Follicular lymphoma (FL), derived from germinal centre (GC) B cells, is a kind of systemic neoplasm. Even though FL is indolent, it remains an incurable haematology Neoplasm. Accumulating evidence has suggested that the circulating cytokine is associated with the development of FL, yet the causal relationship between FL and circulating cytokines remains undetermined. Therefore, we conducted a two-sample Mendelian randomization (MR) to confirm the causal link between FL and levels of circulating cytokines with the use of summary data on circulating cytokines and FL. All these data from genome-wide association study were derived from the Genome-wide pQTL mapping which contains 14,824 individuals. FL data were acquired exclusively from FinnGen, where 218,792 individuals (522 cases vs. 218,270 controls) were involved. Various statistical methods, including the inverse variance weighted method (IVW), weighted median (WME), simple model, weighted model (WM) and MR-Egger, were used to evaluate the potential causal connection between circulating cytokines and FL. Sensitivity analysis, which involves the examination of the heterogeneity, pleiotropy, and leave-one-out method, was also performed to ensure more trustworthy results. A bidirectional MR test was performed to evaluate the direction of causal association between circulating cytokines and FL. Combining all the steps of MR analysis, we revealed four causal cytokines: C-X-C motif chemokine ligand 5 (CXCL5), interleukin-15 receptor A (IL15RA), interleukin-20 (IL20), and neurotrophin-3 (NT-3). The risk of FL may be inversely linked to CXCL5 (OR=0.73, CI: 0.545-0.979, P=0.036), IL-15RA (OR=0.669, CI: 0.451-0.993, P=0.046), and IL-20 (OR=0.565, CI: 0.325-0.981, P=0.043) but positively linked to NT-3 (OR=1.872, CI: 1.063-3.297, P=0.03). In addition, in our study, no causal effect of FL on cytokines was demonstrated and no significant heterogeneity and pleiotropy were found. Our research revealed the causal relationship between cytokines and FL, along with both the anti-protective effect of CXCL5, IL-15RA, and IL-20 and the protective effect of neurotrophin-3 on FL. These findings aim to provide new clues regarding the pathogenesis of FL and to extend the potential of circulating cytokines to therapeutic interventions.
In this work, the corn straw (CS) with concentrations of 3%, 6%, and 9% (w/v) were pretreated by rumen fluid (RF) and then used for batched mesophilic biogas production. The results showed that after a 6-day pretreatment, volatile fatty acid (VFAs) production of 3.78, 8.27, and 10.4 g/L could be found in 3%, 6%, and 9%, respectively. When concerning with biogas production, the highest accumulative methane production of 149.1 mL CH4/g volatile solid was achieved by 6% pretreated CS, which was 22% and 45% higher than 3% and 9%, respectively. Also, it was 3.6 times higher than the same concentration of unpretreated CS. The results of the microbial community structure analysis revealed that the 6% CS pretreatment not only maintained a microbial community with the highest richness and diversity, but also exhibited the highest relative abundance of Firmicutes (45%) and Euryarchaeota (3.9%). This high abundance was conducive to its elevated production of VFAs and methane. These findings provide scientific reference for the utilization of CS and support the development of agricultural waste resource utilization and environmental protection.
Lead halide molecular ferroelectrics represent an important class of luminescent ferroelectrics, distinguished by their high chemical and structural tunability, excellent processability and distinctive luminescent characteristics. However, their inherent instability, prone to decomposition upon exposure to moisture and light, hinders their broader ferroelectric applications. Herein, for the first time, we present a series of isoreticular metal-organic framework (MOF)-type lead halide luminescent ferroelectrics, demonstrating exceptional robustness under ambient conditions for at least 15 months and even when subjected to aqueous boiling conditions. Unlike conventional metal-oxo secondary building units (SBUs) in MOFs adopting highly centrosymmetric structure with limited structural distortion, our lead halide-based MOFs occupy structurally deformable [Pb2X]+ (X=Cl-/Br-/I-) SBUs that facilitate a c-axis-biased displacement of Pb2+ centers and substantially contribute to thermoinducible structural transformation. Importantly, this class of MOF-type lead halide ferroelectrics undergo ferroelectric-to-paraelectric phase transitions with remarkably high Curie temperature of up to 505 K, superior to most of molecular ferroelectrics. Moreover, the covalent bonding between phosphorescent organic component and the light-harvesting inorganic component achieves efficient spin-orbit coupling and intersystem crossing, resulting in long-lived afterglow emission. The compelling combination of high stability, ferroelectricity and afterglow emission exhibited by lead halide MOFs opens up many potential opportunities in energy-conversion applications.
