Differential effects of β-hydroxybutyrate and α-ketoglutarate on HCT-116 colorectal cancer cell viability under normoxic and hypoxic low-glucose conditions: exploring the role of SRC, HIF1α, ACAT1, and SIRT2 genes

Recent therapeutic strategies have highlighted the potential of beta-hydroxybutyrate (BHB) and alpha-ketoglutarate (alpha-KG) as effective anticancer agents, particularly for colon cancer. These metabolites can modulate cellular metabolism and induce epigenetic changes, inhibiting tumor growth. Nonetheless, certain cancer cells may utilize ketone bodies, like BHB as nutrient sources under hypoxic conditions, potentially reducing treatment efficacy. Understanding these mechanisms is crucial for optimizing cancer therapies. This study evaluated the effects of BHB and alpha-KG on HCT-116 colorectal cancer cell viability under normoxic and low-glucose hypoxic conditions. HCT-116 cell lines were treated with different doses of BHB and alpha-KG in normoxic and low-glucose hypoxic conditions, and then cell viability was assessed by the MTT assay. Moreover, the mRNA expression levels of SRC, hypoxia-inducible factor 1 alpha (HIF-1 alpha), acetyl-CoA acetyltransferase 1 (ACAT1), and sirtuin 2 (SIRT2) genes were determined using quantitative reverse transcriptase-polymerase chain reaction (q RT-PCR). BHB significantly increased the proliferation of HCT-116 colon cancer cells under low-glucose hypoxic conditions, while alpha-KG maintained cell viability in normoxic conditions but not in hypoxia. BHB treatment reduced SIRT2 mRNA levels and increased ACAT1, SRC, and HIF-1 alpha expression. Conversely, alpha-KG decreased ACAT1, SRC, and HIF-1 alpha expression and increased SIRT2 levels in normoxia but could not reverse gene expression during hypoxia. Our study demonstrated that BHB and alpha-KG exhibited complex interactions with colon cancer cell viability under varying oxygen and glucose conditions. While BHB promoted cell proliferation in hypoxic environments, alpha-KG showed protective effects in normoxic conditions. This research contributed to the growing body of evidence supporting the role of metabolic modulators in cancer therapy and emphasized the importance of understanding tumor microenvironments to optimize treatment outcomes. However, the need for further research into the metabolic pathways is underscored to enhance therapeutic strategies for cancer treatment

Association between diffusion tensor imaging measurements and cognitive performances in people with multiple sclerosis: A systematic review and meta-analysis

Background: Alterations in structural connectivity of brain networks have been linked to complex cognitive functions in people with multiple sclerosis (PwMS). However, a definitive consensus on the optimal diffusion tensor imaging (DTI) markers as indicators of cognitive performance remains incomplete and inconclusive. This systematic review and meta-analysis aimed to explore the evidence on the correlation between DTI metrics and cognitive functions in PwMS. Methods: A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Scopus, and the Web of Science up to March 2024 to identify studies reporting the correlation between DTI metrics and cognitive functions. Cognitive function was assessed using the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test (CVLT), and Brief Visuospatial Memory Test-Revised (BVMT-R). The pooled correlation coefficients were estimated using R software version 4.4.0 with the random effect model. Results: Out of 1952 studies, 38 studies on 2055 PwMS fulfilled the inclusion criteria. The meta-analysis indicated that the SDMT exhibited the greatest correlation with corpus callosum fractional anisotropy (FA) (r = 0.54, 95 CI: 0.4 to 0.66, p-value < 0.001, I-2 = 34.1 , p-heterogeneity = 0.19) and mean diffusivity (MD) (r = -0.48, 95 CI: 0.61 to -0.33, p-value < 0.001, I-2 = 0 , p-heterogeneity = 0.77), white matter FA (r = 0.39, 95 CI: 0.24 to 0.52, p-value < 0.001, I-2 = 0 , p-heterogeneity = 0.1), and fornix FA (r = 0.35, 95 CI: 0.12 to 0.54, p-value = 0.003, I-2 = 50.7 , p-heterogeneity = 0.18) and MD (r = -0.35, 95 CI: 0.49 to -0.19, p-value < 0.001, I-2 = 0 , p-heterogeneity = 0.5). Conclusion: DTI measurements, including corpus callosum FA and MD, white matter FA, and fornix FA and MD, represent the indicators of cognitive performance in PwMS. Nonetheless, these findings warrant cautious interpretation due to the restricted kinds of cognitive tests and methodological variability across studies

