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Molecules (Basel, Switzerland) Apr 2023This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects... (Review)
Review
This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects (curcumin, quercetin, resveratrol, epigallocatechin gallate, and apigenin) and chemotherapeutics such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, etc. According to WHO data, research has been limited to five cancers with the highest morbidity rate (lung, colorectal, liver, gastric, and breast cancer). A systematic review of articles published in the past five years (from January 2018 to January 2023) was carried out with the help of all Web of Science databases and the available base of clinical studies. Based on the preclinical studies presented in this review, polyphenols can enhance drug efficacy and reduce chemoresistance through different molecular mechanisms. Considering the large number of studies, curcumin could be a molecule in future chemotherapy cocktails. One of the main problems in clinical research is related to the limited bioavailability of most polyphenols. The design of a new co-delivery system for drugs and polyphenols is essential for future clinical research. Some polyphenols work in synergy with chemotherapeutic drugs, but some polyphenols can act antagonistically, so caution is always required.
Topics: Polyphenols; Curcumin; Resveratrol; Antioxidants; Drug Therapy, Combination
PubMed: 37175156
DOI: 10.3390/molecules28093746 -
Frontiers in Aging 2023With an increasing aging population, the burden of age-related diseases magnifies. To alleviate this burden, geroprotection has been an area of intense research focus...
With an increasing aging population, the burden of age-related diseases magnifies. To alleviate this burden, geroprotection has been an area of intense research focus with the development of pharmacological interventions that target lifespan and/or healthspan. However, there are often sex differences, with compounds mostly tested in male animals. Given the importance of considering both sexes in preclinical research, this neglects potential benefits for the female population, as interventions tested in both sexes often show clear sexual dimorphisms in their biological responses. To further understand the prevalence of sex differences in pharmacological geroprotective intervention studies, we performed a systematic review of the literature according to the PRISMA guidelines. Seventy-two studies met our inclusion criteria and were classified into one of five subclasses: FDA-repurposed drugs, novel small molecules, probiotics, traditional Chinese medicine, and antioxidants, vitamins, or other dietary supplements. Interventions were analyzed for their effects on median and maximal lifespan and healthspan markers, including frailty, muscle function and coordination, cognitive function and learning, metabolism, and cancer. With our systematic review, we found that twenty-two out of sixty-four compounds tested were able to prolong both lifespan and healthspan measures. Focusing on the use of female and male mice, and on comparing their outcomes, we found that 40% of studies only used male mice or did not clarify the sex. Notably, of the 36% of pharmacologic interventions that did use both male and female mice, 73% of these studies showed sex-specific outcomes on healthspan and/or lifespan. These data highlight the importance of studying both sexes in the search for geroprotectors, as the biology of aging is not the same in male and female mice. [website], identifier [registration number].
PubMed: 37305228
DOI: 10.3389/fragi.2023.1172789 -
Archives of Rheumatology Jun 2022Biological medications have been used with an increasing frequency to treat rheumatological diseases. Autoimmune events can be induced by these drugs, such as... (Review)
Review
OBJECTIVES
Biological medications have been used with an increasing frequency to treat rheumatological diseases. Autoimmune events can be induced by these drugs, such as psoriasiform lesions, alopecia, lupus and, vasculitis, which more often affects the skin (small-sized vessels) and eventually other organs. In this review, we describe the clinical profile of patients with vasculitis induced by the main biological agents used in rheumatology.
PATIENTS AND METHODS
We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The PubMed database was used for searching eligible articles. We included case reports, case series, and letter to the editor of patients on anti-tumor necrosis factor-alpha (anti-TNF-a) molecules, as well as tocilizumab, ustekinumab, secukinumab, rituximab, and abatacept, who had vasculitis induced by these agents.
RESULTS
Eighty-one articles were included for final analysis (n=89). Twenty-seven patients were using infliximab, 20 adalimumab, 18 etanercept, seven secukinumab, four certolizumab, four rituximab, three golimumab, three ustekinumab, two abatacept, and one tocilizumab. Unspecific leukocytoclastic vasculitis (LCV) was the most common type of vasculitis (n=37), followed by anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (n=16). The medication was replaced with another biological molecule in 23 cases, with only four relapses. In six cases, the biological was maintained, but vasculitis worsened/persisted in one case, being necessary drug removal.
CONCLUSION
Infections, infusion reaction, cancer, and autoimmune events are well-known side effects of biological therapy. This review demonstrates that vasculitis is another adverse effect of this type of therapy, particularly the anti-TNF-a molecules, and LCV the most reported type of vasculitis.