Methamphetamine is a potent and highly addictive neurotoxic psychostimulant that triggers a spectrum of adverse emotional responses during withdrawal. G-protein coupled receptor 55 (GPR55), a novel endocannabinoid receptor, is closely associated with mood regulation. Herein, we developed a murine model of methamphetamine-induced anxiety- and depressive-like behavior during abstinence which showed a decreased GPR55 expression in the hippocampus. Activation of GPR55 mitigated these behavioral symptoms, concomitantly ameliorating impairments in hippocampal neurogenesis and reducing neuroinflammation. These findings underscore the pivotal role of GPR55 in mediating the neuropsychological consequences of methamphetamine withdrawal, potentially via mechanisms involving the modulation of hippocampal neurogenesis and inflammation.
Photocatalytic CO2 reduction to high-value-added C2+ products presents significant challenges, which is attributed to the slow kinetics of multi-e- CO2 photoreduction and the high thermodynamic barrier for C-C coupling. Incorporating redox-active Co2+/Ni2+ cations into lead halide photocatalysts has high potentials to improve carrier transport and introduce charge polarized bimetallic sites, addressing the kinetic and thermodynamic issues, respectively. In this study, a coordination-driven synthetic strategy is developed to introduce 3d transition metals into the interlamellar region of layered organolead iodides with atomic precision. The resultant bimetallic halide hybrids exhibit selective photoreduction of CO2 to C2H5OH using H2O vapor at the evolution rates of 24.9-31.4 µmol g-1 h-1 and high selectivity of 89.5-93.6%, while pristine layered lead iodide yields only C1 products. Band structure calculations and photoluminescence studies indicate that the interlayer Co2+/Ni2+ species greatly contribute to the frontier orbitals and enhance exciton dissociation into free carriers, facilitating carrier transport between adjacent lead iodide layers. In addition, Bader charge distribution calculations and in situ experimental spectroscopic studies reveal that the asymmetric Ni-O-Pb bimetallic catalytic sites exhibit intrinsic charge polarization, promoting C-C coupling and leading to the formation of the key *OC-CHO intermediate.
BACKGROUND: Arg-gingipain A (RgpA) is the primary virulence factor of Porphyromonas gingivalis and contains hemagglutinin adhesin (HA), which helps bacteria adhere to cells and proteins. Hemagglutinin's functional domains include cleaved adhesin (CA), which acts as a hemagglutination and hemoglobin-binding actor. Here, we confirmed that the HA and CA genes are immunogenic, and using adjuvant chemokine to target dendritic cells (DCs) enhanced protective autoimmunity against P. gingivalis-induced periodontal disease. METHODS: C57 mice were immunized prophylactically with pVAX1-CA, pVAX1-HA, pVAX1, and phosphate-buffered saline (PBS) through intramuscular injection every 2 weeks for a total of three administrations before P. gingivalis-induced periodontitis. The DCs were analyzed using flow cytometry and ribonucleic acid sequencing (RNA-seq) transcriptomic assays following transfection with CA lentivirus. The efficacy of the co-delivered molecular adjuvant CA DNA vaccine was evaluated in vivo using flow cytometry, immunofluorescence techniques, and micro-computed tomography. RESULTS: After the immunization, both the pVAX1-CA and pVAX1-HA groups exhibited significantly elevated P. gingivalis-specific IgG and IgG1, as well as a reduction in bone loss around periodontitis-affected teeth, compared to the pVAX1 and PBS groups (p < 0.05). The expression of CA promoted the secretion of HLA, CD86, CD83, and DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) in DCs. Furthermore, the RNA-seq analysis revealed a significant increase in the chemokine (C-C motif) ligand 19 (p < 0.05). A notable elevation in the quantities of DCs co-labeled with CD11c and major histocompatibility complex class II, along with an increase in interferon-gamma (IFN-γ) cells, was observed in the inguinal lymph nodes of mice subjected to CCL19-CA immunization. This outcome effectively illustrated the preservation of peri-implant bone mass in rats afflicted with P. gingivalis-induced peri-implantitis (p < 0.05). CONCLUSIONS: The co-administration of a CCL19-conjugated CA DNA vaccine holds promise as an innovative and targeted immunization strategy against P. gingivalis-induced periodontitis and peri-implantitis.
