Human Health Risk Assessment and Exposure Evaluation by Monte-Carlo Simulation Method for Aflatoxin M1 in Widely Consumed Infant Dried Powder Milk in Iran.

Monitoring aflatoxin M1 (AFM1) in dairy products and milk-based foods is very important. The main purpose of this research was to investigate and determine the amount and human health risk assessment of aflatoxin M1 (AFM1) in the most famous and widely used brands of infant dried powder milk (IDPM) consumed in Iran. For this study, 45 imported IDPM (IM-IDPM) samples and 45 domestically produced IDPM (DO-IDPM) samples (a total of 90 samples) were selected randomly. All samples were analyzed for AFM1 using a competitive enzyme-linked immunosorbent assay (ELISA) technique. The mean level and the percentage of positive samples for AFM1 in DO-IDPM were 9.2 ± 5.4 ng/kg and 73.3%, and for IM-IDPM, they were 5.1 ± 3.8 ng/kg and 33.3%, respectively. The average level of AFM1 in all samples was lower than the EU and Iranian national standards (25 ng/kg). AFM1 intake through IDPM consumption by Iranian infants less than one-year-old was lower than the allowable level, but the hazard quotient for infants less than 6 months was higher than the allowable level. Although the concentration of AFM1 in IDPM consumed in Iran is not hazardous, since Iranian infants may be exposed to AFM1 through other sources, including baby food, breast milk, raw and pasteurized milk, continuous monitoring of IDMP quality in Iranian markets should be taken.

Profiling Inflammatory Biomarkers following Curcumin Supplementation: An Umbrella Meta-Analysis of Randomized Clinical Trials.

Objective: Several meta-analyses have shown that curcumin can reduce inflammatory biomarkers, but the findings are inconsistent. The objective of the present umbrella meta-analysis was to provide a more accurate estimate of the overall effects of curcumin on inflammatory biomarkers. Methods: The following international databases were systematically searched until March 20, 2022: PubMed, Scopus, Embase, Web of Science, and Google Scholar. A random-effects model was applied to evaluate the effects of curcumin on inflammatory biomarkers. Meta-analysis studies investigating the effects of curcumin supplementation on inflammatory biomarkers with corresponding effect sizes (ES) and confidence intervals (CI) were included in the umbrella meta-analysis. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence. Results: A meta-analyses of ten studies with 5,870 participants indicated a significant decrease in C-reactive protein (CRP) (ES = -0.74; 95% CI: -1.11, -0.37, p < 0.001; I2 = 62.1%, p=0.015), interleukin 6 (IL-6) (ES = -1.07; 95% CI: -1.71, -0.44, p < 0.001; I2 = 75.6%, p < 0.001), and tumour necrosis factor α (TNF-α) levels (ES: -1.92, 95% CI: -2.64, -1.19, p < 0.0; I2 = 18.1%, p=0.296) following curcumin supplementation. Greater effects on CRP and TNF-α were evident in trials with a mean age >45 years and a sample size >300 participants. Conclusion: The umbrella of meta-analysis suggests curcumin as a promising agent in reducing inflammation as an adjunctive therapeutic approach in diseases whose pathogenesis is related to a higher level of inflammatory biomarkers.

Dimethyl Fumarate Attenuates Di-(2-Ethylhexyl) Phthalate-Induced Nephrotoxicity Through the Nrf2/HO-1 and NF-κB Signaling Pathways.

