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Breast Cancer Research : BCR Jul 2024Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene...
BACKGROUND
Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer.
METHOD
First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy.
RESULTS
The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978-0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response.
CONCLUSION
These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.
Topics: Humans; Breast Neoplasms; Female; Neoadjuvant Therapy; Promoter Regions, Genetic; Biomarkers, Tumor; Middle Aged; Cell-Free Nucleic Acids; Adult; Prognosis; Antineoplastic Combined Chemotherapy Protocols; Aged; Treatment Outcome; Gene Expression Profiling
PubMed: 38965610
DOI: 10.1186/s13058-024-01860-3 -
Journal of Medical Case Reports Jul 2024Intellectual disability is a neurodevelopmental disorder characterized by significant impairments in intellectual functioning and adaptive behavior. Cognitive...
BACKGROUND
Intellectual disability is a neurodevelopmental disorder characterized by significant impairments in intellectual functioning and adaptive behavior. Cognitive flexibility and attention are crucial cognitive domains often affected in children with intellectual disability. This case report explores the novel use of transcranial alternating current stimulation, a noninvasive brain stimulation technique, to enhance these cognitive functions. The study's novelty lies in its focus on alpha-wave frequency transcranial alternating current stimulation targeting specific Brodmann areas and its potential sustained impact on cognitive flexibility and attention in the pediatric population with intellectual disability.
CASE PRESENTATION
The case study involved two elementary school students, both 7 years old with mild intellectual disability, one male and one female, both with Turkic ethnicity, from Shahid Fahmideh School for Exceptional Children in Khosrowshah, Iran. Both participants underwent a 2-week intervention with daily 20-minute sessions of transcranial alternating current stimulation at an alpha-wave frequency (10 Hz), targeting Brodmann areas F3 and P3. Cognitive flexibility and attention were assessed using the Wisconsin Card Sorting Test and the Clock Test, administered at four time points: pre-intervention, week 1, week 2, and 1 month post-intervention. Statistical analysis showed significant improvements in both Wisconsin Card Sorting Test and Clock Test scores for both participants compared with baseline, with sustained enhancement over time.
CONCLUSION
The findings from this case report indicate that transcranial alternating current stimulation may be a promising intervention for improving cognitive flexibility and attention in children with intellectual disability. The significant and sustained improvements observed suggest that transcranial alternating current stimulation could have a meaningful clinical impact on the cognitive development of this population. However, further research is needed to confirm the efficacy of transcranial alternating current stimulation and to explore its broader applicability and long-term effects in larger, more diverse populations.
Topics: Humans; Child; Intellectual Disability; Transcranial Direct Current Stimulation; Male; Female; Attention; Cognition; Treatment Outcome; Neuropsychological Tests
PubMed: 38965608
DOI: 10.1186/s13256-024-04625-w -
Journal of Nanobiotechnology Jul 2024Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By...
Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC.
Topics: Animals; Humans; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Aptamers, Nucleotide; Receptors, Transferrin; Mice; Cell Line, Tumor; CCAAT-Enhancer-Binding Proteins; Cell Proliferation; Genetic Therapy; RNA, Small Interfering; Mice, Nude
PubMed: 38965606
DOI: 10.1186/s12951-024-02665-4 -
Cardiovascular Diabetology Jul 2024Despite improved glycemic treatment, the impact of glycation on pathological consequences may persist and contribute to adverse clinical outcomes in diabetes. In the...
BACKGROUND
Despite improved glycemic treatment, the impact of glycation on pathological consequences may persist and contribute to adverse clinical outcomes in diabetes. In the present study we investigated the association between serum protein glycation products and progression of kidney disease as well as incident major adverse cardiovascular events (MACE) in type 1 diabetes.
