RESUMO
BACKGROUND: Cases of myelin oligodendrocyte glycoprotein (MOG) antibody-related disease have a history of coronavirus disease 2019 infection or its vaccination before disease onset. Severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection has been considered to be a trigger of central nervous system autoimmune diseases. CASE SUMMARY: Here we report a 20-year male with MOG-associated transverse myelitis after a SARS-CoV-2 infection. The patient received a near-complete recovery after standard immunological treatments. CONCLUSION: Attention should be paid to the evaluation of typical or atypical neurological symptoms that may be triggered by SARS-CoV-2 infection.
RESUMO
Natural plant-derived compounds with broad-spectrum antimicrobial activity have become an effective strategy against multidrug-resistant bacteria. The present study was designed to compare the antibacterial activity of six chlorogenic acid (CA) isomers extracted from stevia and investigated the underlying antibacterial mechanisms involved. The results indicated that isochlorogenic acid C (ICAC) exhibited the strongest antibacterial activity against the tested bacteria, especially E. coli, at a 2 mg/mL minimum inhibitory concentration (MIC) and 8 mg/mL minimum bactericidal concentration (MBC). At the MBC, ICAC inhibited 72.66% of the clinical multidrug-resistant strains. Scanning electron microscopy (SEM) revealed that ICAC induced considerable morphological alterations in E. coli ATCC25922 and C4E2. The significant increase in the activity of extracellular alkaline phosphatase (AKP) indicated that ICAC damages the permeability of the bacterial cell wall. Additionally, the intracellular membrane (IM) permeability and the content of lipopolysaccharide (LPS), a main component of the outer membrane (OM), were determined. The significant decrease in LPS content and increased leakage of intracellular proteins and K+ from E. coli indicated that ICAC could induce the exfoliation of OM and disrupt IM permeability, resulting in the loss of barrier function. The uptake of propidium iodide (PI), a compromised cell membrane nucleic acid stain, and confocal laser scanning microscopy (CLSM) further demonstrated that ICAC disrupted IM integrity. Moreover, the bactericidal effect and damage to bacterial microstructural function occurred in a dose-dependent manner. These data demonstrate that ICAC has excellent antibacterial activity and is a promising approach for overcoming the antibiotic resistance of pathogenic bacteria.
RESUMO
In this editorial, we comment on an article published in the recent issue of the World Journal of Gastroenterology. Celiac disease (CeD) is a disease occurring in genetically susceptible individuals, which is mainly characterized by gluten intolerance in the small intestine and clinical symptoms such as abdominal pain, diarrhea, and malnutrition. Therefore, patients often need a lifelong gluten-free diet, which greatly affects the quality of life and expenses of patients. The gold standard for diagnosis is intestinal mucosal biopsy, combined with serological and genetic tests. At present, the lack of safe, effective, and satisfactory drugs for CeD is mainly due to the complexity of its pathogenesis, and it is difficult to find a perfect target to solve the multi-level needs of patients. In this editorial, we mainly review the pathological mechanism of CeD and describe the current experimental and improved drugs for various pathological aspects.
