Correction and removal of expression of concern: Total synthesis of tubulysin U and N14-desacetoxytubulysin H.

Correction and removal of expression of concern for 'Total synthesis of tubulysin U and N14-desacetoxytubulysin H' by Bohua Long et al., Org. Biomol. Chem., 2020, 18, 5349-5353, https://doi.org/10.1039/D0OB01109F.

Reporting quality and risk of bias assessment of animal research on Chaihu-Shugan-San for depression: A systematic review.

Objective: Chaihu-Shugan-San (CSS) is a traditional Chinese medicine formula employed to treat depression. We aim to conduct a reporting quality assessment and risk of bias evaluation of animal research on CSS for depression. Methods: To acquire eligible studies, two reviewers searched plentiful databases from inception to October 23rd, 2021. Reporting quality assessment and risk of bias assessment of the included animal studies were evaluated by using Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines and the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, respectively. Results: The initial search identified 720 records, while only 30 studies were included. The result of the reporting quality assessment was inferior, items 17 and 19 were not reported at all. The details of five items (items 3, 6, 7, 10, and 18) were not reported. The outcome of the risk of bias assessment suggested that half of the entries (5/10) displayed an unclear risk of bias and a high risk of bias. Blinding with regard to performance bias and detection bias revealed an unclear risk of bias (100%), followed by baseline characteristics (76.67%) and sequence generation (60%). Random outcome assessment showed a high risk of bias (100%). Conclusion: The included animal studies exhibited methodological defects and imprecise reporting. Hence, the ARRIVE guidelines and SYRCLE's RoB tool should be disseminated among basic medical researchers examining CSS for depression to publish studies with low risk of bias and sufficient reporting so that the animal research can promptly be transformed into clinical research.

Nanomedicine in cancer therapy.

Cancer remains a highly lethal disease in the world. Currently, either conventional cancer therapies or modern immunotherapies are non-tumor-targeted therapeutic approaches that cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects. Recent advances in nanotechnology, accompanied by our growing understanding of cancer biology and nano-bio interactions, have led to the development of a series of nanocarriers, which aim to improve the therapeutic efficacy while reducing off-target toxicity of the encapsulated anticancer agents through tumor tissue-, cell-, or organelle-specific targeting. However, the vast majority of nanocarriers do not possess hierarchical targeting capability, and their therapeutic indices are often compromised by either poor tumor accumulation, inefficient cellular internalization, or inaccurate subcellular localization. This Review outlines current and prospective strategies in the design of tumor tissue-, cell-, and organelle-targeted cancer nanomedicines, and highlights the latest progress in hierarchical targeting technologies that can dynamically integrate these three different stages of static tumor targeting to maximize therapeutic outcomes. Finally, we briefly discuss the current challenges and future opportunities for the clinical translation of cancer nanomedicines.

Expression of concern: Total synthesis of tubulysin U and N14-desacetoxytubulysin H.

Expression of concern for 'Total synthesis of tubulysin U and N14-desacetoxytubulysin H' by Bohua Long et al., Org. Biomol. Chem., 2020, 18, 5349-5353, https://doi.org/10.1039/D0OB01109F.

The antidepressant effects and serum metabonomics of bifid triple viable capsule in a rat model of chronic unpredictable mild stress.

Background: Probiotics have shown potential antidepressant effects. This study evaluated the effect and probable mechanisms of bifid triple viable capsules (BTVCs) on a rat model of chronic unpredictable mild stress (CUMS). Materials and methods: Rats were randomly divided into Normal, CUMS model, fluoxetine hydrochloride (FLX), BTVCs, and FLX+BTVCs groups. Depressive-like behaviours, pathological changes in the hippocampus, changes in serum metabolites and potential biomarkers, and metabolic pathways were detected via behavioural tests, haematoxylin-eosin staining, nissl staining, non-targetted metabolomics, and ingenuity pathway analysis (IPA). Results: The rats displayed depressive-like behaviours after CUMS exposure, but BTVCs ameliorated the depressive-like behaviours. In addition, the pathological results showed that the hippocampal tissue was damaged in rats after CUMS exposure and that the damage was effectively alleviated by treatment with BTVCs. A total of 20 potential biomarkers were identified. Treatment with BTVCs regulated D-phenylalanine, methoxyeugenol, (±)-myristoylcarnitine, 18:3 (6Z, 9Z, 12Z) /P-18:1 (11Z), propionyl-L-carnitine, and arachidonic acid (AA) concentrations, all compounds that are involved with biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, linoleic acid metabolism and AA metabolism. The IPA demonstrated that endothelin-1 signalling and cyclic adenosine monophosphate response element binding protein (CREB) signalling in neurons may be involved in the development of depression. Conclusion: Our findings suggest that BTVCs can alleviate depressive-like behaviours, restore damage to the hippocampus in CUMS rats and regulate serum metabolism, which may be related to endothelin-1 signalling or CREB signalling in neurons.

