Global, regional and national burden of chronic obstructive pulmonary disease over a 30-year period: Estimates from the 1990 to 2019 Global Burden of Disease Study.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the most prevalent chronic respiratory disease. This study investigated the global, regional and country burden of COPD based on gender, age and socio-demographic indices (SDIs) in the last 30-year period from 1990 to 2019. METHODS: The COPD data, including incidence, mortality and disability-adjusted life years (DALYs), were obtained from the 2019 Global Burden of Disease Study. If age-standardized incidence rate (ASIR) or death rate (ASDR) remains almost constant or decreases, the number of cases will still increase as the global population increases substantially. Estimated annual percentage change (EAPC) was calculated to assess incidence, mortality and DALY trends. RESULTS: The incidence of COPD increased by 85.89% from 8,722,966 cases in 1990 to 16,214,828 cases in 2019, and the ASIR decreased from 216.48/100,000 persons in 1990 (95%UI, 204.56-227.33) to 200.49 per 100,000 persons (95%UI, 188.63-212.57) in 2019. The ASIR increased (EAPC = 0.05, 95%CI, 0.01-0.10) in the low SDI region, was stable in the high SDI region, and fell in the other three SDI regions. Men had a higher ASIR than women over the past 30 years, and there were differences in the incidence rates for different age groups. Male mortality and DALYs were higher than female mortality. ASDR decreased by 2.13% (95%CI, -2.23% to -2.02%) per year and the annual age-standardized DALY rate decreased by 1.97% (95%CI, -2.05% to -1.89%). CONCLUSIONS: The ASIR, ASDR and age-standardized DALY rate of COPD declined overall in the last 30 years, and were highest in the low-middle SDI region.

Global, regional, and national trends of syphilis from 1990 to 2019: the 2019 global burden of disease study.

BACKGROUND: Syphilis is a sexually transmitted disease caused by Treponema pallidum, and the infection source is syphilis patients. This study aimed to estimate the incidence, mortality rate, and disability-adjusted life years (DALYs) of syphilis to improve the understanding of the current global situation of syphilis. METHODS: This study collected data on syphilis incidence, mortality, and DALYs from the 2019 Global Burden of Disease database. RESULTS: The global number of incident cases and age-standardized incidence rate (ASIR) increased from 8,845,220 (95% UI: 6,562,510-11,588,860) in 1990 to 14,114,110 (95% UI: 10,648,490-18,415,970) in 2019 and 160.03/100,000 persons (95% UI: 120.66-208.1) to 178.48/100,000 persons (95% UI: 134.94-232.34), respectively. The estimated annual percentage change (EAPC) in the ASIR was 0.16 (95% CI: 0.07-0.26). The EAPC in the ASIR associated with high and high-middle sociodemographic indices increased. The ASIR increased among males but decreased among females, and the incidence peaked among males and females between the ages of 20 and 30 years. The EAPCs in the age-standardized death rate and age-standardized DALY rate decreased. CONCLUSIONS: The incidence and ASIR of syphilis increased worldwide from 1990 to 2019. Only the regions with high and high-middle sociodemographic indices showed an increase in the ASIR. Moreover, the ASIR increased among males but decreased among females. The age-standardized death rate and DALY rate both declined worldwide. The increase in the global ASIR of syphilis is a challenge.

The role of adipose tissue-derived hydrogen sulfide in inhibiting atherosclerosis.

Hydrogen sulfide (H2S) is the third gaseous signaling molecule discovered in the body after NO and CO and plays an important organismal protective role in various diseases. Within adipose tissue, related catalytic enzymes (cystathionine-ß-synthetase, cystathionine-γ-lyase, and 3-mercaptopyruvate transsulfuration enzyme) can produce and release endogenous H2S. Atherosclerosis (As) is a pathological change in arterial vessels that is closely related to abnormal glucose and lipid metabolism and a chronic inflammatory response. Previous studies have shown that H2S can act on the cardiovascular system, exerting effects such as improving disorders of glycolipid metabolism, alleviating insulin resistance, protecting the function of vascular endothelial cells, inhibiting vascular smooth muscle cell proliferation and migration, regulating vascular tone, inhibiting the inflammatory response, and antagonizing the occurrence and development of As.