Assuntos
Doença Celíaca , Dieta Livre de Glúten , Doença Celíaca/diagnóstico , Doença Celíaca/terapia , Doença Celíaca/fisiopatologia , Doença Celíaca/dietoterapia , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/fisiopatologia , Mucosa Intestinal/efeitos dos fármacos , Qualidade de Vida , Biópsia , Predisposição Genética para Doença , Intestino Delgado/fisiopatologia , Intestino Delgado/patologiaRESUMO
BACKGROUND: As part of stress-triggered molecules, immediate early response 3 (IER3) dysregulation has been reported to sustain pro-oncogenic pathways and precede malignant transformation. However, the role of IER3 in glioma pathology is ill-defined. METHODS: Immunohistochemistry (IHC) assay and publicly available glioma datasets were used to calculate the IER3 expression level in glioma. Wound healing, invasion and cell counting kit-8 (CCK8) assays were applied to measure the cell viability and capacities of migration and invasion of glioma cells in vitro. The immunofluorescence (IF) assay was used to assess the expression associations of IER3 with CCL2 and TGFBI. Cox regression analysis and Kaplan-Meier (K-M) curve were introduced to compute the prognosis-predicting value of IER3. Variations in copy number (CNVs), single nucleotide (SNVs), and methylation profiles were analyzed to illustrate the epigenetic modifications of IER3. Gliomas were divided into two subgroups using the restricted cubic spline (RCS) method. RESULTS IER3: was overexpressed and hypomethylated in gliomas and significantly associated with the dismal prognosis of glioma samples. Samples in the high IER3 subgroup were characterized by increased infiltration of tumor-associated monocytes/macrophages (TAMMs), as well as the elevated sensitivity to Dabrafenib, an inhibitor of BRAF. In addition, this subgroup demonstrated a low mutation rate of IDH, high gain rates of BRAF, ELTD1, and PDGFA. Gliomas with relatively low IER3 expression demonstrated a less invasive subtype and were featured by favorable prognosis, increased response to immunotherapy, and adjuvant chemotherapy plus radiotherapy. The IF assay revealed that IER3 was co-localized and co-expressed with TGFBI. The glioma cells with small interfering RNA (siRNA)-silenced IER3 displayed lower migration, invasion, proliferation, and cell viability than the control group. CONCLUSIONS: In this study, we identified IER3 upregulation as an essential biomarker that could assist in adjuvant therapy and prognosis prediction for gliomas.
RESUMO
BACKGROUND: Muscle atrophy is a typical affliction in patients affected by knee Osteoarthritis (KOA). This study aimed to examine the potential pathogenesis and biomarkers that coalesce to induce muscle atrophy, primarily through the utilization of bioinformatics analysis. METHODS: Two distinct public datasets of osteoarthritis and muscle atrophy (GSE82107 and GSE205431) were subjected to differential gene expression analysis and gene set enrichment analysis (GSEA) to probe for common differentially expressed genes (DEGs) and conduct transcription factor (TF) enrichment analysis from such genes. Venn diagrams were used to identify the target TF, followed by the construction of a protein-protein interaction (PPI) network of the common DEGs governed by the target TF. Hub genes were determined through the CytoHubba plug-in whilst their biological functions were assessed using GSEA analysis in the GTEx database. To validate the study, reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Flow Cytometry techniques were employed. RESULTS: A total of 138 common DEGs of osteoarthritis and muscle atrophy were identified, with 16 TFs exhibiting notable expression patterns in both datasets. Venn diagram analysis identified early growth response gene-1 (EGR1) as the target TF, enriched in critical pathways such as epithelial mesenchymal transition, tumor necrosis factor-alpha signaling NF-κB, and inflammatory response. PPI analysis revealed five hub genes, including EGR1, FOS, FOSB, KLF2, and JUNB. The reliability of EGR1 was confirmed by validation testing, corroborating bioinformatics analysis trends. CONCLUSIONS: EGR1, FOS, FOSB, KLF2, and JUNB are intricately involved in muscle atrophy development. High EGR1 expression directly regulated these hub genes, significantly influencing postoperative muscle atrophy progression in KOA patients.
Assuntos
Artroplastia do Joelho , Proteína 1 de Resposta de Crescimento Precoce , Atrofia Muscular , Osteoartrite do Joelho , Humanos , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/etiologia , Atrofia Muscular/genética , Atrofia Muscular/patologia , Artroplastia do Joelho/efeitos adversos , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/patologia , Masculino , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/genética , Complicações Pós-Operatórias/etiologia , Feminino , Mapas de Interação de Proteínas/genética , Biomarcadores/metabolismo , Expressão Gênica/genética , Biologia Computacional/métodosRESUMO
Triple-negative breast cancer (TNBC) is a prevalent malignancy in women, casting a formidable shadow on their well-being. Positioned within the nucleolus, SUMO-specific protease 3 (SENP3) assumes a pivotal role in the realms of development and tumorigenesis. However, the participation of SENP3 in TNBC remains a mystery. Here, we elucidate that SENP3 exerts inhibitory effects on migration and invasion capacities, as well as on the stem cell-like phenotype, within TNBC cells. Further experiments showed that YAP1 is the downstream target of SENP3, and SENP3 regulates tumorigenesis in a YAP1-dependent manner. YAP1 is found to be SUMOylated and SENP3 deconjugates SUMOylated YAP1 and promotes degradation mediated by the ubiquitin-proteasome system. More importantly, YAP1 with a mutation at the SUMOylation site impedes the capacity of wild-type YAP1 in TNBC tumorigenesis. Taken together, our findings firmly establish the pivotal role of SENP3 in the modulation of YAP1 deSUMOylation, unveiling novel mechanistic insight into the important role of SENP3 in the regulation of TNBC tumorigenesis in a YAP1-dependent manner.