Licochalcone E improves insulin sensitivity in palmitic acid-treated HepG2 cells through inhibition of the NLRP3 signaling pathway.

Our previous research demonstrated that compound licochalcone E can reduce glucose tolerance and lipid metabolism in diabetic rats, although its mechanism remains unknown. Here, we used palmitic acid (PA) to establish a PA-treated HepG2 model, and then examined glucose uptake, glucose consumption, and blood lipids to evaluate the effects of licochalcone E within the safe dose range in the model. Polymerase chain reaction (PCR) was used to detect the expression levels of key genes associated with liver gluconeogenesis; enzyme-linked immunosorbent assay (ELISA) was deployed to evaluate the concentration of inflammatory factors; and laser confocal microscopy and western blot were used to determine the levels of reactive oxygen species (ROS) and NLRP3 inflammasome signaling pathway-related proteins, respectively. Finally, molecular simulations were exploited to validate the interaction between licochalcone E and the NLRP3 inflammasome. The results demonstrated that licochalcone E showed no toxicity in the dose range of 2.5-40 µM. In this dose range, licochalcone E substantially increased the uptake and consumption of glucose in the insulin resistance model and dose-dependently reduced the concentration of total cholesterol. The PCR results indicated that licochalcone E dose-dependently reduced the expression of Glucose-6-phosphatase (G6Pase) and Phosphoenolpyruvate carboxykinase (PEPCK) genes and increased the expression of Glucose Transporter 4 (Glut4) in PA-treated HepG2. Moreover, the ELISA results revealed that licochalcone E significantly reduced the expression of TNF-α, IL-1ß, and IL-18. Confocal microscopy results showed that licochalcone E dramatically reduced the generation of ROS and the expressions of NLRP3 and its downstream caspase-1 in PA-treated HepG2 model. Western blot results further indicated that licochalcone E significantly reduced the expression of NLRP3, caspase-1 and IL-1ß in the model. Additionally, molecular simulations demonstrated that licochalcone E has good binding affinity for the NLPR3 inflammasome. We concluded that licochalcone E has the potential to be used as an insulin sensitizer by reducing the release of ROS and inflammatory factors following inhibition of the NLPR3 signaling pathway.

Antidepressant-Like Effects of Chaihu Shugan Powder () on Rats Exposed to Chronic Unpredictable Mild Stress through Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis.

OBJECTIVE: To investigate the antidepressant-like effects of Chaihu Shugan Powder (CSP, ) and to explore its underlying mechanisms. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into control (CON), chronic unpredictable mild stress (CUMS), fluoxetine (FLU), and CSP groups, 8 rats in each group. All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model. The open field test (OFT), forced swimming test (FST), and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues. The mRNA and protein levels of glucose-regulated protein (GRP) 78, spliced X-box-binding protein (XBP)-1, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and c-Jun N-terminal kinase (JNK) in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis, respectively. RESULTS: Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats, as revealed by enhanced time and distance in the center of the OFT (P<0.05), an increased preference for sucrose, and longer swimming time and shorter immobility time during the FST (all P<0.05). In addition, CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons (P<0.05). The mRNA and protein expression levels of GRP78, spliced XBP-1, and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins (all P<0.05), whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats. CONCLUSION: CSP can improve depression-like behavior in rats exposed to CUMS, possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.

Clinicopathological features and prognostic analysis of 77 patients with multiple primary cancers.

