Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are ...not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Aspirin and curcumin have been reported to be beneficial to anti-aging in a variety of biological models. Here, we synthesized a novel compound, curcumin acetylsalicylate (CA), by combining aspirin ...and curcumin. We characterized how CA affects the lifespan of
(
) worms. Our results demonstrated that CA extended the lifespan of worms in a dose-dependent manner and reached its highest anti-aging effect at the concentration of 20 μM. In addition, CA reduced the deposition of lipofuscin or "age pigment" without affecting the reproductivity of worms. CA also caused a rightward shift of
lifespan curves in the presence of paraquat-induced (5 mM) oxidative stress or 37 °C acute heat shock. Additionally, CA treatment decreased the reactive oxygen species (ROS) level in
and increased the expression of downstream genes superoxide dismutase
, glutathione S-transferase
, heat shock protein
and catalase-1
. Notably, CA treatment resulted in nuclear translocation of the DAF-16 transcription factor, which is known to stimulate the expression of SOD-3, GST-4, HSP-16, and CTL-1. CA did not produce a longevity effect in
mutants. In sum, our data indicate that CA delayed the aging of
without affecting reproductivity, and this effect may be mediated by its activation of DAF-16 and subsequent expression of antioxidative genes, such as
and
. Our study suggests that novel anti-aging drugs may be developed by combining two individual drugs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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Ischemic diseases, such as ischemic heart diseases and ischemic stroke, are the leading cause of death worldwide. Angiogenic therapy is a wide-ranging approach to fighting ischemic ...diseases. However, compared with anti-angiogenesis therapy for tumors, less attention has been paid to therapeutic angiogenesis. Recently, Traditional Chinese medicine (TCM) has garnered increasing interest for its definite curative effect and low toxicity. A growing number of studies have reported that TCM formulas, extracts, and compounds from herbal medicines exert pro-angiogenic activity, which has been confirmed in a few clinical trials. For comprehensive analysis of relevant literature, global and local databases including PubMed, Web of Science, and China National Knowledge Infrastructure were searched using keywords such as “angiogenesis,” “neovascularization,” “traditional Chinese medicine,” “formula,” “extract,” and “compound.” Articles were chosen that are closely and directly related to pro-angiogenesis. This review summarizes the pro-angiogenic activity and the mechanism of TCM formulas, extracts, and compounds; it delivers an in-depth understanding of the relationship between TCM and pro-angiogenesis and will provide new ideas for clinical practice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
BackgroundEndovascular thrombectomy is the recommended treatment for acute ischaemic stroke, but the optimal blood pressure management strategy during the procedure under general anaesthesia remains ...controversial. In this study protocol, we propose an intraoperative intensive blood pressure range (110–140 mm Hg systolic blood pressure) based on a retrospective analysis and extensive literature review. By comparing the outcomes of patients who had an acute ischaemic stroke undergoing mechanical thrombectomy under general anaesthesia with standard blood pressure management (140–180 mm Hg systolic blood pressure) versus intensive blood pressure management, we aim to determine the impact of intraoperative intensive blood pressure management strategy on patient prognosis.Methods and analysisThe study is a double-blinded, randomised, controlled study, with patients randomised into either the standard blood pressure management group or the intensive blood pressure management group. The primary endpoint of the study will be the sequential analysis of modified Rankin Scale scores at 90 days after mechanical thrombectomy.Ethics and disseminationThe study has been approved by the ethics committee of Shanghai Changhai Hospital with an approval number CHEC2023-015. The results of the study will be published in peer-reviewed international journals.Trial registration numberChiCTR2300070764.
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Artemisinin (Qinghaosu) and its semi-synthetic derivatives have been demonstrated to alleviate neuroinflammatory response in the central nerve system (CNS). In this review, we ...summarized that artemisinins are capable to treat neuroinflammtion-related CNS diseases in both direct (via regulating inflammatory process in the CNS, exerting anti-oxidative stress and neuroprotective effect, and preventing Aβ accumulation) and indirect (via maintaining BBB integrity, suppressing systemic inflammation and alleviating intestinal inflammtion) manner. However, the precise mechanism of their anti-neuroinflammatory effects and potential neurotoxicity, which hindered further progress in these aspects, remains unclear. We suggest that further understanding of the PK/PD properties and structure-action relationship of atemisinin and its derivatives will facilitate the development of new therapeutics with better curative effects and safety.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
Abstract Background Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the ...treatment of NASH remain uncertain. Methods A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg − 1 ), curcumin (Cur, 40 mg·kg − 1 ) and metformin (Met, 50 mg·kg − 1 ) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml − 1 , 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. Results The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. Conclusion NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aims to explore the effect of an extract of Atractylodes lancea (A. lancea) on antibiotics-induced intestinal tract disorder and the probable therapeutic mechanisms employed by this ...extract to ameliorate these disorders.
