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BackgroundAnxiety symptoms are common in mental diseases and a variety of physical disorders, especially in disorders related to stress. More and more basic studies have indicated that gut microbiota can regulate brain function through the gut-brain axis, and dysbiosis of intestinal microbiota was related to anxiety. However, there is no specific evidence to support treatment of anxiety by regulating intestinal microbiota.AimsTo find evidence supporting improvement of anxiety symptoms by regulation of intestinal microbiota.MethodsThis systematic review of randomised controlled trials was searched based on the following databases: PubMed, EMBASE, the Cochrane Library, OVID, Web of Knowledge, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP databases and SinoMed. The retrieval time dated back to 25 July 2018. Then we screened research literatures based on established inclusion and exclusion criteria. Quality evaluation for each included study was done using the Cochrane risk of bias and the Jadad scale.ResultsA total of 3334 articles were retrieved and 21 studies were included which contained 1503 subjects. In the 21 studies, 14 chose probiotics as interventions to regulate intestinal microbiota and six chose non-probiotic ways such as adjusting daily diets. Probiotic supplements in seven studies contained only one kind of probiotic, two studies used a product that contained two kinds of probiotics and the supplements used in the other five studies included at least three kinds of probiotics. In the studies that used treatment as usual plus interventions regulating intestinal flora (IRIF) as interventions (five studies), only non-probiotic ways were effective (two studies), which means 40% of studies were effective; in the studies that used IRIF alone (16 studies, 11 studies used probiotic ways and 5 studies used non-probiotic ways), 56% of studies could improve anxiety symptoms, and 80% of studies that conducted the non-probiotic interventions were effective, while 45% of studies that used probiotic supplementations had positive effects on anxiety symptoms. Overall, 11 studies showed a positive effect on anxiety symptoms by regulating intestinal microbiota, which indicated 52% of the 21 studies were effective, and there were five studies that used probiotic supplements as interventions and six used non-probiotic interventions. In addition, it should be noted that six of seven studies showed that regulation of intestinal microbiota could treat anxiety symptoms, the rate of efficacy was 86%.ConclusionsWe find that more than half of the studies included showed it was positive to treat anxiety symptoms by regulation of intestinal microbiota. There are two kinds of interventions (probiotic and non-probiotic interventions) to regulate intestinal microbiota, and it should be highlighted that the non-probiotic interventions were more effective than the probiotic interventions. More studies are needed to clarify this conclusion since we still cannot run meta-analysis so far.

Increasing observational and experimental trial data have shown that mental stress can lead to an increase in adverse clinical cardiovascular events. Mental stress affects the heart by inducing ischaemia and precipitating myocardial infarction (MI) or direct myocardial injury. Mental stress leads to systemic inflammation. Inflammation is known to cause rapid atheromatous plaque progression, instability and thrombosis—the classic type 1 MI. Inflammation can also lead to type 2 MI or myocarditis and injury. The published data linking systemic inflammation, mental stress and cardiovascular disease will be reviewed to establish the linkage between mind and heart, thereby highlighting the importance of holistically managing the patient, not only addressing separate organ systems. Finally, recent trial evidence showing the value of anti-inflammatory drugs in cardiovascular and mental conditions will be briefly considered.

T cell immunoglobulin and mucin protein 3 (Tim-3) is an immune checkpoint and plays a vital role in immune responses during acute myeloid leukemia (AML). Targeting Tim-3 kills two birds with one stone by balancing the immune system and eliminating leukemia stem cells (LSCs) in AML. These functions make Tim-3 a potential target for curing AML. This review mainly discusses the roles of Tim-3 in the immune system in AML and as an AML LSC marker, which sheds new light on the role of Tim-3 in AML immunotherapy.

Ferroptosis is a newly discovered iron-dependent form of regulated cell death driven by phospholipid peroxidation and associated with processes including iron overload, lipid peroxidation, and dysfunction of cellular antioxidant systems. Ferroptosis is found to be closely related to many diseases, including cancer at every stage. Epithelial–mesenchymal transition (EMT) in malignant tumors that originate from epithelia promotes cancer-cell migration, invasion, and metastasis by disrupting cell–cell and cell–cell matrix junctions, cell polarity, etc. Recent studies have shown that ferroptosis appears to share multiple initiators and overlapping pathways with EMT in cancers and identify ferroptosis as a potential predictor of various cancer grades and prognoses. Cancer metastasis involves multiple steps, including local invasion of cancer cells, intravasation, survival in circulation, arrest at a distant organ site, extravasation and adaptation to foreign tissue microenvironments, angiogenesis, and the formation of “premetastatic niche”. Numerous studies have revealed that ferroptosis is closely associated with cancer metastasis. From the cellular perspective, ferroptosis has been implicated in the regulation of cancer metastasis. From the molecular perspective, the signaling pathways activated during the two events interweave. This review briefly introduces the mechanisms of ferroptosis and discusses how ferroptosis is involved in cancer progression, including EMT, cancer angiogenesis, invasion, and metastasis.