RESUMO
In China's central heating, there are two modes for calculating heating costs, which are divided into Charging by flow mode which charges according to the amount of use and Charging by area mode which charges according to the floor area. The Charging by flow mode has been increasingly adopted by numerous urban central heating buildings. Thus it is worth investigating whether occupants experience varying levels of thermal comfort under these two modes. To address this, a field test and subjective questionnaire survey were conducted on residential buildings in cold regions of China during the heating season. The study assessed 134 residential occupants utilizing radiator heating, comprising 66 in Charging by area and 68 in Charging by flow modes. A collection of 1206 valid data points was obtained, with 609 in Charging by area mode and 597 in Charging by flow mode. The findings reveal noteworthy disparities in the duration, area, and strength of heating equipment usage between the two modes. While there are no marked variances in the interior and exterior environmental conditions under both modes, residents in the Charging by flow mode experience enhanced thermal comfort, acceptability and expectation, as well as better air quality satisfaction. Perceived control can greatly enhance individuals' thermal sensation in temperatures below 18 °C and above 24 °C. The impact of perceived control on thermal expectation is linear with temperature adjustments. The heightened degree of sensing control in Charging by flow mode lowers residents' expectations of high temperatures, broadens the range of acceptable low temperatures and accomplishes energy conservation and carbon reduction while ensuring optimal comfort.
RESUMO
OBJECTIVE: The incidence of degenerative diseases of the lumbar spine has increased in recent years. Unilateral pedicle screw combined with contralateral translaminar facet screw fixation offers the advantages of less trauma, better stability, and fewer complications. However, the surgical difficulty and suboptimal pinning accuracy of translaminar facet screw placement in clinical practice limit its use. Therefore, in this study, we designed a novel suspended 3D-printed navigation module to facilitate fast and accurate intraoperative screw placement. The aim of this study is to investigate the digital design, precise implementation, and evaluation methods for placing unilateral pedicle screws in the lumbar spine combined with translaminar facet screw placement using a new suspended 3D navigation module. METHODS: This retrospective study included 46 patients with single-level lumbar lesions who underwent spine surgery at the Affiliated Hospital of Putian University between June 2022 and December 2023. The suspended navigation module was designed digitally. Preoperative screw placement was simulated using 3D printed models, followed by an intraoperative accurate screw placement facilitated by the navigation module and a postoperative evaluation of the accuracy of screw placement. The absolute difference in three-dimensional coordinates of the inlet and outlet points of the preoperative design and the postoperative screw-nail channel served as the precision index. RESULTS: In a study involving 46 patients, surgery was successful with 92 pedicle screws and 46 translaminar facet screws placed without any penetration of the cortex. The difference in coordinates before and after screw insertion was minimal, with entry points varying between 1.21 to 1.36 mm and exit points between 1.97 to 2.46 mm. When screw accuracy met certain thresholds, there was no significant difference between preoperative design and postoperative coordinates, indicating precise replication of the surgical plan. CONCLUSION: The new suspended 3D navigation module enables the precise placement of unilateral pedicle screws in the lumbar spine combined with translaminar pedicle screws for precise surgery.