METHODS
Fructosamine, advanced glycation end products (AGEs), and methylglyoxal-modified hydro-imidazolone (MG-H1) were measured from baseline serum samples in the FinnDiane study (n = 575). Kidney disease progression was defined as steep eGFR decline (> 3 mL/min/1.73 m/year) or progression of albuminuria (from lower to higher stage of albuminuria). MACE was defined as acute myocardial infarction, coronary revascularization, cerebrovascular event (stroke), and cardiovascular death.
RESULTS
Fructosamine was independently associated with steep eGFR decline (OR 2.15 [95% CI 1.16-4.01], p = 0.016) in the fully adjusted model (age, sex, baseline eGFR). AGEs were associated with steep eGFR decline (OR 1.58 per 1 unit of SD [95% CI 1.07-2.32], p = 0.02), progression to end-stage kidney disease (ESKD) (HR 2.09 per 1 unit of SD [95% CI 1.43-3.05], p < 0.001), and pooled progression (to any stage of albuminuria) (HR 2.72 per 1 unit of SD [95% CI 2.04-3.62], p < 0.001). AGEs (HR 1.57 per 1 unit of SD [95% CI 1.23-2.00], p < 0.001) and MG-H1 (HR 4.99 [95% CI 0.98-25.55], p = 0.054) were associated with incident MACE. MG-H1 was also associated with pooled progression (HR 4.19 [95% CI 1.11-15.89], p = 0.035). Most AGEs and MG-H1 associations were no more significant after adjusting for baseline eGFR.
CONCLUSIONS
Overall, these findings suggest that protein glycation products are an important risk factor for target organ damage in type 1 diabetes. The data provide further support to investigate a potential causal role of serum protein glycation in the progression of diabetes complications.
Topics: Humans; Diabetes Mellitus, Type 1; Female; Male; Disease Progression; Glycation End Products, Advanced; Middle Aged; Glomerular Filtration Rate; Risk Factors; Adult; Diabetic Nephropathies; Biomarkers; Incidence; Cardiovascular Diseases; Risk Assessment; Fructosamine; Kidney; Time Factors; Albuminuria; Prognosis; Prospective Studies; Imidazoles; Ornithine
PubMed: 38965604
DOI: 10.1186/s12933-024-02316-w -
Cardiovascular Diabetology Jul 2024Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility... (Comparative Study)
Comparative Study
BACKGROUND
Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories.
METHODS
In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m, 25 ≤ BMI < 30 kg/m, and BMI ≥ 30 kg/m, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories.
RESULTS
During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (P < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed.
CONCLUSIONS
MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.
Topics: Humans; Male; Body Mass Index; Middle Aged; Female; Cardiovascular Diseases; Risk Assessment; Prospective Studies; Cause of Death; Aged; Genetic Predisposition to Disease; Obesity; United Kingdom; Multifactorial Inheritance; Phenotype; Time Factors; Prognosis; Adult; Obesity, Metabolically Benign; Cardiometabolic Risk Factors; Risk Factors; Genetic Risk Score
PubMed: 38965592
DOI: 10.1186/s12933-024-02332-w -
Trials Jul 2024Cleft lip and palate (CLP) are among the most common congenital anomaly that affects up to 33,000 newborns in India every year. Nasoalveolar moulding (NAM) is a...
A multi-centric, single-blinded, randomized, parallel-group study to evaluate the effectiveness of nasoalveolar moulding treatment in non-syndromic patients with complete unilateral cleft lip, alveolus and palate (NAMUC study): a study protocol for a randomized controlled trial.
BACKGROUND
Cleft lip and palate (CLP) are among the most common congenital anomaly that affects up to 33,000 newborns in India every year. Nasoalveolar moulding (NAM) is a non-surgical treatment performed between 0 and 6 months of age to reduce the cleft and improve nasal aesthetics prior to lip surgery. The NAM treatment has been a controversial treatment option with 51% of the cleft teams in Europe, 37% of teams in the USA and 25 of cleft teams in India adopting this methodology. This treatment adds to the already existing high burden of care for these patients. Furthermore, the supporting evidence for this technique is limited with no high-quality long-term clinical trials available on the effectiveness of this treatment.