Chemotherapy of glioblastoma (GBM) has not yielded success due to inefficient blood-brain barrier (BBB) penetration and poor glioma tissue accumulation. Aerobic glycolysis, as the main mode of energy supply for GBM, safeguards the rapid growth of GBM while affecting the efficacy of radiotherapy and chemotherapy. Therefore, to effectively inhibit aerobic glycolysis, increase drug delivery efficiency and sensitivity, a novel temozolomide (TMZ) nanocapsule (ApoE-MT/siPKM2 NC) is successfully designed and prepared for the combined delivery of pyruvate kinase M2 siRNA (siPKM2) and TMZ. This drug delivery platform uses siPKM2 as the inner core and methacrylate-TMZ (MT) as the shell component to achieve inhibition of glioma energy metabolism while enhancing the killing effect of TMZ. By modifying apolipoprotein E (ApoE), dual targeting of the BBB and GBM is achieved in a "two birds with one stone" style. The glutathione (GSH) responsive crosslinker containing disulfide bonds ensures "directional blasting" cleavage of the nanocapsules to release MT and siPKM2 in the high GSH environment of glioma cells. In addition, in vivo experiments verify that ApoE-MT/siPKM2 NC has good targeting ability and prolongs the survival of tumor-bearing nude mice. In summary, this drug delivery system provides a new strategy for metabolic therapy sensitization chemotherapy.
Nucleotide binding and oligomeric domain-like receptor X1 (NLRX1), a member of the NLR family, is associated with the physiological and pathological processes of inflammation, autophagy, immunity, metabolism and mitochondrial regulation, and has been demonstrated to have pro- or antitumor effects in various tumor types. However, the biological function of NLRX1 in esophageal squamous cell carcinoma (ESCC) has remained elusive. In the present study, by using bioinformatics methods, the differential expression of NLRX1 at the mRNA level was examined. Overall survival, clinical correlation, receiver operating characteristic curve, Cox regression, co-expression, enrichment, immune infiltration and drug sensitivity analyses were carried out. A nomogram and a calibration curve were constructed. Changes in protein expression levels were investigated by immunohistochemistry and western blotting. The impact of NLRX1 on i) cell proliferation was evaluated by Cell Counting Kit-8 assays; ii) migration was examined by wound-healing assays; iii) migration and invasion were evaluated by Transwell assays; and iv) apoptosis was assessed by Annexin V/PI staining and flow cytometry. The results revealed that, compared to normal adjacent tissue, NLRX1 was lowly expressed in ESCC, and patients with low NLRX1 expression had a shorter survival time. NLRX1 was an independent prognostic factor for ESCC and was associated with tumor grading. Patients in the low-NLRX1 group showed a decrease in the infiltration of activated natural killer cells, monocytes and M0 macrophages, and these immune-cell infiltration levels were positively correlated with NLRX1 expression. Knocking down NLRX1 promoted the proliferation of KYSE450 cells, while overexpression of NLRX1 inhibited the proliferation of ECA109 cells. NLRX1 negatively regulated the PI3K/AKT signaling pathway in ESCC. These findings indicate that, through several mechanisms, NLRX1 suppresses tumor growth in ESCC, which offers new insight for investigating the causes and progression of ESCC, as well as for identifying more efficient therapeutic approaches.
Water evaporation-induced electricity generators (WEGs) are regarded as one of the most promising solutions for addressing the increasingly severe environmental pollution and energy crisis. Owing to the potential carbon emission in the preparation process of WEGs, whether WEG represents a clean electricity generation technology is open to question. Here, a brand-new strategy is proposed for manufacturing negative carbon emission WEG (CWEG). In this strategy, the microalgae film is used as the electricity generation interface of WEG, which achieves a stable open-circuit voltage (Voc) of 0.25 V and a short-circuit current (Isc) of 3.3 µA. Since microalgae can capture carbon dioxide during its growing process, CWEG holds great promise to generate electricity without carbon emissions in the full life cycle compared with other WEGs. To the best of the author's knowledge, this is the first work using microalgae films to fabricate WEG. Therefore, it is believed that this work not only provides a new direction for designing high-efficiency and eco-friendly WEG but also offers an innovative approach to the resource utilization of microalgae.
