric diseases in the 21st century, while its pathogenesis is not yet fully understood. Currently, besides to the monoaminergic system, the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) signaling is one of the most attractive signaling pathways for treating depression. Mitogen and stress-activated kinase (MSK) 1 and 2 are nuclear proteins activated downstream of the ERK1/2 or p38 MAPK pathways, and it has been demonstrated that MSKs are involved in the BDNF-CREB signaling. Here we assumed that MSKs may play a role in depression, and various methods including the chronic social defeat stress (CSDS) model of depression, western blotting, immunofluorescence and virus-mediated gene transfer were used together. It was found that CSDS fully enhanced the expression of both phosphorylated MSK1 and total MSK1 in the hippocampus but not the medial prefrontal cortex (mPFC). CSDS did not influence the expression of phosphorylated MSK2 and total MSK2 in the two brain regions. Genetic over-expression of hippocampal MSK1 fully prevented not only the CSDS-induced depressive-like behaviors but also the CSDS-induced dysfunction in the hippocampal BDNF-CREB signaling and neurogenesis in mice, while genetic knockdown of hippocampal MSK1 aggravated the CSDS-induced depressive-like symptomatology in mice. Our results collectively suggest that although CSDS evidently enhances the activity of hippocampal MSK1, it is not a contributor to the CSDS-induced dysfunction in the brain but a defensive feedback regulator which protects against CSDS. Therefore, hippocampal MSK1 participates in the pathogenesis of depression and is a feasible and potential antidepressant target.

Kangxianruangan granule­containing serum mediated inhibition of hepatic oval cell differentiation into hepatocellular carcinoma cells via the Wnt­1/ß­catenin signaling pathway.

Hepatocellular carcinoma is a malignancy with poor clinical prognosis. Hepatic oval cells (HOCs) tend to differentiate into cancerous hepatocellular carcinoma cells (HCCs) in the tumor microenvironment. The purpose of the present study was to explore the role of kangxianruangan granule (KXRG)­containing serum in inhibiting the differentiation of HOCs into HCCs via the Wnt­1/ß­catenin signaling pathway. N­methyl­N'­nitro­N­nitrosoguanidine (MNNG) was applied to induce the transformation of the rat HOC cell line WB­F344 into HCCs. The overexpression plasmid, Wnt­1­up, was utilized to increase Wnt­1 expression. Subsequently, high, medium and low concentrations of KXRG were applied to MNNG­treated WB­F344 cells to assess the inhibitory effect of KXRG on cell differentiation. Flow cytometry was conducted to detect the cell cycle distribution, apoptotic rate and expression of cytokeratin­19 (CK­19) protein in cells. An immunofluorescence double staining protocol was used to detect the expression of Wnt­1 and ß­catenin. ELISAs were performed to detect α fetoprotein in the cell supernatants. Reverse transcription­quantitative PCR and western blotting were conducted to detect the mRNA and protein expression levels of Wnt­1, ß­catenin, Cyclin D1, C­myc, matrix metalloproteinase­7 (MMP­7), Axin2 and epithelial cell adhesion molecule (EpCAM) in cells. Compared with the normal group, the apoptotic rate, proportion of S phase cells, concentration of AFP in the cell supernatant, level of CK­19 protein, and mRNA and protein expression levels of Wnt­1, ß­catenin, Cyclin D1, C­myc, MMP­7, Axin2 and EpCAM were all significantly increased in the model group. Addition of KXRG significantly reduced the aforementioned indicators compared with the model group. Moreover, Wnt­1 overexpression further increased the aforementioned indicators compared with the model group, whereas KXRG significantly inhibited these effects. The results indicated that KXRG inhibited the differentiation of HOCs into HCCs via the Wnt­1/ß­catenin signaling pathway, which suggested the potential clinical application of KXRG for the prevention of hepatocellular carcinoma.

Virus-mediated decrease of LKB1 activity in the mPFC diminishes stress-induced depressive-like behaviors in mice.

As a highly prevalent neuropsychiatric disorder worldwide, the pathophysiology of depression is not yet fully understood and based on multiple factors among which chronic stress is critical. Numerous previous studies have shown the role of central mammalian target of rapamycin complex 1 (mTORC1) signaling in depression. However, so far it remains elusive by which way chronic stress down-regulates the activity of central mTORC1. Liver kinase b1 (LKB1) has been demonstrated to regulate the activity of the mTORC1 signaling cascade by phosphorylating AMP activated protein kinase (AMPK). Here, this study aimed to explore whether LKB1 participates in depression by regulating the downstream AMPK-mTORC1 signaling, and various methods including mouse models of depression, western blotting and immunofluorescence were used together. Our results showed that chronic stress significantly enhanced the expression of both phosphorylated LKB1 and total LKB1 in the medial prefrontal cortex (mPFC) but not the hippocampus. Furthermore, genetic knockdown of LKB1 in the mPFC fully reversed not only the depressive-like behaviors induced by chronic stress in mice but also the effects of chronic stress on the activity of AMPK and the mTORC1 system. Taken together, this study preliminarily suggests that LKB1 in the mPFC could be a feasible target for antidepressants. This study also provides support for the potential use of LKB1 inhibition strategies against the chronic stress-related neuropsychiatric disorders.

