TMEM100 acts as a TAK1 receptor that prevents pathological cardiac hypertrophy progression.

Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53-75 and 85-107) directly interacts with the C-terminal region of TAK1 (amino acids 1-300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy.

The complete mitochondrial genome and phylogenetic analysis of Rattus tanezumi (Niethammer, 1975), captured from North China.

Rattus tanezumi (Niethammer, 1975) is one of the commensal rodent species in South China. With the development of transportation and climate change, R. tanezumi has gradually migrated north and become the dominant rat species for the past few years. In this study, we assembled a complete mitochondrial genome of R. tanezumi, captured from North China. The mitogenome contains 16,307 nucleotide pairs, including 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, as well as one non-coding control region. Based on whole mitogenome phylogenetical analysis showed that R. tanezumi captured from North China had a close phylogenetic relationship with that from Japan and South Korea. These findings are valuable for further studies on the evolution, genetic diversity, and taxonomy of Asian commensal rodent.

Myeloid-derived suppressor cells alleviate adverse ventricular remodeling after acute myocardial infarction.

The fundamental pathophysiological mechanism in the progression of chronic heart failure following acute myocardial infarction (AMI) is ventricular remodeling, in which innate and adaptive immunity both play critical roles. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to function in a range of pathological conditions, such as infections, inflammation, autoimmune diseases, and tumors. However, it is unclear how MDSCs contribute to cardiac remodeling following AMI. This study aimed to identify the function and underlying mechanism of MDSCs in controlling cardiac remodeling following AMI. Following AMI in mice, MDSCs frequencies changed dynamically, considerably increased on day 7 in blood, spleens, lymph nodes and hearts, and decreased afterwards. Consistently, mice with AMI displayed enhanced cardiac function on day 14 post-AMI, reduced infract size and higher survival rates on day 28 post-AMI following the adoptive transfer of MDSCs. Furthermore, MDSCs inhibited the inflammatory response by decreasing pro-inflammatory cytokine (TNF-α, IL-17, Cxcl-1, and Cxcl-2) expression, up-regulating anti-inflammatory cytokine (TGF-ß1, IL-10, IL-4, and IL-13) expression, reducing CD3+ T cell infiltration in the infarcted heart and enhancing M2 macrophage polarization. Mechanistically, MDSCs improved the release of anti-inflammatory factors (TGF-ß1 and IL-10) and decreased the injury of LPS-induced cardiomyocytes in vitro in a manner dependent on cell-cell contact. Importantly, blockade of IL-10 partially abolished the cardioprotective role of MDSCs. This study found that MDSCs contributed to the restoration of cardiac function and alleviation of adverse cardiac remodeling after AMI possibly by inhibiting inflammation.

Bioinformation Analysis of Differential Expression Proteins in Different Processes of COVID-19.

COVID-19 is a highly infectious respiratory disease whose progression has been associated with multiple factors. From SARS-CoV-2 infection to death, biomarkers capable of predicting different disease processes are needed to help us further understand the molecular progression of COVID-19 disease. The aim is to find differentially expressed proteins that are associated with the progression of COVID-19 disease or can be potential biomarkers, and to provide a reference for further understanding of the molecular mechanisms of COVID-19 occurrence, progression, and treatment. Data-independent Acquisition (DIA) proteomics to obtain sample protein expression data, using R language screening differentially expressed proteins. Gene Ontology and Kyoto Encyclopedia for Genes and Genomes analysis was performed on differential proteins and protein-protein interaction (PPI) network was constructed to screen key proteins. A total of 47 differentially expressed proteins were obtained from COVID-19 incubation patients and healthy population (L/H), mainly enriched in platelet-related functions, and complement and coagulation cascade reaction pathways, such as platelet degranulation and platelet aggregation. A total of 42 differential proteins were obtained in clinical and latent phase patients (C/L), also mainly enriched in platelet-related functions and in complement and coagulation cascade reactions, platelet activation pathways. A total of 10 differential proteins were screened in recovery and clinical phase patients (R/C), mostly immune-related proteins. The differentially expressed proteins in different stages of COVID-19 are mostly closely associated with coagulation, and key differential proteins, such as FGA, FGB, FGG, ACTB, PFN1, VCL, SERPZNCL, APOC3, LTF, and DEFA1, have the potential to be used as early diagnostic markers.

Drug-coated balloons for the treatment of ostial left anterior descending or ostial left circumflex artery lesions: a patient-level propensity score-matched analysis.

