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Molecules (Basel, Switzerland) Jun 2024Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on... (Review)
Review
Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl intoxication) has been verified over the past two decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes and type 2 diabetes, and in the prevention of intoxications. Low-dose ozone acts as a redox bioregulator: the restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase in the antioxidant repair markers, here mainly shown as a glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, and relevant data are displayed, evaluated and comprehensively discussed: the repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone-treated groups and depending on the indication, the stress markers are simultaneously reduced, and the redox system regains its balance.
Topics: Oxidative Stress; Ozone; Oxidation-Reduction; Humans; Mitochondria; Reactive Oxygen Species; Animals; Antioxidants; Biomarkers
PubMed: 38930804
DOI: 10.3390/molecules29122738 -
Antioxidants (Basel, Switzerland) Jun 2024In the light of growing concerns faced by Western societies due to aging, natality decline, and epidemic of cardio-metabolic diseases, both preventable and treatable,... (Review)
Review
In the light of growing concerns faced by Western societies due to aging, natality decline, and epidemic of cardio-metabolic diseases, both preventable and treatable, new and effective strategical interventions are urgently needed in order to decrease their socio-economical encumbrance. The recent focus of research has been redirected towards investigating the potential of haskap ( L.) as a novel functional food or superfruit. Therefore, our present review aims to highlight the latest scientific proofs regarding the potential of L. (LC), a perennial fruit-bearing plant rich in polyphenols, in reversing cardio-metabolic dysfunctions. In this regard, a systematic search on two databases (PubMed and Google Scholar) from 1 January 2016 to 1 December 2023 was performed, the keyword combination being L. AND the searched pharmacological action, with the inclusion criteria consisting of in extenso original articles, written in English. The health-enhancing characteristics of haskap berries have been examined through in vitro and in vivo studies from the 35 included original papers. Positive effects regarding cardiovascular diseases and metabolic syndrome have been assigned to the antioxidant activity, hypolipidemic and hypoglycemic effects, as well as to the hepatoprotective and vasoprotective potential. Latest advances regarding LCF mechanisms of action are detailed within this review as well. All these cutting-edge data suggest that this vegetal product would be a good candidate for further clinical studies.
PubMed: 38929133
DOI: 10.3390/antiox13060694 -
International Journal of Molecular... Jun 2024Fluoxetine, a commonly prescribed medication for depression, has been studied in Alzheimer's disease (AD) patients for its effectiveness on cognitive symptoms. The aim... (Review)
Review
Fluoxetine, a commonly prescribed medication for depression, has been studied in Alzheimer's disease (AD) patients for its effectiveness on cognitive symptoms. The aim of this systematic review is to investigate the therapeutic potential of fluoxetine in cognitive decline in AD, focusing on its anti-degenerative mechanisms of action and clinical implications. According to PRISMA, we searched MEDLINE, up to 1 April 2024, for animal and human studies examining the efficacy of fluoxetine with regard to the recovery of cognitive function in AD. Methodological quality was evaluated using the ARRIVE tool for animal AD studies and the Cochrane tool for clinical trials. In total, 22 studies were analyzed (19 animal AD studies and 3 clinical studies). Fluoxetine promoted neurogenesis and enhanced synaptic plasticity in preclinical models of AD, through a decrease in Aβ pathology and increase in BDNF, by activating diverse pathways (such as the DAF-16-mediated, TGF-beta1, ILK-AKT-GSK3beta, and CREB/p-CREB/BDNF). In addition, fluoxetine has anti-inflammatory properties/antioxidant effects via targeting antioxidant Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome. Only three clinical studies showed that fluoxetine ameliorated the cognitive performance of people with AD; however, several methodological issues limited the generalizability of these results. Overall, the high-quality preclinical evidence suggests that fluoxetine may have neuroprotective, antioxidant, and anti-inflammatory effects in AD animal models. While more high-quality clinical research is needed to fully understand the mechanisms underlying these effects, fluoxetine is a promising potential treatment for AD patients. If future clinical trials confirm its anti-degenerative and neuroprotective effects, fluoxetine could offer a new therapeutic approach for slowing down the progression of AD.
Topics: Fluoxetine; Alzheimer Disease; Humans; Animals; Cognitive Dysfunction; Disease Models, Animal; Neurogenesis; Neuronal Plasticity
PubMed: 38928248
DOI: 10.3390/ijms25126542 -
International Journal of Molecular... Jun 2024A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory... (Review)
Review
A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). The study analysed articles published in JCR journals from 2019 to 2024. The search strategy comprised the MESH, free terms of "Neuroinflammation", and selective searches for the following single biomarkers that had previously been selected from the relevant literature: "High mobility group box 1/HMGB1", "Toll-Like-Receptor 4/TLR-4", "Interleukin-1/IL-1", "Interleukin-6/IL-6", "Transforming growth factor beta/TGF-β", and "Tumour necrosis factor-alpha/TNF-α". These queries were all combined with the MESH terms "Epileptogenesis" and "Epilepsy". We found 243 articles related to epileptogenesis and neuroinflammation, with 356 articles from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 55 evaluated by the authors. A total of 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. As conclusion, this systematic review provides acceptable support for five biomarkers, including TNF-α and some of its soluble receptors (sTNFr2), HMGB1, TLR-4, CCL2 and IL-33. Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control of epileptic seizures. Their value will be better defined by future studies.