Hippocampal miR-206-3p participates in the pathogenesis of depression via regulating the expression of BDNF.

As a widely-known neuropsychiatric disorder, the exact pathogenesis of depression remains elusive. MiRNA-206 (miR-206) is conventionally known as one of the myomiRs and has two forms: miR-206-3p and miR-206-5p. Recently, miR-206 has been demonstrated to regulate the biosynthesis of brain-derived neurotrophic factor (BDNF), a very popular target involved in depression and antidepressant responses. Here we assumed that miR-206 may play a role in depression, and various methods including the chronic social defeat stress (CSDS) model of depression, quantitative real-time reverse transcription PCR, western blotting, immuofluorescence and virus-mediated gene transfer were used together. It was found that CSDS robustly increased the level of miR-206-3p but not miR-206-5p in the hippocampus. Both genetic overexpression of hippocampal miR-206-3p and intranasal administration of AgomiR-206-3p induced not only notable depressive-like behaviors but also significantly decreased hippocampal BDNF signaling cascade and neurogenesis in naïve C57BL/6J mice. In contrast, both genetic knockdown of hippocampal miR-206-3p and intranasal administration of AntagomiR-206-3p produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, it was found that the antidepressant-like effects induced by miR-206-3p inhibition require the hippocampal BDNF-TrkB system. Taken together, hippocampal miR-206-3p participates in the pathogenesis of depression by regulating BDNF biosynthesis and is a feasible antidepressant target.

Hippocampal PPARα Plays a Role in the Pharmacological Mechanism of Vortioxetine, a Multimodal-Acting Antidepressant.

As a well-known multimodal-acting antidepressant, vortioxetine is thought to aim at several serotonin (5-HT) receptors and the 5-HT transporter. However, recently more and more proteins besides 5-HT are being reported to participate in the antidepressant mechanism of vortioxetine. As a widely known nuclear hormone receptor, peroxisome proliferator activated receptor α (PPARα) possesses transcriptional activity and is very important in the brain. Several reports have suggested that hippocampal PPARα is implicated in antidepressant responses. Here we speculate that hippocampal PPARα may participate in the antidepressant mechanism of vortioxetine. In this study, chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS), behavioral tests, the western blotting and adenovirus associated virus (AAV)-mediated gene knockdown methods were used together. It was found that vortioxetine administration significantly reversed the inhibitory actions of both CUMS and CSDS on the hippocampal PPARα expression. Pharmacological blockade of PPARα notably prevented the antidepressant actions of vortioxetine in the CUMS and CSDS models. Moreover, genetic knockdown of PPARα in the hippocampus also significantly blocked the protecting effects of vortioxetine against both CUMS and CSDS. Therefore, the antidepressant effects of vortioxetine in mice require hippocampal PPARα.

Xanthoceraside administration produces significant antidepressant effects in mice through activation of the hippocampal BDNF signaling pathway.

Current available antidepressants have various adverse reactions and slow pharmacodynamics, so it is necessary to find novel antidepressants for effective treatment. Xanthoceraside (XAN), a novel triterpenoid saponin extracted from the fruit husks of Xanthoceras sorbifolium Bunge, has anti-amnesic and neuroprotective properties. The purpose and significance of this study is to assess whether XAN has antidepressant effects in mice using the forced swim test (FST), tail suspension test (TST) and chronic unpredictable mild stress (CUMS) model of depression. The effects of XAN treatment on the hippocampal brain-derived neurotrophic factor (BDNF) signaling pathway and neurogenesis were examined. The antidepressant mechanism of XAN was explored using a BDNF inhibitor (K252a) and an anti-BDNF antibody. It was found that XAN administration significantly reversed the depressive-like behaviors of CUMS-treated mice. XAN treatment also significantly prevented the decreasing effects of CUMS on the hippocampal BDNF signaling and neurogenesis. The antidepressant effects of XAN in mice were blocked by both administration of K252a and anti-BDNF antibody. Collectively, these findings indicate that XAN possesses antidepressant effects in mice which are mediated by activation of hippocampal BDNF signaling pathway, thus providing the first evidence that XAN can be a potential antidepressant candidate.

High prevalence of Clonorchis sinensis infection in Guangxi, Southern China.

