Non-coding RNAs in leukemia drug resistance: new perspectives on molecular mechanisms and signaling pathways.

Like almost all cancer types, timely diagnosis is needed for leukemias to be effectively cured. Drug efflux, attenuated drug uptake, altered drug metabolism, and epigenetic alterations are just several of the key mechanisms by which drug resistance develops. All of these mechanisms are orchestrated by up- and downregulators, in which non-coding RNAs (ncRNAs) do not encode specific proteins in most cases; albeit, some of them have been found to exhibit the potential for protein-coding. Notwithstanding, ncRNAs are chiefly known for their contribution to the regulation of physiological processes, as well as the pathological ones, such as cell proliferation, apoptosis, and immune responses. Specifically, in the case of leukemia chemo-resistance, ncRNAs have been recognized to be responsible for modulating the initiation and progression of drug resistance. Herein, we comprehensively reviewed the role of ncRNAs, specifically its effect on molecular mechanisms and signaling pathways, in the development of leukemia drug resistance.

Patent ductus arteriosus stenting as therapeutic bridge in a patient with type A3 truncus arteriosus variant with multiple comorbidities.

Type A3 truncus arteriosus describes pulmonary atresia with non-confluent mediastinal pulmonary arteries in which one pulmonary artery arises from a patent ductus arteriosus and the contralateral pulmonary artery from the aorta resulting in ductal dependent pulmonary blood flow. We describe a premature neonate with caudal regression syndrome and type A3 truncus arteriosus who was palliated with a ductal stent allowing completion of a prolonged neonatal ICU hospitalisation for multiple comorbidities.

Synergism of mechanisms underlying early-stage changes in retina function in male hyperglycemic db/db mice in the absence and presence of chemically-induced dyslipidemia.

The study was designed to quantify retina function in a spontaneous mutation mouse model of diabetes, in which sustained dyslipidemia was induced chemically. The goal of the study was to identify if dyslipidemia in the presence of hyperglycemia resulted in either a synergistic, or a merely additive, exacerbation of retinal and visual dysfunctions in diabetes. Two cohorts of mice, male C57BL/6 and C57BL/KsJ-db/db mice were divided into two groups each. One group of each strain received the triblock copolymer, poloxamer 407 (P-407), administered by intraperitoneal injection ("WT P-407" and "db/db P-407" groups) with saline as a control in the remaining two groups ("WT" and "db/db" groups). Blood glucose, total cholesterol (TC) and total triglyceride (TG) levels were quantified using enzyme-based colorimetric assays. Retina function was measured using electroretinography (ERG) and visual acuity was determined by behaviorally assessing parameters of the optomotor reflex. TC and TG levels were normal in both saline controls (WT) and db/db mice but were significantly elevated in the WT P-407 group (p < 0.01 for TC; p < 0.001 for TG), while levels of the same lipids were further elevated in the db/db P-407 group when compared to the WT P-407 group levels (p < 0.001 for both TC and TG). Behavioral assessment of the optomotor reflex indicated reduced visual acuity for the db/db P-407 group when compared to either the WT P-407 or the db/db groups (p < 0.001, p < 0.0001). ERG measurements of scotopic retina function showed a significant decline in the scotopic b-wave amplitude of the WT P-407 animals (p < 0.01) and a further reduction for the db/db P-407 group when compared to controls (p < 0.0001). Very significant, strong correlations between scotopic b-wave amplitude and implicit time to TC (r = - 0.8376, p = < 0.0001 and r = 0.7069, p = 0.0022, respectively) and TG levels (r = - 0.8554, p = < 0.0001 and r = 0.7150, p = 0.0019, respectively) were found. Dyslipidemia in the presence of hyperglycemia synergistically exacerbated the severity of retinal dysfunction in diabetes. P-407 administration significantly elevated plasma TC and TG levels in male wild-type (WT) and diabetic mice (db/db), but the resulting hyperlipidemia was more significantly pronounced in the diabetic mice. While elevated plasma lipid and blood glucose levels were individually correlated with a decline in retinal function, the combination of both exacerbated retinal dysfunction. This model of combined hyperglycemia and dyslipidemia can be used to dissect individual contributions of features of the metabolic syndrome to the pathogenesis of retinal dysfunction in diabetes.