Hydrogen sulfide plays a potential alternative for the treatment of metabolic disorders of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication that tends to occur in patients with diabetes, obesity, or insulin resistance, with a higher late mortality rate. Sustained hyperglycemia, increased free fatty acids, or insulin resistance induces metabolic disorders in cardiac tissues and cells, leading to myocardial fibrosis, left ventricular hypertrophy, diastolic and/or systolic dysfunction, and finally develop into congestive heart failure. The close connection between all signaling pathways and the complex pathogenesis of DCM cause difficulties in finding effective targets for the treatment of DCM. It reported that hydrogen sulfide (H2S) could regulate cell energy substrate metabolism, reduce insulin resistance, protect cardiomyocytes, and improve myocardial function by acting on related key proteins such as differentiation cluster 36 (CD36) and glucose transporter 4 (GLUT4). In this article, the relative mechanisms of H2S in alleviating metabolic disorders of DCM were reviewed, and how H2S can better prevent and treat DCM in clinical practice will be discussed.

[Molecular mechanism of Ganoderma against gastric cancer based on network pharmacology and experimental test].

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between ß-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. ß-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that ß-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.

Toll-like receptor 2 regulates metabolic reprogramming in gastric cancer via superoxide dismutase 2.

Toll-like receptors (TLRs) play critical roles in host defense after recognition of conserved microbial- and host-derived components, and their dysregulation is a common feature of various inflammation-associated cancers, including gastric cancer (GC). Despite the recent recognition that metabolic reprogramming is a hallmark of cancer, the molecular effectors of altered metabolism during tumorigenesis remain unclear. Here, using bioenergetics function assays on human GC cells, we reveal that ligand-induced activation of TLR2, predominantly through TLR1/2 heterodimer, augments both oxidative phosphorylation (OXPHOS) and glycolysis, with a bias toward glycolytic activity. Notably, DNA microarray-based expression profiling of human cancer cells stimulated with TLR2 ligands demonstrated significant enrichment of gene-sets for oncogenic pathways previously implicated in metabolic regulation, including reactive oxygen species (ROS), p53 and Myc. Moreover, the redox gene encoding the manganese-dependent mitochondrial enzyme, superoxide dismutase (SOD)2, was strongly induced at the mRNA and protein levels by multiple signaling pathways downstream of TLR2, namely JAK-STAT3, JNK MAPK and NF-κB. Furthermore, siRNA-mediated suppression of SOD2 ameliorated the TLR2-induced metabolic shift in human GC cancer cells. Importantly, patient-derived tissue microarrays and bioinformatics interrogation of clinical datasets indicated that upregulated expression of TLR2 and SOD2 were significantly correlated in human GC, and the TLR2-SOD2 axis was associated with multiple clinical parameters of advanced stage disease, including distant metastasis, microvascular invasion and stage, as well as poor survival. Collectively, our findings reveal a novel TLR2-SOD2 axis as a potential biomarker for therapy and prognosis in cancer.

[Alpha-momordicin Regulates Hepatocyte Cytokine Expression].

OBJECTIVE: To investigate the regulation effect of α-momordicin (α-MMC) on the synthesis and secretion of cytokines in hepatocytes cells. METHODS: Hepatocytes L02 were treated with 189 µg/mL α-MMC with culture supernatant and lysate samples were harvested in different timepoint. Expressions of T-helper 17 (TH17) cytokine profile in samples were detected by the Bio-Plex 200 suspension chip assay system. RESULTS: Compared with 0 h, after the α-MMC treatment of L02 hepatocytes for 2 h, 4 h and 8 h, the intracellular synthesis of cytokines interleukin (IL)-1b, IL-6, IL-17A, IL-31, IL-33, soluble CD40 ligand (sCD40L), tumor necrosis factor-α (TNF-α) were all significantly decreased (P<0.05), and IL-6, IL-4, IL-17A, and sCD40L secreted into the extracellular fluid also decreased significantly (P<0.05). CONCLUSION: α-MMC can significantly inhibit the synthesis and secretion of cytokines such as IL-6, IL-17A and TNF-α in hepatocytes, which may become a side effect of its anti-tumor application.

Hsa_circ_0009910 promotes carcinogenesis by promoting the expression of miR-449a target IL6R in osteosarcoma.