This study aimed to clarify the nephroprotective effect of dimethyl fumarate (DMF) against Di (2-ethylhexyl) phthalate (DEHP)-induced nephrotoxicity in both in vitro and in vivo models. The HEK-293 cells were exposed to different concentrations of DMF plus IC50 concentration of monoethylhexyl phthalate (MEHP) (the main metabolite of DEHP). Then, some of the oxidative stress parameters including ROS, MDA, and GSH, and cytotoxicity (MTT assay) were determined in treated cells. For in vivo evaluation, rats were divided into 7 groups (n = 6 per group). Corn oil group (gavage), DEHP group (200 mg/kg dissolved in corn oil, gavage), DMF (15, 30, and 60 mg/kg, gavage) plus DEHP (200 mg/kg) groups, DMF (60 mg/kg, gavage) alone, and vitamin E (20 mg/kg, intraperitoneal (IP)) plus DEHP (200 mg/kg) group. This treatment continued for 45 days. Then, BUN and creatinine were evaluated by a commercial kit based on the urease enzymatic method and the Jaffe method, respectively. Mitochondrial oxidative stress and mitochondrial dysfunction parameters were evaluated using appropriate reagents, and gene expression of the p65 nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNFα), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were evaluated by real-time PCR method. High concentrations of DMF significantly increased cell viability, and GSH content and significantly decreased ROS and MDA levels compared with the MEHP group in HEK-293 cells. DMF (60 mg/kg) significantly decreased BUN and creatinine levels compared with the DEHP group. Mitochondrial function and mitochondrial swelling were significantly improved in DMF group (60 mg/kg) compared with the DEHP group. DMF (30 and 60 mg/kg) significantly improved MMP collapse compared with the DEHP group. DMF (30 and 60 mg/kg) significantly decreased ROS levels compared with the DEHP group in isolated kidney mitochondria. DMF (60 mg/kg) significantly decreased MDA levels and significantly increased GSH content compared with DEHP group in isolated kidney mitochondria. The mRNA expression levels of Nrf2 and HO-1 were significantly reduced in the DEHP group compared to the control group and were significantly increased in the DMF group compared to the DEHP group. p65NF-κB and TNFα mRNA expression levels were significantly increased in the DEHP group compared to the control group. However, DMF significantly decreased p65NF-κB and TNFα mRNA expression compared to the DEHP group. DMF can act as a nephroprotective agent against DEHP partly through modulation of oxidative stress, mitochondrial function, and inflammation.

Efficacy of vitamin D supplementation as an adjunct therapy for improving inflammatory and oxidative stress biomarkers: An umbrella meta-analysis.

BACKGROUND: Vitamin D supplementation has attracted a lot of attention as a potential modulator of inflammation and oxidative stress, while some studies have reported controversial findings. In this regard, the purpose of this study was to summarize existing systematic reviews and meta-analyses of clinical trials that determined the effects of supplementation with vitamin D on inflammatory and oxidative biomarkers. METHODS: The following international databases were systematically searched till March 20th, 2022: PubMed, Scopus, Embase, Web of Science, and Google Scholar. A random-effects model was applied to evaluate the effects of vitamin D on inflammatory and oxidative stress biomarkers. RESULTS: Overall, 23 meta-analyses were qualified in this umbrella meta-analysis. Our findings revealed that the vitamin D supplementation significantly reduced serum C-reactive protein (CRP) (ES = -0.42; 95% CI: -0.55, -0.29, p < 0.001), tumor necrosis factor-α (TNF-α) (ES = -0.27; 95% CI: -0.42, -0.12; p < 0.001), and malondialdehyde (MDA) concentrations (ES = -0.37; 95% CI: -0.48, -0.25, p < 0.001). However, no significant changes were illustrated regarding interleukin-6 (IL-6) (ES = -0.35, 95% CI: -0.80, 0.10; p = 0.125), total antioxidant capacity (TAC) (ES = 0.68; 95% CI: -0.31, 1.66, p = 0.179), and glutathione (GSH) activity (ES = 0.08; 95% CI: -0.44, 0.60, p = 0.757). CONCLUSION: The present umbrella meta-analysis indicated that supplementation of vitamin D in adults can improve CRP, TNF-α, and MDA levels under various health conditions. Vitamin D could be considered an adjuvant therapy for relieving inflammation and oxidative stress.

Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by neuroinflammation, formation of Lewy bodies, and progressive loss of dopaminergic neurons in the substantia nigra of the brain. In this review, we summarize evidence obtained by animal studies demonstrating neuroinflammation as one of the central pathogenetic mechanisms of PD. We also focus on the protein factors that initiate the development of PD and other neurodegenerative diseases. Our targeted literature search identified 40 pre-clinical in vivo and in vitro studies written in English. Nuclear factor kappa B (NF-kB) pathway is demonstrated as a common mechanism engaged by neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), as well as the bacterial lipopolysaccharide (LPS). The α-synuclein protein, which plays a prominent role in PD neuropathology, may also contribute to neuroinflammation by activating mast cells. Meanwhile, 6-OHDA models of PD identify microsomal prostaglandin E synthase-1 (mPGES-1) as one of the contributors to neuroinflammatory processes in this model. Immune responses are used by the central nervous system to fight and remove pathogens; however, hyperactivated and prolonged immune responses can lead to a harmful neuroinflammatory state, which is one of the key mechanisms in the pathogenesis of PD.

A comprehensive survey into the role of microRNAs in ovarian cancer chemoresistance; an updated overview.

Ovarian cancer (OC), a frequent malignant tumor that affects women, is one of the leading causes of cancer-related death in this group of individuals. For the treatment of ovarian cancer, systemic chemotherapy with platinum-based drugs or taxanes is the first-line option. However, drug resistance developed over time during chemotherapy medications worsens the situation. Since uncertainty exists for the mechanism of chemotherapy resistance in ovarian cancer, there is a need to investigate and overcome this problem. miRNAs are engaged in various signaling pathways that contribute to the chemotherapeutic resistance of ovarian cancer. In the current study, we have tried to shed light on the mechanisms by which microRNAs contribute to the drug resistance of ovarian cancer and the use of some microRNAs to combat this chemoresistance, leading to the worse outcome of ovarian cancer patients treated with systemic chemotherapeutics.

Iron Chelators in Treatment of Iron Overload.

Patients suffering from iron overload can experience serious complications. In such patients, various organs, such as endocrine glands and liver, can be damaged. Although iron is a crucial element for life, iron overload can be potentially toxic for human cells due to its role in generating free radicals. In the past few decades, there has been a major improvement in the survival of patients who suffer from iron overload due to the application of iron chelation therapy in clinical practice. In clinical use, deferoxamine, deferiprone, and deferasirox are the three United States Food and Drug Administration-approved iron chelators. Each of these iron chelators is well known for the treatment of iron overload in various clinical conditions. Based on several up-to-date studies, this study explained iron overload and its clinical symptoms, introduced each of the above-mentioned iron chelators, and evaluated their advantages and disadvantages with an emphasis on combination therapy, which in recent studies seems a promising approach. In numerous clinical conditions, due to the lack of accurate indicators, choosing a standard approach for iron chelation therapy can be difficult; therefore, further studies on the issue are still required. This study aimed to introduce each of these iron chelators, combination therapy, usage doses, specific clinical applications, and their advantages, toxicity, and side effects.

Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer.

Silymarin contains a group of closely-related flavonolignan compounds including silibinin, and is extracted from Silybum marianum species, also called milk thistle. Silymarin has been shown to protect the liver in both experimental models and clinical studies. The chemopreventive activity of silymarin has shown some efficacy against cancer both in vitro and in vivo. Silymarin can modulate apoptosis in vitro and survival in vivo, by interfering with the expression of cell cycle regulators and apoptosis-associated proteins. In addition to its anti-metastatic activity, silymarin has also been reported to exhibit anti-inflammatory activity. The chemoprotective effects of silymarin and silibinin (its major constituent) suggest they could be applied to reduce the side effects and increase the anti-cancer effects of chemotherapy and radiotherapy in various cancer types, especially in gastrointestinal cancers. This review examines the recent studies and summarizes the mechanistic pathways and down-stream targets of silymarin in the therapy of gastrointestinal cancer.