Targeting AhR as a Novel Therapeutic Modality against Inflammatory Diseases

For decades, activation of Aryl Hydrocarbon Receptor (AhR) was excluded from consideration as a therapeutic approach due to the potential toxic effects of AhR ligands and the induction of the cytochrome P450 enzyme, Cyp1a1, following AhR activation. However, it is now understood that AhR activation not only serves as an environmental sensor that regulates the effects of environmental toxins, but also as a key immunomodulator where ligands induce a variety of cellular and epigenetic mechanisms to attenuate inflammation. Thus, the emergence of further in-depth research into diverse groups of compounds capable of activating this receptor has prompted reconsideration of its use therapeutically. The aim of this review is to summarize the body of research surrounding AhR and its role in regulating inflammation. Specifically, evidence supporting the potential of targeting this receptor to modulate the immune response in inflammatory and autoimmune diseases will be highlighted. Additionally, the opportunities and challenges of developing AhR-based therapies to suppress inflammation will be discussed.

Toxicity Effects of Microplastics and Nanoplastics with Cadmium on the Alga Microcystis Aeruginosa

The objective of this paper is to present a thorough analysis of the toxicity of microplastics (MPs) and nanoplastics (NPs) with the heavy metal cadmium (Cd). These components were studied separately and combined to determine how these environmental toxins affect Microcystis aeruginosa (M. aeruginosa) in fresh water. The combined toxicity of MPs or NPs and Cd to M. aeruginosa showed an aggressive and negative effect after 96 h of exposure. Due to the higher adsorption ability of NPs, the accumulation of Cd inside cells with NPs was lower than that found inside the cells with MPs. But the difference in toxicity between the MPs and NPs was not significant. Meanwhile, the more produce of the extracellular polymeric substance (EPS) in the presence of NPs, the more complex effect of EPS bonded to heavy metals, which reduce the toxic effect on the algal cells. Notably, the production of microcystin-LR (MC-LR) under different treatments has demonstrated that the presence of combined MPs/NPs with Cd can potentially raise some of the toxin risks harming the aquatic environment. Our findings highlight the great potential ecological risks of the combined Cd and MPs/NPs in the aquatic system.

RISK FACTORS AND CAUSES OF INFERTILITY

Infertility is the inability of a couple to achieve pregnancy over an average period of one year (in a woman under 35 years of age) or 6 months (in a woman above 35 years of age) despite adequate, regular (3-4 times per week), unprotected sexual intercourse. There are some risk factors that may give chances for infertility like Age, diabetes, eating disorders, including anorexia nervosa and bulimia, excessive use of alcohol, exposure to environmental toxins, such as lead and pesticides, over exercising etc. Infertility may be caused by a number of different factors, either in the male or female reproductive systems. So therefore it is most important to identify the cause and treat the infertility for becoming fertile to a woman.

Investigation of the Effects of Probiotics on Sub-Chronic Neonicotinoid Toxicity in Rats

Probiotics have been shown to have positive effects when it comes to combating various health issues when consumed, preventing even the absorption of environmental toxins. One of the main environmental toxins encountered today is pesticide residues. Neonicotinoids, widely applied today in countries that have approved of them, are a known class of insecticides with an excellent and effective potency. Neonicotinoids have been shown to cause various toxic effects, either acutely or chronically, on human health and on beneficial insects when exposed. To clarify the assumption that probiotics could counteract these toxic effects, especially on vital organs, the probiotic yeast “Saccharomyces boulardii” (S. boulardii) was tested against the neonicotinoids, acetamiprid (ACE) and imidacloprid (IMI), as it has outstanding physiological and metabolic properties. The results obtained from the studies indicated that although ACE and IMI induced liver, kidney, brain and bowel damage, there was a considerable level of protection by the dietary supplementation of S. boulardii, as it reduced the absorption of these insecticides.

Hsp40 Affinity to Identify Proteins Destabilized by Cellular Toxicant Exposure

Environmental toxins and toxicants can damage proteins and threaten cellular proteostasis. Most current methodologies to identify misfolded proteins in cells survey the entire proteome for sites of changed reactivity. We describe and apply a quantitative proteomics methodology to identify destabilized proteins based on their binding to the human Hsp40 chaperone DNAJB8. These protein targets are validated by an orthogonal limited proteolysis assay using parallel reaction monitoring. We find that brief exposure of HEK293T cells to meta-arsenite increases the affinity of two dozen proteins to DNAJB8, including known arsenite-sensitive proteins. In particular, arsenite treatment destabilizes both the pyruvate dehydrogenase complex E1 subunit and several RNA-binding proteins. This platform can be used to explore how environmental toxins impact cellular proteostasis, and to identify the susceptible proteome.

Anti-Hepatotoxic Effect of Vananimbuka (Glycosmis pentaphylla Retz.)

Liver, one of the largest of organs and a chief site for intense metabolism and excretion. It has a surprising role in the maintenance, performance and regulating homeostasis of the body. The major functions of liver are carbohydrate, protein, and fat metabolism, detoxification, secretion of bile and storage of vitamin. Maintaining a healthy liver is a crucial factor for overall health and well-being. But it is continuously and frequently exposed to environmental toxins, abused by poor food habits and alcohol. Prescribed and over-the-counter drugs can eventually lead to various liver ailments like hepatitis and liver cirrhosis. Thus liver diseases are some of the fatal health issues in the world today. According to Ayurveda, Yakrut is considered as one of the 15 koshtangas. It is also considered as sthana of ranjaka pitta and plays an important role in maintenance of agni. Hepatic disorders can be compared to yakrut vikaras and yakrutpleeha vikaras. In ayurveda Vananimbuka discribtion is available for yakrut vikara.