PURPOSE: The purpose of this study was to analyze the characteristics, diagnosis and treatment principles and prognosis of multiple primary cancers (MPC). METHODS: A total of 77 patients with MPC admitted in the Central Hospital of Changsha from December 2013 to December 2018 were enrolled in this retrospective analysis. The survival of these 77 patients with complete follow-up data was calculated. RESULTS: There were 77 patients with multiple primary cancers, including 70 patients with double primary cancers, 6 patients with three primary cancers, and 1 patient with four primary cancers. Among the 77 MPC patients, there were 4 synchronous carcinomas (SC), 58 metachronous carcinomas (MC), and 15 unknown cases. The 3, 5, and 10-year overall survival rates of 77 patients with follow-up data were 86.5%, 18.2%, and 12.9%, respectively. The median survival time of 4 SC and 58 MC patients was 12 months and 108 months, respectively. The median survival time was 48.5 months in 23 patients with an interval of less than 5 years, and 108 months in 29 patients with first and second primary cancers whose interval was more than 5 years. The median survival time of 26 patients with second primary lung cancer was 84 months, and that of 23 patients with second primary non-lung cancer was 156 months. CONCLUSIONS: MPCs are more likely to occur in the colorectum, and the prognosis of patients with metachronous cancer is better than that of patients with synchronous cancer. The longer the interval between two cancers, the better the prognosis will be. The prognosis of the second primary non-lung cancer patients is better than that of the lung cancer patients.

The Immunoregulatory Role of Myeloid-Derived Suppressor Cells in the Pathogenesis of Rheumatoid Arthritis.

Myeloid-derived suppressor cells (MDSCs) are a group of cells that regulate the immune response and exert immunosuppressive effects on various immune cells. Current studies indicate that MDSCs have both anti-inflammatory effects and proinflammatory effects on rheumatoid arthritis (RA) and RA animal models. MDSCs inhibit CD4+ T cells, which secrete proinflammatory factors such as IFN-γ, IL-2, IL-6, IL-17, and TNF-α, by inhibiting iNOS, ROS, and IFN-γ and promoting the production of the anti-inflammatory factor IL-10. MDSCs can suppress dendritic cells by reducing MHC-II and CD86 expression, expand Treg cells in vitro through the action of IL-10, inhibit B cells through NO and PGE2, and promote Th17 cell responses by secreting IL-1ß. As a type of osteoclast precursor cell, MDSCs can differentiate into osteoclasts through activation of the NF-κB pathway via IL-1α. Overall, our study reviews the research progress related to MDSCs in RA, focusing on the effects of MDSCs on various types of cells and aiming to provide ideas to help reveal the important role of MDSCs in RA.

Total glucosides of paeony for the treatment of rheumatoid arthritis: A methodological and reporting quality evaluation of systematic reviews and meta-analyses.

OBJECTIVE: To assess the methodological, reporting and evidence quality of systematic reviews and meta-analyses of total glucosides of paeony (TGP) for rheumatoid arthritis (RA). METHODS: We comprehensively searched the literature in numerous databases from inception to July 29th, 2020. Two appraisers collected data and assessed the methodological and reporting quality of the included reviews by revised A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool and the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA), respectively. The level of evidence quality was evaluated by employing the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) scale. RESULTS: Eleven relevant articles were collected. The results from AMSTAR-2 showed that the methodological quality of all included reviews was critically low; no authors met the standard of those critical domains (0%), particularly in item 2, item 4 and item 7. The PRISMA scores ranged from 16.5 to 25, and one meta-analysis almost conformed to the PRISMA structure. According to GRADE, the 11 studies included 59 outcomes: 27 had very low quality, 22 had low quality, 10 had moderate quality, and none had high quality evidence. The most prominent downgrading factors were risk of bias, followed by publication bias, inconsistency, imprecision, and indirectness. CONCLUSIONS: Although included studies summarized that TGP was effective and safe in the treatment of RA, the methodological and reporting quality and the quality of evidence was poor overall; decision-makers should be prudent when using TGP in treating RA patients. High-quality and multicenter studies investigating TGP for RA are urgently needed.

Total synthesis of tubulysin U and N14-desacetoxytubulysin H.

A concise and efficient procedure for the total synthesis of tubulysin U and N14-desacetoxytubulysin H has been developed with high stereoselectivity on a gram scale. This synthesis features an elegant cascade one-pot process to install the challenging thiazole moiety and the employment of stereoselective reductions and a series of high-yield mild reactions to ensure the requisite stereochemistry, reaction scale, and yield and to avoid the vexing epimerization occurring during peptide formation.

