Natural Products for Preventing and Managing Anthracycline-Induced Cardiotoxicity: A Comprehensive Review.

Doxorubicin (DOX) is an anthracycline anticancer agent that is highly effective in the treatment of solid tumors. Given the multiplicity of mechanisms involved in doxorubicin-induced cardiotoxicity, it is difficult to identify a precise molecular target for toxicity. The findings of a literature review suggest that natural products may offer cardioprotective benefits against doxorubicin-induced cardiotoxicity, both in vitro and in vivo. However, further confirmatory studies are required to substantiate this claim. It is of the utmost importance to direct greater attention towards the intricate signaling networks that are of paramount importance for the survival and dysfunction of cardiomyocytes. Notwithstanding encouraging progress made in preclinical studies of natural products for the prevention of DOX-induced cardiotoxicity, these have not yet been translated for clinical use. One of the most significant obstacles hindering the development of cardioprotective adjuvants based on natural products is the lack of adequate bioavailability in humans. This review presents an overview of current knowledge on doxorubicin DOX-induced cardiotoxicity, with a focus on the potential benefits of natural compounds and herbal preparations in preventing this adverse effect. As literature search engines, the browsers in the Scopus, PubMed, Web of Science databases and the ClinicalTrials.gov register were used.

Potential of Chlorogenic Acid in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Animal Studies and Clinical Trials-A Narrative Review.

Chlorogenic acid (CGA) is a natural polyphenol found in coffee, tea, vegetables, and fruits. It exhibits strong antioxidant activity and possesses several other biological properties, including anti-inflammatory effects, antimicrobial activity, and insulin-sensitizing properties. Moreover, it may improve lipid and glucose metabolism. This review summarizes the available information on the therapeutic effect of CGA in metabolic dysfunction-associated steatotic liver disease (MASLD). As the literature search engine, the browsers in the PubMed, Scopus, Web of Science databases, and ClinicalTrials.gov register were used. Animal trials and clinical studies suggest that CGA has promising therapeutic potential in treating MASLD and hepatic steatosis. Its mechanisms of action include antioxidant, anti-inflammatory, and anti-apoptotic effects via the activation of the Nrf2 signaling pathway and the inhibition of the TLR4/NF-κB signaling cascade. Furthermore, the alleviation of liver disease by CGA also involves other important molecules such as AMPK and important physiological processes such as the intestinal barrier and gut microbiota. Nevertheless, the specific target cell and key molecule to which CGA is directed remain unidentified and require further study.

Potential of Curcumin in the Management of Skin Diseases.

Curcumin is a polyphenolic molecule derived from the rhizoma of Curcuma longa L. This compound has been used for centuries due to its anti-inflammatory, antioxidant, and antimicrobial properties. These make it ideal for preventing and treating skin inflammation, premature skin ageing, psoriasis, and acne. Additionally, it exhibits antiviral, antimutagenic, and antifungal effects. Curcumin provides protection against skin damage caused by prolonged exposure to UVB radiation. It reduces wound healing times and improves collagen deposition. Moreover, it increases fibroblast and vascular density in wounds. This review summarizes the available information on the therapeutic effect of curcumin in treating skin diseases. The results suggest that curcumin may be an inexpensive, well-tolerated, and effective agent for treating skin diseases. However, larger clinical trials are needed to confirm these observations due to limitations in its in vivo use, such as low bioavailability after oral administration and metabolism.

Does Resveratrol Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)?

Metabolic dysfunction-associated steatotic liver disease (MASLD) is influenced by a variety of factors, including environmental and genetic factors. The most significant outcome is the alteration of free fatty acid and triglyceride metabolism. Lipotoxicity, impaired autophagy, chronic inflammation, and oxidative stress, as well as coexisting insulin resistance, obesity, and changes in the composition of gut microbiota, are also considered crucial factors in the pathogenesis of MASLD. Resveratrol is a polyphenolic compound that belongs to the stilbene subgroup. This review summarises the available information on the therapeutic effects of resveratrol against MASLD. Resveratrol has demonstrated promising antisteatotic, antioxidant, and anti-inflammatory activities in liver cells in in vitro and animal studies. Resveratrol has been associated with inhibiting the NF-κB pathway, activating the SIRT-1 and AMPK pathways, normalizing the intestinal microbiome, and alleviating intestinal inflammation. However, clinical studies have yielded inconclusive results regarding the efficacy of resveratrol in alleviating hepatic steatosis or reducing any of the parameters found in MASLD in human patients. The lack of homogeneity between studies, low bioavailability of resveratrol, and population variability when compared to animal models could be the reasons for this.

Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients.