BACKGROUND: Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. METHODS: We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. RESULTS: Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. CONCLUSIONS: The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

RNF13 protects against pathological cardiac hypertrophy through p62-NRF2 pathway.

Heart failure (HF) severely impairs human health because of its high incidence and mortality. Cardiac hypertrophy is the main cause of HF, while its underlying mechanism is not fully clear. As an E3 ubiquitin ligase, Ring finger protein 13 (RNF13) plays a crucial role in many disorders, such as liver immune, neurological disease and tumorigenesis, whereas the function of RNF13 in cardiac hypertrophy remains largely unknown. In the present study, we found that the protein expression of RNF13 is up-regulated in the transverse aortic constriction (TAC)-induced murine hypertrophic hearts and phenylephrine (PE)-induced cardiomyocyte hypertrophy. Functional investigations indicated that RNF13 global knockout mice accelerates the degree of TAC-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis and heart dysfunction. On the contrary, adeno-associated virus 9 (AAV9) mediated-RNF13 overexpression mice alleviated cardiac hypertrophy. Furthermore, we demonstrated that adenoviral RNF13 attenuates the PE-induced cardiomyocyte hypertrophy and down-regulates the expression of cardiac hypertrophic markers, while the opposite results were observed in the RNF13 knockdown group. The RNA-sequence of RNF13 knockout and wild type mice showed that RNF13 deficiency activates oxidative stress after TAC surgery. In terms of the mechanism, we found that RNF13 directly interacted with p62 and promoted the activation of downstream NRF2/HO-1 signaling. Finally, we proved that p62 knockdown can reverse the effect of RNF13 in cardiac hypertrophy. In conclusion, RNF13 protects against the cardiac hypertrophy via p62-NRF2 axis.

Genetic diversity and molecular evolution of Seoul virus in Hebei province, China.

Seoul virus (SEOV) is a major pathogen which causes hemorrhagic fever with renal syndrome (HFRS), and is present all over the world. However, there are currently few long-term systematic studies of SEOV's phylogenetic and evolutionary mechanisms in epidemic areas. Thus, in this study, we used RT-PCR combined with NGS to obtain the genomes of six SEOV viruses from 1993, as well as 56 Hebei province-specific tissue samples from 1999 to 2022. Phylogenetic analysis showed that the SEOV samples could be divided into seven groups and showed geographic clustering. The geographic region may be the main factor affecting the genetic diversity of SEOV. We also found that SEOV was subject to strong overall purifying selection and positive selection at certain sites during evolution. Recombination events and high nucleotide substitution rates were also shown to accelerate SEOV's evolution. Evolutionary feature of the L segment is more representative of complete genome. Our detailed analysis provides a deeper understanding of the genetic diversity and evolutionary drivers of SEOV within its primary epidemic areas. It will be important to further monitor epidemiological trends and drivers of variation to help increase our understanding of the pathogenicity of SEOV infections.

Long-term outcomes of drug-coated balloon treatment of calcified coronary artery lesions: a multicenter, retrospective, propensity matching study.

Background: Coronary artery calcification (CAC) is associated with high rates of restenosis and adverse clinical events after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Objectives: The aim of this study was to evaluate the long-term clinical outcomes of drug-coated balloon (DCB)-only treatment for de novo lesions with and without CAC. Methods: Patients with de novo coronary disease treated with the DCB-only strategy were retrospectively enrolled from three centers and categorized into a CAC group and a non-CAC group. The primary endpoint was the target lesion failure (TLF) rate during the 3-year follow-up. Secondary endpoints included the occurrence of major adverse cardiac events (MACEs), target lesion revascularization (TLR), cardiac death, myocardial infarction (MI) and any revascularization. Propensity score matching (PSM) was conducted to assemble a cohort of patients with similar baseline characteristics. Results: A total of 1,263 patients with 1,392 lesions were included, and 243 patients were included in each group after PSM. Compared with the non-CAC group, the incidence rates of TLF (9.52% vs. 4.94%, odds ratio [OR]: 2.080; 95% confidence interval [CI]: 1.083-3.998, P = 0.034) and TLR (7.41% vs. 2.88%, OR: 2.642; 95% CI: 1.206-5.787, P = 0.020) in the CAC group were higher. The incidence rates of MACE (12.35% vs. 7.82%, OR: 1.665; 95% CI: 0.951-2.916, P = 0.079), cardiac death (2.06% vs. 2.06%, OR: 0.995; 95% CI: 0.288-3.436, P = 0.993), MI (1.23% vs. 0.82%, OR: 2.505; 95% CI: 0.261-8.689, P = 0.652) and any revascularization (12.76% vs. 9.67%, OR: 1.256; 95% CI: 0.747-2.111, P = 0.738) were similar between groups. Conclusions: CAC increased the incidence of TLF and TLR without a substantial increase in the risk of MACE, cardiac death, MI, or any revascularization in patients treated with DCB-only angioplasty during the 3-year follow-up.