An Overview of the Pharmacological Properties of Calebin-A.

The natural polyphenol, calebin-A, was recently discovered and identified as a novel phytopharmaceutical with anti-inflammatory, anti-tumor, and antiproliferative properties. Calebin-A occurs naturally in trace quantities in Curcuma longa/C cassia, commonly known as turmeric, from the Zingiberaceae family. Calebin-A is a curcumin analog or 'chemical cousin' of curcumin with a similar chemical structure. Although few research studies have been conducted on the pharmacological and therapeutic properties of calebin-A, it is a very promising molecule with a variety of pharmacological properties. Some studies have suggested that calebin-A is helpful in treating various cancers due to its inhibitory effect on cell growth and anti-inflammatory properties. Other studies have suggested that calebin-A may improve neurocognitive status associated with neurodegeneration caused by Alzheimer's disease (AD) by inhibiting the aggregation of ß-amyloid. Finally, several studies have proposed that calebin-A may potentially be therapeutically beneficial in treating patients with obesity. This novel compound downregulates nuclear factor (NF)-κB-mediated processes involved with cancer, such as tumor cell invasion, proliferation, metastasis, and, most profoundly, inflammation. Moreover, calebin-A influences the activities of mitogen-activated protein kinases (MAPKs) in cancer cells. The present review identifies and discusses the pharmacological and phytochemical properties of calebin-A, as well as its therapeutic benefits and limitations, for future scientists and clinicians interested in exploring calebin-A's medicinal qualities.

Fluvastatin: a choice for COVID-19 associated mucormycosis management.

SARS-CoV-2 invades the respiratory tract epithelium and can result in systemic inflammation prior to an infection caused by either bacteria or fungus. COVID-19-associated mucormycosis (CAM) is a serious condition that can occur during the time of the disease due to increased administration of corticosteroids. Various studies have suggested that statins may improve clinical outcomes in COVID-19 patients. According to several preclinical reports, fluvastatin was shown to exert direct and indirect synergistic antifungal activity. Thus, fluvastatin could be considered a potential antifungal agent when no other option is available. Furthermore, in comparison with other statins, fluvastatin exhibits the fewest drug/drug interactions with anti-Mucorales azoles (e.g., isavuconazole and posaconazole), as well as with medicines that are used in solid organ transplant recipients (e.g., cyclosporine) and HIV-positive individuals (e.g., ritonavir); two groups of patients that have a higher risk of infection with Mucorales fungi following a SARS-CoV-2 infection.

A Review on the Efficacy and Safety of Intrathecal Administration of Novel Medications for Leptomeningeal Metastases in Solid Cancers.

Leptomeningeal disease (LMD) is a rare and lethal manifestation that may occur in the advanced stages of solid tumors and hematological malignancies. With advances in diagnostic techniques, the detection and confirmation of the presence of LMD have increased. Although its optimal treatment remains a challenge, the use of the intrathecal route for the delivery of novel therapeutics is now considered a promising drug delivery strategy to complement radiation and systemic-based therapies. Although methotrexate, cytarabine, and thiotepa have a long history in the treatment of LMD, other medications have also been shown to be beneficial. In this article, we have reviewed the effects of novel medications administered via the intrathecal route for the treatment of solid tumors. We have searched PubMed, Scopus, and Google Scholar databases till the end of September 2021 using the following keywords: ''leptomeningeal disease'', ''leptomeningeal carcinomatosis'', ''leptomeningeal metastases'', ''solid tumors'', ''solid cancers'', and ''intrathecal''. Our literature findings have uncovered that most studies on LMD, which occurs secondary to solid cancers, are available as 'case reports', and few clinical trials have been conducted to date. Single-drug (monotherapy) or combination drug therapy, administered via the intrathecal route, especially in metastatic breast and lung cancer, has been shown to improve patients' symptoms and overall lifespan, while exhibiting a low and acceptable prevalence of side effects. However, judgments/conclusions about the effectiveness and safety of these drugs still require further clinical evaluation.

Therapeutic potential of phytochemicals for cystic fibrosis.