Huang-Qi San improves glucose and lipid metabolism and exerts protective effects against hepatic steatosis in high fat diet-fed rats.

Numerous researches supported that non-alcoholic fatty liver disease (NAFLD) was an emerging problem associated with increased visceral adiposity (obesity), diabetes and related metabolic disorders. Huang-Qi San (HQS) is composed of three traditional Chinese medicines (Astragali Radix, Pueraria Radix and Cortex Mori Radicis) with a weight ratio of 1:2:1. HQS has been reported to be effective in improving glucose-lipid metabolism, but its underlying mechanism on NAFLD has not been fully understood. The purpose of the present study was to assess the protective effects of HQS on obesity-induced hepatic steatosis in rats fed with high fat diet (HFD). Our data revealed that administration of HQS (1.2 and 2.4 g/kg body weight) resulted in significant reduction in body weight (BW) and organs coefficients of visceral fat. The full-Body CT scan demonstrated that HQS reduced liver fat ratio, visceral and subcutaneous fat mass in a dose-dependent manner. Additionally, HQS decreased plasma TC, TG, FFA and FABP4 levels, normalized glucose and insulin levels, and improved the glucose tolerance. Pathological examination showed that HQS alleviated hepatic steatosis and reduced the cell size of epididymal visceral adipose tissue. Hepatic lipid accumulation was also reduced by HQS treatment compared with HFD fed rats. RNA-Seq analysis combining with qPCR demonstrated that the mRNA expression of some important glucose and lipid metabolism-related genes including Acat2, Apoc4, Bhmt, Cyp3a62, Cyp51, Egln3 (Phd3), Fads1, Fads2, Gnmt, Hmgcs1 and Pemt, were significantly changed by HQS treatment. Taken together, these results suggested that HQS had beneficial effects on glucose-lipid metabolism and hepatic steatosis, and its mechanism might be related to the functions of the genes in regulating glucose and lipid metabolism.

A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Paeonia lactiflora Pall. On the Treatment of Alzheimer's Disease.

OBJECTIVE: To investigate the potential active compounds and underlying mechanisms of Paeonia lactiflora Pall. (PLP) on the treatment of Alzheimer's disease (AD) based on network pharmacology. METHODS: The active components of PLP were collected from Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible target proteins were predicted using TCMSP, SwissTargetPrediction, and STITCH databases. The putative AD-related target proteins were identified from Therapeutic Target Database (TTD), GeneCards, and MalaCards database. The compound-target-disease network interactions were established to obtain the key targets about PLP acting on AD by network topology analysis. Then, the function annotation and signaling pathways of key targets were performed by GO and KEGG enrichment analysis using DAVID tools. Finally, the binding capacity between active ingredients and key targets was validated by molecular docking using SystemsDock tools. RESULTS: There were 7 active compounds involving in 151 predicted targets identified in PLP. Besides, a total of 160 AD-related targets were identified. Among these targets, 30 shared targets of PLP and AD were acquired. After topological analysis of the PLP potential target-AD target network, 33 key targets that were highly responsible for the therapeutic effects of PLP on AD were obtained. Further GO and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in cell apoptosis and inflammatory response and maintained the function of neurons to accomplish the anti-AD activity. The molecular docking analysis verified that the 7 active compounds had definite affinity with the key targets. CONCLUSIONS: The ameliorative effects of PLP on AD were predicted to be associated with regulating neural cell apoptosis, inflammatory response, and neurotrophy via various pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, and neurotrophin signaling pathway.

A combined molecular biology and network pharmacology approach to investigate the multi-target mechanisms of Chaihu Shugan San on Alzheimer's disease.