RESUMO
BACKGROUND AND PURPOSE: Psoriasis results from the interplay of innate and adaptive immunity in the skin. Oroxylin A (OA) has shown anti-inflammatory effects in various disorders. This study explores oroxylin A potential in treating psoriasis, particularly its impact on type I macrophage (Mφ1) polarization. EXPERIMENTAL APPROACH: Oroxylin A-mediated therapeutic effects were evaluated using imiquimod-induced or IL-23-injected psoriatic mice models, followed by proteomics assays to predict potential signalling and targeting proteins. Immunofluorescence and immunoblot assays verified that oroxylin A suppresses NF-kB signalling in M1 macrophages. Co-immunoprecipitation and microscale thermophoresis (MST) assays further demonstrated that p62 (sequestosome 1) is the target protein for oroxylin A in macrophages. Oroxylin A-p62-mediated suppression of psoriasis was validated in an imiquimod-induced p62 conditional knockout (cKO) mice model. KEY RESULTS: Oroxylin A demonstrated therapeutic efficacy in murine models induced by imiquimod or IL-23 by attenuating cutaneous inflammation and mitigating Mφ1 polarization via NF-κB signalling. Proteomics analysis suggested SQSTM1/p62 as a key target, confirmed to interact directly with oroxylin A. Oroxylin A disrupted the p62-PKCζ interaction by binding to PB1 domain of p62. Its anti-inflammatory effects were significantly reduced in macrophages from p62 cKO mice compared to the wild-type (WT) mice in psoriasis model, supporting oroxylin A role in suppressing Mφ1 polarization through its interaction with p62. CONCLUSION AND IMPLICATIONS: Our findings demonstrated oroxylin A suppressed psoriasiform skin inflammation in mouse models by blocking the PKCζ-p62 interaction, subsequently inhibiting the activation of NF-κB p65 phosphorylation in macrophages.
RESUMO
Herein, a novel ionic hydrogen-bonded organic framework (iHOF-12) was synthesized. The 5-fold interpenetrating network structure and charge-assisted synergistic effects enable iHOF-12 to maintain robustness under demanding conditions and attain excellent proton conductivity of 1.23 × 10-2 S cm-1, which contributes to the enhancement of the DMFC performance.
RESUMO
Hydrogen-bonded organic frameworks (HOFs) are crystalline materials assembled by intermolecular hydrogen-bonding interactions, and their hydrogen-bonding structures are effective pathways for proton transport. Herein, we synthesize iHOF-45 using 4,4'-diaminodiphenylmethane and 1,3,6,8-pyrenetetrasulfonicacid sodium salt with 2D hydrogen-bonding networks. The introduction of ionic bond based on the weak hydrogen-bonding force was employed to enhance the stability of ionic HOFs (iHOFs). Thermal analyses demonstrated that iHOF-45 exhibited excellent thermal stability up to 332 °C. The proton conductivity of iHOF-45 was evaluated, demonstrating a notable increase with rising temperature and RH. At 100 °C and 98% RH, the conductivity reached 5.25 × 10-3 S cm-1. The activation energy (Ea) of iHOF-45 was calculated to be 0.281 eV for 98% RH, and the proton conduction was attributed to the Grotthuss mechanism, whereby the protons were transported in 2D hydrogen-bonding networks. Moreover, iHOF-45 was doped into SPEEK to prepare composite membranes, the proton conductivity of the 15%-iHOF-45/SPEEK membrane reached 9.52 × 10-2 S cm-1 at 80 °C and 98% RH, representing a 45.1% increase over that of the SPEEK. This suggests that doping enhances the proton conductivity of SPEEK and providing a reference for the development of high proton conductivity materials.