The aim of this review was to review and discuss various phytochemicals that exhibit beneficial effects on mutated membrane channels, and hence, improve transmembrane conductance. These therapeutic phytochemicals may have the potential to decrease mortality and morbidity of CF patients. Four databases were searched using keywords. Relevant studies were identified, and related articles were separated. Google Scholar, as well as gray literature (i.e., information that is not produced by commercial publishers), were also checked for related articles to locate/identify additional studies. The relevant databases were searched a second time to ensure that recent studies were included. In conclusion, while curcumin, genistein, and resveratrol have demonstrated effectiveness in this regard, it should be emphasized that coumarins, quercetin, and other herbal medicines also have beneficial effects on transporter function, transmembrane conductivity, and overall channel activity. Additional in vitro and in vivo studies should be conducted on mutant CFTR to unequivocally define the mechanism by which phytochemicals alter transmembrane channel function/activity, since the results of the studies evaluated in this review have a high degree of heterogenicity and discrepancy. Finally, continued research be undertaken to clearly define the mechanism(s) of action and the therapeutic effects that therapeutic phytochemicals have on the symptoms observed in CF patients in an effort to reduce mortality and morbidity.

The Epigenetic Contribution to the Pathogenesis of Psoriasis: Recent Advances.

Psoriasis is defined as a chronic autoimmune disorder of the skin in which abnormal proliferation and differentiation of keratinocytes are blamed as the central culprit of disease etiopathogenesis. A complex interplay between environmental factors and genetic risk factors has been suggested to trigger the disease. However, epigenetic regulation appears to connect external stimuli and genetic abnormalities in the development of psoriasis. The discordance in the prevalence of psoriasis between monozygotic twins and environmental factors that contribute to its onset have caused a paradigm shift regarding the mechanisms underlying the pathogenesis of this disease. Epigenetic dysregulation may be involved in aberrancies of keratinocyte differentiation, T-cell activation, and other plausible cells, leading to the initiation and perpetuation of psoriasis. Epigenetics is characterized by heritable alterations in the transcription of genes without nucleotide change and is commonly considered at three levels, i.e., DNA methylation, histone modifications, and microRNAs. To date, scientific evidence has indicated abnormal DNA methylation, histone modifications, and non-coding RNA transcription in psoriatic patients. In order to reverse aberrant epigenetic changes in psoriasis patients, several compounds and drugs (epi-drugs) have been developed to affect the major enzymes involved in the methylation of DNA, or the acetylation of histones, which aim to correct the aberrant methylation and acetylation patterns. A number of clinical trials have suggested the therapeutic potential of such drugs in the treatment of psoriasis. In the present review, we attempt to clarify recent findings with respect to epigenetic irregularities in psoriasis and discuss future challenges.

Nanomedicine-mediated therapeutic approaches for pulmonary arterial hypertension.

Nanomedicine has emerged as a field in which there are opportunities to improve the diagnosis, treatment and prevention of incurable diseases. Pulmonary arterial hypertension (PAH) is known as a severe and fatal disease affecting children and adults. Conventional treatments have not produced optimal effectiveness in treating this condition. Several reasons for this include drug instability, poor solubility of the drug and a shortened duration of pharmacological action. The present review focuses on new approaches for delivering anti-PAH drugs using nanotechnology with the aim of overcoming these shortcomings and increasing their efficacy. Solid-lipid nanoparticles, liposomes, metal-organic frameworks and polymeric nanoparticles have demonstrated advantages for the potential treatment of PAH, including increased drug bioavailability, drug solubility and accumulation in the lungs.

Association of C-reactive protein with histological, elastographic, and sonographic indices of non-alcoholic fatty liver disease in individuals with severe obesity.

BACKGROUND: Inflammation is critical in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). hs-CRP, an inflammatory marker, is considered one of the prognostic predictors of hepatic damage progression in NAFLD in some studies. METHODS: We assessed the concordance of hs-CRP concentrations and liver steatosis, steatohepatitis, and fibrosis based on elastography, sonography and liver biopsy findings in patients with severe obesity undergoing bariatric surgery. RESULTS: Among 90 patients, 56.7% showed steatohepatitis and 8.9% severe fibrosis. Hs-CRP were significantly associated with liver histology in an adjusted regression model (OR 1.155, 95% CI 1.029-1.297, p = 0.014; OR 1.155, 1.029-1.297, p = 0.014; OR 1.130, 1.017-1.257, p = 0.024 for steatosis, steatohepatitis, and fibrosis, respectively). The ROC curve, a cutoff of hs-CRP = 7 mg/L, showed a reasonable specificity (76%) for detecting biopsy-proven fibrosis and steatosis. CONCLUSION: hs-CRP was associated with any degree of histologically diagnosed liver damage, and it had a reasonable specificity for predicting biopsy-proven steatosis and fibrosis in obese individuals. Further studies are needed to identify non-invasive biomarkers that could predict NALFD progression due to the relevant health risks linked to liver fibrosis.

