Folate-Modified Curcumin-Loaded Nanoparticles for Overcoming Delivery Challenges in Cancer Treatment: A Narrative Review.

Curcumin, as an anti-tumor agent, is not widely used in cancer treatment due to the lack of effective levels of its metabolites in cancerous tissue. Addressing the barriers to the carrier and delivery of drugs to the specific sites of therapeutic action while reducing side effects is a priority. Folate receptor expression is high in malignant and low in normal cells. Folate as a targeted ligand could selectively target cancer cells. Thus, this narrative review aimed to provide an overview of the studies that have investigated the different types of folate-modified curcumin as a carrier and deliverer and their structural properties that enhance therapeutic drug efficacy. A literature search was performed using PubMed, Scopus, Web of Science, and Google Scholar databases. Thirty-eight preclinical studies addressing this topic were identified. The findings of the current review have shown that folate-modified nanoparticles containing curcumin as a promising therapeutic approach can be effective in improving different types of cancers. In vitro studies have shown a higher cellular uptake and cytotoxicity effect, higher cell inhibition, and anti-proliferation with a lower dosage of curcumin. In vivo studies have shown more tumor suppression and smaller tumor volume without toxicity after the administration of folate-modified nanoparticles containing curcumin. Future clinical trials are needed to confirm the beneficial effect of folate-modified curcumin as a new drug delivery platform for cancer treatment.

Relationship Between Human FCγRIIA rs1801274 G Allele and Risk of Death Among Different SARS-CoV-2 Variants.

Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and spread very quickly across the world. Different responses to infections have been related to fragment crystallizable gamma-receptor II alpha (FcγRIIA) polymorphisms. The purpose of this investigation was to determine if FCγRIIA rs1801274 polymorphism was related to COVID-19 mortality among different variants of SARS-CoV-2. The FCγRIIA rs1801274 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism technique in 1,734 recovered and 1,450 deceased patients. Deceased patients had significantly higher minor allele frequency of the FCγRIIA rs1801274 G allele than in the recovered cases. The COVID-19 mortality was associated with FCγRIIA rs1801274 GG and AG genotypes in the Delta variant and with FCγRIIA rs1801274 GG genotypes in the Alpha and Omicron BA.5 variants. The reverse transcription-quantitative polymerase chain reaction Ct values revealed statistically significant differences between individuals with a G allele and those with an A allele. In conclusion, among the several SARS-CoV-2 variants, there may be a correlation between the mortality rate of COVID-19 and the G allele of FCγRIIA rs1801274. To confirm our findings, thorough research is still required.

Current evidence on dietary factors and kidney allograft function in kidney transplant recipients: a systematic review.

BACKGROUND: Currently, there is no accounted-for consensus and practical standard when counseling diet modification for kidney transplant recipients (KTRs). There are many differences between transplant centers regarding what KTRs are needed to follow a diet, what dietary factors and supplements are allowed, and how long KTRs should follow a modified diet. Relatively few scatter data are available for dietary factors in KTRs. Thus, we aimed to systematically review the literature on the purported dietary factors for kidney function. METHODS: A systematic literature search was performed between February and March 2022 and updated in February 2023 using PubMed, Scopus, Web of Science, and Google Scholar. We included human observational and interventional studies that evaluated a dietary factor on kidney function and graft survival in KTRs. Data were extracted, and the risk of bias was assessed using established tools relevant to the study design. RESULTS: Of the 5341 citations retrieved, seven prospective cohorts, five cross-sectional, seventeen randomized, and ten non-randomized clinical trials were included that evaluated seven purported dietary factors. Almost half of the studies (n = 22; 56%) were classified as having a low degree of bias and sufficient support. Twenty-one studies (54%) reported a positive effect on KTRs. DASH and Mediterranean diets decreased graft failure, low-sodium diet reduced blood pressure, and antioxidants improved creatinine, GFR, and graft function. Of these, only twelve studies (31%) were at low risk of bias. CONCLUSION: Some dietary factors, including DASH, Mediterranean, moderate protein, and low-sodium diet, as well as antioxidants, may be associated with improved survival and kidney function in KTRs. However, more research is needed.

