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Abstract Background Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood. Methods This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions. Results (1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression. Conclusions Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

Abstract Since cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway was discovered in 2013, great progress has been made to elucidate the origin, function, and regulating mechanism of cGAS–STING signaling pathway in the past decade. Meanwhile, the triggering and transduction mechanisms have been continuously illuminated. cGAS–STING plays a key role in human diseases, particularly DNA‐triggered inflammatory diseases, making it a potentially effective therapeutic target for inflammation‐related diseases. Here, we aim to summarize the ancient origin of the cGAS–STING defense mechanism, as well as the triggers, transduction, and regulating mechanisms of the cGAS–STING. We will also focus on the important roles of cGAS–STING signal under pathological conditions, such as infections, cancers, autoimmune diseases, neurological diseases, and visceral inflammations, and review the progress in drug development targeting cGAS–STING signaling pathway. The main directions and potential obstacles in the regulating mechanism research and therapeutic drug development of the cGAS–STING signaling pathway for inflammatory diseases and cancers will be discussed. These research advancements expand our understanding of cGAS–STING, provide a theoretical basis for further exploration of the roles of cGAS–STING in diseases, and open up new strategies for targeting cGAS–STING as a promising therapeutic intervention in multiple diseases.

Thyroid carcinoma (TC) is a prevalent malignancy of the endocrine system, with a notable rise in its detection rate in recent decades. The primary therapeutic approaches for TC now encompass thyroidectomy and radioactive iodine therapy, yielding favorable prognoses for the majority of patients. TC survivors may necessitate ongoing surveillance, remedial treatment, and thyroid hormone supplementation, while also enduring the adverse consequences of thyroid hormone fluctuations, surgical complications, or side effects linked to radioactive iodine administration, and encountering enduring physical, psychosocial, and economic hardships. In vitro and in vivo studies of natural products against TC are demonstrating the potential of these natural products as alternatives to the treatment of thyroid cancer. This therapy may offer greater convenience, affordability, and acceptability than traditional therapies. In the early screening of natural products, we mainly use a combination of database prediction and literature search. The pharmacological effects on TC of selected natural products (quercetin, genistein, apigenin, luteolin, chrysin, myricetin, resveratrol, curcumin and nobiletin), which hold promise for therapeutic applications in TC, are reviewed in detail in this article through most of the cell-level evidence, animal-level evidence, and a small amount of human-level evidence. In addition, this article explores possible issues, such as bioavailability, drug safety.

BackgroundTraumatic brain injury (TBI) is one of the most serious types of trauma and imposes a heavy social and economic burden on healthcare systems worldwide. The development of emerging biotechnologies is uncovering the relationship between TBI and gut flora, and gut flora as a potential intervention target is of increasing interest to researchers. Nevertheless, there is a paucity of research employing bibliometric methodologies to scrutinize the interrelation between these two. Therefore, this study visualized the relationship between TBI and gut flora based on bibliometric methods to reveal research trends and hotspots in the field. The ultimate objective is to catalyze progress in the preclinical and clinical evolution of strategies for treating and managing TBI.MethodsTerms related to TBI and gut microbiota were combined to search the Scopus database for relevant documents from inception to February 2023. Visual analysis was performed using CiteSpace and VOSviewer.ResultsFrom September 1972 to February 2023, 2,957 documents published from 98 countries or regions were analyzed. The number of published studies on the relationship between TBI and gut flora has risen exponentially, with the United States, China, and the United Kingdom being representative of countries publishing in related fields. Research has formed strong collaborations around highly productive authors, but there is a relative lack of international cooperation. Research in this area is mainly published in high-impact journals in the field of neurology. The “intestinal microbiota and its metabolites,” “interventions,” “mechanism of action” and “other diseases associated with traumatic brain injury” are the most promising and valuable research sites. Targeting the gut flora to elucidate the mechanisms for the development of the course of TBI and to develop precisely targeted interventions and clinical management of TBI comorbidities are of great significant research direction and of interest to researchers.ConclusionThe findings suggest that close attention should be paid to the relationship between gut microbiota and TBI, especially the interaction, potential mechanisms, development of emerging interventions, and treatment of TBI comorbidities. Further investigation is needed to understand the causal relationship between gut flora and TBI and its specific mechanisms, especially the “brain-gut microbial axis.”

Objectives We conducted this study to assess the application effect of the family doctor contract service mode of ‘basic package+personalised package’ in the management of hypertension patients.Design Observational study.Setting The study was conducted at a community health centre in Southwest China. Data were collected from 1 January 2018 to 31 December 2020.Participants From 1 January 2018 to 31 December 2020, hypertensive patients (age ≥65 years) who participated in the contract services of family doctors at a community health service centre in Chengdu, Southwest China, were selected as the study subjects.Main outcome measures The primary outcomes included mean blood pressure (systolic, diastolic) and the rate of blood pressure control, secondary outcomes included the level of cardiovascular disease risk and self-management ability. Assessments of baseline and 6 months after signing up were conducted on all outcomes. The major statistical analysis methods included two independent sample t-tests, paired t-tests, Pearson’s χ2 test, McNemar’s test, two independent sample Mann-Whitney U tests and paired sample marginal homogeneity tests.Results Of the 10 970 patients screened for eligibility, 968 (8.8%) were separated into an observation group (receiving ‘basic package+personalised package (hypertension)’ service) (n=403) and a control group (receiving ‘basic package’ service) (n=565) according to the type of service package they received. In comparison to the control group, the observation group had lower mean systolic blood pressure (p=0.023), higher blood pressure control rate (p

Metabolic reprogramming is one of the cancer hallmarks, important for the survival of malignant cells. We investigated the prognostic value of genes associated with metabolism in thyroid carcinoma (THCA). A prognostic risk model of metabolism-related genes (MRGs) was built and tested based on datasets in The Cancer Genome Atlas (TCGA), with univariate Cox regression analysis, LASSO, and multivariate Cox regression analysis. We used Kaplan-Meier (KM) curves, time-dependent receiver operating characteristic curves (ROC), a nomogram, concordance index (C-index) and restricted mean survival (RMS) to assess the performance of the risk model, indicating the splendid predictive performance. We established a three-gene risk model related to metabolism, consisting of PAPSS2, ITPKA, and CYP1A1. The correlation analysis in patients with different risk statuses involved immune infiltration, mutation and therapeutic reaction. We also performed pan-cancer analyses of model genes to predict the mutational value in various cancers. Our metabolism-related risk model had a powerful predictive capability in the prognosis of THCA. This research will provide the fundamental data for further development of prognostic markers and individualized therapy in THCA.

Background: Increasing attention has been attracted by the role of circular RNAs (circRNAs) in ocular diseases. Previous study has revealed that circ_0005941 (also known as circFTO, an alpha-ketoglutarate–dependent dioxygenase) was upregulated in the vitreous humor of diabetic retinopathy (DR), while its underlying mechanism in DR remains unknown.Methods: Retinal vascular endothelial cells (RVECs) treated with high glucose (HG) were used to establish the DR cell model. The in vivo assays were conducted using streptozotocin-induced diabetic mice. The circular structure and stability of circFTO were identified by Sanger sequencing and RNase R treatment. RT-qPCR analysis was used to detect the RNA expression. The levels of the mRNA-encoded protein thioredoxin-interacting protein (TXNIP) or angiogenesis-associated proteins (VEGFA, PDGF, and ANG2) and blood–retinal barrier (BRB)-related proteins (ZO-1, Occludin, and Claudin-5) were measured by Western blot. The viability of RVECs was measured using CCK-8 assays. The angiogenesis of RVECs was assessed using tube formation assays in vitro. Endothelial permeability assays were conducted to examine the function of the BRB. The binding between genes was explored using RNA pulldown and luciferase reporter assays.Results: CircFTO was upregulated in HG-treated RVECs. CircFTO deficiency reversed the HG-induced increase in the viability and angiogenesis of RVECs and alleviated HG-mediated impairment of the BRB. MiR-128-3p bound with circFTO and was downregulated in HG-treated RVECs. TXNIP was a downstream target gene of miR-128-3p. TXNIP was highly expressed in the DR cell model. Rescue assays revealed that circFTO promoted angiogenesis and impaired the blood–retinal barrier by upregulating TXNIP. In the DR mouse model, circFTO silencing inhibited angiogenesis and promoted BRB recovery in vivo.Conclusion: CircFTO promotes angiogenesis and impairs the blood–retinal barrier in vitro and in vivo by binding with miR-128-3p to upregulate TXNIP in DR.

Hypothermia therapy is a promising therapeutic strategy for traumatic brain injury (TBI); however, some trials have shown that hypothermia therapy has a negative effect on patients with TBI. The treatment of hypothermia in children with TBI remains controversial. We conducted a search of six online databases to validate the literature on comparing hypothermia with normal therapy for children with TBI. Eight randomized controlled trials (514 patients) were included. The meta-analysis indicated that hypothermia therapy may increase the Glasgow Outcome Scale (GOS) scores. However, in terms of improving the rate of complications, intracranial pressure (ICP), mortality, cerebral perfusion pressure (CPP), and length of stay both in hospital as well as pediatric ICU, the difference was not statistically significant. Hypothermia therapy may have clinical advantages in improving the GOS scores in children with TBI compared with normothermic therapy, but hypothermia therapy may have no benefit in improving the incidence of complications, ICP, mortality, CPP, and length of stay both in pediatric ICU as well as hospital. The decision to implement hypothermia therapy for children with TBI depends on the advantages and disadvantages from many aspects and these must be considered comprehensively.