BACKGROUND: Soil-transmitted helminths (STHs), such as hookworm, roundworm and whipworm, and food-borne trematodiases, including Clonorchis sinensis, remain a public health problem worldwide, especially in tropical and subtropical regions. OBJECTIVE: We aimed to determine the current prevalence of these parasites in Guangxi, China, which is located in a subtropical region. METHODS: A cross-sectional study and a 4-year longitudinal surveillance study were carried out. Stool samples were collected and examined microscopically for parasite eggs using the modified Kato-Katz thick smear method. RESULTS: The study subjects selected using stratified random cluster sampling for the cross-sectional study and longitudinal surveillance study numbered 15,683 and 24,429, respectively. In the cross-sectional study, hookworm, roundworm, whipworm, pinworm, C. sinensis, and tapeworm were found. The total prevalence of soil-transmitted helminths (STHs) was 6.4% (95% CI, 6.0-6.8). The prevalences of C. sinensis, hookworm, roundworm, whipworm, and pinworm were 10.6%, 4.2%, 0.3%, 0.3%, and 1.8%, respectively. The prevalence of C. sinensis in males (14.0%, 95% CI, 13.3-14.8) was significantly higher than in females (7.2%, 95% CI, 6.7-7.8) (P = 0.0001). The prevalence also was significantly higher in the medical worker group (20.8%, 95% CI, 12.9-28.7) than in all other occupational groups (10.5%, 95% CI, 10.0-11.0) (P = 0.0001). The prevalence of hookworm in females (5.3%, 95% CI, 4.8-5.8) was significantly higher than in males (3.0%, 95% CI, 2.6-3.3) (P = 0.0001). In the longitudinal surveillance study, the prevalence of C. sinensis and STHs in 2016, 2017, 2018, and 2019 were 12.0%, 6.0%, 11.0%, and 10.0% and 2.6%, 2.8%, 1.5%, and 1.5%, respectively. CONCLUSIONS: Adult male and occupation of and medical workers are risk factors for infection with C. sinensis and hookworm. The prevalence rate of C. sinensis remains high while those of the other STHs are decreasing, suggesting that enhanced health education should be focused on C. sinensis in Guangxi.

Antidepressant-like effects of 1-methylnicotinamide in a chronic unpredictable mild stress model of depression.

Depression is one of the most common psychiatric disorders, and there is strong demand for developing novel antidepressants with better efficacy and less adverse effects. 1-Methylnicotinamide (MNA) is a main metabolite of nicotinamide and has been demonstrated to possess biological effects in the brain. This study aimed to evaluate the antidepressant-like effects of MNA in mice, and the possible antidepressant mechanism was also determined. The forced swim test (FST), tail suspension test (TST), chronic unpredictable mild stress (CUMS) model of depression, western blotting method and K252a (a pharmacological inhibitor of the BDNF receptor) were used together in the present study. It was found that a single injection of MNA (100 and 200 mg/kg) displayed notable antidepressant-like potential in the FST and TST without affecting the locomotor activity of mice. Repeated administration of MNA (100 and 200 mg/kg) for 2 weeks fully reversed not only the CUMS-induced depressive-like symptoms in mice but also the CUMS-induced decrease in the hippocampal BDNF signaling pathway. Furthermore, the usage of K252a fully blocked the antidepressant-like effects of MNA in the FST, TST and CUMS model of depression. Collectively, MNA possess an antidepressant-like effect in mice which is mediated, at least in part, through promoting the hippocampal BDNF signaling pathway.

Antidepressant-like activity of L-701324 in mice: A behavioral and neurobiological characterization.

Antidepressants currently used in clinical practice have limitations such as low efficacy, slow onset and various adverse reactions. It has become necessary to develop novel antidepressants beyond monoaminergic drugs. L-701,324 is a potent NMDA receptor antagonist, and the purpose of this study was to investigate the possible antidepressant effects of L-701,324 in mice. Here, various methods including the forced swim test (FST), tail suspension test (TST), chronic unpredictable mild stress (CUMS) model of depression, western blotting and immunofluorescence, were used together. A single injection of L-701,324 exhibited antidepressant-like potential in the FST and TST without affecting the locomotor activity of mice. Repeated injection of L-701,324 not only prevented CUMS-induced depressive-like behaviors in mice, but also ameliorated the downregulating effects of CUMS on the hippocampal BDNF signaling cascade and neurogenesis. Furthermore, K252a, a potent inhibitor of the BDNF system, fully blocked the antidepressant-like activity of L-701,324 in mice. K252a administration also abolished the activating actions of L-701,324 on the hippocampal BDNF signaling cascade and neurogenesis in CUMS-treated mice. Collectively, these data indicated that L-701,324 possesses antidepressant-like activity in mice, which was mediated, at least in part, by promoting the hippocampal BDNF system.