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Among individuals diagnosed with type 2 diabetes mellitus (T2DM), an abnormal accumulation of visceral fat heightens the cardiovascular risk (CVR), and the major reason for death for these people is atherosclerotic cardiovascular disease (ASCVD). This study aimed to gain further insights into the longitudinal relationship between CVR and visceral fat area (VFA) in patients with T2DM, and to compare the predictive performance of additional abdominal obesity measures and VFA for changes in CVR. This prospective cohort study included 316 patients with T2DM who were followed up for more than one year, and VFA was measured by the bioimpedance method. This study investigated the prospective association between a VFA percentage change (∆VFA, %) and CVR, and evaluated the potential nonlinear relationships between ∆VFA (%) and the increase 10-year ASCVD risk. Furthermore, the area under the pooled curve (AUC) was contrasted for both ∆VFA (%) and other abdominal obesity indices. The excessive VFA loss group showed lower low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), triglyceride-glucose index, LDL-C/HDL-C, brachial-ankle pulse wave velocity, 10-year ASCVD risk, atherogenic index of plasma, TC/HDL-C, and apolipoproteins B/apolipoproteins A-1 than the VFA gain group (all β [Formula: see text] 0, HR [Formula: see text] 1, all P [Formula: see text] 0.05) after covariate controlling. VFA reduction of more than 14.82% led to a reduction in the stated risk. Moreover, ∆VFA (%) demonstrated superior predictive value for changes in ASCVD risk, with an AUC of 0.585 (95% CI: 0.513-0.656), compared to other obesity indices. Excessive VFA reduction improved 10-year ASCVD risk in patients diagnosed with T2DM. VFA was a more effective predictor of 10-year ASCVD risk changes than other abdominal obesity measures. This investigation has been registered with the Chinese Clinical Trial Registry (ChiCTR2400086569). Show less

Lifestyle improvement may help reverse prediabetes. Indicators such as Life's Essential 8 (LE8) and biological aging measures (phenotypic age, cardiovascular biological age) partially reflect metabolic status in prediabetes, but their predictive value for cardiovascular mortality and stroke in this population remains unclear. We analyzed data from 74,678 White participants with prediabetes in the UK Biobank, defined by either HbA1c (5.7-6.4%) or fasting glucose (6.1-6.9 mmol/L). Follow-up continued until October 10, 2023. Cox regression was used to examine associations between LE8, phenotypic age (PhenoAge), cardiovascular biological age (CBA), and outcomes of cardiovascular (CVD) mortality and stroke. Restricted cubic spline (RCS) models identified biological age risk thresholds. Mediation analysis assessed whether proteins such as CST3, EFEMP1, FES, IGFBP2, IGFBP6, LPA, PCSK9, and TIMP1 mediated these effects. Over a median follow-up of 13.4 years, 2263 participants died from CVD causes. Each 1-year increase in CBA or PhenoAge was associated with a ~ 10% higher risk of CVD mortality (CBA aHR = 1.10; PhenoAge aHR = 1.09; both P < 0.001), while each 1-point increase in LE8 score was linked to a 3% lower risk (HR = 0.97, P < 0.001). The risk biological ages for these two indicators were also identified: PhenoAge ≥ 58.52 years and CBA ≥ 62.42 years. Similar trends were observed for stroke. Mediation analysis revealed that CST3, TIMP1, IGFBP2, and IGFBP6 contributed to the biological pathways between aging/lifestyle and CVD outcomes. The combined LE8 and PhenoAge model showed the strongest predictive performance for CVD mortality (AUC = 0.716) and stroke (AUC = 0.638) over 15 years. LE8 combined with phenotypic age provides prognostic value for CVD outcomes in prediabetes. These findings highlight the potential of lifestyle modification and delayed biological aging in reversing prediabetes and underscore comorbidity-related proteins as promising therapeutic targets. Show less