Long-term outcomes of less drug-eluting stents by the use of drug-coated balloons in de novo coronary chronic total occlusion intervention: A multicenter observational study.

Background: Data on drug-coated balloons (DCB) for de novo coronary chronic total occlusion (CTO) are limited. We aimed to investigate the long-term outcomes of substitution of drug-eluting stents (DES) by DCB. Methods: We compared the outcomes of less DES strategy (DCB alone or combined with DES) and DES-only strategy in treating de novo coronary CTO in this prospective, observational, multicenter study. The primary endpoints were major adverse cardiovascular events (MACE), target vessel revascularization, myocardial infarction, and death during 3-year follow-up. The secondary endpoints were late lumen loss (LLL) and restenosis until 1-year after operation. Results: Of the 591 eligible patients consecutively enrolled between January 2015 and December 2019, 281 (290 lesions) were treated with DCB (DCB-only or combined with DES) and 310 (319 lesions) with DES only. In the DCB group, 147 (50.7%) lesions were treated using DCB-only, and the bailout stenting rate was relatively low (3.1%). The average stent length per lesion in the DCB group was significantly shorter compared with the DES-only group (21.5 ± 25.5 mm vs. 54.5 ± 26.0 mm, p < 0.001). A total of 112 patients in the DCB group and 71 patients in the DES-only group (38.6% vs. 22.3%, p < 0.001) completed angiographic follow-up until 1-year, and LLL was much less in the DCB group (-0.08 ± 0.65 mm vs. 0.35 ± 0.62 mm, p < 0.001). There were no significant differences in restenosis occurrence between the two groups (20.5% vs. 19.7%, p > 0.999). The Kaplan-Meier estimates of MACE at 3-year (11.8% vs. 12.0%, log-rank p = 0.688) was similar between the groups. Conclusion: Percutaneous coronary intervention with DCB is a potential "stent-less" therapy for de novo CTO lesions with satisfactory long-term clinical results compared to the DES-only approach.

Expression of angiotensin converting enzyme 2 mRNA in different SARS-CoV-2 infection states and times.

To measure the expression of angiotensin converting enzyme 2 (ACE2) mRNA in SARS-CoV-2 infection with different infection status and at different stages during infection, we used RT-qP CR to measure the expression of ACE2 mRNA. Measurements were analyzed by two-way repeated measures analysis of variance (RMANOVA). Expression of ACE2 mRNA was downregulated in initial stages of SARS-CoV-2 infection both in the asymptomatic infection (ASY) group and the confirmed cases (CON) group (t=-8.0845, P < 0.0001; t=-8.1904, P < 0.0001, respectively). The expression of ACE2 mRNA in the incubation period of CON group was lower compared with the intinal period of ASY group (F = 6.084, p = 0.016, partialη2 = 0.070). Relative expression of ACE2 mRNA was upregulated at the late stage of SARS-CoV-2 infection in the ASY and CON groups (F = 23.489, p = 0.000, partialη2 = 0.225; F = 46.555, p = 0.000, partialη2 = 0.365, respectively). The relative expression of ACE2 mRNA was down-regulated (mean ± SEM:0.69 ± 0.03) after inoculation with SARSCoV- 2 Spike pseudovirus, and there was a statistical difference (one-way t test, mean diffience =-0.31, 95%CI: -0.37˜-0.24, t=-8.1904, P < 0.0001). The expression of ACE2 mRNA is downregulated in the initial stage of SARS-CoV-2 infection, and then upregulated in the late stage of SARS-CoV-2 infection. The lower expression of ACE2 mRNA during the incubation period can lead to clinical symptoms. Downregulation of ACE2 mRNA was related to the interaction between SARS-CoV-2 S protein and ACE2.Communicated by Ramaswamy H. Sarma.