Curcumin and chemokines: mechanism of action and therapeutic potential in inflammatory diseases.

Chemokines belong to the family of cytokines with chemoattractant properties that regulate chemotaxis and leukocyte migration, as well as the induction of angiogenesis and maintenance of hemostasis. Curcumin, the major component of the Curcuma longa rhizome, has various pharmacological actions, including anti-inflammatory, immune-regulatory, anti-oxidative, and lipid-modifying properties. Chemokines and chemokine receptors are influenced/modulated by curcumin. Thus, the current review focuses on the molecular mechanisms associated with curcumin's effects on chemoattractant cytokines, as well as putting into context the many studies that have reported curcumin-mediated regulatory effects on inflammatory conditions in the organs/systems of the body (e.g., the central nervous system, liver, and cardiovascular system). Curcumin's effects on viral and bacterial infections, cancer, and adverse pregnancy outcomes are also reviewed.

Statins and peripheral neuropathy in diabetic and non-diabetic cases: a systematic review.

OBJECTIVES: Peripheral neuropathy (PN), as an adverse reaction attributed to statin drugs, as well as the beneficial neuroprotective properties of statins, have been widely reported and discussed in the literature. The aim of this study was to systematically review original publications that investigated the association of statin use and PN in diabetic and non-diabetic models, whether determined as a result of laboratory experimentation, or in a clinical setting. KEY FINDINGS: A comprehensive search of the databases Google Scholar, PubMed/MEDLINE and Scopus was conducted. Sixty-six articles, which evaluated the link between statins and PN in either a clinical or in-vivo/in-vitro condition were included. Statin treatment in neuropathy-induced animal models demonstrates favourable neurological effects in both the morphological and functional aspects of neurons. However, an extended duration of statin treatment is minimally associated with the development of non-diabetic idiopathic neuropathy. Importantly, statins have the potential to regress diabetic PN through anti-inflammatory, anti-oxidant and immunomodulatory properties. SUMMARY: When interpreting the results from studies that deal with the relationship between statins and PN, it is important to determine the mechanism(s) underlying the development of any potential neuropathies (in the presence or absence of diabetes), the type of model used (human or animal) and the duration of statin treatment.

Neutrophil extracellular trap: A key player in the pathogenesis of autoimmune diseases.

Numerous studies suggest that neutrophils might have a crucial role in the pathogenesis of systemic autoimmune diseases through neutrophil extracellular trap (NET) formation, production of pro-inflammatory cytokines, and organ destruction. NET components that are released into extracellular spaces can be considered autoantigens, which contribute to causing a break in self-tolerance. Subsequently, this leads to the development of autoimmune responses in predisposed individuals. Additionally, an imbalance between NET formation and NET degradation may prolong immune system contact with these modified autoantigens and enhance NET-induced tissue damage. In this review, we discuss the generation and clearance of the NET, as well as the role of NETosis in the pathogenesis of autoimmune disorders, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), multiple sclerosis (MS), psoriasis, antiphospholipid syndrome (APS), and Type-1 diabetes mellitus (T1DM).

Anticancer potential of curcumin-cyclodextrin complexes and their pharmacokinetic properties.

Cancer is one of the most common diseases throughout the world, with many treatment modalities currently being used, and new treatment strategies being sought. Most chemotherapeutic molecules have shown extensive toxicity for normal cells, which leads to severe adverse effects. Chemotherapy may also lead to drug resistance, which is one of the major obstacles to the clinical treatment of cancer. Curcumin, a polyphenolic natural compound, has long been considered a therapeutic molecule for a variety of diseases and possesses anti-cancer, anti-oxidant, and anti-inflammatory properties. However, its use is limited due to its hydrophobic nature, poor solubility in water at acidic or neutral pH, and limited bioavailability at the tumor site. Cyclodextrin complexes of curcumin increase curcumin's water solubility, as well as its physicochemical stability to hydrolysis and photochemical decomposition. The most common type of cyclodextrin used for pharmaceutical preparations is ß-cyclodextrin. This review focuses on different curcumin-cyclodextrin formulations and compares their pharmacokinetic parameters and efficacy.

