Erratum: CircZCCHC2 decreases pirarubicin sensitivity and promotes triple-negative breast cancer development via the miR-1200/TPR axis.

[This corrects the article DOI: 10.1016/j.isci.2024.109057.].

Genome-Wide Association Study of Body Conformation Traits in Tashi Goats (Capra hircus).

Identifying genetic markers of economically valuable traits has practical benefits for the meat goat industry. To better understand the genomic variations influencing body conformation traits, a genome-wide association study was performed on Tashi goats, an indigenous Chinese goat breed. A total of 155 Tashi goats were phenotyped for eight body conformation traits: body height, body length, chest depth, chest width, chest girth, rump width, rump height, and cannon bone circumference. Then, 100 Tashi goats were randomly selected for whole-genome sequencing and genotyped. We obtained 1676.4 Gb of raw data with an average sequencing depth of 6.2X. Clean reads were aligned to the ARS1.2 reference genome, and 11,257,923 single nucleotide polymorphisms (SNPs) were identified. The structure analysis showed that these Tashi goats were almost not genetically related. The 109, 20, 52, 14, 62, 51, 70, and 7 SNPs were significantly associated with body height, body length, chest depth, chest width, chest girth, rump width, rump height, and cannon bone circumference. Within the ±500 kb region of significant SNPs, 183 genes were annotated. The most significantly enriched KEGG pathway was "olfactory transduction", and the most significantly enriched gene ontology (GO) terms were "cellular process", "cellular anatomical entity", and "molecular transducer activity". Interestingly, we found several SNPs on chromosomes 10 and 11 that have been identified multiple times for all eight body conformation traits located in two fragments (114 kb and 1.03 Mb). In chr.10:25988403-26102739, the six SNPs were tightly linked, the TACTAG genotype was the highest at 91.8%, and the FNTB (Farnesyltransferase, CAAX Box Beta) and CHURC1 (Churchill Domain Containing 1) genes were located. In chr.11:88216493-89250659, ten SNPs were identified with several dependent linkage disequilibrium (LD) blocks, and seven related genes were annotated, but no significant SNP was located in them. Our results provide valuable biological information for improving growth performance with practical applications for genomic selection in goats.

CircZCCHC2 decreases pirarubicin sensitivity and promotes triple-negative breast cancer development via the miR-1200/TPR axis.

Triple-negative breast cancer (TNBC) has attracted attention due to its poor prognosis and limited treatment options. The mechanisms underlying the association between circular RNAs (circRNAs) and the occurrence and development of TNBC remain unclear. CircZCCHC2 is observed to be upregulated in TNBC cells, tissues, and plasma exosomes. Knockdown of circZCCHC2 inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of TNBC cells in vitro and in vivo. Pirarubicin (THP) treatment downregulated circZCCHC2, and circZCCHC2 affected the sensitivity to THP. CircZCCHC2/miR-1200/translocated promoter region, the nuclear basket protein (TPR) pathway was cascaded and verified. It is demonstrated that circZCCHC2 plays a crucial role in the malignant progression of TNBC via the miR-1200/TPR axis, thereby activating the RAS-RAF-MEK-ERK pathway. The present results indicate that circZCCHC2 has the potential to serve as a novel prognostic biomarker for TNBC.

Rosmarinic Acid Activates the Nrf2/ARE Signaling Pathway via the miR-25-3p/SIRT6 Axis to Inhibit Vascular Remodeling.

The vital pathological processes in intimal hyperplasia include aberrant vascular smooth muscle cells (VSMCs) proliferation, migration, and phenotypic switching. Rosmarinic acid (RA) is a natural phenolic acid compound. Nevertheless, the underlying mechanism of RA in neointimal hyperplasia is still unclear. Our analysis illustrated that miR-25-3p mimics significantly enhanced PDGF-BB-mediated VSMCs proliferation, migration, and phenotypic switching while RA partially weakened the effect of miR-25-3p. Mechanistically, we found that miR-25-3p directly targets sirtuin (SIRT6). The suppressive effect of the miR-25-3p inhibitor on PDGF-BB-induced VSMCs proliferation, migration, and phenotypic switch was partially eliminated by SIRT6 knockdown. The suppression of the PDGF-BB-stimulated Nrf2/ARE signaling pathway that was activated by the miR-25-3p inhibitor was exacerbated by the SIRT6 knockdown. In in vivo experiments, RA reduced the degree of intimal hyperplasia while miR-25-3p agomir partially reversed the suppressive effect of RA in vascular remodeling. Our results indicate that RA activates the Nrf2/ARE signaling pathway via the miR-25-3p/SIRT6 axis to inhibit vascular remodeling.