The Role of ΔFosB in the Pathogenesis of Levodopa-Induced Dyskinesia: Mechanisms and Therapeutic Strategies

Levodopa-induced dyskinesia (LID) represents a significant complication associated with the long-term administration of levodopa (L-DOPA) for the treatment of Parkinson's disease (PD). This review examines the critical role of Delta FosB, a transcription factor, in the pathogenesis of LID and explores potential therapeutic interventions. Delta FosB accumulates within the striatum in response to chronic dopaminergic stimulation, thereby driving maladaptive changes that culminate in dyskinesia. Its persistent expression modifies gene transcription, influencing neuronal plasticity and contributing to the sustained presence of dyskinetic movements. This study explains how Delta FosB functions at the molecular level, focusing on its connections with dopamine D1 receptors, the cAMP/PKA signaling pathway, and its regulatory effects on downstream targets such as DARPP-32 and GluA1 AMPA receptor subunits. Additionally, it examines how neuronal nitric oxide synthase (nNOS) affects Delta FosB levels and the development of LID. This review also considers the interactions between Delta FosB and other signaling pathways, such as ERK and mTOR, in the context of LID and striatal plasticity. Emerging therapeutic strategies targeting Delta FosB and its associated pathways include pharmacological interventions like ranitidine, 5-hydroxytryptophan, and carnosic acid. Furthermore, this study addresses the role of JunD, another component of the AP-1 transcription factor complex, in the pathogenesis of LID. Understanding the molecular mechanisms by which Delta FosB contributes to LID offers promising avenues for developing novel treatments that could mitigate dyskinesia and improve the quality of life for PD patients undergoing long-term L-DOPA therapy

MXene Nanoconfinement of SAM-Modified Molecularly Imprinted Electrochemical Biosensor for Point-of-Care Monitoring of Carcinoembryonic Antigen

The high rate of cancer worldwide and the heavy costs imposed on governments and humanity have always motivated researchers to develop point-of-care (POC) biosensors for easy diagnosis and monitoring of cancer treatment. Herein, we report on a label-free impedimetric biosensor based on Ti(3)C(2)T(x) MXene and imprinted ortho-phenylenediamine (o-PD) for the detection of carcinoembryonic antigen (CEA), a biomarker for various cancers surveillance, especially colorectal cancer (CRC). Accordingly, MXene was drop-casted on the surface of a disposable silver electrode to increase the sensitivity and create high-energy nanoareas on the surface, which are usable for protein immobilization and detection. A self-assembled monolayer (SAM) was exploited for oriented CEA immobilization on the MXene-modified electrode. The monomer-protein interaction and successful protein removal were confirmed by molecular docking and atomic force microscopy (AFM) investigations to evaluate the quality of the fabricated molecularly imprinted polymer (MIP). Also, the role of MXene in increasing the electrical field inside the nanoareas was simulated using COMSOL Multiphysics software. A suitable limit of detection (9.41 ng/mL), an appropriate linear range of detection (10 to 100 ng/mL) in human serum, and a short detection time (10 min) resulted from the use of SAM/MIP next to MXene. This biosensor presented outstanding repeatability (97.60) and reproducibility (98.61). Moreover, acceptable accuracy (between 93.04 and 116.04) in clinical serum samples was obtained compared with immunoassay results, indicating the high potential of our biosensor for real sample analysis. This biomimetic and disposable sensor provides a cost-effective method for facile and POC monitoring of cancer patients during treatment

Clinical and Dermoscopic Comparison of the Efficacy and Safety of 5 Fluorouracil Topical Cream and 1 Niacinamide Topical Gel in the Treatment of Actinic Keratosis: A Randomized Controlled Trial