Prevalent copy number alteration is the most prominent genetic characteristic associated with ovarian cancer (OV) development, but its role in immune evasion has not been fully elucidated. In this study, we identified RAD21, a key component of the cohesin complex, as a frequently amplified oncogene that could modulate immune response in OV. Through interrogating the RAD21-regulated transcriptional program, we found that RAD21 directly interacts with YAP/TEAD4 transcriptional corepressors and recruits the NuRD complex to suppress interferon (IFN) signaling. In multiple clinical cohorts, RAD21 overexpression is inversely correlated with IFN signature gene expression in OV. We further demonstrated in murine syngeneic tumor models that RAD21 ablation potentiated anti-PD-1 efficacy with increased intratumoral CD8· T cell effector activity. Our study identifies a RAD21-YAP/TEAD4-NuRD corepressor complex in immune modulation, and thus provides a potential target and biomarker for precision immunotherapy in OV.

Dysregulation of the cell cycle machinery leads to genomic instability and is a hallmark of cancer associated with chemoresistance and poor prognosis in colorectal cancer (CRC). Identifying and targeting aberrant cell cycle machinery is expected to improve current therapies for CRC patients. Here,upregulated polo‐like kinase 1 (PLK1) signaling, accompanied by deregulation of cell cycle‐related pathways in CRC is identified. It is shown that aberrant PLK1 signaling correlates with recurrence and poor prognosis in CRC patients. Genetic and pharmacological blockade of PLK1 significantly increases the sensitivity to oxaliplatin in vitro and in vivo. Mechanistically, transcriptomic profiling analysis reveals that cell cycle‐related pathways are activated by oxaliplatin treatment but suppressed by a PLK1 inhibitor. Cell division cycle 7 (CDC7) is further identified as a critical downstream effector of PLK1 signaling, which is transactivated via the PLK1‐MYC axis. Increased CDC7 expression is also found to be positively correlated with aberrant PLK1 signaling in CRC and is associated with poor prognosis. Moreover, a CDC7 inhibitor synergistically enhances the anti‐tumor effect of oxaliplatin in CRC models, demonstrating the potential utility of targeting the PLK1‐MYC‐CDC7 axis in the treatment of oxaliplatin‐based chemotherapy. Hyperactivity of PLK1‐MYC‐CDC7 axis correlates with recurrence and poor prognosis in colorectal cancer. Genetic and pharmacological blockade of this axis significantly increases the sensitivity to oxaliplatin in vitro and in vivo, providing potential clinical advantage in using PLK1 or CDC7 inhibitor in combination with chemotherapy regimens in treatment of CRC patients.

In recent years, tumor organoid technology has emerged as a crucial bridge connecting basic research and clinical applications with a deeper understanding of tumor biology. This technology enables reconstruction of tumor-native structures in vitro and their microenvironments, providing new possibilities for assessing individual responses and optimizing treatment strategies. This paper details the application prospects of organoid technology in tumor immune microenvironment reconstruction, personalized therapy, and drug screening. It also analyzes the current challenges faced by organoid technology in clinical translation, including model standardization, the integrity of immune microenvironment reconstruction, and the importance of interdisciplinary collaboration. Furthermore, we discuss how emerging technologies, such as 3D bioprinting and microfluidic chips, are driving advancements in tumor research. In the future, tumor organoid technology will used to support precision immunotherapy by establishing standardized processes and databases to enhance data comparability and reproducibility. creating a closed-loop system of “patient-organoid-multi-omics data-clinical decision support” will further promote the development of precision medicine and facilitate clinical application.