PubMed: 36017201
DOI: 10.46497/ArchRheumatol.2022.9049 -
The Cochrane Database of Systematic... Jun 2016Venous leg ulcers are common, chronic wounds caused by venous diseases, with a high recurrence rate and heavy disease burden. Compression therapy (bandages or stockings)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Venous leg ulcers are common, chronic wounds caused by venous diseases, with a high recurrence rate and heavy disease burden. Compression therapy (bandages or stockings) is the first choice treatment for venous leg ulcers. However, when ulcers remain unhealed, medication can also be used with or without compression therapy. Sulodexide, a highly purified glycosaminoglycan (a naturally occurring molecule) has antithrombotic and profibrinolytic properties (it reduces the formation of blood clots) as well as anti-inflammatory effects. Sulodexide has been studied as a potential treatment for venous leg ulcers.
OBJECTIVES
To assess the efficacy and safety of sulodexide for treating venous leg ulcers.
SEARCH METHODS
In July 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; Chinese Biomedical Literature Database (CBM); China National Knowledge Infrastructure Database (CNKI); Wan Fang and VIP. We also searched clinical trials registries to identify ongoing studies, as well as references listed in relevant publications. There were no restrictions based on date of publication, language or study setting.
SELECTION CRITERIA
Randomised controlled trials (RCTs) involving people with a diagnosis of venous leg ulcers which compared sulodexide with placebo or any other drug therapy (such as pentoxifylline, flavonoids, aspirin), with or without compression therapy.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. The authors independently selected studies, extracted data and assessed risk of bias. We pooled data to present the risk ratio (RR) with 95% confidence interval (CI), or presented a narrative summary. We assessed overall evidence quality according to the GRADE approach.
MAIN RESULTS
We included four RCTs with a total of 463 participants (aged 42 years to 93 years); one report was only available as a published abstract.Meta-analysis of three RCTs suggests an increase in the proportion of ulcers completely healed with sulodexide as an adjuvant to local treatment (including wound care and compression therapy) compared with local treatment alone (rate of complete healing with sulodexide 49.4% compared with 29.8% with local treatment alone; RR 1.66; 95% CI 1.30 to 2.12). This evidence for sulodexide increasing the rate of complete healing is low quality due to risk of bias. It is unclear whether sulodexide is associated with any increase in adverse events (4.4% with sulodexide versus 3.1% with no sulodexide; RR 1.44; 95% CI 0.48 to 4.34). The evidence for adverse events is very low quality, downgraded twice for risk of bias and once for imprecision.
AUTHORS' CONCLUSIONS
Sulodexide may increase the healing of venous ulcers, when used alongside local wound care, however the evidence is only low quality and the conclusion is likely to be affected by new research. It is not clear whether sulodexide is associated with adverse effects. The standard dosage, route and frequency of sulodexide reported in the trials was unclear. Further rigorous, adequately powered RCTs examining the effects of sulodexide on healing, ulcer recurrence, quality of life and costs are necessary.
Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Fibrinolytic Agents; Glycosaminoglycans; Humans; Middle Aged; Randomized Controlled Trials as Topic; Varicose Ulcer
PubMed: 27251175
DOI: 10.1002/14651858.CD010694.pub2 -
Oncotarget Dec 2016The L1 cell adhesion molecule (L1CAM) extensively participates in nervous system development and the malignant progression of human tumours. The prognostic value of... (Meta-Analysis)
Meta-Analysis Review
The L1 cell adhesion molecule (L1CAM) extensively participates in nervous system development and the malignant progression of human tumours. The prognostic value of L1CAM for the survival of patients with solid tumours remains controversial. The present meta-analysis was thus performed to highlight the relationship between L1CAM expression and prognosis in cancer patients. Relevant publications were identified after searching several widely used databases, including PubMed, EMBASE and the ISI Web of Science. A fixed-effect or random-effect meta-analytical model was employed to correlate L1CAM expression with different outcome measures in both entire tumours and stratified subgroups. 37 studies in total with 8552 patients were eligible for the final analysis. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) suggested that high L1CAM expression had an unfavourable impact on overall survival (HR=2.06, 95%CI 1.65-2.57, P<0.001), disease-specific survival (HR=2.45, 95%CI 1.48-4.05, P<0.001), disease-free survival (HR=2.42, 95%CI 1.4-4.19, P=0.002) and progression-free survival/recurrence-free survival (HR=2.07, 95%CI 1.41-3.05, P<0.001). Subgroup analysis revealed a similar correlation in most tumour types. Overall, L1CAM might be an effective poor prognostic factor for patients with various tumour types.