The number of prognostic and predictive factors for pancreatic ductal adenocarcinoma (PDAC) is limited. Fibroblast growth factor receptors (FGFRs) are emerging as potential therapeutic targets, especially in cases with FGFR2 gene fusions. However, the prognostic relevance of FGFR1, FGFR2, and FGFR4 protein expression in PDAC remains unclear. Immunohistochemical analysis of FGFR1, FGFR2, and FGFR4 was performed on 99 PDAC and 60 adjacent normal pancreatic tissue samples. Protein expression was quantified using the H-score method and correlated with clinicopathological variables and survival. Publicly available datasets from the GEO repository and the cancer genome atlas (TCGA) were used for pathway enrichment analysis and validation of findings at the mRNA level. FGFR2 and FGFR4 showed differential expression between tumor and normal tissues, while FGFR1 did not. High FGFR4 protein expression was significantly associated with shorter disease-free survival (DFS) in both univariable and multivariable analyses. FGFR2 high expression cases showed a trend towards poor DFS, while FGFR1 had no prognostic impact. In silico analysis confirmed that high FGFR4 mRNA levels are associated with worse DFS. Co-expression and enrichment analysis linked FGFR4 overexpression with developmental, metabolic, and stemness-related processes. FGFR4 showed the strongest prognostic association among the FGFR family members studied, with high protein expression correlating with shorter disease-free survival in PDAC patients. These findings underscore the potential of FGFR4 as a biomarker for recurrence risk, while also highlighting the complexity of FGFR-related signaling and its context-dependent clinical relevance. Show less

Elevated levels of triglycerides in the bloodstream, a condition known as hypertriglyceridemia, represent a significant risk factor for the development of metabolic disorders and cardiovascular diseases. One key regulator of lipid metabolism is the transcription factor cAMP-responsive element-binding protein 3-like 3 (CREB3L3), which is expressed in the liver, intestine, and adipose tissue. CREB3L3 is localized to the endoplasmic reticulum membrane, and in vertebrates plays a crucial role in plasma lipid homeostasis. However, the precise molecular mechanisms underlying Creb3l3's influence on cellular lipid metabolism remains undefined. To address this knowledge gap, we generated zebrafish mutants lacking both creb3l3 orthologs (creb3l3a and creb3l3b). Gene expression analysis revealed that key creb3l3 target genes, such as apoC2 and apoA4, were significantly downregulated in the intestines of these double mutants. Using two zebrafish lipoprotein reporter lines, we assessed lipoprotein dynamics in creb3l3 mutants. Despite producing similar total levels of lipoproteins, creb3l3 mutants exhibited impaired lipoprotein turnover, suggesting a disruption in circulating lipid clearance. Additionally, histological analysis showed an accumulation of intestinal lipids, characterized by an increased number and size of enterocyte lipid droplets. These findings indicate that creb3l3 is essential for regulating postprandial lipid flux in enterocytes through altering the balance between lipid storage and secretion. Our study highlights a critical, unappreciated role of Creb3l3 in maintaining intestinal lipid homeostasis. Show less

Increased hepatic triacylglycerol (TG) storage in lipid droplets (LDs) is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Human carboxylesterase 1 (CES1) regulates TG storage and secretion in hepatocytes, but the mechanism remains to be elucidated. We performed studies in rat hepatoma McArdle RH7777 cells stably transfected with CES1 cDNA and in Ces1d-deficient mice using a variety of biochemical, pharmacological and cell biology approaches including the assessment of gene expression, confocal immunofluorescence microscopy, lipid synthesis measurements and quantitative mass spectrometry. CES1-expressing cells accrued more TG compared to cells lacking CES1 when incubated with oleic acid. CES1 increased the expression of Show less