The components with hypoglycemic activity in Plumeria rubra were isolated and purified by various column chromatography techniques and activity tracing methods. The physical and chemical properties of all the purified monomer compounds were characterized and analyzed, and a total of six compounds were isolated and identified, including 6â³-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(1), 6î-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1îâ6â³)-ß-D-glucoside(2), 2-hydroxy-6-methoxy-benzyl-benzoate-2-O-ß-D-glucoside(3), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(4), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1îâ6â³)-ß-D-glucoside(5), and 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1îâ6â³)-ß-D-xyloside(6). Compounds 1 and 2 were new compounds, and compounds 3-6 were isolated from Plumeria for the first time. The α-glucosidase inhibitory activity of six identified compounds was tested. The results show that compounds 1-6 show certain inhibitory activity with an IC_(50) value ranging from 8.2 to 33.5 µmol·L~(-1).
Apocynaceae , Glucosides , Glucosides/chemistry , Benzoates
The outbreak of the COVID-10 variant Omicron epidemic in Shanghai in 2022 had a huge impact on residents' food security. This study examines the roles, challenges, and sustainability of online community group food purchasing by analyzing survey data collected from 1168 households in Shanghai between March and May 2022, in the aftermath of COVID-19. This study demonstrates that online community group food purchasing played a crucial role in ensuring residents' food access and food security during the pandemic. However, this study also reveals that residents expressed concerns about the risk of epidemic transmission, food safety, increased prices, and difficulty in safeguarding rights. Only 21.5 % of residents are willing to continue using online community group purchasing. Based on the above conclusions, this study offers some suggestions.
Traditional Chinese medicine (TCM) possesses the potential of providing good curative effects with no side effects for the effective management of slow transit constipation (STC), an intestinal disease characterized by colonic dyskinesia. Mulberry leaves (Morus alba L.) and black sesame (Sesamum indicum L.), referred to as SH, are processed and conditioned as per standardized protocols. SH has applications as food and medicine. Accordingly, we investigated the therapeutic potential of SH in alleviating STC. The analysis of SH composition identified a total of 504 compounds. The intervention with SH significantly improved intestinal motility, reduced the time for the first black stool, increased antioxidant activity, and enhanced water content, thereby effectively alleviating colon damage caused by STC. Transcriptome analysis revealed the SH in the treatment of STC related to SOD1, MUC2, and AQP1. The analysis of 16S rRNA gene sequences indicated notable differences in the abundance of 10 bacteria between the SH and model. Metabolomic analysis further revealed that SH supplementation increased the levels of nine metabolites associated with STC. Integrative analysis revealed that SH modulated amino acid metabolism, balanced intestinal flora, and targeted key genes (i.e., SOD1, MUC2, AQP1) to exert its effects. SH also inhibited the AQP1 expression and promoted SOD1 and MUC2 expression.
Constipation , Morus , Plant Leaves , Sesamum , Morus/chemistry , Constipation/drug therapy , Plant Leaves/chemistry , Sesamum/chemistry , Animals , Plant Extracts/pharmacology , Plant Extracts/chemistry , Gastrointestinal Microbiome/drug effects , Metabolomics/methods , Male , Gastrointestinal Motility/drug effects , Gastrointestinal Transit/drug effects , Antioxidants/pharmacology , Antioxidants/chemistry , Gene Expression Profiling , Disease Models, Animal , Multiomics
BACKGROUND: To investigate the potential of Native T1-mapping in predicting the prognosis of patients with chronic kidney disease (CKD). METHODS: We enrolled 119 CKD patients as the study subjects and included 20 healthy volunteers as the control group, with follow-up extending until October 2022. Out of these patients, 63 underwent kidney biopsy measurements, and these patients were categorized into high (25-50%), low (< 25%), and no renal interstitial fibrosis (IF) (0%) groups. The study's endpoint event was the initiation of renal replacement therapy, kidney transplantation, or an increase of over 30% in serum creatinine levels. Cox regression analysis determined factors influencing unfavorable kidney outcomes. We employed Kaplan-Meier analysis to contrast kidney survival rates between the high and low T1 groups. Additionally, receiver-operating characteristic (ROC) curve analysis assessed the predictive accuracy of Native T1-mapping for kidney endpoint events. RESULTS: T1 values across varying fibrosis degree groups showed statistical significance (F = 4.772, P < 0.05). Multivariate Cox regression pinpointed 24-h urine protein, cystatin C(CysC), hemoglobin(Hb), and T1 as factors tied to the emergence of kidney endpoint events. Kaplan-Meier survival analysis revealed a markedly higher likelihood of kidney endpoint events in the high T1 group compared to the low T1 value group (P < 0.001). The ROC curves for variables (CysC, T1, Hb) tied to kidney endpoint events demonstrated area under the curves(AUCs) of 0.83 (95%CI: 0.75-0.91) for CysC, 0.77 (95%CI: 0.68-0.86) for T1, and 0.73 (95%CI: 0.63-0.83) for Hb. Combining these variables elevated the AUC to 0.88 (95%CI: 0.81-0.94). CONCLUSION: Native T1-mapping holds promise in facilitating more precise and earlier detection of CKD patients most at risk for end-stage renal disease.