Metastases to the central nervous system (CNS) in patients with non-small cell lung cancer constitute an extremely difficult clinical problem, and their occurrence is associated with a poor prognosis. Due to the existence of the blood-brain barrier (BBB) and the action of proteins responsible for the transport of drugs, e.g. P-glycoprotein (P-gp), the penetration of drugs into the CNS is insufficient. Until recently, the only method of CNS metastases treatment was radiotherapy and neurosurgery. The advancement of molecular biology allowed discover targets for molecularly targeted therapies. One of targets is abnormal anaplastic lymphoma kinase, which results from the rearrangement of the ALK gene in patients with non-small cell lung cancer (NSCLC). ALK rearrangement occurs in only about 4.5% of NSCLC patients, but its presence favors brain metastases. The ALK inhibitors (ALKi) were modified to obtain molecules with high ability to penetrate into the CNS. This was achieved by modifying the structure of individual molecules, which became, inter alia, less substrates for P-gp. These modifications caused that less than 10% of patients experience progression in CNS during new ALK inhibitors treatment. This review summarizes the knowledge about the action of BBB, the pharmacodynamics and pharmacokinetics of ALKi, with particular emphasis on their ability to penetrate the CNS and the intracranial activity of individual drugs from different generations of ALK inhibitors.

ALK gene rearrangement favors the development of central nervous system (CNS) metastases in patients with NSCLC. New generations of ALK inhibitors penetrate the CNS and induce an intracranial response and protect against new brain lesions.

Alterations of urinary perchlorate levels in euthyroid postpubertal children with autism spectrum disorder.

BACKGROUND: Perchlorates ClO4(-) are known environmental and food contaminants that act as inhibitors of iodine uptake by the thyroid gland; however, information concerning their possible association with the development of autism spectrum disorder (ASD) is still missing. The current study is first presenting the alterations in perchlorate urine levels in euthyroid children with ASD. OBJECTIVES: To examine urinary perchlorates and iodides in euthyroid children diagnosed with ASD, compared to age-, and BMI-matched neurotypical controls, and to verify the association between these two ions in ASD. METHODS: Ions were determined in 24 h urine samples determined by ion chromatography-conductivity cell detection (IC-CD) and ion chromatography-pulsed amperometric detection (IC-PAD) techniques, respectively, in a total of 130 postpubertal euthyroid children with normal BMI (the mean age 14.46 years, SD = 1.32; the mean BMI 20.6, SD = 1.37), divided into age- and BMI-matched groups of ASD patients and neurotypical, healthy children (control). RESULTS: The ASD group presented with significantly higher perchlorate urine levels than the controls (median = 1.05 µg/L, interquartile range(IQR) = 1.5 versus median = 0.09 µg/L, IQR = 0.097, respectively), as well as lower iodide urine levels (median = 100.2 µg/L, IQR = 37 versus median = 156.95 µg/L, IQR = 26.11, respectively). The ASD group presented significantly lower TSH and higher free thyroid hormone (fT4, fT3) levels than the controls. In regression analyses, perchlorate urine levels showed significant positive relationships with normal BMI values and serum TSH, and inverse relationships with serum fT4. Urinary iodide levels showed significant inverse relationships with BMI values. The absence of ASD was associated with decreased odds of perchlorate urine levels (OR = 0.012, 95 % confidence interval [CI] 0.0002-0.76), and increased odds of iodide urine levels (OR = 1.15, 95 %CI 1.05-1.27). CONCLUSIONS: ASD may have an independent and significant impact on perchlorate as well as iodide levels in urine of euthyroid lean postpubertal children. Perchlorate levels do not appear to be directly associated with iodide levels in euthyroid children.

Perchlorate - properties, toxicity and human health effects: an updated review.

Interest in perchlorate as environmental pollutant has increased since 1997, when high concentrations have been found in the waters of the Colorado River, USA. Perchlorate is very persistent in nature and it is slowly degraded. Although harmful effects of large doses of perchlorate on thyroid function have been proven, the environmental effects are still unclear. The primary objective of the present review is to collect prevailing data of perchlorate exposure and to discuss its impact on human health. The results show that more than 50% of reviewed works found significant associations of perchlorate exposure and human health. This review consists of the following sections: general information of perchlorate sources, its properties and determination methods, role and sources in human body including food and water intake, overview of the scientific literature on the research on the effect of perchlorate on human health from 2010 to 2020. Finally, conclusions and recommendations on future perchlorate studies concerning human exposure are presented.

The Role of GPR120 Receptor in Essential Fatty Acids Metabolism in Schizophrenia.