Topics: Humans; Biomarkers; Neuroinflammatory Diseases; HMGB1 Protein; Epilepsy; Cytokines; Toll-Like Receptor 4; Drug Resistant Epilepsy
PubMed: 38928193
DOI: 10.3390/ijms25126488 -
PloS One 2024Vitamins D, E, A, B, C, and Omega-3 play crucial roles in modulating inflammatory and oxidative stress pathways, both implicated in abdominal aortic aneurysm (AAA)...
BACKGROUND
Vitamins D, E, A, B, C, and Omega-3 play crucial roles in modulating inflammatory and oxidative stress pathways, both implicated in abdominal aortic aneurysm (AAA) development. Recent research has explored the potential impact of dietary supplements on AAA progression. The systematic review aims to assess interventional studies investigating the effects of various dietary supplements on the development and severity of abdominal aortic aneurysms.
METHOD
A systematic search using relevant keywords related to abdominal aortic aneurysm and dietary supplements was conducted across four databases (PubMed, Embase, Scopus, and Web of Science). Quality assessment for animal studies employed SYRCLE and the Cochrane Collaboration Risk of Bias Tool for randomized control trials. The study protocol is registered in PROSPERO under the registry code CRD42023455958.
RESULTS
Supplementation with Omega-3, Vitamins A, C, D, E, and the Vitamin B family exhibited positive effects in AAA progression. These supplements contributed to a reduction in AAA diameter, elastin degradation, inflammatory responses, and reactive oxygen species. Additional supplements such as Zinc, methionine, and phytoestrogen also played roles in mitigating AAA progression.
CONCLUSION
The findings of this study underscore the potential role of dietary supplements in the progression of AAA. Predominantly based on animal studies, the results indicate that these supplements can limit AAA progression, primarily evidenced by their ability to mitigate inflammatory processes and oxidative stress pathways.
Topics: Aortic Aneurysm, Abdominal; Dietary Supplements; Humans; Disease Progression; Animals; Vitamins; Fatty Acids, Omega-3; Oxidative Stress
PubMed: 38923975
DOI: 10.1371/journal.pone.0305265 -
Clinics and Practice May 2024Isotretinoin is the drug of choice for severe acne. We sought to examine the potential link between isotretinoin and insulin resistance. (Review)
Review
BACKGROUND
Isotretinoin is the drug of choice for severe acne. We sought to examine the potential link between isotretinoin and insulin resistance.
METHODS
We conducted a systematic review and meta-analysis in accordance with the PRISMA statement. A comprehensive search of the PubMed/MEDLINE, SCOPUS, and Cochrane databases was performed until 12 January 2022 utilizing the PICO (Patient, Intervention, Comparison, Outcome) tool. Fifteen English-language studies focusing on isotretinoin-treated acne patients were included. Serum levels of insulin, glucose, and adiponectin were evaluated before and after treatment, and insulin sensitivity was assessed using the HOMA-IR. A meta-analysis was conducted using RevMan 5.4.1 software, and a quality assessment was undertaken using the ROBINS-I tool.
RESULTS
The meta-analysis unveiled a statistically significant rise in the post-treatment levels of adiponectin, an anti-inflammatory agent, which inhibits liver glucose production while enhancing insulin sensitivity (SMD = 0.86; 95% confidence interval (95% CI) = 0.48-1.25, -value < 0.0001; I = 58%). Our subgroup analysis based on study type yielded consistent findings. However, no statistically significant outcomes were observed for insulin, glucose levels, and the HOMA-IR.
CONCLUSIONS
There is not a clear association between isotretinoin and insulin resistance, but it appears to enhance the serum levels of adiponectin, which participates in glucose metabolism.
PubMed: 38921259
DOI: 10.3390/clinpract14030081 -
Frontiers in Immunology 2024Immune checkpoint inhibitors (ICIs) are effective for non-small cell lung cancer (NSCLC) treatment, but the response rate remains low. Programmed cell death ligand 1... (Meta-Analysis)
Meta-Analysis
Prognostic significance of programmed cell death ligand 1 blood markers in non-small cell lung cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis.
BACKGROUND
Immune checkpoint inhibitors (ICIs) are effective for non-small cell lung cancer (NSCLC) treatment, but the response rate remains low. Programmed cell death ligand 1 (PD-L1) in peripheral blood, including soluble form (sPD-L1), expression on circulating tumor cells (CTCs PD-L1) and exosomes (exoPD-L1), are minimally invasive and promising markers for patient selection and management, but their prognostic significance remains inconclusive. Here, we performed a meta-analysis for the prognostic value of PD-L1 blood markers in NSCLC patients treated with ICIs.