Kidney Failure, Chronic , Renal Insufficiency, Chronic , Humans , Kidney , Prognosis , Glomerular Filtration Rate , Fibrosis , Hemoglobins , Predictive Value of Tests
A growing number of applications generate streaming data, making data stream mining a popular research topic. Classification-based streaming algorithms require pre-training on labeled data. Manually labeling a large number of samples in the data stream is impractical and cost-prohibitive. Stream clustering algorithms rely on unsupervised learning. They have been widely studied for their ability to effectively analyze high-speed data streams without prior knowledge. Stream clustering plays a key role in data stream mining. Currently, most data stream clustering algorithms adopt the online-offline framework. In the online stage, micro-clusters are maintained, and in the offline stage, they are clustered using an algorithm similar to density-based spatial clustering of applications with noise (DBSCAN). When data streams have clusters with varying densities and ambiguous boundaries, traditional data stream clustering algorithms may be less effective. To overcome the above limitations, this article proposes a fully online stream clustering algorithm called fast boundary peeling stream clustering (FBPStream). First, FBPStream defines a decay-based kernel density estimation (KDE). It can discover clusters with varying densities and identify the evolving trend of streams well. Then, FBPStream implements an efficient boundary micro-cluster peeling technique to identify the potential core micro-clusters. Finally, FBPStream employs a parallel clustering strategy to effectively cluster core and boundary micro-clusters. The proposed algorithm is compared with ten popular algorithms on 15 data streams. Experimental results show that FBPStream is competitive with the other ten popular algorithms.
Patients with lymphangioleiomyomatosis (LAM) are considered high risk for most surgeries and require specific anesthetic considerations mainly because of the common spontaneous pneumothorax (PTX). To explore whether intraoperative mechanical ventilation could increase the risk of PTX in those patients, we included 12 surgical patients with LAM in this study, of whom four (33.3%) experienced postoperative PTX. According to our results, patients with higher CT grade, poorer pulmonary function, and a history of preoperative PTX might be more likely to develop postoperative PTX. However, intraoperative mechanical ventilation did not show obvious influence, which might help clinicians reconsider the perioperative management of LAM patients.
Lung Neoplasms , Lymphangioleiomyomatosis , Pneumothorax , Humans , Pneumothorax/epidemiology , Pneumothorax/etiology , Lymphangioleiomyomatosis/epidemiology , Incidence , Respiration, Artificial/adverse effects , Lung Neoplasms/surgery
INTRODUCTION: Our study aimed to assess the independent and joint effects of leisure-time physical activity and sedentary behavior with urinary incontinence (UI). METHODS: Data were obtained from the National Health and Nutrition Examination Survey 2011-2016. The primary endpoint was the risk of different subtypes of UI, including stress UI, urgency UI, and mixed UI. The primary exposures were leisure-time physical activity and sedentary behavior. Sedentary behavior was assessed by screen time. Weighted univariate and multivariate logistic regression models were used to observe the independent and joint relationship of leisure-time physical activity and sedentary behavior with UI risk (including stress UI, urgency UI, and mixed UI). RESULTS: In total, 6,927 female participants were included in this analysis. 3,377 females did not have UI, 1,534 had stress UI, 836 had urgency UI, and 1,180 had mixed UI. Screen time with ≥5h/day was associated with increased odds of urgency UI [odds ratio (OR) =1.31, 95% confidence intervals (CI): 1.06-1.61], which indicated the relationship of sedentary behavior and urgency UI. Engaging in leisure-time physical activity with of ≥750 metabolic equivalent (MET)·min/week was found to be significantly associated with reduced likelihood of mixed UI (OR=0.68, 95%CI: 0.55-0.85). Additionally, the interaction term of leisure-time physical activity<750 MET· min/week and screen time≥5h/day was observed to be linked with increased odds of urgency and mixed UI. CONCLUSION: Participants experiencing a lower level of leisure-time physical activity and a higher level of sedentary behavior together might enhance the urgency and mixed UI risk.