IFN-γ, SCF, MIP1b and IL-16 Were Associated with Risk of Diabetic Nephropathy: A Mendelian Randomization Study.

Background: The impact of inflammatory factors on the risk of diabetic nephropathy (DN) is inconsistent. Two-sample Mendelian randomization (MR) analyses were used to detect the causal role of inflammatory factors in DN risk. Methods: Inflammatory factor GWAS summary data were collected from a meta-analysis including 8,293 Finnish participants, and DN information was extracted from a GWAS of 213,746 individuals from FinnGen. The MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) outlier test was used for the removal of horizontal pleiotropic outliers. Multivariable MR analysis was also used to adjust for pleiotropy. Results: IFN-γ [ORIVW: 1.33; 95% CI: 1.09-1.63; p=0.005] and SCF [ORIVW: 1.25, 1.02-1.52; p = 0.027] were associated with an increased risk of DN. MIP1b [ORIVW: 0.92; 95% CI: 0.85-0.98; p = 0.022] and IL-16 [ORIVW: 0.89, 0.81-0.99; p = 0.043] showed negative associations with the risk of DN. We validated our MR results with MR-PRESSO analyses. Significant horizontal pleiotropy was not found. Moreover, in the multivariable MR analysis, the associations between cytokines and DN risk remained. Conclusion: Our MR results based on genetic data contribute to a better understanding of the pathogenesis of DN and provide evidence for a causal effect of inflammatory factors on DN. These findings support targeting specific inflammatory factors to alleviate DN risk.

Regulating d-Orbital Hybridization of Subgroup-IVB Single Atoms for Efficient Oxygen Reduction Reaction.

Highly active single-atom electrocatalysts for the oxygen reduction reaction are crucial for improving the energy conversion efficiency, but they suffer from a limited choice of metal centers and unsatisfactory stabilities. Here, this work reports that optimization of the binding energies for reaction intermediates by tuning the d-orbital hybridization with axial groups converts inactive subgroup-IVB (Ti, Zr, Hf) moieties (MN4) into active motifs (MN4O), as confirmed with theoretical calculations. The competition between metal-ligand covalency and metal-intermediate covalency affects the d-p orbital hybridization between the metal site and the intermediates, converting the metal centers into active sites. Subsequently, dispersed single-atom M sites coordinated by nitrogen/oxygen groups have been prepared on graphene (s-M-N/O-C) catalysts on a large-scale with high-energy milling and pyrolysis. Impressively, the s-Hf-N/O-C catalyst with 5.08 wt% Hf exhibits a half-wave potential of 0.920 V and encouraging performance in a zinc-air battery with an extraordinary cycling life of over 1600 h and a large peak power-density of 256.9 mW cm-2. This work provides promising single-atom electrocatalysts and principles for preparing other catalysts for the oxygen reduction reaction.

Construction of cellulose acetate-based composite nanofiber films with effective antibacterial and filtration properties.

In recent years, the safety of public health has attracted more and more attention. In order to avoid the spread of bacteria and reduce the diseases caused by their invasion of the human body, novel filtration and antibacterial materials have attracted more and more attention. In this work, the antibacterial agents silver nanoparticles (AgNPs) and cetylpyridine bromide (CPB) were introduced into a cellulose acetate (CA) nanofiber film by electrospinning technology to prepare CA-based composite films with good antibacterial and filtration properties. The results of the antibacterial test of the composite nanofiber films showed that AgNPs and CPB had synergistic antibacterial effects and exhibited good antibacterial properties against a variety of bacteria. In addition, in vitro cytotoxicity, skin irritation and skin sensitization experiments proved that the CA/AgNPs, CA/CPB and CA/CPB/AgNPs films produced no skin irritation or sensitization in the short term. These are expected to become potential materials for the preparation of new antibacterial masks. This work provides a new idea for developing materials with good antibacterial properties for enhancing protection via filtration masks.

LncRNA Miat knockdown enhances pirarubicin-mediated anticancer sensitivity in breast cancer cells.