Circular RNAs (circRNAs) have recently shown capabilities as gene regulators in mammals. Some of them interact with microRNAs (miRNAs) and function as sponges to affect related miRNAs' activities. In this study, the molecular function of circRNA_0009910 and its potential downstream miRNA targets were explored. The expression levels of hsa_circ_0009910 were found to be overexpressed in osteosarcoma (OS) cells. Knockdown of circ_0009910 induced cell proliferation inhibition, cell cycle arrest, and apoptosis in OS cells. The target miRNA was predicted to be miR-449a, whose expression was downregulated in OS cells. Inhibition of miR-449a abolished the effect of circ_0009910 knockdown on cell growth and apoptosis. The expression of miR-449a were found to be negatively correlated with that of circ_0009910 in OS tissues. Direct interaction of circ_0009910 and miR-449a was confirmed through dual-luciferase assays. Moreover, IL6R was predicted as a potential target of miR-449a. Overexpression of miR-449a decreased the mRNA and protein levels of IL6R. Restoration of IL6R impaired the miR-449a induced inhibition of cell proliferation, cell cycle arrest, and apoptosis. The mRNA expression of IL6R was inversely correlated with miR-449a in OS tissues. In addition, JAK1/STAT3 signaling pathway was regulated by circ_0009910/miR-449a/IL6R axis. Taken together, we suggested that circ_0009910 acted as a sponge of miR-449a and upregulated miR-449a functional target IL6R, thereby contributed to carcinogenesis of OS.

Posttranslational modification of E-cadherin by core fucosylation regulates Src activation and induces epithelial-mesenchymal transition-like process in lung cancer cells.

E-cadherin is often dysregulated in aggressive lung cancer, the mechanism of which cannot always be explained at the level of transcription. In 66 patients with lung cancer, immunohistochemical staining demonstrated that co-localization of E-cadherin and core fucose by Lens culinaris agglutinin was significantly less extensive in tumor than in nontumor tissue. Through gain and loss of fucosylation experiments in the giant lung carcinoma cell lines 95C and 95D, our results revealed that E-cadherin core fucosylation in 95C cells overexpressing α-1, 6-fucosyltransferase (Fut8) inhibited Fut8-95C cell migration, whereas knockdown of Fut8 in 95D cells enhanced migration of short-interfering RNA-targeting Fut8 (siFut8)-95D cells. The level of active Src (phosphorylated Src [Y416]) was significantly reduced in Fut8-95C cells, but elevated in siFut8-95D cells. In protein complexes immunoprecipitated from Fut8-95C cell lysates with anti-E-cadherin, less phosphorylated Src (Y416) and more ß-catenin were observed, but immunoprecipitates from siFut8-95D cells, containing less core fucosylated E-cadherin, contained an elevated level of phospho-Src Y416. In Fut8-95C cells, phosphorylation of Akt (Y315, Y326) and GSK-3ß (S9) was significantly reduced, but ß-catenin (S37) phosphorylation was enhanced. Expression of N-cadherin and Snail1 was also reduced in Fut8-95C cells, but significantly increased in siFut8-95D cells. Intriguingly, when Src kinase activity was inhibited by treatment of cells with PP2 and SU6656, regulation of N-cadherin, Snail1 and cell migration by E-cadherin core fucosylation was abrogated in both Fut8-95C and siFut8-95D cells. Therefore, posttranslational modification of E-cadherin by less core fucosylation recruited and activated Src, and induced an epithelial-mesenchymal transition-like process in lung cancer cells.

Evaluating the enantioselective distribution, degradation and excretion of epoxiconazole in mice following a single oral gavage.

1. The enantiomeric enrichment or degradation of epoxiconazole has been reported in grape, soil, tubifex and mealworm beetle. But, little is known about its enantioselective behaviors in mammals. 2. To further understand differences in the distribution, degradation and excretion of epoxiconazole enantiomers in vivo, male CD-1 mice were selected as the test model to investigate the enantioselective behaviors after a single oral gavage. Mice were sacrificed after 1 h, 3 h, 7 h, 12 h, 24 h, 48 h, 72 h treatment, blood, tissues and excretions were collected for epoxiconazole analysis by LC-MS/MS. 3. On the Lux-Cellulose-1 chiral column, an enrichment of the second eluting (+)-epoxiconazole was generally observed, and feces and urine showed similar EF with major tissues. 4. To elucidate the potential role of intestinal bacterial flora in stereospecific degradation of epoxiconazole, mice fecal flora were cultured in vitro and incubated with epoxiconazole for 48 h. Results showed that (-)-epoxiconazole was preferentially degraded by intestinal bacterial. 5. These results may provide useful information for risk assessment of epoxiconazole on non-target animals.

Unique method for removal of knotted lumbar epidural catheter: A case report.