Risk prediction and disease prevention are the innovative care challenges of the 21st century. Apart from freeing the individual from the pain of disease, it will lead to low medical costs for society. Until very recently, risk assessments have ushered in a new era with the emergence of omics technologies, including genomics, transcriptomics, epigenomics, proteomics, and so on, which potentially advance the ability of biomarkers to aid prediction models. While risk prediction has achieved great success, there are still some challenges and limitations. We reviewed the general process of omics-based disease risk model construction and the applications in four typical diseases. Meanwhile, we highlighted the problems in current studies and explored the potential opportunities and challenges for future clinical practice.
PURPOSE: According to some cohort studies, an association exists between acute intermittent porphyria (AIP) and liver cancer. However, establishing a definitive causal relationship between porphyria and hepatocellular carcinoma (HCC) remains challenging. Prexisting studies regarding porphyria biomarkers and alcohol-related hepatocellular carcinoma (AR-HCC) make possible an entry point. In this study, we aimed to investigate the causal relationships between biomarkers of two types of porphyria, AIP and congenital erythropoietic porphyria (CEP), and AR-HCC. METHODS: Single-nucleotide polymorphisms (SNPs) associated with porphobilinogen deaminase (PBGD) and uroporphyrinogen-III synthase (UROS), along with outcome data on AR-HCC, were extracted from public genome-wide association studies (GWAS). The GWAS data were then used to explore the potential causal relationships via a two-sample Mendelian randomization (MR) analysis. The effect estimates were calculated using the random-effect inverse-variance-weighted (IVW) method. Additionally, the Cochrane's Q test, MR-Egger test, and leave-one-out analysis were conducted to detect heterogeneity and pleiotropy in the MR results. RESULTS: Using the IVW method as the primary causal effects model in the MR analyses, we found that both PBGD (effect estimate = 1.51; 95% CI, from 1.08 to 2.11, p = 0.016) and UROS (effect estimate = 1.53; 95% CI, from 1.08 to 2.18, p = 0.018) have a significant causal effect on AR-HCC. CONCLUSION: Our findings revealed a causal effect of both PBGD and UROS on AR-HCC, suggesting that both AIP and CEP have a causal association with AR-HCC.
Carcinoma, Hepatocellular , Liver Neoplasms , Porifera , Porphyria, Acute Intermittent , Porphyrias , Humans , Animals , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Biomarkers
An imidazolyl hydrogen-bonded organic framework (HOF-T) with outstanding thermal and water stability was constructed by C-Hâ¯N hydrogen bonding and C-Hâ¯π interactions. UO22+ can be selectively captured by the imidazole group of HOF-T and rapidly reduced to UO2 under visible light irradiation, realizing exceptional uranium removal with high capacity and fast kinetics.
Histone deacetylase 6 (HDAC6) plays a crucial role in the acetylation of non-histone proteins and is notably implicated in angiogenesis, though its underlying mechanisms were previously not fully understood. This study conducted transcriptomic and proteomic analyses on vascular endothelial cells with HDAC6 knockdown, identifying endoglin (ENG) as a key downstream protein regulated by HDAC6. This protein is vital for maintaining vascular integrity and plays a complex role in angiogenesis, particularly in its interaction with bone morphogenetic protein 9 (BMP9). In experiments using human umbilical vein endothelial cells (HUVECs), the pro-angiogenic effects of BMP9 were observed, which diminished following the knockdown of HDAC6 and ENG. Western blot analysis revealed that BMP9 treatment increased SMAD1/5/9 phosphorylation, a process hindered by HDAC6 knockdown, correlating with reduced ENG expression. Mechanistically, our study indicates that HDAC6 modulates ENG transcription by influencing promoter activity, leading to increased acetylation of transcription factor SP1 and consequently altering its transcriptional activity. Additionally, the study delves into the structural role of HDAC6, particularly its CD2 domain, in regulating SP1 acetylation and subsequently ENG expression. In conclusion, the present study underscores the critical function of HDAC6 in modulating SP1 acetylation and ENG expression, thereby significantly affecting BMP9-mediated angiogenesis. This finding highlights the potential of HDAC6 as a therapeutic target in angiogenesis-related processes.
Endothelial Cells , Growth Differentiation Factor 2 , Humans , Histone Deacetylase 6/metabolism , Growth Differentiation Factor 2/metabolism , Endoglin/metabolism , Phosphorylation , Endothelial Cells/metabolism , Angiogenesis , Proteomics , Transcription Factors/metabolism