Pirarubicin (THP) is a widely used antitumor agent in clinical practice, but its reduced sensitivity during treatment has limited its use. The aim of this study was to investigate the role and mechanism of LncRNA Miat knockdown in improving THP sensitivity. We assessed the role of Miat overexpression/knockdown on THP-mediated 4T1 anticancer activity by CCK8, TUNEL, flow cytometry, wound healing assay, Transwell, Ca2+ , real time quantitative PCR (RT-qPCR) and Western blot. The results showed that Miat expression was higher in 4T1 mouse breast cancer cells than in HC11 mouse mammary epithelial cells, while THP decreased Miat expression in 4T1. Miat knockdown in combination with further reduced cell viability, promoted apoptosis and inhibited migration compared to THP alone. This may be related to the reduction of calcium ions in 4T1. In conclusion, Miat knockdown enhanced the sensitivity of THP to 4T1 by inhibiting calcium channels.

Astaxanthin protects against pirarubicin-induced H9c2 cardiomyocytes by adjusting microRNA-494-3p-mediated MDM4/p53 signalling pathway.

PURPOSE: Pirarubicin (THP) is an antitumour drug widely used in clinical practice, but its cardiotoxicity limits its application. THP cardiotoxicity must be treated as soon as possible. There is an urgent need to find drugs that alleviate THP cardiotoxicity. The purpose of this study was to investigate the effects and mechanisms of Astaxanthin (AST) on THP-induced cardiomyocytes. METHODS: Rat cardiomyocytes H9c2 were induced with THP. The effects of AST on THP-induced H9c2 and its mechanism were investigated by CCK8, reactive oxygen species assay, tunnel assay, flow cytometry, RT-qPCR, and Western blot. RESULTS: AST increased cell viability, inhibited apoptosis and accelerated cell cycle progression, reduced oxidative damage and inflammatory response in THP-induced H9c2; down-regulated miR-494-3p expression, promoted MDM4 expression, inhibited p53 activation, and suppressed apoptosis-related protein expression. Overexpression of MiR-494-3p reversed the above effects of AST. CONCLUSIONS: AST can inhibit H9c2 apoptosis induced by THP and attenuate H9c2 damage by THP, which may be achieved by downregulating miR-494-3p, upregulating MDM4, and inhibiting p53.

LncRNA Miat knockdown protects against pirarubicin-induced cardiotoxicity by targeting miRNA-129-1-3p.

Pirarubicin (THP) is a widely used antitumor drug in clinical practice, but its cardiotoxicity limits its use. The aim of this study was to investigate the protective effect and mechanism of knockdown of lncRNA Miat in THP-induced cardiotoxicity. The extent of damage to immortalized cardiomyocytes in mice was assessed by CCK8, TUNEL, ROS, Ca2+ , RT-qPCR, and Western blot. The relative levels of Miat in THP-treated cardiomyocytes (HL-1) were measured. The protective effect of Miat on THP-treated HL-1 was assessed. The binding relationship between lncRNA Miat and mmu-miRNA-129-1-3p was verified by a dual luciferase reporter gene assay. The protective role of Miat/miRNA-129-1-3p in THP-induced HL-1 was explored by performing a rescue assay. THP reduced cell viability, induced apoptosis, triggered oxidative stress and calcium overload. Expression of Miat in HL-1 was significantly elevated after THP treatment. Miat knockdown significantly alleviated the cardiotoxicity of THP. MiR-129-1-3p is a direct target of Miat. Knockdown of miR-129-1-3p reversed the protective effect of Miat knockdown on HL-1. Miat knockdown can alleviate THP-induced cardiomyocyte injury by regulating miR-129-1-3p.

MiR-494-3p aggravates pirarubicin-induced cardiomyocyte injury by regulating MDM4/p53 signaling pathway.

OBJECTIVE: Pirarubicin (THP) is a widely used antitumor drug in clinical practice, but its cardiotoxicity limits its use. There is an urgent need to find drugs to alleviate the cardiotoxicity of THP. This study aimed to investigate the effect and mechanism of miR-494-3p on THP-induced cardiomyocytes. METHODS: THP induced immortalized mouse cardiomyocytes HL-1, silenced or overexpressed miR-494-3p. The effects of miR-494-3p on HL-1 contained in THP were investigated by CCK8, flow cytometry, ROS detection, JC-1 mitochondrial membrane potential detection, TUNEL cell apoptosis detection, RT-qPCR, and Western blot. RESULTS: miR-494-3p could reduce cell viability, increase oxidative damage, and promote cell apoptosis; at the same time, it inhibited the expression of MDM4, promoted the activation of p53, and promoted the expression of apoptosis-related proteins. MiR-494-3p inhibitors have the opposite effect. CONCLUSION: miR-494-3p can aggravate THP damage to HL-1, which may be achieved by downregulating MDM4 and promoting p53. miR-494-3p is one of the important miRNAs in THP-induced cardiotoxicity, which provides theoretical support for its possible use as a therapeutic target for THP-induced cardiovascular disease.