Topics: Biomarkers, Tumor; Carcinogenesis; Humans; Neoplasms; Nervous System; Neural Cell Adhesion Molecule L1; Prognosis; Survival Analysis
PubMed: 27833079
DOI: 10.18632/oncotarget.13236 -
Pharmaceuticals (Basel, Switzerland) Jun 2023Curcumin is a polyphenolic compound, derived from Curcuma longa, and it has several pharmacological effects such as antioxidant, anti-inflammatory, and antitumor.... (Review)
Review
Curcumin is a polyphenolic compound, derived from Curcuma longa, and it has several pharmacological effects such as antioxidant, anti-inflammatory, and antitumor. Although it is a pleiotropic molecule, curcumin's free form, which is lipophilic, has low bioavailability and is rapidly metabolized, limiting its clinical use. With the advances in techniques for loading curcumin into nanostructures, it is possible to improve its bioavailability and extend its applications. In this review, we gather evidence about the comparison of the pharmacokinetics (biodistribution and bioavailability) between free curcumin (Cur) and nanostructured curcumin (Cur-NPs) and their respective relationships with antitumor efficacy. The search was performed in the following databases: Cochrane, LILACS, Embase, MEDLINE/Pubmed, Clinical Trials, BSV regional portal, ScienceDirect, Scopus, and Web of Science. The selected studies were based on studies that used High-Performance Liquid Chromatography (HPLC) as the pharmacokinetics evaluation method. Of the 345 studies initially pooled, 11 met the inclusion criteria and all included studies classified as high quality. In this search, a variety of nanoparticles used to deliver curcumin (polymeric, copolymeric, nanocrystals, nanovesicles, and nanosuspension) were found. Most Cur-NPs presented negative Zeta potential ranging from -25 mV to 12.7 mV, polydispersion index (PDI) ranging from 0.06 to 0.283, and hydrodynamic diameter ranging from 30.47 to 550.1 nm. Selected studies adopted mainly oral and intravenous administrations. In the pharmacokinetics analysis, samples of plasma, liver, tumor, lung, brain, kidney, and spleen were evaluated. The administration of curcumin, in nanoparticle systems, resulted in a higher level of curcumin in tumors compared to free curcumin, leading to an improved antitumor effect. Thus, the use of nanoparticles can be a promising alternative for curcumin delivery since this improves its bioavailability.
PubMed: 37513855
DOI: 10.3390/ph16070943 -
Antioxidants (Basel, Switzerland) Apr 2022Recent studies indicate that cerebrovascular diseases and processes of atherosclerosis originate in the childhood era and are largely influenced by chronic inflammation.... (Review)
Review
Recent studies indicate that cerebrovascular diseases and processes of atherosclerosis originate in the childhood era and are largely influenced by chronic inflammation. Some features of vascular dysfunction in adulthood may even be programmed prenatally via genetic influences and an unfavorable intrauterine milieu. Oxidative stress, defined by an imbalance between the production and generation of reactive oxygen species (ROS) in cells and tissues and the capability of an organism to scavenge these molecules via antioxidant mechanisms, has been linked to adverse cardiovascular health in adults, yet has not been systematically reviewed in the pediatric population. We performed a systematic search as per the PRISMA guidelines in PubMed/Medline and Cochrane Reviews and detected, in total, 1228 potentially eligible pediatric articles on systemic inflammation, oxidative stress, antioxidant use, cardiovascular disease and endothelial dysfunction. The abstracts and full-text manuscripts of these were screened for inclusion and exclusion criteria, and a total of 160 articles were included. The results indicate that systemic inflammation and oxidative stress influence cardiovascular health in many chronic pediatric conditions, including hypertension, obesity, diabetes mellitus types 1 and 2, chronic kidney disease, hyperlipidemia and obstructive sleep apnea. Exercise and diet may diminish ROS formation and enhance the total serum antioxidant capacity. Antioxidant supplementation may, in selected conditions, contribute to the diminution of the oxidative state and improve endothelial function; yet, in many areas, studies provide unsatisfactory results.
PubMed: 35624760
DOI: 10.3390/antiox11050894 -
Life (Basel, Switzerland) Oct 2022Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present... (Review)
Review
Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present systematic review was to provide a comprehensive and critical analysis of the state of the art regarding its biological activities and pharmaceutical and food applications. In addition, the study identified essential oils rich in alpha-phellandrene and summarized their main biological activities as a preliminary screening to encourage subsequent studies on their single components. With this review, we selected and critically analyzed 99 papers, using the following bibliographic databases: PubMed, SciELO, Wiley and WOS, on 8 July 2022. Data were independently extracted by four authors of this work, selecting those studies which reported the keyword "alpha-phellandrene" in the title and/or the abstract, and avoiding those in which there was not a clear correlation between the molecule and its biological activities and/or a specific concentration from its source. Duplication data were removed in the final article. Many essential oils have significant amounts of alpha-phellandrene, and the species and are frequently cited. Some studies on the above-mentioned species show high alpha-phellandrene amounts up to 82.1%. There were 12 studies on alpha-phellandrene as a pure molecule showed promising biological functions, including antitumoral, antinociceptive, larvicidal and insecticidal activities. There were 87 research works on EOs rich in alpha-phellandrene, which were summarized with a focus on additional data concerning potential biological activities. We believe this data is a useful starting point to start new research on the pure molecule, and, in particular, to distinguish between the synergistic effects of the different components of the OEs and those due to alpha-phellandrene itself. Toxicological data are still lacking, requiring further investigation on the threshold values to distinguish the boundary between beneficial and toxic effects, i.e., mutagenic, carcinogenic and allergenic. All these findings offer inspiration for potential applications of alpha-phellandrene as a new biopesticide, antimicrobial and antitumoral agent. In particular, we believe our work is of interest as a starting point for further studies on the food application of alpha-phellandrene.