Chronic lymphocytic leukemia (CLL) is characterized by malignant B lymphocyte accumulation and progressive immune dysfunction. The immune checkpoint molecule TIM-3 and its ligand galectin-9 (Gal-9) contribute to T cell exhaustion, impairing anti-tumour immunity. Interleukin-27 (IL-27) has pleiotropic immunomodulatory properties, but its impact on TIM-3 and Gal-9 expression in CLL remains unclear. Peripheral blood mononuclear cells (PBMCs) from 20 treatment-naive CLL patients were cultured with or without IL-27 (100 ng/mL) for 72 h. Flow cytometry assessed TIM-3 and Gal-9 expression on CD4 IL-27 stimulation significantly increased TIM-3 expression on CD8 IL-27 may enhance immunosuppressive mechanisms in CLL by modulating immune checkpoint expression, potentially contributing to disease progression. These ex vivo findings in PBMCs from CLL patients indicate the IL-27-associated modulation of checkpoint expression under the conditions tested. In the absence of parallel healthy-donor controls, CLL specificity cannot be established in this study. Show less

Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous subtype of breast cancer. miRNAs play an essential role in TNBC pathogenesis and prognosis. Obesity is linked with an increased risk for several cancers, including breast cancer. Obesity is also related to the dysregulation of miRNA expression in adipose tissues. However, there is limited knowledge about race- and obesity-specific differential miRNA expression in TNBC. We performed miRNA sequencing of 48 samples (24 tumor and 24 adjacent non-tumor tissues) and RNA sequencing of 24 tumors samples from Black (AA) and White (EA) TNBC patients with or without obesity. We identified 55 miRNAs exclusively associated with tumors in obese EA patients and 33 miRNAs in obese AA patients, each capable of distinguishing tumor tissues from obese from lean individuals within their respective racial groups. In EA, we detected 41 significant miRNA-mRNA correlations. Notably, miR-181b-5p and miR-877-5p acted as negative regulators of tumor-suppressor genes (e.g., Show less

Recent research suggests that the ketogenic diet (KD) has the potential to serve as an effective treatment option for neuropsychiatric disorders, targeting both dysfunctions in brain metabolism and cardiometabolic comorbidities. In many patients, KDs may ameliorate comorbidities such as obesity, metabolic syndrome and type 2 diabetes. However, the long-term effects of KDs on cardiovascular health remain an important topic of investigation, due to considerable inter-individual variability in how KDs may impact lipid metabolism. While some studies have shown no significant change in cholesterol levels, and some have shown improvements, still others have highlighted the potential of KDs to induce or exacerbate hyperlipidemia. To shed new light on this ongoing controversy, we present both beneficial and concerning effects of a 3-month intervention with Ketogenic Metabolic Therapy (KMT) (1.5:1 ratio) on a wide range of cardiometabolic health markers in seven outpatients with bipolar disorder and comorbid dyslipidemia. Cardiometabolic assessments were based on markers of lipoprotein burden, such as apolipoprotein B (apoB), lipoprotein (a) (Lp(a)), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and total cholesterol (TC), markers of inflammation, such high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor (TNF-α), markers of oxidative stress, such as malondialdehyde-modified LDL (MDA-LDL) and nitrotyrosine, molecules that relate to endothelial function, such as homocysteine and advanced glycation end products (AGE), and anthropometric measures, such as BMI and fat mass. Mean changes between pre-KMT and post-KMT measurements were calculated. In addition, within-person changes in outcomes of interest were visually summarized using boxplots. Beneficial cardiometabolic effects included a decrease in mean Lp(a) of 6.6 mg/dl (-21%), a reduction in mean triglyceride of 40.6 mg/dl (-30%), a reduction in mean apoB of 0.14 g/L (-10,5%) and an increase in mean HDL-C of 3 mg/dL (+5%), a reduction in mean hsCRP of 0.94 mg/L (-45%), a reduction in mean TNF-α of 1.31 pg/ml (-7%), a reduction in mean MDA-LDL of 36.77 U/L (-38%), a reduction in mean nitrotyrosine of 225 nmol/L (-28%), a mean weight reduction of 4 kg (-4,6%), a mean visceral fat reduction of 0.69% (-10%) and a mean fat mass reduction of 3.7 kg (-12%). However, some concerning effects were also observed. Of note, mean homocysteine levels increased by 1.94 umol/L (+18%) and mean AGE levels increased by 30.9 ug/ml (+106%). Moreover, mean LDL-C was increased by 14 mg/dl (+9%) and mean total cholesterol was increased by 7 mg/dl (+3%). Based on these findings, it is concluded that comprehensive Ketogenic Metabolic Therapy provided to outpatients with bipolar disorder can be beneficial in improving a broad range of cardiometabolic health markers, including lipid metabolism, inflammation, oxidative stress and anthropometric measures. Tentatively, these findings suggest that at least a proportion of patients with bipolar disorder may find remarkable improvements in cardiometabolic health adopting a metabolic treatment such as the ketogenic diet. However, potentially concerning effects on markers such as homocysteine and AGE call for well-formulated, individualized KDs. Show less