Metabolic Disorders/Obesity Is a Primary Risk Factor in Hidradenitis Suppurativa: An Immunohistochemical Real-World Approach

<b><i>Background:</i></b> Hidradenitis suppurativa (HS) is an inflammatory, potentially scarring disease of the hair follicle, affecting the apocrine gland-bearing skin areas. The major comorbid disorders associated with the occurrence or the aggravation of the disease are obesity and smoking. Numerous efforts to dissociate these factors led to controversial results. <b><i>Objectives:</i></b> To assess the importance of metabolic disorders/obesity, smoking/environmental toxins, and inflammation in HS by utilizing the differential expression of major relevant protein markers in lesional skin of obese/smoking versus non-obese/non-smoking HS patients. <b><i>Methods:</i></b> Lesional skin specimens deriving from two groups of HS patients (BMI &#x3e;30 and smokers, <i>n</i> = 12 vs. BMI &#x3c;30 and non-smokers, <i>n</i> = 10) were stained with antibodies raised against irisin, PPARγ, and IGF-1R, which correlate with metabolic disorders/obesity, EGFR and AhR, associated with smoking, and IL-17, IL-17R, and S100A8, as markers of inflammation. <b><i>Results:</i></b> Metabolic disorders/obesity-related markers exhibited marked differential expression between the two groups, while smoking-associated markers a limited one. IL-17R expression was stronger in obese/smokers, and S100A8 staining exhibited intense strong immunoreactivity in both groups without significant difference. <b><i>Conclusions:</i></b> The notion that obesity plays a role in HS development appears to be supported by the prominent regulation of the associated lesional biomarkers. Tobacco smoking might contribute less to HS than previously suspected.

Recent Progress in Environmental Toxins-Induced Cardiotoxicity and Protective Potential of Natural Products

Humans are unconsciously exposed to environmental toxins including heavy metals as well as various pesticides, which have deleterious effects on human health. Accumulating studies pointed out that exposure to environmental toxins was associated with various cardiopathologic effects. This review summarizes the main mechanisms of cardiotoxicity induced by environmental toxins (cadmium, arsenic and pesticides) and discusses the potential preventive effects of natural products. These findings will provide a theoretical basis and novel agents for the prevention and treatment of environmental toxins-induced cardiotoxicity. Furthermore, the limitations of current studies, future needs and priorities are discussed.

P-296 Examining the link between environmental toxin exposure and uterine leiomyoma: a systematic review

Study question Is there an association between exposure to certain environmental toxins and the prevalence of uterine leiomyoma in women? Summary answer Some evidence was obtained to suggest an association between phthalate esters, bisphenol A, heavy metals, persistent organic pollutants and the prevalence of uterine fibroids. What is known already Environmental toxins are naturally occurring, or human made chemicals that can act as endocrine disrupting chemicals (EDCs) by binding and activating estrogen receptors in the body. Uterine fibroids, often called leiomyoma are non-cancerous growths occurring in the uterus. Though often asymptomatic, they can cause pain, infertility, pregnancy complications and are a leading cause for hysterectomy. The aetiology of leiomyoma is not fully understood but both estrogen and progesterone have been implicated in their growth. We aimed to investigate the epidemiological evidence for the association between EDCs and the prevalence of fibroids. Study design, size, duration We undertook a systematic review and in keeping with PRISMA guidelines, a structured search of Medline, Embase, Scopus, and Web of Science was conducted (to October 2020). Case-control, cross-sectional, cohort and experimental studies were included. Participants/materials, setting, methods The included studies analyzed the association between one or more toxins and the occurrence, or growth of leiomyoma in humans, including human cell lines. The types of toxins, patient characteristics, association and outcome, body concentration of toxin and confounding variables were extracted and analyzed. Quality assessment was performed using the Newcastle-Ottawa Scale. Main results and the role of chance In total, 34 studies were included. The majority (76%) of studies revealed a significant association between the exposure studied and the prevalence of uterine leiomyoma. In examining body burden in cases vs controls, phthalate esters showed an association with increased odds of uterine leiomyoma, except in one case where a negative association was observed. In vitro experimental studies examining the effect of alkyl-phenols such as bisphenol A (BPA), octylphenol (OP) and nonylphenol (NP) demonstrated that these environmental estrogens can act to promote the proliferation of leiomyoma cells through a number of mechanisms, typically including the estrogen receptor alpha (ERa) signalling pathway. There were conflicting results for the association between alkyl-phenols and fibroids in case-control studies. A positive association between cadmium was demonstrated in only two studies. There were conflicting results for the association between lead, mercury, arsenic and uterine fibroids. Several metabolites of organophosphate esters, alternative plasticizers, and persistent organic pollutants were associated with an increased risk of uterine fibroids. Limitations, reasons for caution Separating these exposures from the multiple other factors that could affect the outcome of leiomyoma is challenging, but an important issue for future research. Wider implications of the findings The link between some environmental toxins and uterine fibroids discussed is in agreement with previous literature. However, our review provides a more in depth analysis on specific dosage effects, odds ratios, and potential gene mechanisms of the exposures. This information could contribute to more accurate preventative measures. Trial registration number not applicable