Chaihu Shugan San (CSS) is a well-known herbal formula used to nourish liver and blood, promote blood circulation and Qi flow in Traditional Chinese Medicine. Modern pharmacological studies and clinical uses showed that CSS could ameliorate cognitive dysfunction of Alzheimer's disease (AD). The present study aimed to elucidate the multi-target mechanisms of CSS on AD using network pharmacology analysis and verify its effect by biological experiments. Firstly, a total of 152 active compounds in CSS, 520 predicted biological targets and 160 AD-related targets were identified. Subsequently, the networks including herb-compound-target network, AD-target network, and CSS potential target-AD target network were constructed. 60 key targets highly responsible for the beneficial effect of CSS on AD were identified by central network topological analysis. They were significantly characterized as nuclear or cytoplasmic proteins with molecular function of protein binding. They were also enriched in various biological processes through PI3K-Akt signaling pathway, MAPK signaling pathway and HIF signaling pathway by GO function and KEGG pathway enrichment analysis. Pretreatment with CSS ameliorated Aß-induced neural cell death and reduced the number of apoptotic cells in differentiated PC12 cells. Moreover, increased phosphorylation of Akt accompanied with decreased Bax expression was found after CSS pretreatment, suggesting that Akt signaling pathway was involved in the protective effect of CSS against neural cells death. The present study systematically revealed the multi-target mechanisms of CSS on AD using network pharmacology approach, as well as validated the protective effect of CSS against Aß-induced neural cells death through Akt signaling pathway. It provided indications for further mechanistic studies and also for the development of CSS as a potential treatment for AD patients.

iTRAQ-based proteomics reveals SOD2 as a potential salivary biomarker in liver cancer.

BACKGROUND: Salivary proteomic analysis has been extensively used in a wide range of cancer, but not in hepatocellular carcinoma. The aim of this study was to identify potential salivary biomarkers for hepatocellular carcinoma clinical screening. METHODS: In this study, we performed isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analysis to detect differentially expressed proteins between saliva samples from 15 hepatocellular carcinoma patients and 15 healthy controls. Enzyme-linked immunosorbent assay (ELISA) verification was undertaken in saliva samples from 14 hepatocellular carcinoma patients and 14 healthy controls. RESULTS: Overall, 133 proteins with significant differential expression level (ratio > 1.5 or < 0.67) were detected. Using bioinformatic analysis, two candidate proteins were selected and subsequently verified by ELISA. The increased expression of superoxide dismutase 2, mitochondrial (SOD2) in hepatocellular carcinoma patients was confirmed by ELISA, with an area under the curve value of 0.9082. CONCLUSIONS: iTRAQ-based quantitative proteomics revealed that SOD2 might serve as a potential salivary biomarker for hepatocellular carcinoma detection. Our results indicated that a noninvasive and inexpensive salivary test might be established for hepatocellular carcinoma detection.

Autophagy in Alzheimer's disease and promising modulatory effects of herbal medicine.

Alzheimer's disease (AD) is a progressive and unremitting neurodegenerative disorder characterized by memory loss and cognitive impairment. It affects the quality of life of victims severely. The prevalence of AD has been increasing in recent years. Therefore, it is of great importance to elucidate the pathogenesis of AD and find out effective therapeutic approaches. Autophagy, a primary intracellular way of degrading aggregated proteins and damaged organelles, has been discovered to be involved in the pathological changes of AD. In the last few years, much progress has been made in finding autophagy regulators from natural products, providing new insights to develop treatment strategy for AD by targeting autophagy. In the present review, we provided an overview of the recent research progress regarding the function role of autophagy in AD, the regulation mechanisms of autophagy-lysosomal pathway as well as therapeutic potential of herbal medicine on AD by targeting autophagy.

Combating Neurodegenerative Diseases with the Plant Alkaloid Berberine: Molecular Mechanisms and Therapeutic Potential.

Neurodegenerative diseases are among the most serious health problems affecting millions of people worldwide. Such diseases are characterized by a progressive degeneration and / or death of neurons in the central nervous system. Currently, there are no therapeutic approaches to cure or even halt the progression of neurodegenerative diseases. During the last two decades, much attention has been paid to the neuroprotective and anti-neurodegenerative activities of compounds isolated from natural products with high efficacy and low toxicity. Accumulating evidence indicates that berberine, an isoquinoline alkaloid isolated from traditional Chinese medicinal herbs, may act as a promising anti-neurodegenerative agent by inhibiting the activity of the most important pathogenic enzymes, ameliorating intracellular oxidative stress, attenuating neuroinflammation, triggering autophagy and protecting neurons against apoptotic cell death. This review attempts to summarize the current state of knowledge regarding the therapeutic potential of berberine against neurodegenerative diseases, with a focus on the molecular mechanisms that underlie its effects on Alzheimer's, Parkinson's and Huntington's diseases.