METHODS
Eligible studies were obtained by searching PubMed, EMBAS, Web of Science, and Cochrane Library prior to November 30, 2023. The associations between pre-treatment, post-treatment and dynamic changes of blood PD-L1 levels and progression-free survival (PFS)/over survival (OS) were analyzed by estimating hazard ratio (HR) and 95% confidence interval (CI).
RESULTS
A total of 26 studies comprising 1606 patients were included. High pre- or post-treatment sPD-L1 levels were significantly associated with worse PFS (pre-treatment: HR=1.49, 95%CI 1.13-1.95; post-treatment: HR=2.09, 95%CI 1.40-3.12) and OS (pre-treatment: HR=1.83, 95%CI 1.25-2.67; post-treatment: HR=2.60, 95%CI 1.09-6.20, P=0.032). High pre-treatment exoPD-L1 levels predicted a worse PFS (HR=4.24, 95%CI 2.82-6.38, P<0.001). Pre-treatment PD-L1 CTCs tended to be correlated with prolonged PFS (HR=0.63, 95%CI 0.39-1.02) and OS (HR=0.58, 95%CI 0.36-0.93). Patients with up-regulated exoPD-L1 levels, but not sPD-L1, after ICIs treatment had significantly favorable PFS (HR=0.36, 95%CI 0.23-0.55) and OS (HR=0.24, 95%CI 0.08-0.68).
CONCLUSION
PD-L1 blood markers, including sPD-L1, CTCs PD-L1 and exoPD-L1, can effectively predict prognosis, and may be potentially utilized for patient selection and treatment management for NSCLC patients receiving ICIs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; B7-H1 Antigen; Biomarkers, Tumor; Prognosis
PubMed: 38915398
DOI: 10.3389/fimmu.2024.1400262 -
Clinical Epigenetics Jun 2024Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a... (Review)
Review
BACKGROUND
Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes.
MAIN BODY
By understanding the epigenetic alterations that drive MHC downregulation, insights are gained into the molecular mechanisms underlying immune escape, tumor progression, and immunotherapy resistance. This systematic review examines the current literature on epigenetic mechanisms that contribute to MHC deregulation in esophageal, gastric, pancreatic, hepatic and colorectal malignancies. Potential clinical implications are discussed of targeting aberrant epigenetic modifications to restore MHC expression and 0 the effectiveness of immunotherapeutic interventions.
CONCLUSION
The integration of epigenetic-targeted therapies with immunotherapies holds great potential for improving clinical outcomes in patients with gastrointestinal malignancies and represents a compelling avenue for future research and therapeutic development.
Topics: Humans; Gastrointestinal Neoplasms; Epigenesis, Genetic; Major Histocompatibility Complex; Gene Expression Regulation, Neoplastic; Immunotherapy; DNA Methylation; Tumor Escape
PubMed: 38915093
DOI: 10.1186/s13148-024-01698-8 -
Frontiers in Endocrinology 2024There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM)...
There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using "smart pumps" or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL (3.9 mmol/L), although any form of carbohydrate (e.g., sucrose, which consists of glucose and fructose, or honey, sugary soft drinks, or fruit juice) containing glucose may be used. Using automatic insulin delivery systems, the oral glucose dose can be decreased to 0.1 g/kg. Practical flow charts are included to aid clinical decision-making. Although representing the official position of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED), these guidelines are applicable to the global audience and are especially pertinent in the era of CGM and other advanced technologies.
Topics: Humans; Hypoglycemia; Child; Adolescent; Blood Glucose Self-Monitoring; Insulin; Hypoglycemic Agents; Blood Glucose; Diabetes Mellitus, Type 1; Insulin Infusion Systems; Risk Assessment; Practice Guidelines as Topic; Disease Management
PubMed: 38894740
DOI: 10.3389/fendo.2024.1387537 -
Molecules (Basel, Switzerland) May 2024Chronic kidney disease (CKD) presents a formidable global health concern, affecting one in six adults over 25. This review explores the potential of phenolic compounds... (Review)
Review
Chronic kidney disease (CKD) presents a formidable global health concern, affecting one in six adults over 25. This review explores the potential of phenolic compounds in managing CKD and its complications. By examining the existing research, we highlight their diverse biological activities and potential to combat CKD-related issues. We analyze the nutritional benefits, bioavailability, and safety profile of these compounds. While the clinical evidence is promising, preclinical studies offer valuable insights into underlying mechanisms, optimal dosages, and potential side effects. Further research is crucial to validate the therapeutic efficacy of phenolic compounds for CKD. We advocate for continued exploration of their innovative applications in food, pharmaceuticals, and nutraceuticals. This review aims to catalyze the scientific community's efforts to leverage phenolic compounds against CKD-related challenges.
Topics: Humans; Renal Insufficiency, Chronic; Phenols; Animals; Dietary Supplements; Biological Availability
PubMed: 38893451
DOI: 10.3390/molecules29112576