Immunomodulatory Therapeutic Effects of Curcumin on M1/M2 Macrophage Polarization in Inflammatory Diseases.

BACKGROUND: Due to their plasticity, macrophages exert critical effects on both promoting and suppressing inflammatory processes. Pathologic inflammatory conditions are frequently correlated with dynamic alterations in macrophage activation, with classically activated M1 cells associated with the promotion and maintenance of inflammation and M2 cells being linked to the resolution or smouldering of chronic inflammation. Inflammation deputes a common feature of various chronic diseases and the direct involvement in the insurgence and development of these conditions. Macrophages participate in an autoregulatory loop characterizing the inflammatory process, as they produce a wide range of biologically active mediators that exert either deleterious or beneficial effects during the inflammation. Therefore, balancing the favorable ratios of M1/M2 macrophages can help ameliorate the inflammatory landscape of pathologic conditions. Curcumin is a component of turmeric with many pharmacological properties. OBJECTIVE: Recent results from both in-vivo and in-vitro studies have indicated that curcumin can affect polarization and/or functions of macrophage subsets in the context of inflammation-related diseases. There is no comprehensive review of the impact of curcumin on cytokines involved in macrophage polarization in the context of inflammatory diseases. The present review will cover some efforts to explore the underlying molecular mechanisms by which curcumin modulates the macrophage polarization in distant pathological inflammatory conditions, such as cancer, autoimmunity, renal inflammation, stroke, atherosclerosis, and macrophage-driven pathogenesis. RESULTS: The accumulation of the findings from in vitro and in vivo experimental studies suggests that curcumin beneficially influences M1 and M2 macrophages in a variety of inflammatory diseases with unfavorable macrophage activation. CONCLUSION: Curcumin not only enhances anti-tumor immunity (via shifting M polarization towards M1 phenotype and/or up-regulation of M1 markers expression) but ameliorates inflammatory diseases, including autoimmune diseases (experimental autoimmune myocarditis and Behcet's disease), nephropathy, chronic serum sickness, stroke, and atherosclerosis.

Immunometabolism Dysfunction in the Pathophysiology and Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and joint damage. Systemic complications and progressive disability are burdens that lead to a significant socio-economic costs in patients with RA. Current RA biomarkers used in predicting, diagnosing, and monitoring the treatment of the disease have not been very successful. Moreover, only 60% of patients show a satisfactory response to current biological and conventional therapies. Studies on immunometabolism have suggested that dysregulated enzymes, transcription factors, metabolites, and metabolic pathways could be considered potential therapeutic targets for the treatment of RA. Factors such as the high concentration of various intermediate molecules arising from metabolism, hypoxia, lack of nutrients, and other metabolic alterations affect local immune responses and preserve a state of chronic inflammation in synovial tissues. Fortunately, in vitro and in vivo studies have shown that targeting specific metabolic pathways is associated with a decreased level of inflammation. Specifically, targeting metabolic intermediates, such as succinate or lactate, has shown promising clinical outcomes in RA treatment. These findings open an avenue for the identification of novel biomarkers for diagnosis, prognosis, and determining the success of various treatments in RA patients, as well as the discovery of new therapeutic targets.