BACKGROUND: Actinic keratosis (AK) is a common skin condition treated by dermatologists; however, the effectiveness, superiority, and potential side effects of current treatment protocols are still debated. AIM: This study aimed to compare the effectiveness and safety of 5 fluorouracil topical cream and 1 niacinamide topical gel in patients with AK. METHODS: In a randomized clinical trial, 26 patients with 95 AK lesions were assigned to receive either 5 fluorouracil topical cream twice daily for 4 weeks or 1 niacinamide topical gel twice daily for 3 months. Photography and dermoscopy before and after treatment were used to evaluate the outcomes. RESULTS: The study included 26 patients who underwent randomization and treatment. Analysis of the improvement response after treatment through photography and dermoscopy scores, as well as patients' perspectives, showed that the fluorouracil group had significantly better outcomes than the niacinamide group. However, treatment complications including burning, itching, and erythema were significantly more frequent in the fluorouracil group than in the niacinamide group. CONCLUSIONS: Although 5 fluorouracil cream is more effective than 1 niacinamide gel in treating AK lesions, it is also associated with more frequent side effects

Implants with or without Leukocyte- and Platelet-Rich Fibrin (L-PRF): A Systematic Review on Dental Implant Stability

BackgroundTo examine the impact of applying leukocyte- and platelet-rich fibrin (L-PRF) on the stability of dental implants using implant stability quotient (ISQ) measurements.MethodsA systematic search of the main databases was conducted to source the literature. Studies that met the established inclusion and exclusion criteria were selected for this review. The focus was solely on randomized controlled trials (RCTs) and controlled clinical trials (CCTs).ResultsAfter conducting a comprehensive search, a total of 1984 studies were identified. Following evaluation based on our inclusion and exclusion criteria, a refined selection of 7 studies was chosen for detailed review in this analysis.ConclusionsOur findings indicate that the use of leukocyte- and platelet-rich fibrin (L-PRF) may enhance the stability of implants following surgical procedures. This suggests that L-PRF may accelerate the healing process, reduce the loading time, and improve outcomes for patients undergoing implant surgery, potentially reducing the risk of implant failures and complications

Progressive hemorrhagic intracranial dermoid cyst: A case report with imaging and diagnostic considerations

This report describes the case of a 35-year-old woman with a recurrent ruptured intracranial dermoid cyst. These rare congenital lesions account for less than 1 of intracranial tumors globally. The patient was first diagnosed in her adolescence and underwent surgical excision with shunt placement at the age of 23, which provided symptom relief for 6 years. Her symptoms later recurred, including headaches, blurred vision, and progressive weakness. Imaging revealed a hemorrhagic lobulated mass that compressed the brainstem, encased vascular structures, caused a midline shift, and led to ventricular dilation. These findings suggested possible incomplete removal of the cyst wall during the initial surgery. This case highlights the challenges of diagnosing and managing recurrent intracranial dermoid cysts. It emphasizes the need for long-term monitoring, detailed imaging to assess recurrence and complications, and a multidisciplinary approach to treatment to improve outcomes

The association of ultra-processed food intake with neurodegenerative disorders: a systematic review and dose-response meta-analysis of large-scale cohorts

OBJECTIVES: Our systematic review and meta-analysis aimed to uncover the relationship between UPFs intake and neurodegenerative disorders, including multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), cognitive impairment, and dementia. SETTING: A systematic search was conducted using the Scopus, PubMed/MEDLINE, and ISI Web of Science databases without any limitation until June 24, 2023. Relative risk (RR) and 95 confidence interval (CI) were pooled by using a random-effects model, while validated methods examined quality and publication bias via Newcastle-Ottawa Scale, Egger's regression asymmetry, and Begg's rank correlation tests, respectively. RESULTS: Analysis from 28 studies indicated that a higher UPFs intake was significantly related to an enhanced risk of MS (RR = 1.15; 95 CI: 1.00, 1.33; I(2 )= 37.5; p = 0.050; n = 14), PD (RR = 1.56; 95 CI: 1.21, 2.02; I(2 )= 64.1; p = 0.001; n = 15), and cognitive impairment (RR = 1.17; 95 CI: 1.06, 1.30; I(2 )= 74.1; p = 0.003; n = 17), although not AD or dementia. We observed that a 25 g increment in UPFs intake was related to a 4 higher risk of MS (RR = 1.04; 95 CI: 1.01, 1.06; I(2 )= 0.0; p = 0.013; n = 7), but not PD. The non-linear dose-response relationship indicated a positive non-linear association between UPF intake and the risk of MS (P(nonlinearity) = 0.031, P(dose-response )= 0.002). This association was not observed for the risk of PD (P(nonlinearity) = 0.431, P(dose-response )= 0.231). CONCLUSION: These findings indicate that persistent overconsumption of UPFs may have an adverse impact on neurodegenerative conditions, potentially leading to a decline in quality of life and reduced independence as individuals age

