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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 -
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 -
Biomedicines Jun 2024The efficacy and safety of PD-L1 inhibitors in the treatment of cervical cancer is an ongoing research question. This review aims to establish a clear profile of... (Review)
Review
BACKGROUND AND OBJECTIVES
The efficacy and safety of PD-L1 inhibitors in the treatment of cervical cancer is an ongoing research question. This review aims to establish a clear profile of atezolizumab, examining its impact on survival outcomes, response rates, and safety measured by serious adverse events (SAEs).
MATERIALS AND METHODS
A literature search was conducted using PubMed, Scopus, and Web of Science, focusing on articles published up to February 2024. The review followed the PRISMA guidelines and synthesized outcomes from four randomized trial studies involving atezolizumab administered at 1200 mg IV every three weeks, alone or in combination with chemoradiotherapy.
RESULTS
A total of 284 patients received atezolizumab, the majority being advanced stage cervical cancer (IVA-IVB). Median follow-up times ranged from 9 weeks to 32.9 months. It was found that combining atezolizumab with standard therapies extended median progression-free survival (PFS) from 10.4 to 13.7 months and overall survival (OS) from 22.8 to 32.1 months, according to the phase III trial. Monotherapy and initial treatment settings with atezolizumab also showed promising efficacy, with disease-free survival rates at 24 months reaching 79% compared to 52% with standard therapy alone. However, the treatment was associated with high rates of SAEs, reaching up to 79% in more intensive treatment combinations.
CONCLUSIONS
Atezolizumab demonstrates significant potential in improving PFS and OS in patients with cervical cancer, supporting its inclusion as a first-line treatment option. Despite the efficacy benefits, the high incidence of SAEs necessitates careful patient selection and management strategies to mitigate risks. This systematic review supports the continued evaluation of atezolizumab in broader clinical trials to refine its therapeutic profile and safety measures in the context of cervical cancer treatment.
PubMed: 38927498
DOI: 10.3390/biomedicines12061291 -
Frontiers in Nutrition 2024Excessive calorie intake poses a significant threat to female fertility, leading to hormonal imbalances and reproductive challenges. Overconsumption of unhealthy fats...
INTRODUCTION
Excessive calorie intake poses a significant threat to female fertility, leading to hormonal imbalances and reproductive challenges. Overconsumption of unhealthy fats exacerbates ovarian dysfunction, with an overproduction of reactive oxygen species causing oxidative stress, impairing ovarian follicle development and leading to irregular ovulation and premature ovarian failure. Interest in biological matrices with high antioxidant properties to combat diet-related oxidative stress has grown, as they contain various bioactive factors crucial for neutralizing free radicals potentially preventing female reproductive health. This systematic review evaluates the female reproductive impact of biological matrices in mitigating oxidative damages induced by over calory habits and, in particular, high fat diets.
METHODS
A comparative approach among mammalian models was utilized to interpret literature available data. This approach specifically investigates the antioxidant mechanisms of biological matrices on early and late ovarian folliculogenesis, under physiological and hormone-induced female reproductive cycle. Adhering to the PRISMA 2020 guidelines, only English-language publications from peer-reviewed international indexes were considered.
RESULTS
The analysis of 121 publications meeting the inclusion criteria facilitated the identification of crucial components of biological matrices. These components, including carbocyclic sugars, phytonutrients, organosulfur compounds, and vitamins, were evaluated for their impact on ovarian follicle resilience, oocyte quality, and reproductive lifespan. The detrimental effects of oxidative stress on female fertility, particularly exacerbated by high saturated fat diets, are well-documented. studies across mammalian preclinical models have underscored the potential of antioxidants derived from biological matrices to mitigate diet-induced conditions. These antioxidants enhance steroidogenesis and ovarian follicle development, thereby improving oocyte quality. Additionally, discussions within these publications emphasized the clinical significance of these biological matrices, translating research findings into practical applications for female health.
CONCLUSION
Further research is essential to fully exploit the potential of these matrices in enhancing female reproduction and mitigating the effects of diets rich in fatty acids. This requires intensified studies and comprehensive collection of data before clinical trials. The promotion of ovarian resilience offers promising avenues for enhancing understanding and advancing female reproductive health world-wide.
PubMed: 38915855
DOI: 10.3389/fnut.2024.1415455 -
Annals of Surgery Open : Perspectives... Jun 2024The aim of this systematic review and meta-analysis is to identify current robotic assistance systems for percutaneous liver ablations, compare approaches, and determine...
OBJECTIVE
The aim of this systematic review and meta-analysis is to identify current robotic assistance systems for percutaneous liver ablations, compare approaches, and determine how to achieve standardization of procedural concepts for optimized ablation outcomes.
BACKGROUND
Image-guided surgical approaches are increasingly common. Assistance by navigation and robotic systems allows to optimize procedural accuracy, with the aim to consistently obtain adequate ablation volumes.