A growing body of evidence confirms abnormal fatty acid (FAs) metabolism in the pathophysiology of schizophrenia. Omega-3 polyunsaturated fatty acids (PUFAs) are endogenous ligands of the G protein-coupled receptors, which have anti-inflammatory properties and are a therapeutic target in many diseases. No clinical studies are concerned with the role of the GPR120 signaling pathway in schizophrenia. The aim of the study was to determine the differences in PUFA nutritional status and metabolism between patients with schizophrenia (SZ group) and healthy individuals (HC group). The study included 80 participants (40 in the SZ group, 40 in the HC group). There were no differences in serum GPR120 and PUFA concentrations and PUFA intake between the examined groups. In the HC group, there was a relationship between FAs in serum and GPR120 concentration (p < 0.05): α-linolenic acid (ALA) (R = -0.46), docosahexaenoic acid (DHA) (R = -0.54), omega-3 PUFAs (R = -0.41), arachidonic acid (AA) (R = -0.44). In the SZ group, FA serum concentration was not related to GPR120 (p > 0.05). In the HC group, ALA and DHA serum concentrations were independently associated with GPR120 (p < 0.05) in the model adjusted for eicosapentaenoic acid (EPA) and accounted for 38.59% of GPR120 variability (p < 0.05). Our results indicate different metabolisms of FAs in schizophrenia. It is possible that the diminished anti-inflammatory response could be a component connecting GPR120 insensitivity with schizophrenia.

Chemical elements and preeclampsia - An overview of current problems, challenges and significance of recent research.

OBJECTIVES: Data on the elemental status, redistribution of the elements, role of occupational exposure and dietary assessment in preeclampsia (PE) are scarce. There are many disparities in the findings of essential and non-essential elements' role in PE. In this article we overview the changes in the content of selected elements in pregnancy complicated with the disorder of complex and not fully understood etiology. We have focused on important limitations and highlighted shortcomings in research from the last ten years period. METHODS: The Scopus and PubMed electronic databases have been searched for English-language articles published within the time interval 2008-2018, with full text available and with the key words "preeclampsia" and "chemical element" (i.e. separately: Cd, Pb, As, Ni, Mo, Co, Cr, Mn, Se, I, Fe, Sr, Cu, Zn, Mg, K and Na) appearing in the title, abstract or keywords. RESULTS: A total of 48 publications were eligible for this overview. Surprisingly only 4% of papers considered environmental exposure, 8%- diet and 2 %- comorbid diseases. In most published papers, occupational exposure was neglected. Meta-analysis was possible for seven elements in serum (Ca, Cu, Fe, Mg, Mn, Se, Zn), and two elements (Se, Zn) in plasma. It showed negative shift for most elements, however only several were statistically significant. CONLUSIONS: The overview of the published data on PE and chemical elements yields varied results. Some of the reasons may be the difference in not duly validated method of determination, and huge discrepancies in study designs. The lack of detailed description of studied and control population and small number of samples constitute the most common limitations of such studies. Many of them describe the use of a single analytical procedure, therefore the quality of research may be insufficient to obtain reliable results. A history of elements' status and intake before and during pregnancy is usually not examined. Dietary assessment should be done at different stages of pregnancy, and whenever possible in the periconceptional period as well. It still needs to be established whether the deficiency of certain elements or their excess may be an etiopathogenic factor and a developmental cause of PE, and if it may serve as a target of actions in the causal treatment or even prevention of the occurrence of this disease.

Alterations of Hair and Nail Content of Selected Trace Elements in Nonoccupationally Exposed Patients with Chronic Depression from Different Geographical Regions.

The aim of this study was to determine if altered levels of selected trace elements manifest themselves during chronic depression. To identify elements strongly associated with chronic depression, relationships between the elemental contents of hair and nails and the interelement correlations were checked. Inductively coupled plasma mass spectrometry and ion chromatography were used to evaluate the contents of Zn, Cu, Co, Pb, Mn, and Fe in hair and nail samples from a total of 415 subjects (295 patients and 120 healthy volunteers). The study included logistic regression models to predict the probability of chronic depression. To investigate possible intercorrelations among the studied elements, the scaled principal component analysis was used. The research has revealed differences in TE levels in the group of depressed men and women in comparison to the healthy subjects. Statistically significant differences in both hair and nails contents of several elements were observed. Our study also provides strong evidence that the intermediary metabolism of certain elements is age- and gender-dependent. Zn, Mn, Pb, and Fe contents in hair/nails seem to be strongly associated with chronic depression. We found no statistically significant residence-related differences in the contents of studied elements in nonoccupationally exposed patients and healthy subjects.