Three days after acclimatization, nine male and nine female specific-pathogen-free (SPF) mice were randomly assigned into three groups: Group C (normal saline), Group M (antibiotic: cefradine + gentamicin), and Group T (antibiotic + A. lancea extract). Each mouse in Groups M and T received intragastric (i.g.) gavage antibiotics containing cefradine and gentamicin sulfate (0.02 ml/g
/D
) for 7 days. A. lancea extract (0.02 ml/g
/D
) was administered by i.g. gavage to Group T mice for 7 days following the cessation of antibiotic therapy. Group M received an equivalent volume of normal saline for 7 days, while Group C received an equivalent volume of normal saline for 14 days. Afterwards, we collected mouse feces to assess changes in intestinal microbiota by 16S ribosomal ribonucleic acid (rRNA) sequencing and metabolomics. In addition, serum samples were gathered and analyzed using liquid chromatography-mass spectrometry (LS-MS). Finally, we performed a correlation analysis between intestinal microbiota and metabolites.
After treatment with antibiotic, the richness and diversity of the flora, numbers of wall-breaking bacteria and Bacteroidetes, and the numbers of beneficial bacteria decreased, while the numbers of harmful bacteria increased. After i.g. administration of A. lancea extract, the imbalance of microbial flora began to recover. Antibiotics primarily influence the metabolism of lipids, steroids, peptides, organic acids, and carbohydrates, with lipid compounds ranking first. Arachidonic acid (AA), arginine, and proline have relatively strong effects on the metabolisms of antibiotic-stressed mice. Our findings revealed that A. lancea extract might restore the metabolism of AA and L-methionine. The content of differential metabolites detected in the serum of Group T mice was comparable to that in the serum of Group C mice, but significantly different from that of Group M mice. Compared to putative biomarkers in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, it was found that altered metabolites, such as amino acids, glycerol, and phospholipids, were primarily associated with the metabolism.
The effective mechanisms of A. lancea extract in regulating the disorder of intestinal flora in mice are related to the mechanisms of A. lancea. It could relate to lipid metabolism, bile acid metabolism, and amino acid metabolism. These results will provide a basis for further explaining the mechanism by which A. lancea regulats intestinal flora.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction
Low back pain (LBP) is the most prevalent form of chronic pain in active-duty military personnel worldwide. Electroacupuncture (EA) and neuromuscular electrical stimulation (NMES) are ...the two most widely used treatment methods in the military, while evidence for their benefits is lacking. The aim of this randomized clinical trial is to investigate the effectiveness of EA vs. NMES in reducing pain intensity among active-duty navy personals with chronic LBP.
Methods
The study is designed as a single-center, randomized controlled trial. The primary outcome is a positive categorical response for treatment success in the first-time follow-up, which is predesignated as a two-point or greater decrease in the NRS score and combined with a score > 3 on the treatment satisfaction scale. The secondary outcomes include pain intensity, rate of treatment success, and Oswestry Disability Index (ODI) fear-avoidance beliefs questionnaire (FABQ) score along with muscular performance. The first follow-up starts on the first day after completing the last treatment session, and then the 4-weeks and 12-weeks follow-up are applied
via
telephone visit.
Results
Eighty-five subjects complete the treatment diagram and are included in the analysis. For the primary outcome, no difference has been found between EA and NMES, with 65.1% (28 in 43) individuals reporting a positive response to EA treatment, while 53.5% (23 in 43) in NMES. However, for longer follow-ups, superiority in positive response of EA has been found in 4-weeks (26 in 39, 66.7% vs. 16 in 40, 40%;
P
= 0.018) and 12-weeks (24 in 36, 66.7% vs. 12 in 36, 33.3%;
P
= 0.005) follow-up. In the regression analysis, baseline pain intensity and FABQ score are identified to be highly associated with positive treatment outcomes. Finally, the subgroup analysis suggests that EA treatment is associated with better long-term outcomes in patients with LBP with a severe pain score (NRS score >4, Figure 4B) and stronger fear-avoidance beliefs.
Conclusion
Both the EA and NMES are associated with a positive response in treating military LBP, and the former offers lasting benefits in the later follow-ups. Thus, electroacupuncture is a more recommended treatment for military LBP. A lot of research is needed to verify an efficient and standardized treatment session, with more information and evidence about indications for these treatments.
Trial registration
ChiCTR, (ChiCTR2100043726); registered February 27, 2021.
Purpose
To assess the correlation between the type and degree of cystocele and stress urinary incontinence (SUI) by transperineal ultrasound.
Methods
A retrospective study evaluated 207 women who ...were diagnosed with cystocele by transperineal ultrasound. One hundred and six women who were diagnosed with SUI by a full urodynamic study were enrolled in the SUI group, 101 women without SUI were enrolled in the prolapse group, and 100 normal women with neither SUI nor POP were enrolled as the control group. In the transperineal ultrasound study, the bladder neck, the lowest point of the bladder wall, bladder neck funneling, the retrovesical angle, and the urethra inclination angle were observed at rest and Valsalva.
Results
It was found that 87.7% of patients in the SUI group were diagnosed with cystourethrocele, which was significantly higher than the 47.5% in the prolapse group. In addition, 93.4% of patients in the SUI group were diagnosed with Grade I or II cystocele and 6.6% were Grade III, which was significantly higher than that in the prolapse group. Bladder neck funneling on ultrasonography had a sensitivity of 59.4% and a specificity of 64.1% for the detection of SUI. It was significantly higher in cystourethrocele than isolated cystocele (
P
< 0.05).
Conclusion
The type and degree of cystocele can be diagnosed by transperineal ultrasound. Cystourethrocele and bladder neck funneling are highly correlated with SUI. Bladder neck funneling may be an important symptom of SUI.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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