PubMed: 36295037
DOI: 10.3390/life12101602 -
Heliyon Feb 2024Biologic or small-molecule therapies are highly effective for the treatment of inflammatory bowel disease (IBD), and approval by the FDA has significantly increased both...
BACKGROUND
Biologic or small-molecule therapies are highly effective for the treatment of inflammatory bowel disease (IBD), and approval by the FDA has significantly increased both their clinical use and the development of novel regimens. However, the identification and management of their associated toxicities poses challenges for clinicians and researchers.
METHODS
A systematic review and meta-analysis of randomized controlled trials (RCTs) published from January 1, 2000, to October 15, 2022, and in the databases. A random-effects model with logit transformation was applied to the analysis heterogeneity between studies was evaluated using the I statistic with incidence and 95 % confidence interval (CI) for any adverse events (AEs), and serious AEs (SAEs).
RESULTS
In Crohn's disease (CD), the total AE incidence was 67.0 % (95 % CI, 66.2%-67.8 %; I = 97.2 %) for any AEs and 7.3 % (6.9-7.7; 97.2) for serious AEs. In ulcerative colitis (UC), the overall incidence of any and serious AEs was 63.6 % (63.0-64.3; 98.1) and 5.7 % (5.4-6.0; 88.9), respectively. The most common AEs were infections (21.5 [20.3-22.8], 32.6 [31.0-34.2], 25.9 [24.5-27.2], and 13.7 [10.7-16.7]) in CD patients that were treated with TNF antagonists, anti-integrins, anti-IL agents, and JAK inhibitors, respectively, and in UC patients also were infections (22.8 [21.7-24.0], 27.4 [25.9-28.9], and 18.4 [16.7-20.2]), respectively, as well as increases in lactic dehydrogenase levels (23.1 [20.8-25.4]) with JAK inhibitors.
CONCLUSION
This study offers a comprehensive summary of toxic side effects of IBD treatments and a useful reference for both patients and clinicians.
PubMed: 38370239
DOI: 10.1016/j.heliyon.2024.e25357 -
The British Journal of Surgery Oct 2014Many studies have investigated the systemic and local expression of biomarkers in patients with abdominal aortic aneurysm (AAA). The natural history of AAA varies... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Many studies have investigated the systemic and local expression of biomarkers in patients with abdominal aortic aneurysm (AAA). The natural history of AAA varies between patients, and predictors of the presence and diameter of AAA have not been determined consistently. The aim of this study was to perform a systematic review, meta-analysis and meta-regression of studies comparing biomarkers in patients with and without AAA, with the aim of summarizing the association of identified markers with both AAA presence and size.
METHODS AND RESULTS
Literature review identified 106 studies suitable for inclusion. Meta-analysis demonstrated a significant difference between matrix metalloproteinase (MMP) 9, tissue inhibitor of matrix metalloproteinase 1, interleukin (IL) 6, C-reactive protein (CRP), α1-antitrypsin, triglycerides, lipoprotein(a), apolipoprotein A and high-density lipoprotein in patients with and without AAA. Although meta-analysis was not possible for MMP-2 in aortic tissue, tumour necrosis factor α, osteoprotegerin, osteopontin, interferon γ, intercellular cell adhesion molecule 1 and vascular cell adhesion molecule 1, systematic review suggested an increase in these biomarkers in patients with AAA. Meta-regression analysis identified a significant positive linear correlation between aortic diameter and CRP level.
CONCLUSION
A wide variety of biomarkers are dysregulated in patients with AAA, but their clinical value is yet to be established. Future research should focus on the most relevant biomarkers of AAA, and how they could be used clinically.
Topics: Aortic Aneurysm, Abdominal; Aortitis; Biomarkers; Enzymes; Humans; Lipid Metabolism; Lipids; Proteins; Regression Analysis
PubMed: 25131707
DOI: 10.1002/bjs.9593