Extreme hypertriglyceridemia, defined as triglyceride (TG) levels ≥1000 mg/dL, is almost always indicative of chylomicronemia. The current diagnostic approach categorizes individuals with chylomicronemia into familial chylomicronemia syndrome (FCS; prevalence 1-10 per million), caused by the biallelic combination of pathogenic variants that impair the lipolytic action of lipoprotein lipase (LPL), or multifactorial chylomicronemia syndrome (MCS, 1 in 500). A pragmatic framework should emphasize the severity of the phenotype and the risk of complications. Therefore, we endorse the term "persistent chylomicronemia" defined as TG ≥1000 mg/dL in more than half of the measurements to encompass patients with the highest risk for pancreatitis, regardless of their genetic predisposition. We suggest classification of PC into four subtypes: 1) genetic FCS, 2) clinical FCS, 3) PC with "alarm" features, and 4) PC without alarm features. Although patients with FCS most likely have PC, the vast majority with PC do not have genetic FCS. Proposed alarm features are: (a) history of recurrent TG-induced acute pancreatitis, (b) recurrent hospitalizations for severe abdominal pain without another identified cause, (c) childhood pancreatitis, (d) family history of TG-induced pancreatitis, and/or (e) post-heparin LPL activity <20 % of normal value. Alarm features constitute the strongest risk factors for future acute pancreatitis risk. Patients with PC and alarm features have very high risk of pancreatitis, comparable to that in patients with FCS. Effective, innovative treatments for PC, like apoC-III inhibitors, have been developed. Combined with lifestyle modifications, these agents markedly lower TG levels and risk of pancreatitis in the very-high-risk groups, irrespective of the monogenic etiology. Pragmatic definitions, education, and focus on patients with PC specifically those with alarm features could help mitigate the risk of acute pancreatitis and other complications. Show less

The magnitude of weight reduction in the SURMOUNT-1 trial of the dual GLP-1 and GIP receptor agonist tirzepatide suggests that this treatment may be particularly effective in addressing the treatment needs of people with severe obesity (body mass index >40 kg m Show less

Beef quality is critically determined by intramuscular fat (IMF) deposition. Retinoic acid (RA), the active metabolite of vitamin A, plays an essential regulatory role in IMF development. To systematically investigate RA-mediated regulation of IMF formation in cattle, we established a concentration gradient of RA supplementation and employed a systematic screening approach to identify the optimal dosage for modulating bovine intramuscular adipocytes (IMAs) proliferation and differentiation. Subsequently, leveraging integrated multi-omics approaches, we screened the key downstream molecular targets through which RA governs IMF biosynthesis, and clarified the potential regulatory mechanism of this target. Our experimental data establish that RA promotes the proliferation of IMAs through modulation of G1/S phase progression. Concurrently, RA enhances triglyceride biosynthesis in IMAs by activating PPARγ-mediated cell differentiation and LPL-mediated intracellular lipid accumulation. Integrated transcriptomics and metabonomics analyses identified FABP4, CD36, EBF2, LRP1 and CAV1 as key candidate genes involved in RA-mediated IMF production. Functional interrogation revealed that FABP4 knockdown markedly attenuated lipid accumulation in IMAs, a phenotype rescued through RA supplementation, confirming FABP4 as the critical effector mediating vitamin A's regulation of bovine IMF deposition. These results provide a new understanding of how nutritional factors affect beef quality at the molecular level. Show less