Global, regional, and national time trends in cancer mortality attributable to high fasting plasma glucose: an age-period cohort analysis.

BACKGROUND: High fasting plasma glucose (HFPG) is the fastest-growing risk factor for cancer deaths worldwide. We reported the cancer mortality attributable to HFPG at global, regional, and national levels over the past three decades and associations with age, period, and birth cohort. METHODS: Data for this study were retrieved from the Global Burden of Disease Study 2019, and we used age-period-cohort modelling to estimate age, cohort and period effects, as well as net drift (overall annual percentage change) and local drift (annual percentage change in each age group). RESULTS: Over the past 30 years, the global age-standardized mortality rate (ASMR) attributable to HFPG has increased by 27.8%. The ASMR in 2019 was highest in the male population in high sociodemographic index (SDI) areas (8.70; 95% CI, 2.23-18.04). The net drift for mortality was highest in the female population in low SDI areas (2.33; 95% CI, 2.12-2.55). Unfavourable period and cohort effects were found across all SDI quintiles. Cancer subtypes such as "trachea, bronchus, and lung cancers", "colon and rectal cancers", "breast cancer" and "pancreatic cancer" exhibited similar trends. CONCLUSIONS: The cancer mortality attributable to HFPG has surged during the past three decades. Unfavourable age-period-cohort effects on mortality were observed across all SDI quintiles, and the cancer mortality attributable to HFPG is expected to continue to increase rapidly in the future, particularly in lower SDI locations. This is a grim global public health issue that requires immediate attention.

CircEGFR reduces the sensitivity of pirarubicin and regulates the malignant progression of triple-negative breast cancer via the miR-1299/EGFR axis.

Circular RNAs (circRNAs) have been found to be involved in cancer progression and chemotherapy sensitivity. However, the biological function of circRNAs in triple-negative breast cancer (TNBC) and its effect on the sensitivity to pirarubicin (THP) chemotherapy are still unclear. CircEGFR (hsa_circ_0080220) was screened and verified by bioinformatics analysis, proving it was highly expressed in TNBC cell lines, patient tissues, and plasma exosomes, and was associated with poor prognosis of patients. The expression level of circEGFR in patient tissue has potential diagnostic value to distinguish TNBC tissue from normal breast tissue. In vitro studies confirmed that overexpression of circEGFR promoted the proliferation, migration, invasion, and EMT of TNBC cells and decreased the sensitivity of THP treatment while silencing circEGFR showed the opposite effect. The circEGFR/miR-1299/EGFR pathway was cascaded and verified. CircEGFR regulated malignant progression of TNBC by regulating EGFR via sponging miR-1299. THP can inhibit the malignant phenotype of MDA-MB-231 cells by downregulating the expression of circEGFR. In vivo studies confirmed that overexpression of circEGFR can promote tumor growth and EMT and reduce tumor sensitivity to THP treatment. Silencing circEGFR inhibited the malignant progression of the tumor. These results revealed circEGFR is a promising biomarker for TNBC diagnosis, therapeutic and prognosis.

Fatty acid binding protein 1 and fatty acid synthetase over-expression have differential effects on collagen III synthesis and cross-linking in Zongdihua pig primary adipocytes.

The purpose of this study was to determine whether FABP1 and FAS regulate expression of collagen and its crosslinking via lysyl oxidase in isolated adipocytes from Zongdihua pigs. We aimed to identify biochemical processes affecting meat quality using molecular tools to provide a basis for breeding improvement of these animals. We measured expression levels of FABP1 and related genes using qRT-PCR in longissimus dorsi muscle and subcutaneous adipose tissues. Primary adipocytes from fat tissues were isolated and FABP1 and FAS were over-expressed from recombinant plasmids. Sequence analysis of the cloned genes indicated that FABP1 encodes a hydrophobic protein of 128 amino acids and contained 12 predicted phosphorylation sites and no transmembrane regions. The basal levels of FABP1 and FAS expression in pig tissues were 3-3.5-fold higher in subcutaneous fat compared with muscle (P < 0.01). Recombinant expression plasmids were successfully transfected into the cloned preadipocytes and (a) over-expression of FAS resulted in significantly increased expression of COL3A1 (P < 0.05) and significantly inhibited lysyl oxidase LOX expression (P < 0.01); (b) over-expression of FABP1 significantly increased COL3A1 expression (P < 0.01) and significantly inhibited LOX expression (P< 0.05) and significantly reduced lysyl oxidase activity (P < 0.01). Therefore, FAS enhanced FABP1 expression resulting in increased collagen accumulation and this preliminarily suggested that FAS and FABP1 can serve as fat-related candidate genes and provide a theoretical basis for the study of fat deposition in Zongdihua pigs.