METHODS
Several databases (PubMed/MEDLINE, ProQuest, Science Direct, Research Rabbit, and IEEE Xplore) were systematically searched for robotic preclinical and clinical percutaneous liver ablation studies, and relevant original manuscripts were included according to the Preferred Reporting items for Systematic Reviews and Meta-Analyses guidelines. The endpoints were the type of device, insertion technique (freehand or robotic), planning, execution, and confirmation of the procedure. A meta-analysis was performed, including comparative studies of freehand and robotic techniques in terms of radiation dose, accuracy, and Euclidean error.
RESULTS
The inclusion criteria were met by 33/755 studies. There were 24 robotic devices reported for percutaneous liver surgery. The most used were the MAXIO robot (8/33; 24.2%), Zerobot, and AcuBot (each 2/33, 6.1%). The most common tracking system was optical (25/33, 75.8%). In the meta-analysis, the robotic approach was superior to the freehand technique in terms of individual radiation (0.5582, 95% confidence interval [CI] = 0.0167-1.0996, dose-length product range 79-2216 mGy.cm), accuracy (0.6260, 95% CI = 0.1423-1.1097), and Euclidean error (0.8189, 95% CI = -0.1020 to 1.7399).
CONCLUSIONS
Robotic assistance in percutaneous ablation for liver tumors achieves superior results and reduces errors compared with manual applicator insertion. Standardization of concepts and reporting is necessary and suggested to facilitate the comparison of the different parameters used to measure liver ablation results. The increasing use of image-guided surgery has encouraged robotic assistance for percutaneous liver ablations. This systematic review analyzed 33 studies and identified 24 robotic devices, with optical tracking prevailing. The meta-analysis favored robotic assessment, showing increased accuracy and reduced errors compared with freehand technique, emphasizing the need for conceptual standardization.
PubMed: 38911657
DOI: 10.1097/AS9.0000000000000406 -
Journal of Experimental Orthopaedics Jul 2024The purpose of this study was to quantify and compare the clinical relevance of the different intra-articular corticosteroids (CS) effects in vivo for osteoarthritis... (Review)
Review
PURPOSE
The purpose of this study was to quantify and compare the clinical relevance of the different intra-articular corticosteroids (CS) effects in vivo for osteoarthritis (OA) treatment.
METHODS
The search was conducted on PubMed, Cochrane, and Web of Science in October 2023. The PRISMA guidelines were used. Inclusion criteria: animal or human randomized controlled trials (RCTs), English language and no time limitation, on the comparison of different intra-articular CS for OA treatment. The articles' quality was assessed using the Cochrane RoB2 and GRADE guidelines for human RCTs, and SYRCLE's tool for animal RCTs.
RESULTS
Eighteen RCTs were selected (16 human and 2 animal studies), including 1577 patients (1837 joints) and 31 animals (51 joints). The CS used were triamcinolone (14 human and 2 animal studies), methylprednisolone (7 human and 1 animal study), betamethasone (3 human studies) and dexamethasone (1 human study). All studies addressed knee OA except for three human and one animal study. A meta-analysis was performed on the comparison of methylprednisolone and triamcinolone in humans with knee OA analysing VAS pain at very short- (≤2 weeks), short- (>2 and ≤4 weeks), mid- (>4 and ≤8 weeks), long- (>8 and ≤ 12 weeks), and very long-term (>12 and ≤24 weeks). Triamcinolone showed better post-injection values compared to methylprednisolone at very short-term ( = 0.028). No difference in terms of VAS improvement was observed at any follow-up.
CONCLUSIONS
The available preclinical and clinical literature provides limited evidence on the comparison of different CS, hindering the possibility of determining the best CS approach in terms of molecule and dose for the intra-articular injection of OA joints.
LEVEL OF EVIDENCE
Level I.
PubMed: 38911187
DOI: 10.1002/jeo2.12060 -
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 -
International Journal of Molecular... Jun 2024Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in... (Meta-Analysis)
Meta-Analysis Review
Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in clinical practice. This meta-analysis aims to assess the effect of IL-10 immunotherapy on renal ischemia-reperfusion injury. Medline, Embase, Cochrane-library, Google Scholar and clinicaltrials.gov were searched up to 31 March 2023. Preclinical and clinical interventional studies investigating IL-10 immunotherapy for renal ischemia-reperfusion were eligible for inclusion. The primary endpoint was renal function (serum creatinine) following ischemia-reperfusion. The secondary endpoints included mitochondrial integrity, cellular proliferation, regulated cell death (TUNEL assay), expression of inflammatory cytokines (TNF-α, IL-6 and IL-1β), M1/M2 macrophage polarization, tissue integrity (tubular injury score), long-term kidney fibrosis (fibrotic area %) and adverse events (pulmonary toxicity, cardiotoxicity hepatotoxicity). The search returned 861 records. From these, 16 full texts were screened and subsequently, seven animal studies, corresponding to a population of 268 mice/rats, were included. Compared to the control treatment, IL-10 immunotherapy reduced serum creatinine more effectively within 24 h of administration (95% CI: -9.177, -5.601, I = 22.42%). IL-10 immunotherapy promoted mitochondrial integrity and cellular proliferation and reduced regulated cell death (95% CI: -11.000, -4.184, I = 74.94%). It decreased the expression of TNF-α, IL-6 and IL-1β, led to M2 polarization of the local macrophages, reduced tubular injury score (95% CI: -8.917, -5.755, I = 22.71%), and long-term kidney fibrosis (95% CI: -6.963, -3.438, I = 0%). No adverse outcomes were captured. In Conclusion, IL-10 immunotherapy safely improves outcomes in animal models of renal ischemia-reperfusion; the translational potential of IL-10 immunotherapy needs to be further investigated in clinical trials.