Drug-coated balloon in the treatment of coronary left main true bifurcation lesion: A patient-level propensity-matched analysis.

Aims: An increasing body of evidence suggests that drug-coated balloon (DCB) angioplasty represents a valuable option for revascularization in selected patients with coronary bifurcation disease. However, there remains a paucity of real-world observational evidence on the efficacy of DCB in left main (LM) true bifurcation lesion. We compared clinical and angiographic outcomes of hybrid [DCB + drug-eluting stent (DES)] versus DES-only strategy (provisional stenting or two-stent strategies) in de novo LM true bifurcated lesions. Methods: The primary endpoint was the 2-year composite rate of target lesion failure (TLF): cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target lesion revascularization (CD-TLR). A routine 1-year angiographic follow-up was scheduled. Propensity-score matching was utilized to assemble a cohort of patients with similar baseline characteristics. Results: Among 1077 eligible patients, 199 who received DCB treatment and 398 who were assigned to DES therapy had similar propensity scores and were included in the analysis. TLF within 2 years occurred in 13 patients (7.56%) assigned to DCB group, and 52 patients (14.36%) assigned to DES group (odds ratio: 0.487; 95% confidence interval: 0.258-0.922; P = 0.025; Log-rank P = 0.024). Compared with the DES group, the DCB group resulted in a lower rate of CD-TLR (2.91% vs. 9.42%; P = 0.007). Cardiac death, TVMI, all-cause mortality, and stent thrombosis were comparable between both groups. Patients treated with DES-only were associated with a higher late lumen loss (0.42 ± 0.62 mm vs. 0.13 ± 0.42 mm, P < 0.001) compared with the DCB group at 1 year. In sensitivity analysis, the DCB group also presented a lower incidence of TLF, CD-TLR and stent thrombosis both compared to the two-stent strategy and compared to provisional stenting (Ps < 0.05). Conclusion: The 2-year results of PCI utilizing DCB for LM true bifurcation lesions are superior to employing DES alone in terms of safety and effectiveness.

Long-term outcomes of drug-coated balloons in patients with diffuse coronary lesions.

Background: Drug-coated balloons (DCB), alone or in combination with drug-eluting stents (DES), may be used to treat diffuse coronary lesions. We aimed to explore the efficacy and safety of DCB in patients with diffuse coronary lesions. Methods: Consecutive patients with diffuse coronary lesions (lesion length > 25 mm) who underwent DCB and/or DES between January 2015 and December 2019 were included in this prospective, observational, multicenter study. The DCB group included 355 patients (360 lesions), of which 142 patients (143 lesions, 39.7%) received the DCB-only strategy and 213 patients (217 lesions, 60.3%) received the hybrid strategy (DCB combined with DES). The DES group included 672 patients (831 lesions) treated with DES alone. Target lesion revascularization (TLR) during 3-year follow-up was the primary outcome of interest. The secondary outcome was major adverse cardiac events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction, and target vessel revascularization. Results: The two groups had comparable baseline clinical and lesion characteristics. Lesion length was similar (43.52 ± 16.46 mm vs. 44.87 ± 15.80 mm, P = 0.181), but the stent length in the DCB group was significantly shorter (24.02 ± 23.62 mm vs. 51.89 ± 15.81 mm, P < 0.001). Ten lesions (2.8%) in the DCB group received bailout stents. Over 3 years of follow-up, no significant difference in TLR incidence between the groups (7.3 vs. 8.3%, log-rank P = 0.636) was observed. Incidence of MACE also did not differ significantly (11.3 vs. 13.7%, log-rank P = 0.324). No thrombosis events occurred in the DCB group, while four patients (0.6%) in the DES group experienced stent thrombosis (log-rank P = 0.193). Moreover, similar TLR and MACE rates were observed between DCB-only and hybrid strategies (TLR: 6.4 vs. 8.0%, log-rank P = 0.651; MACE: 11.4 vs. 11.2%, log-rank P = 0.884). Conclusion: Long-term outcomes show that the efficacy and safety of the DCB strategy (DCB alone or combined with DES) are similar to those of DES alone in diffuse coronary lesions. These findings suggest that this strategy is a promising alternative for select patients with diffuse coronary lesions.

Stentless at ostium: a novel approach for treating ostial left anterior descending or left circumflex coronary artery lesions with drug-coated balloons.