Comprehensive analysis of the roles of fatty acid transport related proteins in clear cell renal cell carcinoma.

OBJECTIVE: This study aimed to explore the clinical significance of fatty acid transport-related protein (FATRP) in patients with clear cell renal cell carcinoma(ccRCC). METHODS: RNA-seq data and corresponding clinical data of ccRCC were obtained from TCGA data portal. Seventeen key FATRP genes were comprehensively investigated using bioinformatics approaches to systematically investigate their expression patterns in ccRCC. In addition, the correlation between the expression levels of these genes and clinicopathological features in ccRCC was further explored. RESULTS: Among the 17 key FATRP genes, only FABP5, FABP6, and FABP7 could be regarded as ideal biomarkers for ccRCC, as they were highly expressed in ccRCC tumor tissues, and positively correlates with tumor progression and poor prognosis. FABP6 had the highest copy number variations (CNV) events (63.07 %), and ccRCC patients with FABP6 amplification had a better prognosis than the unaltered group. DNA methylation levels of FABP6 and FABP7 were downregulated in ccRCC tumor tissues compared to those in normal tissues. FABP5 showed the opposite results. Moreover, a novel four FATRP gene (FABP1, FABP5, FABP7, FATP2) and three clinical parameter (age, stage, and grade) prediction model was constructed and that comprised a significant independent prognostic signature. CONCLUSIONS: Only a few FATRP genes are upregulated in ccRCC tumor tissue, and positively correlate with tumor progression and poor prognosis. The accuracy of a single gene of these FATRP genes as predictors of progression and prognosis of ccRCC is limited. The performance of the novel prediction model proposed by this study was much better than that of any single gene.

Ginsenoside F1 attenuates pirarubicin-induced cardiotoxicity by modulating Nrf2 and AKT/Bcl-2 signaling pathways.

Background: Pirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear. Methods: We investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis. Results: THP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects. Conclusion: In conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.

Identification of prognostic genes signature and construction of ceRNA network in pirarubicin treatment of triple-negative breast cancer.

BACKGROUND: The altered long non-coding RNA (lncRNA), circular RNA (circRNA) and mRNA expression in triple-negative breast cancer (TNBC) after pirarubicin (THP) treatment can be a critical factor in the development of tumor. Here, we identify a set of lncRNA, circRNA, and mRNA that can reveal the molecular target and molecular mechanism of THP, and can be used to predict the prognostic characteristics of TNBC. METHODS: Affymetrix GeneChip sequencing was performed to determine whether lncRNA, circRNA, and mRNA were changed in MDA-MB-231 cells after THP treatment, and qRT-PCR was used to verify the accuracy of GeneChip results. Bioinformatics methods were used to analyze the differentially expressed (DE) lncRNA, circRNA and mRNA, and the co-expression network and ceRNA network were constructed. The STRING database, Kaplan-meier Mapper database, GEPIA database, and Tumor Immunity Estimation Resource were used to screen hub genes with clinical value and important significance. RESULTS: THP 5 µM could significantly inhibit proliferation, migration and invasion of MDA-MB-231 cells for 24 h. 1547 DE lncRNAs, 4992 DE circRNAs, and 5777 DE mRNAs were identified. The reliability of the GeneChip was verified by qRT-PCR. An mRNA-lncRNA/circRNA co-expression network was constructed based on the Pearson correlation coefficient. Finally, we established a new ceRNA network, including three circRNAs, five miRNAs, and three mRNAs. The mRNAs are associated with immune infiltration. The mRNAs and miRNAs are significantly associated with survival outcomes in TNBC. CONCLUSION: The results reveal the molecular target and mechanism of THP treatment of TNBC. These ceRNA network can be used as molecular targets for the treatment of TNBC patients and as molecular biomarkers to predict patient prognosis.

Icariin alleviates atherosclerosis by regulating the miR-205-5p/ERBB4/AKT signaling pathway.