Ectopic fat deposition refers to lipid accumulation that affects metabolic function and tissue characteristics. Japanese Black cattle are distinguished by their high intramuscular fat content, which contributes to their distinctive character. However, the genetic mechanisms underlying these traits remain unclear. This study compared gene expression patterns in different muscle regions to identify genes associated with intramuscular fat accumulation. First, we conducted RNA sequencing to analyze differences in gene expression profiles among the sternocleidomastoid, pectoralis minor, and pectoralis major muscles. In addition, single-cell nuclear RNA sequencing was conducted to investigate the cellular composition of these muscle tissues. Distinct gene expression patterns were observed among the different muscles. In the pectoralis, which contains a high proportion of intramuscular fat, adipocyte-related genes such as This study provides novel insight into the genetic regulation of intramuscular fat accumulation. It improves our understanding of the molecular mechanisms underlying their distinctive meat characteristics. Show less

Methylation of CpG islands plays a crucial role in the regulation of gene expression. The study of DNA methylation profiles offers deep insights into key oncogenic processes and facilitates the differentiation of tumor entities at the epigenetic level. Methylation profiling was performed on 8 CNS tumors (6 children, 1 adolescent, 1 young adult) with inconclusive diagnoses, available frozen tissue, and surgeries dating back over 5 years. Our goal was to correlate the resulting methylation classes with the clinical-radiological data and to evaluate the diagnostic and prognostic power of this analysis. The resulting molecularly defined diagnoses were: pilocytic astrocytoma (3 cases), pilocytic astrocytoma subclass Show less

The proportion of mutations that are dominant is a fundamental genetic parameter affecting the rate of adaptation, the efficacy of selection, and the maintenance of variation in populations. Yet, estimates for this parameter vary greatly. Here we directly quantify the rates and genetic targets of dominant and recessive mutations in the yeast mating pathway by performing parallel genetic screens in haploid ( Show less

This study aimed to explore the career adaptability status of cardiovascular specialist nurses (CSNs) through latent profile analysis (LPA), identify distinct subgroups and their demographic features, and determine factors influencing different adaptability categories. CSNs play a vital role in treating and rehabilitating patients with cardiovascular conditions. However, the existing literature offers limited insights into the career adaptability of CSNs in China. A multicenter, cross-sectional survey involving 659 Chinese CSNs was conducted. LPA was utilized to classify career adaptability profiles based on responses to the Career Adaptation Abilities Scale Short Form (CAAS-SF). Influencing factors were assessed using the Conditions of Work Effectiveness Questionnaire-II (CWEQ-II) and the General Self-Efficacy Scale (GSES). Differences among identified profiles were analyzed through ANOVA, chi-square tests, and multinomial logistic regression to explore relevant socio-demographic characteristics and influencing variables. A four-profile model provided the best fit, identifying groups labeled as “high adaptability” (Class 4, These findings provide evidence to assist nursing administrators in developing training programs to enhance CSNs’ career adaptability. The variables identified as associated with profile membership may enable more tailored training strategies. Show less

Our previous investigations identified miR-30a-3p as a differentially expressed miRNA in ovine mammary tissue across sheep breeds with distinct lactation performance and different physiological stages. However, its regulatory mechanisms controlling mammary gland development and lactation remain unexplored. In this study, the effect of miR-30a-3p on the proliferation of ovine mammary epithelial cells (MECs) and the target genes of miR-30a-3p were investigated. The regulatory effects of miR-30a-3p on the expression of the target genes and the content of triglycerides in ovine MECs were also analyzed. The transfection of miR-30a-3p mimic was found to promote cell viability and the number of proliferated ovine MECs using CCK8 and Edu assays. On the contrary, the miR-30a-3p inhibitor showed the opposite results with the miR-30a-3p mimic. These results suggest that miR-30a-3p promotes the proliferation of ovine MECs. The dual luciferase assay revealed that Phosphatase and Tensin Homolog ( Show less