BACKGROUND: Currently, there is no optimal treatment strategy for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. This study explored effectiveness and safety of drug-coated balloons (DCB) in individuals presenting with ostial LAD or LCx lesions. METHODS: A total of 137 patients with de novo ostial LAD or LCx lesions scheduled for DCB treatment were prospectively recruited into the study. After mandatory lesion preparation, DCB-only or hybrid strategy [DCB + drug-eluting stent (DES)] were performed on 120 patients (87.59%). The primary endpoint was the rate of 2-year target lesion revascularization (TLR). Rates of major adverse cardiovascular events (MACE), cardiac death, target vessel myocardial infarction (TVMI), and vessel thrombosis were explored as the secondary outcomes. Quantitative coronary angiography software was used to analyze coronary angiograms. RESULTS: Of the participants, 58 were treated with DCB-only and 62 with hybrid strategy. Relative to the DCB-only group, patients in the hybrid group had longer target lesions (15.47 ± 10.08 vs. 36.85 ± 9.46 mm, P<0.001) and higher Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) scores (23.47 ± 5.22 vs. 29.98 ± 3.18, P<0.001). During follow-up (731 ± 64 days), neither the primary endpoint (TLR) nor the secondary endpoints (including MACE, cardiac death, TVMI, and vessel thrombosis) differed statistically between the two groups (all P > 0.05). Treatment strategy (DCB-only or hybrid) was not a significant risk factor for TLR. Patients who underwent DCB-only exhibited less late lumen loss compared with the patients who underwent hybrid strategy (-0.26 ± 0.59 vs. 0.42 ± 0.47 mm, P<0.001) at 1-year angiographic follow-up. CONCLUSIONS: With regards to safety and efficacy, the strategy of DCB as a standalone therapy was similar in comparison with the hybrid strategy of DCB + DES for ostial LAD and ostial LCx lesions. This approach might be effective and technically easy in treating ostial LAD and LCx diseases.

Clinical outcomes of drug-coated balloon in coronary lesions: a real-world, all-comers study.

BACKGROUNDS: Although drug-eluting stents are the most common interventional devices for patients with coronary disease, drug-coated balloons (DCBs) represent a novel therapeutic alternative in certain scenarios. This prospective, observational all-comers study explored the clinical outcomes of DCB use in patients with coronary lesions. METHODS AND RESULTS: All patients treated with DCBs were enrolled in this study, including patients with in-stent restenosis (ISR) or de novo lesions. The primary outcome was the target lesion revascularization (TLR) rate at one year. We enrolled 2306 patients with 2660 lesions and performed DCB angioplasty in 399 patients (17.3%) with ISR and 1907 patients (82.7%) with de novo lesions. During follow-up (366 ± 46 days), the TLR rate was lower in the de novo lesion group (1.31%) compared to the ISR group (7.02%) [odds ratio (OR) 0.176, 95% confidence interval (CI) 0.101-0.305, p < 0.001]. Patients with de novo lesions had a lower yearly incidence of MACE compared to ISR patients (2.73 vs. 9.27%, respectively, OR 0.274, 95% CI 0.177-0.424, p < 0.001) and a lower incidence of any revascularization (5.09 vs. 13.03%, OR 0.358, 95% CI 0.251-0.510, p < 0.001). No significant differences between groups were observed in the rates of cardiac death (OR 0.783, 95% CI 0.258-2.371, p = 0.655) or MI (OR 0.696, 95% CI 0.191-2.540, p = 0.573). CONCLUSIONS: DCB angioplasty in this all-comers, real-world, prospective study was safe and efficient with low TLR and MACE rates. Thus, DCB appears to be an attractive alternative for the stent-less treatment of de novo coronary lesions. ISR in-stent restenosis; OR odds ratio; CI confidence interval; TLR target lesion revascularization; MACE major adverse cardiovascular events; MI myocardial infraction. MACE defined as the composite outcome of cardiac death, myocardial infarction, and target vessel revascularization. Any revascularization includes any percutaneous coronary intervention, and coronary artery bypass grafting.

Drug-Coated Balloon-Only Angioplasty Outcomes in Diabetic and Nondiabetic Patients with De Novo Small Coronary Vessels Disease.