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.

Evaluation of non-invasive arterial stiffness parameters and their relationship with physical activity, anthropometric indices and lipid profiles in healthy middle-aged adults: Results of the PERSIAN cohort study.

BACKGROUND: Arterial stiffness (AS) indicates the initial stage of cardiovascular disease (CVD), which is associated with modifiable and lifestyle risk factors. We aimed to examine the association of AS with anthropometric indices, lipid profiles and physical activity (PA). METHODS: Six hundred and fifty-eight healthy middle-aged adults were selected and anthropometric indices [body mass index, waist circumferences (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), neck circumferences, a body shape index (ABSI), body roundness index (BRI), body fat mass (BFM), visceral fat area, fat-free mass (FFM), lipid profiles and PA] were measured. AS is measured by carotid-femoral pulse wave velocity (cf-PWV) and central augmentation index (cAIx). RESULTS: Our results show that cf-PWV was positively associated with TGs (ß = 0.10, P = .01) and anthropometric indices correlated with WC (ß = 0.11, P = .02), WHR (ß = 0.09, P = .03), WHtR (ß = 0.1, P = .02) and BRI (ß = 0.09, P = .04). cAIx was independently positively associated with cholesterol (ß = 0.08, P = .03), WC (ß = 0.1, P = .03), WHR (ß = 0.09, P = .02), ABSI (ß = 0.09, P = .01), BRI (ß = 0.08, P = .05), visceral fat area (ß = 0.09, P = .03) and BFM (ß = 0.08, P = .04) and negatively associated with PA (ß = -0.08, P = .03). CONCLUSIONS: WC, WHR and BRI were associated with both cf-PWV and cAIx. TGs and WHtR were associated with cf-PWV, while cAIx was associated with ABSI, improving these indices may be helpful to prevent CVD.

Impact of curcumin on fatty acid metabolism.

Free fatty acids (FFAs) and fatty acid synthesis (FAS) activity have significantly contributed to disease states such as insulin resistance, obesity, type 2 diabetes, myocardial infarction, blood pressure, and several types of cancer. Currently, several treatment options are available for patients with these conditions. Due to safety concerns, adverse effects, limited efficacy, and low tolerability associated with many medications, the identification of novel agents with less toxicity and a more favorable outcome is warranted. Curcumin is a phenolic compound derived from the turmeric plant with various biological activities, including anticarcinogenic, antioxidant, antiinflammatory, and hypolipidemic properties. PubMed, Scopus, and Web of Science were searched up to February 2020 for studies that demonstrated the efficacy and mechanisms of curcumin action on FFAs, FAS, and ß-oxidation activity, as well as the desaturation system. Most of the evidence is in-vivo and in-vitro studies that demonstrate that curcumin possesses regulatory properties on FFAs levels through its effects on FAS and ß-oxidation activity as well as desaturation system, which could improve insulin resistance, obesity, and other FFAs-related disorders. The present study provides a review of the existing in-vitro, in-vivo, and clinical evidence on the effect of curcumin on FFAs and FAS activity, ß-oxidation, and desaturation system.

Does Dietary Intake Impact Omentin Gene Expression and Plasma Concentration? A Systematic Review.