Topics: Reperfusion Injury; Animals; Interleukin-10; Humans; Immunotherapy; Kidney; Acute Kidney Injury; Mice
PubMed: 38892418
DOI: 10.3390/ijms25116231 -
Cells Jun 2024Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory... (Review)
Review
Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and associated structures. Mesenchymal stromal/stem cells (MSCs) have emerged as a promising therapy for TMJ repair. This systematic review aims to consolidate findings from the preclinical animal studies evaluating MSC-based therapies, including MSCs, their secretome, and extracellular vesicles (EVs), for the treatment of TMJ cartilage/osteochondral defects and osteoarthritis (OA). Following the PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library databases were searched for relevant studies. A total of 23 studies involving 125 , 149 , 470 , and 74 were identified. Compliance with the ARRIVE guidelines was evaluated for quality assessment, while the SYRCLE risk of bias tool was used to assess the risk of bias for the studies. Generally, MSC-based therapies demonstrated efficacy in TMJ repair across animal models of TMJ defects and OA. In most studies, animals treated with MSCs, their derived secretome, or EVs displayed improved morphological, histological, molecular, and behavioral pain outcomes, coupled with positive effects on cellular proliferation, migration, and matrix synthesis, as well as immunomodulation. However, unclear risk in bias and incomplete reporting highlight the need for standardized outcome measurements and reporting in future investigations.
Topics: Animals; Temporomandibular Joint; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Temporomandibular Joint Disorders; Humans; Osteoarthritis; Extracellular Vesicles; Disease Models, Animal
PubMed: 38891122
DOI: 10.3390/cells13110990 -
Frontiers in Pharmacology 2024(Willd. ex Schult.) DC. (Rubiaceae) is traditionally used by Amazonian indigenous groups to treat inflammatory diseases. To date, there are no systematic reviews and...
BACKGROUND
(Willd. ex Schult.) DC. (Rubiaceae) is traditionally used by Amazonian indigenous groups to treat inflammatory diseases. To date, there are no systematic reviews and meta-analyses on the use of for inflammation control in animals supporting the traditional knowledge about this species. This study was conducted to evaluate the effect of extracts in modulating inflammatory mediators and to determine which types of inflammatory diseases can be treated by this species.
METHODS
We conducted a systematic review and meta-analysis of preclinical studies published before 26 July 2023, identified in PubMed, Embase, and Scopus. Four independent reviewers extracted the data and assessed the risks of bias. The effects of on inflammatory diseases and the inflammatory mediators involved were extracted from the studies. Standardized mean differences (SMD) and 95% confidence intervals (95%CI) of the outcomes were estimated. The meta-analyses were conducted using RevMan 5.4 (Cochrane Collaboration). This protocol was registered in PROSPERO (CRD42023450869).
RESULTS
Twenty-four of 523 studies were included. extracts decreased the cytokines interleukin (IL)-6 (SMD: -0.72, 95%CI: -1.15, -0.29, = 0.001) and transcription factor nuclear factor -B (NF-κB) (SMD: -1.19, 95%CI: -1.89, -0.48, = 0.001). However, the extracts did not significantly alter IL-1 (SMD: -0.16, 95%CI: -0.87, +0.56, = 0.67), IL-10 (SMD: -0.05, 95%CI:-0.35, 0.45, = 0.80), or tumor necrosis factor- (TNF-α) levels (SMD: 0.18, 95%CI: -0.25, 0.62, = 0.41).
CONCLUSION
Many extracts of stem bark, roots, and leaves of , mostly aqueous and hydroethanolic, exhibited anti-inflammatory and/or immunomodulatory activities and low toxicity. The extracts decreased NF-κB and IL-6. These findings suggest that this species has the potential to treat inflammatory diseases in which these markers are increased, according to the ethnopharmacological use. These activities are not related to a specific class of compounds.
UNLABELLED
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450869, Identifier CRD42023450869.
PubMed: 38881881
DOI: 10.3389/fphar.2024.1378408