BackgroundAlthough the link between gut microbiota and depression has been suggested, changes of gut microbiota vary largely among individuals with depression.AimsExplore the heterogeneity of microbiota–gut–brain axis and new pathogenic characteristics in murine models of depression.MethodsAdolescent female mice were randomly divided into control (CON) group (n=10), chronic unexpected mild stress (CUMS) group (n=15) and dexamethasone (DEX) group (n=15). Mice in the DEX group were gavaged twice a day with 0.2 mg/kg of DEX for 5 weeks, whereas CON mice were given the same amount of solvent. Mice in the CUMS group were exposed to stressors. After behavioural evaluations, all mice were sacrificed for harvesting tissues and blood samples. Enzyme-linked immunosorbent assay (ELISA) was conducted for measuring levels of corticosterone (CORT) and interleukin-1β (IL-1β) in sera, whereas levels of protein expression in colon and hippocampal tissues were examined by western blot. Faecal microbial communities were analysed by sequencing 16S rDNAs.ResultsMice in CUMS and DEX groups exhibited severe depression-like behaviours. Compared with CON mice, CUMS-exposed mice showed a significant increase in both α and β diversity. Prevotellaceae and Desulfovibrio were enriched, whereas Bacilli were decreased in the faeces of mice in the CUMS group. DEX-treated mice had a decrease in the abundance of Clostridium XVIII. Levels of occludin in colon tissue of DEX-treated mice were reduced. Relative to mice in the CON and CUMS groups, DEX-treated mice contained higher serum levels of CORT and IL-1β. Compared with CON mice, mice in the DEX and CUMS groups had higher levels of IL-1β in sera and lower levels of glial fibrillary acidic protein (GFAP), Nestin, Synapsin-1 and P2Y12 receptor in the hippocampus.ConclusionsChanges of gut microbiota diversity, intestinal integrity and neuroinflammation in the brain contribute to CUMS-induced depression, whereas pathobionts and excessive immunosuppression with damaged neuronal synapses is a basis of the DEX-induced depression.

BackgroundNon-suicidal self-injury (NSSI) is a frequent and prominent phenomenon in major depressive disorder (MDD). Even though its prevalence and risk factors are relatively well understood, the potential mechanisms of NSSI in MDD remain elusive.AimsTo review present evidence related to the potential mechanisms of NSSI in MDD.MethodsAccording to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, articles for this systematic review were searched on Medline (through PubMed), Embase (through Elsevier), PsycINFO (through OVID) and Web of Science databases for English articles, as well as China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang Data, and the Chongqing VIP Chinese Science and Technology Periodical (VIP) Databases for Chinese articles published from the date of inception to 2 August 2022. Two researchers (BW, HZ) independently screened studies based on inclusion and exclusion criteria and assessed their quality.ResultsA total of 25 157 studies were searched. Only 25 of them were ultimately included, containing 3336 subjects (1535 patients with MDD and NSSI, 1403 patients with MDD without NSSI and 398 HCs). Included studies were divided into 6 categories: psychosocial factors (11 studies), neuroimaging (8 studies), stress and hypothalamic-pituitary-adrenal (HPA) axis (2 studies), pain perception (1 study), electroencephalogram (EEG) (2 studies) and epigenetics (1 study).ConclusionsThis systematic review indicates that patients with MDD and NSSI might have specific psychosocial factors, aberrant brain functions and neurochemical metabolisms, HPA axis dysfunctions, abnormal pain perceptions and epigenetic alterations.

Background/Aims: Estradiol (EST) reduces the risk of stroke and decreases the incidence and progression of the disease because of its neuroprotective roles in inhibiting cell death that occurs in response to a variety of neuronal stimuli such as inflammation and oxidative stress. In this study, we determined the role played by autophagy and Nrf2-ARE signal pathways in the hippocampus regions in modulating cerebral ischemia under different EST conditions. Methods: Western blot analysis and ELISA were used to determine the protein expression of autophagy and Nrf2-ARE pathways; and the levels of pro-inflammatory cytokines (PICs) and a key marker of oxidative stress. Results: Lacking of EST amplifies autophagy and attenuates Nrf2-ARE pathway in the hippocampus CA1 region. Blocking autophagy alleviates neurological deficits following cerebral ischemia with lacking of EST levels and the effects of autophagy are associated with PIC and oxidative stress. Conclusions: EST influences the protein expression of autophagy and Nrf2-ARE signaling in the brain, which is linked to the pathophysiological processes of PICs and oxidative stress. Moreover, inhibition of autophagy plays a beneficial role in modulating neurological deficits after cerebral ischemia observed under conditions of a lower level of EST.