METHOD
The NAMUC study is an investigator-initiated, multi-centre, single-blinded randomized controlled trial with a parallel group design. The study will compare the effectiveness of NAM treatment provided prior to lip surgery against the no-treatment control group in 274 patients with non-syndromic unilateral complete cleft lip and palate. The primary endpoint of the trial is the nasolabial aesthetics measured using the Asher McDade index at 5 years of age. The secondary outcomes include dentofacial development, speech, hearing, cost-effectiveness, quality of life, patient perception, feeding and intangible benefits. Randomization will be carried out via central online system and stratified based on cleft width, birth weight and clinical trial site.
DISCUSSION
We expect the results from this study on the effectiveness of treatment with NAM appliance in the long term along with the cost-effectiveness evaluation can eliminate the dilemma and differences in clinical care across the globe.
TRIAL REGISTRATION
ClinicalTrials.gov CTRI/2022/11/047426 (Clinical Trials Registry India). Registered on 18 November 2022. The first patient was recruited on 11 December 2022. CTR India does not pick up on Google search with just the trial number. The following steps have to be carried out to pick up. How to search: ( https://ctri.nic.in/Clinicaltrials/advsearch.php -use the search boxes by entering the following details: Interventional trial > November 2022 > NAMUC).
Topics: Humans; Cleft Lip; Cleft Palate; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Infant; Single-Blind Method; Treatment Outcome; Infant, Newborn; India; Esthetics; Alveolar Process; Female; Male; Nose; Palatal Obturators
PubMed: 38965585
DOI: 10.1186/s13063-024-08229-z -
Cardiovascular Diabetology Jul 2024The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM)....
Aggravating effect of abnormal low-density protein cholesterol level on coronary atherosclerotic plaque in type 2 diabetes mellitus patients assessed by coronary computed tomography angiography.
BACKGROUND
The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM.
MATERIALS AND METHODS
This study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression.
RESULTS
A total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: β = 0.116; positive remodelling: β = 0.138; spotty calcification: β = 0.091; NOS: β = 0.427; OS: β = 0.659: SIS: β = 1.114; SSS: β = 2.987; PID: β = 2.716, all P value < 0.001).
CONCLUSIONS
Abnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Plaque, Atherosclerotic; Female; Middle Aged; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Aged; Cholesterol, LDL; Predictive Value of Tests; Biomarkers; Vascular Calcification; Risk Factors; Risk Assessment; Dyslipidemias; Retrospective Studies; Coronary Vessels; Severity of Illness Index; Prognosis; Cross-Sectional Studies
PubMed: 38965584
DOI: 10.1186/s12933-024-02304-0 -
Biology Direct Jul 2024Hepatocellular carcinoma (HCC) ranks as the second leading cause of global cancer-related deaths and is characterized by a poor prognosis. Eukaryotic translation...
BACKGROUND
Hepatocellular carcinoma (HCC) ranks as the second leading cause of global cancer-related deaths and is characterized by a poor prognosis. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) have been proved to play important roles in various human cancers, whereas the deubiquitination of EEF1A1 was poorly understood.
METHODS
The binding and regulatory relationship between Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) and EEF1A1 was validated using clinical tissue samples, reverse transcription quantitative real-time fluorescence quantitative PCR (RT-qPCR), Western blotting, co-immunoprecipitation, and immunofluorescence, as well as ubiquitin detection and cyclohexamide tracking experiments. Finally, the impact of the UCHL3/EEF1A1 axis on HCC malignant behavior was analyzed through functional experiments and nude mouse models.
RESULTS
UCHL3 was found to have a high expression level in HCC tissues. Tissue samples from 60 HCC patients were used to evaluate the correlation between UCHL3 and EEF1A1. UCHL3 binds to EEF1A1 through the lysine site, which reduces the ubiquitination level of EEF1A1. Functional experiments and nude mouse models have demonstrated that the UCHL3/EEF1A1 axis promotes the migration, stemness, and drug resistance of HCC cells. Reducing the expression of EEF1A1 can reverse the effect of UCHL3 on the malignant behavior of HCC cells.