Neural epidermal growth factor-like protein 1 (NELL-1) and the exostosin 1/2 complex (EXT1/2) are recently identified target antigens in membranous nephropathy (MN), yet their prevalence and clinical features in Chinese populations remain poorly characterized. This study enrolled 197 consecutive patients with biopsy-proven MN, including 186 with idiopathic membranous nephropathy (IMN) and 11 with secondary membranous nephropathy (SMN). Serum levels of NELL-1 and EXT1/2 antigens were detected Show less

Speech impairment is a recognized but unpredictable adverse effect of sub-thalamic nucleus deep brain stimulation (STN-DBS) for Parkinson's disease (PD). To evaluate the prevalence of speech impairment 1 year after STN-DBS in PD patients and to determine the predictive factors for speech outcome following STN-DBS. Data for 417 patients from the French national PREDISTIM study were collected preoperatively. The combined effect of medical treatment and surgery on speech was compared using specific items from dedicated clinical scales (MDS-UPDRS III.1: primary endpoint) and patient self-assessment questionnaires (items 34 and 35 of the PDQ39: secondary endpoints). For each variable, three patient groups were generated according to speech outcome at 1 year: worsening, stability, and improvement. In the second step analysis, the three groups were compared for demographic and clinical variables at baseline and STN-DBS parameters. There was a significant deterioration in speech of all considered items 1 year after combined STN-DBS and dopaminergic treatment. Four predictive factors for speech deterioration were detected: (i) the absence of preoperative speech impairment (p < 0.001); (ii) severity of motor activity of daily living (MDS-UPDRS II off total score) (p = 0.037); (iii) high-intensity stimulation of the left electrode (i.e., above 3.6 V) (p = 0.046); and (iv) the absence of any change in non-motor experiences of daily life (MDS-UPDRS I total score) (p = 0.048). Speech outcome should be carefully monitored after STN-DBS, especially in PD patients without preoperative speech impairment, with motor difficulties in daily-living activities, and with increased left electrode intensity. ClinicalTrials.gov identifier: NCT02360683. Show less

Alzheimer's and Parkinson's disease are the most prevalent neurological diseases. Amyloid-β, tau, and α-synuclein proteins are known to be implicated in neurodegenerative disease (NDD). Elucidation of precise therapeutic targets remains a challenge. Therefore, the identification of interactomes of amyloid-β precursor protein (APP), microtubule-associated protein tau (MAPT), and α-synuclein (SNCA) proteins is of great interest, aimed at unraveling novel targets. An integrated analysis was employed to identify direct interactors as therapeutic targets, considering protein-protein interactions and subsequent network analysis. Further, it was proposed to identify hub proteins, intended targets, regulatory factors, disease-gene associations, functional enrichment analyses of the protein interactors interfered with gene ontologies and disease-driving pathways. Protein interactome centered on APP, MAPT, and SNCA identified the top hundred high-confidence protein-protein interactions that revealed BACE1, PSEN1, SORL1, GSK3B, CDK5, SNCAIP, PRKN, and APOE as physical and functional protein interactors. The top ten hub proteins were ranked based on multiple centrality measures and topological algorithms. Further, the integrated network of all three protein interactomes contained distinct nodes with edges. Interestingly, regulatory mechanisms have revealed possible regulatory modules, including cleavage, phosphorylation, and ubiquitination. Top interacting proteins were enriched in several ontology terms, such as regulation of neuronal apoptotic processes, amyloid beta fibril formation, and tau protein binding. Pathway analysis mapped the pathways of neurodegeneration-multiple disease, with a significant level of interacting proteins. Finally, the most comprehensive interactome associated with NDD provides insights into protein interactors, regulating the mechanisms of key proteins that can serve as novel therapeutic targets. Show less