Morphology, structure and in vitro digestibility of starches isolated from Ipomoea batatas (L.) Lam. by alkali and ethanol methods.

The tubers of Ipomoea batatas was one of the main sources of starch. This work aimed to assess the effect of extraction methods (alkali method and ethanol method) on the structural and physicochemical properties of Ipomoea batatas starches. The amylose content ranged from 10.18% to 13.35% for starches and from 5.63% to 7.61% for flours compared with isolated starches. I. batatas flours possessed greater water-binding capacity than their starches, but the difference was not significant. Scanning electron micrographs revealed that the I. batatas flour granules were attached to surrounding small particles and fragments, which gathered to form oval clusters. The starches all showed typical C-type X-ray diffraction patterns with the flours' CB-type. The predicted glycaemic index was relatively low, ranging from 59.30 to 79.88 for flour, which is available for functional food. Principal component analysis showed that the three principal components explained 90.71% of the total variation. The flours and starches were divided into three groups according to their properties. Most starches isolated with the ethanol method received higher scores than those isolated with the alkali method. It is possible to conclude that the isolation method exerted a marked effect on the starch properties and on in vitro starch digestibility.

Decreased expression of TRIM21 indicates unfavorable outcome and promotes cell growth in breast cancer.

BACKGROUND: Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase, has been implicated in autoimmune diseases. Dysregulation of TRIM21 contributes to the progression of human malignancies, but its role and clinical significance in breast cancer remain unclear. METHODS: The expression of TRIM21 was examined by quantitative real-time PCR, Western blot, and immunohistochemistry. The role of TRIM21 in the progression of breast cancer was determined using in vitro and in vivo models. The upstream regulation of TRIM21 was investigated by luciferase reporter assay. RESULTS: Here, we showed that TRIM21 expression in breast cancer tissues was decreased at both the mRNA and protein levels in comparison to that in nontumorous tissues. TRIM21 expression was closely associated with tumor size, estrogen receptor, human epidermal growth factor receptor 2, and clinical stage. Low TRIM21 expression was correlated with poor overall and disease-free survival in two independent cohorts containing 1,219 patients with breast cancer. A multivariate Cox regression model suggested TRIM21 as an independent factor for overall survival. In vitro data revealed that TRIM21 expression was suppressed by miR-494-3p directly targeting the 3' untranslated region of TRIM21. Overexpression of TRIM21 impeded cell proliferation and tumor growth in breast cancer, whereas TRIM21 depletion enhanced these capacities. CONCLUSION: Collectively, our findings indicate that TRIM21 serves as a potential prognostic biomarker and functions as a tumor suppressor in breast cancer.

Chaihu-Shugan-San exerts an antidepressive effect by downregulating miR-124 and releasing inhibition of the MAPK14 and Gria3 signaling pathways.

Dysregulation of miR-124 has been reported to be involved in the pathophysiology of depression. Chaihu-Shugan-San, a traditional Chinese medicine, has antidepressive activity; however, the underlying mechanisms remain unclear. In this study, to generate a rodent model of depression, rats were subjected to a combination of solitary confinement and chronic unpredictable mild stress for 28 days. Rats were intragastrically administered Chaihu-Shugan-San (2.835 mL/kg/d) for 4 weeks, once a day. Real-time reverse-transcription quantitative polymerase chain reaction, miRNA microarray, western blot assay and transmission electron microscopy demonstrated that Chaihu-Shugan-San downregulated miR-124 expression and upregulated the mRNA and protein levels of mitogen-activated protein kinase 14 (MAPK14) and glutamate receptor subunit 3 (Gria3). Chaihu-Shugan-San also promoted synapse formation in the hippocampus. The open field test, sucrose consumption test and forced swimming test were used to assess depression-like behavior. After intragastric administration of Chaihu-Shugan-San, sucrose consumption increased, while the depressive behaviors were substantially reduced. Together, these findings suggest that Chaihu-Shugan-San exerts an antidepressant-like effect by downregulating miR-124 expression and by releasing the inhibition of the MAPK14 and Gria3 signaling pathways.