BACKGROUND: Combined spinal-epidural (CSE) anesthesia is the preferred anesthesia method for cesarean delivery. The use of an epidural catheter is essential for administering additional drugs intraoperatively and managing postoperative pain. However, the insertion of epidural catheters is associated with various complications, such as total spinal anesthesia, symptoms indicative of spinal nerve root irritation, and challenges in epidural catheter removal. CASE SUMMARY: We present a case report of a challenging epidural catheter removal due to knotting. The lumbar computed tomography scan results revealed that the catheter formed a tight knot in the epidural space. We used a novel extubation method and successfully removed the catheter. CONCLUSION: The operator can use opposite forces to "spiral" apart the spinal joints by positioning the patient's body in a specific position. The findings indicate that, when combined with imaging examination results, this method is effective for the removal of epidural catheters.

E3 ubiquitin ligase TRIM31: A potential therapeutic target.

Ubiquitination is a key mechanism for post-translational protein modification, affecting protein localization, metabolism, degradation and various cellular physiological processes. Dysregulation of ubiquitination is associated with the pathogenesis of various diseases, such as tumors and cardiovascular diseases, making it a primary area of interest in biochemical research and drug development endeavors. E3 ubiquitin ligases play a pivotal role in modulating the ubiquitination of substrate proteins through their unique recognition functions. TRIM31, a member of the TRIM family of E3 ubiquitin ligases, is aberrantly expressed in different pathophysiological conditions. The biological function of TRIM31 is associated with the occurrence and development of diverse diseases. TRIM31 has been demonstrated to inhibit inflammation by promoting ubiquitin-proteasome-mediated degradation of the sensing protein NLRP3 in the inflammasome. TRIM31 mediates ubiquitination of MAVS, inducing the formation of prion-like aggregates, and triggering innate antiviral immune responses. TRIM31 is also implicated in tumor pathophysiology through its ability to promote ubiquitination of the tumor suppressor protein p53. These findings indicate that TRIM31 is a potential therapeutic target, and subsequent in-depth research of TRIM31 is anticipated to provide information on its clinical application in therapy.

LncRNA-mediated Modulation of Endothelial Cells: Novel Progress in the Pathogenesis of Coronary Atherosclerotic Disease.

Coronary atherosclerotic disease (CAD) is a common cardiovascular disease and an important cause of death. Moreover, endothelial cells (ECs) injury is an early pathophysiological feature of CAD, and long noncoding RNAs (lncRNAs) can modulate gene expression. Recent studies have shown that lncRNAs are involved in the pathogenesis of CAD, especially by regulating ECs. In this review, we summarize the novel progress of lncRNA-modulated ECs in the pathogenesis of CAD, including ECs proliferation, migration, adhesion, angiogenesis, inflammation, apoptosis, autophagy, and pyroptosis. Thus, as lncRNAs regulate ECs in CAD, lncRNAs will provide ideal and novel targets for the diagnosis and drug therapy of CAD.

Cancer burden and risk in the Chinese population aged 55 years and above: A systematic analysis and comparison with the USA and Western Europe.

Background: We analysed the cancer burden among elderly Chinese people over the age of 55 years and compared them to USA and Western Europe to explore the cancer model in China. Methods: We retrieved data on 29 cancers with 34 risk factors from the 2019 Global Burden of Disease database to evaluate the cancer burden in Chinese elderly individuals aged 55 years and older. We then used the age-standardised incidence rate (ASIR), age-standardised death rate (ASDR), age-standardised disability-adjusted life year (DALY) rate, and average annual percentage change (AAPC) to compare the characteristics and change trend of cancers among China, USA, and Western Europe. Results: In 2019, the number of incident cases of 29 cancers among people aged 55 years and above in China increased more than 3-fold compared to 1990, while the number of deaths and DALYs approximately doubled. We also found that the cancer population in China was ageing; meanwhile, the cancer burden became significantly higher for men than for women, and the gap between men and women had widened. Cancers with the highest cancer DALYs were lung cancer (13 444 500; 95% uncertainty interval (UI) = 11 307 100, 15 853 700), stomach cancer (7 303 900; 95% UI = 6 094 600, 8 586 500), oesophageal cancer (4 633 500; 95% UI = 3 642 500, 5 601 200), colon and rectum cancer (4 386 500; 95% UI = 3 769 500, 5 067 200), liver cancer (2 915 100, 95% UI = 2 456 300, 3 463 900), and pancreatic cancer (2 028 400; 95% UI = 1 725 000, 2 354 900). Compared with 1990, the DALY rate and incidence rate of stomach cancer, oesophageal cancer, and liver cancer had markedly decreased. The DALY rate and incidence rate of lung, colon, rectum, and pancreatic cancer had increased significantly, as did the incidence rate of breast cancer in women. Smoking and diet were the top two cancer risk factors, and the impact of ambient particulate matter pollution on cancer increased each year. The overall 29 cancers age-standardised DALY rate and ASDR in China, USA, and Western Europe were similar, and all showed downward trend in the past 30 years. Compared with the USA and Western Europe, the age-standardised DALY rate of liver, nasopharyngeal, oesophageal, stomach, and cervical cancers in China was more prominent. The age-standardised DALY rate of lung cancer and colon and rectum cancer decreased annually in Western Europe and the USA, but increased in China. Conclusions: Over the past 30 years, China had made progress in controlling stomach, oesophageal, and liver cancer. However, lung, colon, rectum, pancreatic, and breast cancers had become more prevalent, having risen alongside economic development. The risks of smoking and dietary were major issues that need to be addressed urgently. The cancer situation in China remains serious; future cancer prevention efforts need to balance economic development with people's physical health, identify key groups, improve the health environment of residents and guide them to live a healthy life, and expand the scope of cancer screening.

TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis.

BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE-/- mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.

Outlook of Ferroptosis-Targeted Lipid Peroxidation in Cardiovascular Disease.

Lipid metabolism is a complex biochemical process that regulates normal cell activity and death. Ferroptosis is a novel mode of programmed cell death different from apoptosis, pyroptosis, and autophagy. Abnormal lipid metabolism may lead to lipid peroxidation and cell rupture death, which are regulated by lipoxygenase (LOX), long-chain acyl-coA synthases, and antioxidant enzymes. Alternatively, Fe2+ and Fe3+ are required for the activity of LOXs and ferroptosis, and Fe2+ can significantly accelerate lipid peroxidation in ferroptosis. Abnormal lipid metabolism is a certain risk factor for cardiovascular disease. In recent years, the important role of ferroptosis in developing cardiovascular disease has been increasingly reported. Reducing lipid accumulation could reduce the occurrence of ferroptosis, thus alleviating cardiovascular disease deterioration. This article reviews the relationship of lipid peroxidation to the general mechanism of ferroptosis and highlights lipid peroxidation as the common point of ferroptosis and cardiovascular disease.

Nerve growth factor causes epinephrine release dysfunction by regulating phenotype alterations and the function of adrenal medullary chromaffin cells in mice with allergic rhinitis.

The presence of allergic rhinitis (AR) is an increased risk factor for the occurrence of bronchial asthma (BA). Nerve growth factor (NGF), in addition to its key role in the development and differentiation of neurons, may also be an important inflammatory factor in AR and BA. However, the pathogenesis of the progression of AR to BA remains to be elucidated. The present study aimed to investigate the ability of NGF to mediate nasobronchial interactions and explore possible underlying molecular mechanisms. In the present study, an AR mouse model was established and histology of nasal mucosa tissue injury was determined. The level of phenylethanolamine N­methyl transferase in adrenal medulla was determined by immunofluorescence. Primary adrenal medullary chromaffin cells (AMCCs) were isolated and cultured from the adrenal medulla of mice. The expression levels of synaptophysin (SYP), STAT1, JAK1, p38 and ERK in NGF­treated and untreated AMCCs were detected by reverse­transcription­quantitative PCR and western blotting. The epinephrine (EPI) and norepinephrine (NE) concentrations were measured by ELISA. It was found that the expression of SYP in AMCCs was enhanced in the presence of NGF, whereas, the concentration of EPI decreased significantly under the same conditions. Furthermore, NGF mediated the phenotypic and functional changes of AMCCs, resulting in decreased EPI secretion via JAK1/STAT1, p38 and ERK signaling. In conclusion, these findings could provide novel evidence for the role of NGF in regulating neuroendocrine mechanisms.

Understanding the Potential Function of Perivascular Adipose Tissue in Abdominal Aortic Aneurysms: Current Research Status and Future Expectation.