Juvenile neuronal ceroid lipofuscinosis (JNCL) is a neurodegenerative lysosomal storage disease caused by the loss of the endolysosomal transmembrane protein, CLN3. The main protein component of lysosomal storage material in JNCL is subunit c of mitochondrial ATP synthase (SCMAS), which is normally degraded within the lysosome by tripeptidyl-peptidase 1 (TPP1) during mitophagy. Previous studies have shown that TPP1 expression is elevated in JNCL, a potential compensatory response, while reduced levels of TPP1 exacerbate disease in a JNCL mouse model. These observations suggest a role for TPP1 in JNCL pathogenesis, and it is possible that lysosomal perturbations from the loss of CLN3 in JNCL could reduce the ability of TPP1 to degrade SCMAS. To test this hypothesis, we introduced a transgene that overexpresses TPP1 in a mouse model of JNCL and find that constitutively elevated TPP1 prevents SCMAS storage. This is associated with correction or significant reduction of other phenotypes of disease including neuroinflammation, an elevated plasma biomarker of neurodegeneration, and a disease-associated loss of brain mass with aging. From a clinical perspective, these results suggest that TPP1 augmentation could be a viable therapeutic strategy for JNCL and other lysosomal diseases that accumulate SCMAS where addressing the primary defect may be difficult or impossible. Show less

(1) Background: the epigenetic mechanisms underlying the progression from acute kidney injury (AKI) to chronic kidney disease (CKD) remain poorly understood; (2) Methods: to investigate this process, we conducted genome-wide DNA methylation sequencing to map the epigenetic changes during the AKI-CKD transition in a mouse model. By integrating DNA methylome and transcriptome analyses, we identified genes and signaling pathways regulated by DNA methylation throughout this progression; (3) Results: our analysis identified four candidate genes- Show less

An emerging approach in surgery is to propose prehabilitation programs to strengthen the patient's functional abilities before surgical interventions, thus helping them cope better with its consequences. In drug-resistant language-dominant temporal lobe epilepsy (LdTLE), surgical treatment carries a risk of increasing cognitive deficits, notably word-finding difficulties (anomia) and verbal memory difficulties that negatively impact personal, social, and occupational activities. In this study, we invited 15 LdTLE patients to enroll in a speech and language prehabilitation program adapted to the specifics of their difficulties, organized daily during the preoperative period. Naming performance (for trained and untrained words) was studied twice before prehabilitation, during prehabilitation, and 1 week and 6 months after surgery. Results were analyzed using a generalized linear mixed effects model. We found a significant effect of prehabilitation on trained items before surgery. Postoperatively, trained items showed a slight and nonsignificant performance increase compared to baseline, whereas untrained items showed a significant decline in the same comparison. We conclude that trained words were better protected from postsurgical decline than untrained words. Our research can contribute to patient support during surgical decision-making; ultimately, prehabilitation might be considered as part of individualized care. These encouraging results lay the groundwork for more detailed or powerful examinations of the protective effect of prehabilitation on language skills. Show less

Breast cancer (BC) is the most prevalent cancer in women and remains the leading cause of cancer-related mortality globally. Its development is influenced by multiple factors, including genetics, environmental, aging, and modulation of various signaling pathways. The heterogeneity of BC together with the emergence of treatment resistance and recurrence have prompted researchers to explore and develop new therapeutic approaches. Recently, oncology research has primarily focused on the development of targeted therapies against molecular abnormalities in BC. These therapies include monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates, PI3K/Akt/mTOR pathway inhibitors, CDK 4/6 inhibitors, PARP inhibitors, antiangiogenic agents, and various other targeted drugs. Immunomodulatory strategies, including immune checkpoint inhibitors (anti-PD-1/PD-L1), CTLA-4 blockers, adoptive T-cell therapy, and cancer vaccines, stimulate immune response against cancer cells. Epigenetic therapies like DNMT and HDAC inhibitors have also shown promise in BC treatment. This review highlights how innovative approaches like targeting intratumoral heterogeneity, liquid biopsy for resistance mutation detection, bypass mechanisms ( Show less