BACKGROUND: The revascularization of small vessels using drug-eluting stents remains challenging. The use of the drug-coated balloon is an attractive therapeutic strategy in de novo lesions in small coronary vessels, particularly in the diabetic group. This study aimed to assess the outcomes of DCB-only angioplasty in small vessel disease. METHODS: A total of 1198 patients with small vessel disease treated with DCB-only strategy were followed. Patients were divided into the diabetic and nondiabetic groups. Clinical and angiographical follow-up were organized at 12 months. The primary endpoints were target lesion failure and secondary major adverse cardiac events. RESULTS: There was a significantly higher rate of target lesion failure among diabetic patients compared to nondiabetic [17 (3.9%) vs. 11 (1.4%), P=0.006], taken separately, the rate of target lesion revascularization significantly differed between groups with a higher rate observed in the diabetic group [9 (2%) vs. 4 (0.5%), P=0.014]. Diabetes mellitus remained an independent predictor for TLF (HR: 2.712, CI: 1.254-5.864, P=0.011) and target lesion revascularization (HR: 3.698, CI: 1.112-12.298, P=0.033) after adjustment. However, no significant differences were observed between groups regarding the target vessel myocardial infarction (0.6% vs. 0.1%, P=0.110) and MACE [19 (4.4%) vs. 21 (2.7%), P=0.120]. CONCLUSION: Drug-coated balloon-only treatment achieved lower incidence rates of TLF and MACE. Diabetes is an independent predictor for target lesion failure and target lesion revascularization at one year following DCB treatment in small coronary vessels. We observed no significant differences between groups regarding MACE in one year.

Protective Effect of Ginsenoside Rb1 Nanoparticles Against Contrast-Induced Nephropathy by Inhibiting High Mobility Group Box 1 Gene/Toll-Like Receptor 4/NF-κB Signaling Pathway.

With the progress made in the widespread application of interventional radiology procedures, there has been an increasing number of patients who suffer from cardiovascular diseases and go through imaging and interventional treatment with iodine contrast medium (ICM) year by year. In turn, there has been an increasing amount of concern over acute kidney injury (AKI) brought about by ICM. As evidenced by numerous studies, the initiation of inflammatory response plays a critical role in the development of ICM-induced AKI. Correspondingly, the strategy of targeting renal inflammatory response and cytokine release could provide an effective solution to mitigating the ICM-induced AKI. Moreover, Ginsenoside Rb1 (GRb1) constitutes one of the major active components of ginseng and features a wide range of vital biological functions. Judging from the research findings, GRb1 could impose antioxidant and anti-inflammatory effects on cardiovascular diseases, in addition to lung, liver and kidney diseases. However, reports on whether GRb1 could impose a protective effect against contrast-induced nephropathy (CIN) are absent. In this study, we have examined the therapeutic effects imposed by GRb1 as well as the potential molecular mechanism by establishing an in vivo and in vitro model of CIN. In addition, we have set up a mouse model of CIN through sequential intravenous injection of indomethacin, N(ω)-nitro-Larginine methyl ester (L-NAME), and iopromide. To further enhance the bioavailability of GRb1, we have encapsulated GRb1 with polyethylene glycol (PEG)/poly lactic-co-glycolic acid (PLGA) nanocarriers to generate GRb1 nanoparticles (NPs) conducting the in vivo experiments. During the in vitro experiments, we have adopted GRb1 to treat NRK-52E cells or cells transfected with the high mobility group box 1 gene (HMGB1) overexpression plasmid. As shown by the in vivo experimental results, GRb1 NPs could evidently improve the renal dysfunction in CIN, diminish the extent of apoptosis of tubular epithelial cells, and reduce the expression of high mobility group box 1 (HMGB1) and cytokines (tumor necrosis factor (TNF-α), interleukin (IL) 6 and IL-1ß). In addition, GRb1 NPs are found to be capable of preventing the activation of Toll-like receptor 4 (TLR4)/NF-κB signaling pathway triggered by contrast medium. The in vitro experimental results have exactly confirmed the findings of the in vivo experiments. In the meantime, through the observation of the in vitro assays, overexpression of HMGB1 can partially counteract the beneficial effects imposed by GRb1. Judging from our research data, GRb1 could impose a protective effect against CIN by inhibiting inflammatory response via HMGB1/TLR4/NF-κB pathway, whereas HMGB1 constitutes a critical molecular target of GRb1.

Role of GALNT4 in protecting against cardiac hypertrophy through ASK1 signaling pathway.