RESUMO
Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our prior investigations disclosed a correlation between p53 downregulation in CD4+ T cells and the occurrence of aGVHD. Notably, the insufficiency of the CCCTC-binding factor (CTCF) emerged as a pivotal factor in repressing p53 expression. However, the existence of additional mechanisms contributing to the reduction in p53 expression remains unclear. Interferon (IFN)-γ, a pivotal proinflammatory cytokine, assumes a crucial role in regulating alloreactive T cell responses and plays a complex part in aGVHD development. IFN-γ has the capacity to induce autophagy, a vital catabolic process facilitating protein degradation, in various cell types. Presently, whether IFN-γ participates in the development of aGVHD by instigating the autophagic degradation of p53 in CD4+ T cells remains an unresolved question. In this study, we demonstrated that heightened levels of IFN-γ in the plasma during aGVHD promoted the activation, proliferation, and autophagic activity of CD4+ T cells. Furthermore, IFN-γ induced the nuclear-to-cytoplasm translocation and autophagy-dependent degradation of p53 in CD4+ T cells. The translocation and autophagic degradation of p53 were contingent upon HMGB1, which underwent upregulation and translocation from the nucleus to the cytoplasm following IFN-γ stimulation. In conclusion, our data unveil a novel mechanism underlying p53 deficiency in CD4+ T cells among aGVHD patients. This deficiency is induced by IFN-γ and relies on autophagy, establishing a link between IFN-γ, HMGB1-mediated translocation, and the autophagic degradation of p53.
RESUMO
Conventional all-starch-based (ASB) gels are weak and lack ductility. The preparation of a robust ASB gel with multi-functionalities e.g., self-healing, anti-freezing, conductivity, and so forth, is highly desirable but challenging. Herein, a new kind of ASB gel was prepared by gelatinizing starch in urea and choline chloride solution (UC) with the aid of water. Its tensile strength was up to 1.08 MPa with a tensile strain of 313 %, and this value hardly changed after 10 days ageing. A high healing efficiency of 98 % can be achieved after 1 h of healing at room temperature, and the healed tensile strength reaches up to ca. 1.06 MPa, which is almost the highest value for ASB gel. The resultant ASB gel can surfer from bending and twisting at -80 °C. Moreover, ASB gel also exhibits excellent biocompatibility and biodegradability. In addition, UC endowed the ASB gel with ion conductivity, allowing it to be used as a flexible strain sensor to monitor human movement. The ion-conductive ASB gel also exhibited thermoelectric ability with a Seebeck coefficient of 2.5 mV K-1, which can be further improved to 5 mV K-1 with a maximum output voltage of 252 mV by introducing a gradient of ionic concentration.
RESUMO
OBJECTIVES: The selection of treatment for dental plaque is closely related to the condition of the plaque on different teeth. This study validated the ability of CNN models in assessing the dental plaque indices. MATERIALS AND METHODS: In 70 (20 male and 50 female) healthy adults (18 to 55 years old), frontal and lateral view intraoral images (210) of plaque disclosing agent stained permanent and deciduous dentitions were obtained. A three-stage method was employed, where the You Look Only Once version 8 (YOLOv8) model was first used to detect the target teeth, followed by the prompt-based Segment Anything Model (SAM) segmentation algorithm to segment teeth. A new single-tooth dataset consisting of 1400 photographs was obtained after applying a two-stage method. Finally, a multi-class classification model DeepPlaq was trained and evaluated on the accuracy of dental plaque indexing based on the Quigley-Hein Index (QHI) scoring system. Classification performance was measured using accuracy, recall, precision, and F1-score. RESULTS: The teeth detector exhibited an accuracy (mean average precision, mAP) of approximately 0.941 ± 0.005 in identifying teeth with plaque disclosing agents. The maximum accuracy attained in the plaque indexing through DeepPlaq was 0.84 (probability that DeepPlaq scored identical to experts), and the smallest average scoring error was less than 0.25 on a 0 to 5 scale for scoring. CONCLUSIONS: A three-stage approach demonstrated excellent performance in detecting and segmenting target teeth, and DeepPlaq model also showed strong performance in assessing dental plaque indices. CLINICAL RELEVANCE: Application of artificial intelligence to the evaluation of dental plaque distribution could enhance diagnostic accuracy and treatment efficiency and accuracy.