The primary aim of this study is to explore distinct patterns of post-traumatic growth (PTG) and fear of cancer progression (FOP) among breast cancer patients through latent profile analysis (LPA). Additionally, we assessed the differences in demographic and disease-related factors among breast cancer patients with varying patterns. Finally, we examined the influence of socio-demographic, disease-related, social support, anxiety, depression, and post-traumatic stress disorder (PTSD) factors on the varying patterns, aiming to assist healthcare providers in developing more effective psychological care strategies for breast cancer patients. A questionnaire survey was conducted on 752 breast cancer patients. Latent profile analysis was employed to explore the patterns of post-traumatic growth and fear of cancer progression in these patients, and multiple logistic regression analysis was used to identify the predictive factors for the different patterns. Based on the fit indices of latent class analysis, a three-class model was identified as the optimal solution, which included the Resisting group, Struggling group, and Growth group. In the Resisting group (24.33%), patients reported low levels of post-traumatic growth and high levels of fear of cancer progression; in the Struggling group (46.14%), patients exhibited moderate levels of post-traumatic growth and low levels of fear of cancer progression; in the Growth group (29.52%), patients demonstrated high levels of post-traumatic growth and moderate levels of fear of cancer progression. Additionally, the multiple logistic regression analysis reveals that marital status, place of residence, education level, disease stage, social support, anxiety, and post-traumatic stress disorder levels in breast cancer patients serve as significant factors influencing the distinct patterns of post-traumatic growth and fear of progression. This study suggests that there is heterogeneity in the PTG and FOP patterns in breast cancer patients. It provides a research basis for promoting the psychological recovery of breast cancer patients and highlights the importance of focusing on the positive effects of PTG while mitigating the negative impact of FOP. Healthcare providers can implement targeted nursing interventions based on the different patterns observed in breast cancer patients. Show less

Lepidic adenocarcinoma is a rare subtype of lung adenocarcinoma that develops from the terminal bronchiolar and acinar epithelia of the lung. Diffuse pneumonic lepidic adenocarcinoma is associated with a poor prognosis. We present the case of a male former smoker with diffuse pneumonic lepidic adenocarcinoma. Show less

The traditional drug discovery process is often lengthy, costly, and characterized by a high failure rate. There is a pressing need for innovative strategies to optimize this process and improve the chances of identifying effective therapeutic candidates. This study aims to utilize computational methods to develop a quantitative structure-activity relationship (QSAR) model that predicts the inhibitory activity of compounds against Fibroblast Growth Factor Receptor 1 (FGFR-1), which is associated with various cancers, including lung and breast cancer. The QSAR model was developed using multiple linear regression (MLR) on a dataset of 1779 compounds from the ChEMBL database. The dataset was curated, and molecular descriptors were calculated using Alvadesc software. Feature selection techniques refined the dataset, and the model's predictive capability was validated through 10-fold cross-validation and external validation with a test set. In silico validation was further performed using molecular docking and molecular dynamics simulations. Additionally, in vitro validation was conducted using MTT, wound healing, and clonogenic assays on A549 (lung cancer), MCF-7 (breast cancer), HEK-293 (normal human embryonic kidney), and VERO (normal African green monkey kidney) cell lines. The QSAR model exhibited strong predictive performance with an R Show less

Leucine Rich Repeat Containing 8A (LRRC8A) anion channels (VRACs) associate with NADPH oxidase 1 (Nox1) and support extracellular superoxide (O We assayed O KO cells were less permeable to extracellular O Loss of LRRC8A reduced O Show less