Pathological myocardial hypertrophy is regulated by multiple pathways. However, its underlying pathogenesis has not been fully explored. The goal of this work was to elucidate the function of polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4) in myocardial hypertrophy and its underlying mechanism of action. We illustrated that GALNT4 was upregulated in the models of hypertrophy. Two cardiac hypertrophy models were established through partial transection of the aorta in GALNT4-knockout (GALNT4-KO) mice and adeno-associated virus 9-GALNT4 (AAV9-GALNT4) mice. The GALNT4-KO mice demonstrated accelerated cardiac hypertrophy, dysfunction, and fibrosis, whereas the opposite phenotype was observed in AAV9-GALNT4 mice. Similarly, GALNT4 overexpression mitigated the degree of phenylephrine-induced cardiomyocyte hypertrophy in vitro whereas GALNT4 knockdown aggravated the hypertrophy. In terms of mechanism, GALNT4 deficiency increased the phosphorylation and activation of ASK1 and its downstream targets (JNK and p38), whereas GALNT4 overexpression inhibited activation of the ASK1 pathway. Furthermore, we demonstrated that GALNT4 can directly bind to ASK1 inhibiting its N-terminally mediated dimerization and the subsequent phosphorylation of ASK1. Finally, an ASK1 inhibitor (iASK1) was able to reverse the effects of GALNT4 in vitro. In summary, GALNT4 may serve as a new regulatory factor and therapeutic target by blocking the activation of the ASK1 signaling cascade.

Decreased circulating follicular regulatory T cells in patients with dilated cardiomyopathy.

Follicular regulatory T cells (Tfr) have critical functions in inflammatory and autoimmune disorders. The main purpose of the current work was to assess Tfr cell frequency in patients with dilated cardiomyopathy (DCM). Flow cytometry showed that, compared with normal controls, DCM cases showed markedly reduced Tfr cell rates and Tfr/Tfh ratios, but significantly increased follicular helper T cell (Tfh) rates. Correlation analysis showed that the Tfr rate in DCM patients was positively correlated with left ventricular ejection fraction (LVEF), and negatively correlated with N-terminal brain natriuretic peptide (NT-proBNP) levels. Lower Foxp3 and higher Bcl-6, ICOS, and PD-1 mRNA expression levels were found in patients with DCM. In addition, plasma interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-21 levels were significantly increased in DCM cases. Moreover, IgG and IgG3 levels were also elevated in individuals with DCM. Correlation analysis showed that the Tfr rate in DCM patients was negatively correlated with IgG and IgG3, while the Tfh rate was positively correlated with IgG and IgG3. Changes in circulating Tfr levels may have a critical immunomodulatory function in DCM and may become a new therapeutic target for DCM.

Clinical Outcomes of Drug-Coated Balloon in Coronary Patients with and without Diabetes Mellitus: A Multicenter, Propensity Score Study.

BACKGROUND: Relative to nondiabetic patients, percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) is associated with inferior clinical outcomes. We aimed to evaluate the outcomes of drug-coated balloon (DCB) in diabetic versus nondiabetic patients. METHODS AND RESULTS: In this observational, prospective, multicenter study, we compared the outcomes of patients with and without DM after undergoing PCI with DCBs. Target lesion failure (TLF) was analyzed as primary endpoint. Secondary endpoints were the rates of target lesion revascularization (TLR), major adverse cardiovascular events (MACE), cardiac death, myocardial infarction (MI), and any revascularization. Propensity score matching was used to assemble a cohort of patients with similar baseline characteristics. Among 2,306 eligible patients, 578 with DM and 578 without DM had similar propensity scores and were included in the analyses. During follow-up (366 ± 46 days), compared with DM patients, patients without DM were associated with a lower yearly incidence of TLF (2.77% vs. 5.36%; OR, 1.991; 95% CI, 1.077 to 3.681; P = 0.025) and TLR (1.90% vs. 4.15%; OR, 2.233; 95% CI, 1.083 to 4.602; P = 0.026). No significant differences were observed with regards to rates of MACE (OR: 1.580, 95% CI: 0.912-2.735; P = 0.100), cardiac death (OR: 1.608, 95% CI: 0.523-4.946; P = 0.403), MI (OR: 4.042, 95% CI: 0.855-19.117; P = 0.057), and any revascularization (OR: 1.534, 95% CI: 0.983-2.393; P = 0.058). CONCLUSIONS: Diabetic patients experience higher TLF and TLR rates following DCB angioplasty without substantial increase in the risk of MACE, cardiac death, MI, or revascularization.