The association between serum vitamin D levels and abnormal lipid profile in pediatrics: A GRADE-assessed systematic review and dose-response meta-analysis of epidemiologic studies

CONTEXT: Several studies have investigated the relationship between serum vitamin D and dyslipidemia in children and adolescents, but the findings have been contradictory. OBJECTIVE: The current systematic review and dose-response meta-analysis investigated the serum vitamin D - dyslipidemia relationship in children and adolescents. DATA SOURCES: ISI Web of Science, Scopus, MEDLINE (PubMed), EMBASE databases, and Google Scholar, were searched up to December 2022. DATA EXTRACTION: Observational studies that investigated the odds of dyslipidemia in categories of serum vitamin D levels in children were included, and their data were extracted. DATA ANALYSIS: Pooling of 17 effect sizes from 15 studies (39 342 participants) showed that subjects with higher serum vitamin D had 27 lower odds of hypertriglyceridemia (odds ratio OR = 0.73; 95% confidence interval CI: 0.60, 0.88). A meta-analysis of 18 effect sizes from 16 studies (39 718 participants) illustrated that highest vs lowest serum vitamin D was related to 22% lower odds of low high-density lipoprotein cholesterol (HDL-c) (OR = 0.78; 95% CI: 0.66, 0.91). Also, a nonlinear association between serum vitamin D and odds of abnormal lipid profile was found: elevating values of 25-hydroxyvitamin D from 35 nmol/L to 55 nmol/L was associated with a decreasing trend in odds of hypertriglyceridemia, hyper low-density lipoprotein cholesterolemia, hypercholesterolemia, and hypo HDL-cholesterolemia. However, no significant linear association was observed. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE), the certainty of all evidence was rated as high. CONCLUSION: This meta-analysis revealed that the level of 25-hydroxyvitamin D was inversely related to odds of abnormal serum triglycerides and HDL-c in children and adolescents. Increasing serum vitamin D from 35 nmol/L to 55 nmol/L was associated with a decreasing trend in the odds of abnormal serum triglycerides, HDL-c, low-density lipoprotein cholesterol, and total cholesterol in children. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. 42023400787

Impact of Melatonin Supplementation on Glycemic Parameters in Patients with Type 2 Diabetes: A Systematic Review and Meta-analysis

BACKGROUND: Several previous studies indicated that melatonin supplementation may positively affect glycemic control in patients with diabetes. However, research on the influence of melatonin supplementation on glycemic parameters remains inconclusive. Therefore, this study aimed to assess the impacts of melatonin supplementation on glycemic parameters in type 2 diabetes by conducting a meta-analysis. METHODS: PubMed/Medline, Scopus, and Web of Science were comprehensively searched until July 2024 to find eligible randomized clinical trials (RCTs). The overall effect sizes were estimated by using the randomeffect model and presented as weighted mean differences (WMD) with a 95 confidence interval (CI). Furthermore, the heterogeneity among the included trials was assessed by performing the Cochran Q test and interpreted based on the I(2) statistic. RESULTS: Of the 1361 papers, eight eligible RCTs were included in this meta-analysis. Our findings indicated that melatonin supplementation significantly decreased fasting blood glucose (WMD = -12.65 mg/dl; 95 CI: -20.38, -4.92; P = 0.001), insulin (WMD = -2.30 muU/ml; 95 CI: -3.20, -1.40; P < 0.001), hemoglobin A1c (WMD = -0.79 ; 95 CI: -1.28, -0.29; P = 0.002), and HOMA-IR (WMD, -0.83; 95 CI: -1.59 to - 0.07; P = 0.03). CONCLUSION: According to the results of the current meta-analysis, persons with type 2 diabetes who supplement with melatonin had improved glycemic control. It looks that supplementing with melatonin at a dose exceeding 6 mg daily for over a period of 12 weeks may be more successful than other forms of intervention. Nevertheless, further research with larger sample sizes is necessary to draw definitive conclusions