An abdominal aortic aneurysm (AAA) is a progressive dilatation of the vascular wall occurring below the aortic fissure, preferably occurring below the renal artery. The molecular mechanism of AAA has not yet been elucidated. In the past few decades, research on abdominal aortic aneurysm has been mainly focused on the vessel wall, and it is generally accepted that inflammation and middle layer fracture of the vessel wall is the core steps in the development of AAA. However, perivascular adipose tissue plays a non-negligible role in the occurrence and development of AAA. The position of PVAT plays a supporting and protective role on the vascular wall, but the particularity of the location makes it not only have the physiological function of visceral fat; but also can regulate the vascular function by secreting a large number of adipokines and cytokines. An abdominal aortic aneurysm is getting higher and higher, with a vascular rupture, low rescue success rate, and extremely high lethality rate. At present, there is no drug to control the progression or reverse abdominal aortic aneurysm. Therefore, it is critical to deeply explore the mechanism of abdominal aortic aneurysms and find new therapeutic ways to inhibit abdominal aortic aneurysm formation and disease progression. An abdominal aortic aneurysm is mainly characterized by inflammation of the vessel wall and matrix metalloprotein degradation. In this review, we mainly focus on the cytokines released by the perivascular adipose tissue, summarize the mechanisms involved in the regulation of abdominal aortic aneurysms, and provide new research directions for studying abdominal aortic aneurysms.

Statin's role on blood pressure levels: Meta-analysis based on randomized controlled trials.

Statins have been proven to be effective in minimizing the risk of cardiovascular adverse events, however, their effect on BP variability is debatable with respect to their significance and their use as a potential anti-hypertensive. Using a meta-analysis approach, the aim of this study was to explore whether certain statins have the potential to lower blood pressure (BP). For the period 2002-2022, Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched for the studies that examined the effect of statins on blood pressure in normotensive or hypertensive individuals. Randomized controlled clinical trials that investigated this effect were included based on our inclusion criteria. Our primary outcomes were changes in systolic and diastolic blood pressure (DBP). The final analysis of the study included 49 RCTs involving 45 173 participants randomized to receive either statins or placebo. Among the two groups, the total weighted mean difference (WMD) for systolic blood pressure (ΔSBP) was -1.42 (95% CI: -2.38, -0.46; p = .004) and diastolic blood pressure (ΔDBP) was 0.82 (95% CI: -1.28, -0.36; p = .0005). Despite various studies suggesting the efficacy of statins in blood pressure lowering to be significant and non-significant both, we observed a decrease in SBP and DBP both, although the change was not as large and could be considered significant. A large multicenter, multi-ethnic, large sample pool size, and a long period follow-up study is still required to assert these claims.

TRIM65 Suppresses oxLDL-induced Endothelial Inflammation by Interaction with VCAM-1 in Atherogenesis.

BACKGROUND AND OBJECTIVE: Endothelial cell activation, characterized by increased levels of vascular cell adhesion molecule 1 (VCAM-1), plays a crucial role in the development of atherosclerosis (AS). Therefore, inhibition of VCAM-1-mediated inflammatory response is of great significance in the prevention and treatment of AS. The tripartite motif (TRIM) protein-TRIM65 is involved in the regulation of cancer development, antivirals and inflammation. We aimed to study the functions of TRIM65 in regulating endothelial inflammation by interacting with VCAM-1 in atherogenesis. METHODS AND RESULTS: In vitro, we report that human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (oxLDL) significantly upregulate the expression of TRIM65 in a time- and dose-dependent manner. Overexpression of TRIM65 reduces oxLDL-triggered VCAM-1 protein expression, decreases monocyte adhesion to HUVECs and inhibits the production of the inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α as well as endothelial oxLDL transcytosis. In contrast, siRNA-mediated knockdown of TRIM65 promotes the expression of VCAM-1, resulting in increased adhesion of monocytes and the release of the inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α and enhances endothelial oxLDL transcytosis. In vivo, we measured the high expression of TRIM65 in ApoE-/- mouse aortic plaques compared to C57BL/6J mouse aortic plaques. Then, we examined whether the blood levels of VCAM-1 were higher in TRIM65 knockout ApoE-/- mice than in control mice induced by a Western diet. Furthermore, Western blot results showed that the protein expression of VCAM-1 was markedly enhanced in TRIM65 knockout ApoE-/- mouse aortic tissues compared to that of the controls. Immunofluorescence staining revealed that the expression of VCAM-1 was significantly increased in atherosclerotic plaques of TRIM65-/-/ApoE-/- aortic vessels compared to ApoE-/- controls. Mechanistically, TRIM65 specifically interacts with VCAM-1 and targets it for K48-linked ubiquitination. CONCLUSION: Our studies indicate that TRIM65 attenuates the endothelial inflammatory response by targeting VCAM-1 for ubiquitination and provides a potential therapeutic target for the inhibition of endothelial inflammation in AS.