CONCLUSION
Our findings revealed that UCHL3 binds and stabilizes EEF1A1 through deubiquitination. UCHL3 and EEF1A1 formed a functional axis in facilitating the malignant progression of HCC, proving new insights for the anti-tumor targeted therapy for HCC.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Ubiquitin Thiolesterase; Humans; Peptide Elongation Factor 1; Ubiquitination; Mice; Animals; Mice, Nude; Disease Progression; Cell Line, Tumor; Male; Female
PubMed: 38965582
DOI: 10.1186/s13062-024-00495-w -
Journal of Experimental & Clinical... Jul 2024Recent studies have highlighted the significant role of the NF-κB signaling pathway in the initiation and progression of cancer. Furthermore, long noncoding RNAs...
BACKGROUND
Recent studies have highlighted the significant role of the NF-κB signaling pathway in the initiation and progression of cancer. Furthermore, long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in sustaining the NF-κB signaling pathway's functionality. Despite these findings, the underlying molecular mechanisms through which lncRNAs influence the NF-κB pathway remain largely unexplored.
METHODS
Bioinformatic analyses were utilized to investigate the differential expression and prognostic significance of XTP6. The functional roles of XTP6 were further elucidated through both in vitro and in vivo experimental approaches. To estimate the interaction between XTP6 and NDH2, RNA pulldown and RNA Immunoprecipitation (RIP) assays were conducted. The connection between XTP6 and the IκBα promoter was examined using Chromatin Isolation by RNA Purification (ChIRP) assays. Additionally, Chromatin Immunoprecipitation (ChIP) assays were implemented to analyze the binding affinity of c-myc to the XTP6 promoter, providing insights into the regulatory mechanisms at play.
RESULTS
XTP6 was remarkedly upregulated in glioblastoma multiforme (GBM) tissues and was connected with adverse prognosis in GBM patients. Our investigations revealed that XTP6 can facilitate the malignant progression of GBM both in vitro and in vivo. Additionally, XTP6 downregulated IκBα expression by recruiting NDH2 to the IκBα promoter, which resulted in elevated levels of H3K27me3, thereby reducing the transcriptional activity of IκBα. Moreover, the progression of GBM was further driven by the c-myc-mediated upregulation of XTP6, establishing a positive feedback loop with IκBα that perpetuated the activation of the NF-κB signaling pathway. Notably, the application of an inhibitor targeting the NF-κB signaling pathway effectively inhibited the continuous activation induced by XTP6, leading to a significant reduction in tumor formation in vivo.
CONCLUSION
The results reveal that XTP6 unveils an innovative epigenetic mechanism instrumental in the sustained activation of the NF-κB signaling pathway, suggesting a promising therapeutic target for the treatment of GBM.
Topics: Humans; Glioblastoma; NF-kappa B; Mice; Animals; Proto-Oncogene Proteins c-myc; Disease Progression; RNA, Long Noncoding; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Signal Transduction; Prognosis; Feedback, Physiological; Brain Neoplasms; Male; Cell Proliferation; Female
PubMed: 38965580
DOI: 10.1186/s13046-024-03109-5 -
Cardiovascular Diabetology Jul 2024Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies...
BACKGROUND
Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM).
METHODS
This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed.
RESULTS
In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%.
CONCLUSIONS
Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers' artificial sweeteners consumption behavior.
Topics: Humans; Cardiovascular Diseases; Male; Female; Middle Aged; United Kingdom; Risk Assessment; Diabetes Mellitus, Type 2; Aged; Incidence; Biological Specimen Banks; Time Factors; Genetic Predisposition to Disease; Adult; Risk Factors; Sweetening Agents; Prospective Studies; Prognosis; Heart Disease Risk Factors; UK Biobank
PubMed: 38965574
DOI: 10.1186/s12933-024-02333-9