Assuntos
Índice de Placa Dentária , Redes Neurais de Computação , Humanos , Feminino , Masculino , Adulto , Adolescente , Pessoa de Meia-Idade , Placa Dentária , Algoritmos , Fotografia Dentária/métodosRESUMO
Five undescribed lignans (1-5), along with sixteen known lignans (6-21), were isolated from the roots of Anthriscus sylvestris using small molecule accurate recognition technology (SMART). The structures of the isolated compounds were determined by comprehensive spectroscopic analyses, and the absolute configurations of compounds 3-5 were elucidated by comparison of their calculated and experimental ECD spectra. Compounds 5, 14-15, 19, and 21 exhibited significantly inhibitory effects against hypoxia-stimulated abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs). Moreover, compounds 5, 14-15, 19, and 21 can significantly restore expression of expression of PASMCs proliferation-related protein, including α-SMA, PCNA, P27, and CyclinD3, which are closely related to cell proliferation.
RESUMO
Although hydrogen production through seawater electrolysis combined with offshore renewable energy can significantly reduce the cost, the corrosive anions in seawater strictly limit the commercialization of direct seawater electrolysis technology. Here, it is discovered that electrolytic anode can be uniformly protected in a seawater environment by constructing NiFeBa-LDH catalyst assisted with additional SO4 2- in the electrolyte. In experiments, the NiFeBa-LDH achieves unprecedented stability over 10 000 h at 400 mA cm-2 in both alkaline saline electrolyte and alkaline seawater. Characterizations and simulations reveal that the atomically dispersed Ba2+ enables the chemical fixation of free SO4 2- on the surface, which generates a dense SO4 2- layer to repel Cl- along with the preferentially adsorbed SO4 2- in the presence of an applied electric field. In terms of the simplicity and effectiveness of catalyst design, it is confident that it can be a beacon for the commercialization of seawater electrolysis technology.
RESUMO
BACKGROUND: Fever is a common side effect following thermal ablation in patients with hepatocellular carcinoma (HCC), yet its impact on prognosis remains unclear. MATERIALS AND METHODS: This retrospective study included initial HCC patients who underwent US-guided percutaneous microwave ablation at 13 hospitals between January 2006 and February 2021. All patients were categorized into afebrile, transient low-grade fever (TLF), and prolonged or high-grade fever (PHF) groups. Primary outcomes included very early recurrence (VER) and early recurrence (ER), secondary outcomes were disease-free survival (DFS) and overall survival (OS). Fever cut-offs for VER/ER were established using restrictive cubic splines and adjusted Cox model. Survival analyses used the Kaplan-Meier method. RESULTS: A total of 1458 initial HCC patients (mean age, 59±11[SD]; 1146 men). Compared to afebrile individuals, patients with TLF (temperatures ranging 37.0-38.8°C for 1-2 d), showed independent protective effects against VER (HR, 0.73; 95% CI: 0.57,0.95; P=0.02) and ER (HR, 0.66; 95% CI: 0.54,0.81; P<0.001), however, PHF showed no differences in VER (HR, 0.99; 95% CI: 0.76,1.30; P=0.96) and ER (HR, 0.86; 95% CI: 0.69,1.07; P=0.17). With a median follow-up of 47 months (IQR:26-79), the median DFS for TLF patients was 40 months, superior to afebrile (30 mo, P=0.019) and PHF patients (33 mo, P=0.049). The 5-year OS rate for TLF patients was 73.2%, higher than afebrile (69.3%, P=0.02) and PHF patients (66.7%, P=0.03). No significant difference was found in DFS and OS between afebrile and PHF patients (P=0.90 and 0.71). Notably, TLF patients exhibited the highest lymphocyte counts increasing median 7 days after ablation (P<0.001 vs. afebrile and P=0.01 vs. PHF). CONCLUSION: Transient low-grade fever following percutaneous microwave ablation in hepatocellular carcinoma patients demonstrated protection against early recurrence, possibly attributed to the short-term activation of lymphocytes.
RESUMO
Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD.
RESUMO
BACKGROUND: Nonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM. METHODS: We utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions. RESULTS: MR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670-0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199-1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain. CONCLUSION: Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication.