Nitidine chloride inhibits G2/M phase by regulating the p53/14-3-3 Sigma/CDK1 axis for hepatocellular carcinoma treatment.

Background: Liver cancer had become the sixth most common cancer. Nitidine chloride (NC) has demonstrated promising anti-HCC properties; however, further elucidation of its mechanism of action is necessary. Methods: The anti-HCC targets of NC were identified through the utilization of multiple databases and ChIPs data analysis. The GO and KEGG analyses to determine the specific pathway affected by NC. The Huh 7 and Hep G2 cells were subjected to a 24-h treatment with NC, followed by evaluating the impact of NC on cell proliferation and cell cycle. The involvement of the p53/14-3-3 Sigma/CDK1 axis in HCC cells was confirmed by qPCR and WB analysis of the corresponding genes and proteins. Results: The GO and KEGG analysis showed the targets were related to cell cycle and p53 signaling pathways. In vitro experiments showed that NC significantly inhibited the proliferation of HCC cells and induced G2/M phase arrest. In addition, qPCR and WB experiments showed that the expression of p53 in HCC cells increased after NC intervention, while the expression of 14-3-3 Sigma and CDK1 decreased. Conclusion: NC can inhibit the proliferation of HCC cells and induce G2/M cell cycle arrest, potentially by regulating the p53/14-3-3 Sigma/CDK1 axis.

Extraocular muscle volume index at the orbital apex with optic neuritis: a combined parameter for diagnosis of dysthyroid optic neuropathy.

OBJECTIVES: To evaluate the diagnostic performance of the extraocular muscle volume index at the orbital apex (AMI) and the signal intensity ratio (SIR) of the optic nerve in dysthyroid optic neuropathy (DON). METHODS: Clinical data and magnetic resonance imaging were collected retrospectively from 63 Graves' ophthalmopathy patients, including 24 patients with DON and 39 without DON. The volume of these structures was obtained by reconstructing their orbital fat and extraocular muscles. The SIR of the optic nerve and axial length of eyeball were also measured. The posterior 3/5 of the retrobulbar space volume was used as the orbital apex to compare parameters in patients with or without DON. Area under the receiver operating characteristic curve (AUC) analysis was used to select the morphological and inflammatory parameters with the highest diagnostic value. A logistic regression was performed to identify the risk factors of DON. RESULTS: One hundred twenty-six orbits (35 with DON and 91 without DON) were analyzed. Most of the parameters in DON patients were significantly higher than in non-DON patients. However, the SIR 3 mm behind the eyeball of the optic nerve and AMI had the highest diagnostic value in these parameters and are independent risk factors of DON by stepwise multivariate logistic regression analysis. Combining AMI and SIR had a higher diagnostic value than a single index. CONCLUSIONS: Combining AMI with SIR 3 mm behind the eyeball's orbital nerve can be a potential parameter for diagnosing DON. CLINICAL RELEVANCE STATEMENT: The present study provided a quantitative index based on morphological and signal changes to assess the DON, allowing clinicians and radiologists to monitor DON patients timely. KEY POINTS: The extraocular muscle volume index at the orbital apex (AMI) has excellent diagnostic performance for dysthyroid optic neuropathy. A signal intensity ratio (SIR) of 3 mm behind the eyeball has a higher AUC compared to other slices. Combining AMI and SIR has a higher diagnostic value than a single index.

Image quality and evaluation ability of magnetic resonance imaging techniques for thyroid-associated ophthalmopathy: Dixon fat-suppression technique vs. spectral attenuated inversion recovery.

Purpose: We aimed to compare two magnetic resonance imaging (MRI) techniques, Dixon and spectral attenuated inversion recovery (SPAIR) fat-suppression, in terms of image quality and suitability for evaluating thyroid-associated ophthalmopathy (TAO) lesion characteristics. Methods: This cross-sectional, retrospective study involved 70 patients with TAO (140 eyes) who underwent orbital coronal MRI examinations, including Dixon-transverse relaxation (T2)-weighted imaging (T2WI) and SPAIR-T2WI, between 2020 and 2022. We compared the fat-suppression quality and artifacts, noise (N), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), signal intensity ratio (SIR) of extraocular muscles (SIR-EOM) and lacrimal glands (SIR-LG), and TAO activity evaluation efficiency. Results: Dixon-T2WI showed a higher frequency of better subjective image quality and suitability for evaluating the characteristics of TAO lesions (65.7% vs. 14.3%) than SPAIR-T2WI. Fat-suppression quality and artifact scores were lower for Dixon-T2WI than for SPAIR-T2WI (p < 0.001). The N, SNR, and CNR values, EOM-SIR, and LG-SIR were higher for orbital coronal Dixon-T2WI than for SPAIR-T2WI (all p < 0.001). Clinical activity scores (CASs) showed positive correlations with SIR. The correlation between EOM-SIR and LG-SIR of orbital coronal Dixon-T2WI with CAS was higher than that of SPAIR-T2WI (0.590 vs. 0.493, all p < 0.001; 0.340 vs. 0.295, all p < 0.01). EOM-SIR and LG-SIR of Dixon-T2WI yielded a higher area under the curve than SPAIR-T2WI for evaluating TAO activity (0.865 vs. 0.760, p < 0.001; 0.695 vs. 0.617, p = 0.017). Conclusion: Dixon-T2WI yields higher image quality than SPAIR-T2WI. Furthermore, it has a stronger ability to evaluate TAO inflammation than SPAIR, with higher sensitivity and specificity in active TAO staging.

Transcriptome-wide assessment of N6-methyladenosine modification identifies different gene expression and infection-associated pathways in Treponema pallidum-infected macrophage.

BACKGROUND: Treponema pallidum (Tp) is a widespread and destructive pathogen that leads to syphilis. As the acknowledged executor of host immunity, macrophage plays vital roles in combating the invasion and migration of Tp. However, the mechanisms of these processes are largely unknown, especially the critical driver genes and associated modifications. OBJECTIVE: We aimed to systematically dissect the global N6-methyladenosine (m6A) RNA modification patterns in Tp-infected macrophages. METHODS: The RNA of Tp-infected/non-infected macrophage was extracted, followed by mRNA sequencing and methylated RNA immunoprecipitation (MeRIP) sequencing. Bioinformatics analysis was executed by m6A peaks and motifs identification, Gene ontology and signaling pathways analysis of differentially expressed genes, and comprehensive comparison. The m6A levels were measured by RNA Methylation Assay, and m6A modified genes were determined by qPCR. RESULTS: Totally, 2623 unique and 3509 common m6A peaks were proved along with related transcripts in Tp-infected macrophages. The common m6A-related genes were enriched in the signals of oxidative stress, cell differentiation, and angiogenesis, while unique genes in those of metabolism, inflammation, and infection. And differentially expressed transcripts revealed various biological processes and pathways associated with catabolic and infection. They also experienced comprehensive analysis due to hyper-/hypo-methylation. And the m6A level of macrophage was elevated, along with qPCR validation of specific genes. CONCLUSION: With a particular m6A transcriptome-wide map, our study provides unprecedented insights into the RNA modification of macrophage stimulated by Tp in vitro, which partially differs from other infections and may provide clues to explore the immune process for syphilis.

Shikonin promotes rat periodontal bone defect repair and osteogenic differentiation of BMSCs by p38 MAPK pathway.

In recent years, the treatment of periodontal bone defect has been a major challenge. Cell-based bone tissue engineering provides an advanced way for bone regeneration. Bone formation hinges on the potential of osteogenesis in bone marrow stromal cells (BMSCs). Shikonin (SHI), an active principle of Radix Lithospermi, has shown a striking role to mitigate osteoporosis of ovariectomized mice, whereas its effects on periodontal bone defect are vague. Herein, we explored the impact of SHI on osteogenic differentiation of BMSCs in vitro and further analyzed the potential mechanisms using an inhibitor of p38 MAPK (SB203580). A rat periodontal bone defect model was built to assess its effects on bone formation in vivo by micro-CT and immunofluorescence. Our results showed SHI with no cytotoxicity could conspicuously enhanced alkaline phosphatase (ALP) activity, calcium accumulation and the expression of runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) of BMSCs in vitro. Increased bone volume/tissue volume (BV/TV) and osteopontin (OPN) expression after SHI administration further demonstrated the capacity of promoting osteogenesis of SHI in vivo. Furthermore, SHI could also increase the phosphorylation of p38. However, the phosphorylation of p38 and expression of osteogenic indicators promoted by SHI were reversed by SB203580, thereby illustrating the positive regulatory relationship between p38 MAPK and SHI-mediated osteogenesis. This finding may help SHI become a promising agent with respect to the therapy of periodontal bone defect.

Bibliometric and visual analysis in the field of tea in cancer from 2013 to 2023.

Objective: Tea has been utilized in cancer research and is progressively gaining wider recognition, with its roles in cancer prevention and treatment being increasingly affirmed. The objective of this study is to investigate the current state and research hotspots in the field of tea's involvement in cancer research from 2013 to 2023, aiming to offer reference and direction for future studies. Methods: We analyzed 4,789 articles published between 2013 and 2022 from the Web of Science database using VOSviewer, R software, and CiteSpace software. Result: Tea-related cancer research showed an overall upward trend, with China leading in publications, followed by the United States, India, Japan, and Italy. China also had significant international collaborations, notably with Harvard University and the Egyptian Knowledge Bank. The 'Journal of Agricultural and Food Chemistry' was the most cited journal. Key topics included 'green tea,' 'cancer,' 'in vitro,' 'oxidative stress,' and 'apoptosis.' Research focused on tea's pharmacological effects, anticancer properties, mechanisms of natural compounds (e.g., polyphenols and EGCG), antioxidant and antimicrobial properties, and molecular mechanisms in cancer treatment. Conclusion: Tea's potential as an anti-cancer medication is gaining global recognition. Our study provides a comprehensive analysis of tea-related cancer research from 2013 to 2023, guiding future investigations in this field.

Community engagement on-site rapid test for chlamydia and gonorrhea among men who have sex with men: a pioneering study in Guangzhou, China.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are prevalent among men who have sex with men (MSM) in China. However, compared to syphilis and HIV, the testing rate for chlamydia and gonorrhea remains low. The purpose of this pilot study was to evaluate the feasibility for conducting rapid nucleic acid test for chlamydia and gonorrhea in MSM community-based organizations (CBO). METHOD: We recruited our participants through an MSM CBO where free HV and syphilis testing were routinely provided. We collected data including social-demographic background, sexual history, chlamydia and gonorrhea testing history, and reasons for accepting this on-site rapid testing. Urine and/or anorectal swab samples were collected and tested for chlamydia and gonorrhea on-site and the testing results were delivered in about 1.5 h. Positive cases received on-site free treatment. RESULTS: From August 2020 to October 2020, 634 MSM visited the CBO for syphilis and HIV testing and 158 (158/634, 24.9%) accepted the on-site chlamydia and gonorrhea rapid test, 135 were finally enrolled. The positive rate fo chlamydia was 16.3% (22/135) and 3.0% (4/135) for gonorrhea, respectively. Only 19.3% participants had previously undergone chlamydia and gonorrhea testing and 68.9% (93/135) participants reported that they had heard of gonorrhea, 47.4% (64/135) had heard of chlamydia. The main reason for testing was "free for charge" (66.2%), followed by "convenient, 'shorter waiting time" (45.2%) and "had high-risk sexual behavior recently" (16.3%). CONCLUSIONS: This pilot study showed that the chlamydia and gonorrhea infection rate remains high among MSM, while the testing rate was low. On-site rapid testing is feasible and potentially preferred by MSM.

The effect of abusive supervision variability on work-family conflict: The role of psychological detachment and optimism.

Although a number of studies have examined the effects of abusive supervision variability, which refers to leaders engaging in differential abuse toward different subordinates within the team on work-related outcomes, scant research has investigated whether and how abusive supervision variability affects non-work outcomes. Drawing on the conservation of resources theory, the current study explores how abusive supervision variability affects work-family conflict through psychological detachment, as well as the moderating role of optimism. Results based on a survey of 260 employees from nine companies show that abusive supervision variability is significantly and positively related to work-family conflict. Psychological detachment mediates the effect of abusive supervision variability on work-family conflict. Optimism moderates the relationship between abusive supervision variability and psychological detachment and the indirect effects of abusive supervision variability on work-family conflict through psychological detachment. This study extends the literature on the effects of abusive supervision variability and provides several important practical implications.

Interference with lysophosphatidic acid receptor 5 ameliorates oxidized low-density lipoprotein-induced human umbilical vein endothelial cell injury by inactivating NOD-like receptor family, pyrin domain containing 3 inflammasome signaling.

Endothelial cell damage induced by oxidized low-density lipoprotein (ox-LDL) plays an important role in the pathogenesis of atherosclerosis (AS). We aimed to explore the effects of lysophosphatidic acid receptor 5 (LPAR5) on ox-LDL-induced damage of human umbilical vein endothelial cells (HUVECs). After HUVECs exposed to ox-LDL, LPAR5 expression was detected by RT-qPCR and western blotting. Then, LPAR5 was silenced and cell viability was determined with a CCK-8 assay. ELISA was employed to analyze the contents of inflammatory factors. The levels of oxidative stress markers were examined by kits. The expression of proteins related to endothelium function, including CD31, α-SMA, iNOS and eNOS, was evaluated with RT-qPCR and western blotting. Additionally, the effects of LPAR5 deletion on the NLRP3 inflammasome signaling in HUVECs under ox-LDL condition were assessed by determining NLRP3, caspase-1 and ASC expression. Afterward, NLRP3 agonist MSU was adopted for exploring the regulation of LPAR5 on NLRP3 inflammasome signaling in ox-LDL HUVECs injury. Results revealed that ox-LDL led to a significant upregulation in LPAR5 expression. NLRP3 knockdown enhanced cell viability, inhibited inflammation and oxidative stress in HUVECs after ox-LDL exposure. Besides, the expression of CD31 and eNOS was increased while that of α-SMA and iNOS was decreased after LPAR5 silencing. Moreover, interference with LPAR5 remarkably downregulated NLRP3, caspase-1 and ASC expression. Furthermore, MSU addition partially abrogated the inhibitory effects of LPAR5 deletion on the inflammation, oxidative stress and endothelium dysfunction of HUVECs. To conclude, we demonstrated that LPAR5 silencing alleviates ox-LDL-induced HUVECs injury by inhibiting NLRP3 inflammasome signaling.

Triglyceride-Glucose Index and Extracellular Volume Fraction in Patients With Heart Failure.

Background: The triglyceride-glucose (TyG) index had been proposed as a reliable surrogate marker of insulin resistance. We aimed to evaluate the association between TyG index and myocardial fibrosis, which was quantified by extracellular volume (ECV) fraction using cardiovascular magnetic resonance (CMR) examination, and their prognostic value in patients with heart failure (HF). Methods: In this retrospective cohort study, 103 hospitalized HF patients were included. ECV fraction was calculated using CMR measurements and T1 mapping. TyG index was calculated using fasting triglyceride and blood glucose. The primary outcome events were defined as all-cause mortality and HF hospitalization during follow-up. Results: During the median follow-up of 12.3 months, 39 patients (37.9%) experienced primary outcome events and had higher levels of TyG index, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and ECV fraction compared with those without events. Multivariate linear regression analysis showed that the TyG index was the significant factor determined for ECV fraction (r partial = 0.36, P = 0.01). In multivariate Cox regression analysis, presence of diabetes [hazard ratio (HR) = 1.28, 95% confidence interval (CI) = 1.01-1.62], higher TyG index (HR = 2.01, 95% CI = 1.03-4.01), ECV fraction (HR = 1.73, 95% CI = 1.04-2.88), and NT-proBNP (HR = 2.13, 95% CI = 1.08-4.20) were independent risk factors for the primary outcome events. Conclusions: TyG index is a novel biomarker of myocardial fibrosis in HF patients and can be considered as a useful risk stratification metric in the management of HF.