PURPOSE: Atherosclerosis (AS) is a cardiovascular disease that has become a major threat to public health worldwide. This study aims to elucidate the effect and mechanism of icariin (ICA) in treating atherosclerosis. METHODS: ApoE-/- mouse AS modeling, ELISA, and hematoxylin-eosin staining were conducted to explore whether icariin has a therapeutic effect on AS. The microRNA (miRNA) chips for ICA treatment of ApoE-/- AS mice were developed; in silico analyses were performed, and signaling pathways were identified. Oxidized low-density lipoprotein (Ox-LDL) was used to induce human aortic vascular smooth muscle cells (HAVSMCs) to build an in vitro AS cell model. Moreover, miR-205-5p was silenced. Finally, cell viability was detected by MTT assay, cell apoptosis by flow cytometry and Western blot, and cell migration by the scratch test. RESULTS: ICA could reduce lipid accumulation in the blood vessels of mice and plaque formation to treat AS. ICA promoted apoptosis and inhibited cell migration of HAVSMCs induced by ox-LDL. Moreover, cell proliferation and migration were inhibited via ICA, which was restored by miR-205-5p silencing. CONCLUSION: ICA can alleviate AS and inhibit the proliferation and migration of HAVSMCs induced by ox-LDL, potentially mediated by the upregulation of miR-205-5p.

Changes in 5-HT1F receptor expression in rats with spasticity following spinal cord injury.

Spasticity is a common complication in patients with spinal cord injury (SCI) and adversely affects patients' quality of life. Little is known about the distribution of the serotonin 1F receptor (5-HT1FR) in the spinal cord, especially in relation to the spasticity caused by SCI. Adult male Wistar rats were divided into a sham-operation group and spinalized group. SCI-induced spasticity was caused by spinal transection at the second sacral segment. The spinal cord below the transection was obtained at the end of the experiment. The expression and distribution of 5-HT1FR in the spinal cord were analyzed. The results showed that the expression of 5-HT1FR (mRNA and protein) exhibited the same downward trend after spinal transection and reached the lowest expression level at 2 and 5 days, respectively. The expression of 5-HT1FR (mRNA and protein) thereafter gradually approached the levels in the sham-operation group after 60 days. Immunostaining suggested that 5-HT1FR showed particularly strong expression in the ventral horn (VH) region. The time course of 5-HT1FR mRNA downregulation is positively correlated with the development of tail spasticity after sacral spinal cord transection. There may be a connection between 5-HT1FR and the occurrence of spasticity, but elucidation of the specific mechanism needs further experimental verification.

Effects of Chronic Remote Ischemic Conditioning on Atrial Fibrillation Burden in Patients with Permanent Pacemakers.

This study aimed to evaluate the effects of chronic remote ischemic conditioning (CRIC) on atrial fibrillation burden in patients with an implanted pacemaker. Sixty-six patients with permanent pacemakers were randomly divided into the CRIC group and control group after 4 weeks of screening. CRIC treatment was performed twice daily for 12 weeks. The remote ischemic conditioning protocol consisted of 4 × 5 minutes inflation/deflation of the blood pressure cuff applied in the upper arm to create intermittent arm ischemia. Sixty-one patients (31 patients in the CRIC group and 30 patients in the control group) completed the study. CRIC was well tolerated by patients after 12 weeks of treatment. The burden of atrial fibrillation (AF) in the CRIC group decreased significantly at 4 weeks compared with that at 0 weeks (14.7% ± 18.5% versus 17.0% ± 20.7%, P < 0.001), which further decreased at 12 weeks compared with that at 0 weeks (8.6% ± 10.2% versus 17.0% ± 20.7%, P < 0.001) and that at 4 weeks (8.6% ± 10.2% versus 14.7% ± 18.5%, P < 0.001), which was not observed in the control group. AF burden also reduced significantly after 12-week CRIC compared with that in the control group (8.6% ± 10.2% versus 17.6% ± 19.5%, P = 0.013). Repeated measurement ANOVA showed that the changes in AF burden were associated with CRIC instead of time (P < 0.01). In addition, there were trends that the longest duration of AF and cumulative numbers of atrial high-rate episodes (AHREs) reduced after 12-week CRIC. This study suggests that a 12-week course of CRIC treatment could reduce AF burden in patients with permanent pacemakers, supporting the widespread use of CRIC in the daily lives of these patients, which needs to be verified in the future.