Prevalence of Amiodarone Induced Hypothyroidism and Hyperthyroidism in Patients with Heart Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Due to the importance of amiodarone-induced hyperthyroidism in patients with heart failure, the purpose of the present systematic review and metaanalysis was to determine the prevalence of thyroid dysfunction (hypothyroidism and hyperthyroidism) in patients with heart disease who received amiodarone. METHODS: Electronic databases including Scopus, PubMed, Web of Science, and Science Direct were searched by two investigators. To assess the heterogeneity between the included studies, the chi-square χ2 test (α=0.05) and I2 index were used. Additionally, a random-effects model with 95% CI was used to estimate the pooled prevalence of thyroid dysfunction due to the heterogeneity of the studies. To identify the cause of heterogeneity, a meta-regression analysis was employed. All analyses were performed using Stata ver13 (Stata Corporation, College Station, TX, USA). RESULTS: The pooled prevalence of hypothyroidism was 23.43% (95% CI: 11.54-35.33) and hyperthyroidism was 11.61% (95% CI: 7.20-16.02). There was no significant association between the prevalence of hypothyroidism and the year of the study (p=0.152), sample size (p=0.805), and mean age of subjects in the sample groups (p=0.623). However, there was a significant association between the prevalence of hyperthyroidism and the year of the study (p=0.037), but no statistically significant association between either the prevalence of hyperthyroidism and sample size (p=0.425), or the prevalence of hyperthyroidism and the mean age of subjects in the sample groups (p=0.447). CONCLUSION: The prevalence of thyroid dysfunction in patients with cardiac arrhythmias receiving amiodarone was considerable. Extreme care should be exercised to improve the monitoring of any thyroid abnormalities that may arise in patients receiving amiodarone.

The ins and outs of lipoprotein(a) assay methods.

Pathophysiological, epidemiological and genetic studies convincingly showed lipoprotein(a) (Lp(a)) to be a causal mediator of atherosclerotic cardiovascular disease (ASCVD). This happens through a myriad of mechanisms including activation of innate immune cells, endothelial cells as well as platelets. Although these certainties whether or not Lp(a) is ready for prime-time clinical use remain debated. Thus, remit of the present review is to provide an overview of different methods that have been employed for the measurement of Lp(a). The methods include dynamic light scattering, multi-angle light scattering analysis, near-field imaging, sedimentation, gel filtration, and electron microscopy. The development of multiple Lp(a) detection methods is vital for improved prediction of ASCVD risk.

Phytochemicals: A potential therapeutic intervention for the prevention and treatment of cachexia.

Cachexia, a multifactorial and often irreversible wasting syndrome, is often associated with the final phase of several chronic disorders. Although cachexia is characterized by skeletal muscle wasting and adipose tissue loss, it is a syndrome affecting different organs, which ultimately results in systemic complications and impaired quality of life. The pathogenesis and underlying molecular mechanisms of cachexia are not fully understood, and currently there are no effective standard treatments or approved drug therapies to completely reverse cachexia. Moreover, adequate nutritional interventions alone cannot significantly improve cachexia. Other approaches to ameliorate cachexia are urgently needed, and thus, the role of medicinal plants has received considerable importance in this respect due to their beneficial health properties. Increasing evidence indicates great potential of medicinal plants and their phytochemicals as an alternative and promising treatment strategy to reduce the symptoms of many diseases including cachexia. This article reviews the current status of cachexia, the molecular mechanisms of primary events driving cachexia, and state-of-the-art knowledge that reports the preventive and therapeutic activities of multiple families of phytochemical compounds and their pharmacological mode of action, which may hold promise as an alternative treatment modality for the management of cachexia. Based on our review of various in vitro and in vivo models of cachexia, we would conclude that phytochemicals may have therapeutic potential to attenuate cachexia, although clinical trials are required to unequivocally confirm this premise.

Curcumin: A dietary phytochemical for boosting exercise performance and recovery.

Curcumin, as the main natural compound in the turmeric plant (Curcuma longa), is a yellowish polyphenol that has been used traditionally in Asian countries as a medicinal herb for various types of disease and pathological conditions caused by inflammation and oxidative stress. In the present review, we conducted a comprehensive literature search for evidence that shows the effect of curcumin on factors influencing exercise performance, including muscle damage, muscle soreness, inflammation, and oxidative stress. During exercise, reactive oxygen species and inflammation are increased. Thus, if there is no balance between endogenous and exogenous antioxidants and increases in oxidative stress and inflammation, which is important for maintaining redox homeostasis in skeletal muscle, it can lead to muscle soreness and muscle damage and ultimately result in reduced exercise performance. Due to the anti-oxidant and anti-inflammatory properties of curcumin, it can increase exercise performance and decrease exercise-induced muscle soreness and muscle damage. It appears that curcumin supplementation can have positive effects on exercise performance and recovery, muscle damage and pain, inflammation, and oxidative stress. However, there is still a need to precisely evaluate factors to more accurately assess/quantify the beneficial therapeutic effects of curcumin with regard to enhancing exercise performance and recovery.