BACKGROUND: Omentin is an adipokine with anti-inflammatory and insulin-sensitizing effects that can play a protective role against cardiovascular disease and diabetes. The aim was to systematically review and summarize the existing evidence on the association between overall dietary intake and omentin gene expression and circulation. SUMMARY: A literature search was conducted in PubMed, Scopus, and Web of Science up to September 2019. Of the 1,940 retrieved articles, 20 relevant studies were included, 6 of which were observational, 11 were clinical trials in humans, and 3 were animal studies. Four randomized controlled trials (RCTs) had a high risk of bias (RoB), 1 had "some concerns", and 2 had a low RoB. Among the nonrandomized studies with comparators, 4 had a serious RoB and 2 had a moderate RoB. In the experimental animal studies with a moderate RoB, conflicting results for omentin serum concentration were found for high-fat and low-fat diets. A high-fat diet (HFD) was shown to reduce omentin gene expression in one animal study. In the observational studies, omentin serum concentration was reduced by Ramadan fasting and saturated fatty acid (SFA) intake, and an increase in omentin gene expression was observed with monounsaturated fatty acid (MUFA) intake. There was no association of dietary inflammatory index (DII), macronutrient intake, or total calorie intake with omentin plasma concentrations. In the human interventional studies, omentin plasma concentration increased with a long-term low-calorie, low-fat diet (LFD), and no change was seen with a HFD or a short-term low-calorie diet (LCD). Key Messages: It seems that a long-term diet with a lower fat content and a balanced distribution of fatty acids, i.e., a higher MUFA and lower SFA intake, may effectively increase omentin plasma concentration, possibly via improved insulin resistance and reduced inflammation, but more research is needed to confirm or refute this.

Therapeutic use of curcumin-encapsulated and curcumin-primed exosomes.

Curcumin, the bioactive pigment of turmeric which has polyphenolic-hydrophobic components, has been used for the treatment of a variety of diseases. However, due to its insignificant intestinal-liver metabolism, low stability, quick systemic elimination and its hydrophobic property with low solubility, curcumin has limited bioavailability. Exosomes are nanovesicles (30-100 nm) released from diverse cell types into extracellular and, ultimately, into bio-fluids in a tightly regulated manner. Exosomes are capable of transferring lipids, proteins, RNAs and DNAs, both with and without direct cell-to-cell contact. Curcumin-encapsulated exosomes are highly bioavailable, soluble and safe, and can reach high concentrations in the blood; they, therefore, have therapeutic potential without toxic effects and immune stimulation. Thus, curcumin-encapsulated exosomes could be superior to other synthetic nanoparticles as a carrier of curcumin. The aim of the current review is to offer an overview of the in vitro, in vivo and clinical studies pertaining to the role of curcumin-primed and curcumin-encapsulated exosomes in the treatment of cancer, oxidative stress, brain disorders, cholesterol, and endothelial dysfunction.

Hormetic effects of curcumin: What is the evidence?

Curcumin (diferuloylmethane), a component of the yellow powder prepared from the roots of Curcuma longa or Zingiberaceae (known as turmeric) is not only widely used to color and flavor food but also used as a pharmaceutical agent. Curcumin demonstrates anti-inflammatory, anticarcinogenic, antiaging, and antioxidant activity, as well as efficacy in wound healing. Notably, curcumin is a hormetic agent (hormetin), as it is stimulatory at low doses and inhibitory at high doses. Hormesis by curcumin could be also a particular function at low doses (i.e., antioxidant behavior) and another function at high dose (i.e., induction of autophagy and cell death). Recent findings suggest that curcumin exhibits biphasic dose-responses on cells, with low doses having stronger effects than high doses; examples being activation of the mitogen-activated protein kinase signaling pathway or antioxidant activity. This indicates that many effects induced by curcumin are dependent on dose and some effects might be greater at lower doses, indicative of a hormetic response. Despite the consistent occurrence of hormetic responses of curcumin in a wide range of biomedical models, epidemiological and clinical trials are needed to assess the nature of curcumin's dose-response in humans. Fortunately, more than one hundred clinical trials with curcumin and curcumin derivatives are ongoing. In this review, we provide the first comprehensive analysis supportive of the hormetic behavior of curcumin and curcumin derivatives.

Saffron against Components of Metabolic Syndrome: Current Status and Prospective.

Saffron, the dried stigmas of Crocus sativus L., is mainly used as a food coloring and flavoring agent. This agricultural product is used in traditional medicine for the treatment of several diseases including asthma, liver disease, menstruation disorders, and, of special interest in this review, metabolic syndrome. Saffron and its active components including crocin, crocetin, and safranal are potential therapeutic candidates for attenuating MetS complications including hypertension, hyperglycemia, obesity, and dyslipidemia. This review summarizes the protective role of saffron and its constituents in the pathogenesis of MetS for a better understanding and hence a better management of this disease.