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The increasing demand for natural products in the United States reflects a cultural shift towards health and sustainability. This trend infiltrates consumer sectors such as the sunscreen industry, amidst concerns about health and environmental impacts of chemical ingredients. The Hawaii Sunscreen Ban has intensified sunscreen formula safety discussions, particularly regarding butylparaben, oxybenzone, and octinoxate. Even at low concentrations, these compounds bleach hard corals eventually leading to their death. As well, these chemicals pose threats to marine ecosystems and raise concerns about human health, particularly systemic absorption and the possibility of causing endocrine disruption. While some argue for chemical-based sunscreens for skin cancer prevention, others advocate for mineral-based alternatives that avoid harmful ingredients. However, public opinion on sunscreen varies, influenced by adverse reactions, socioeconomic status, gender, and cultural perceptions. Future studies should explore diverse demographic perspectives and long-term health and environmental impacts of products containing potentially toxic ingredients. As well, effective communication strategies to promote sunscreen safety and encourage sustainable sun protection practices is needed.

Environmental contaminants such as persistent organic pollutants （POPs） are man-made bioaccumulative compounds with long half-lives that are found throughout the world as a result of heavy use in a variety of consumer products during the twentieth century. Wildlife and animal studies have long suggested adverse effects of exposure to these compounds on human reproductive health, which, according to the endocrine disrupter hypothesis, are ascribed to the compounds＇ potential to interfere with endocrine signaling, especially when exposure occurs during certain phases of fetal and childhood development. An extensive number of epidemiological studies have addressed the possible effects of exposure to POPs on male reproductive health, but the results are conflicting. Thus far, most studies have focused on investigating exposure and the different reproductive health outcomes during adulthood. Some studies have addressed the potential harmful effects of fetal exposure with respect to malformations at birth and/ or reproductive development, whereas only a few studies have been able to evaluate whether intrauterine exposure to POPs has long-term consequences for male reproductive health with measurable effects on semen quality markers and reproductive hormone levels in adulthood. Humans are not exposed to a single compound at a time, but rather, to a variety of different substances with potential divergent hormonal effects. Hence, how to best analyze epidemiological data on combined exposures remains a significant challenge. This review on POPs will focus on current knowledge regarding the potential effects of exposure to POPs during fetal and childhood life and during adulthood on male reproductive health, including a critical revision of the endocrine disruption hypothesis, a comment on pubertal development as part of reproductive development and a comment on how to account for combined exposures in epidemiological research.

Pharmaceutical wastes are emerging as significant groundwater contaminants, raising concerns over their long-term impacts on public health and ecosystems. This review examines the major sources of contamination—such as wastewater treatment plants (WWTPs), septic systems, industrial discharges, and agricultural runoff—and explores how physicochemical properties and subsurface interactions influence their environmental fate. Although advanced analytical tools, such as liquid chromatography–tandem mass spectrometry (LC-MS/MS), have improved detection at trace levels, challenges in effective removal persist. Frequently detected contaminants include non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, antidepressants, and hormone-disrupting compounds, often present in concentrations ranging from nanograms to micrograms per litre. Promising treatment technologies, including advanced oxidation processes and activated carbon adsorption, are discussed alongside their limitations. This review highlights the urgent need for comprehensive monitoring programmes, cost-effective remediation methods, and further investigation into the chronic effects of low-dose pharmaceutical exposure.

Female pet dogs are sterilized by surgically removing their ovaries as a means to eliminate the source of germ cells and sex steroids. Surgical sterilization is inevitably invasive to the animals and costly to their owners, and an alternative method that is non-invasive and affordable has been long sought without success. In this study, a proof-of-concept of sterilizing female dogs by a non-surgical alternative was developed and successfully tested. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Introduction: Serotonin produced in the periphery has been shown to affect glucose and lipid homeostasis. The availability of the amino acid tryptophan, the precursor of serotonin, affects serotonin availability. In addition, the metabolism of tryptophan via the kynurenine pathway produces physiologically active metabolites which have been shown to be altered under conditions of increased adiposity and dysglycemia. There is now evidence demonstrating some environmental xenobiotics, known to affect glucose and lipid homeostasis, can also alter serotonin production and key components of the kynurenine pathway. Recent evidence suggests that exposure to compounds present in petroleum and wastewaters from oil and gas extraction sites can impact endocrine signaling and result in aberrant lipid accumulation and altered glycemic control. However, whether any of these changes can be causally ascribed to altered serotonin synthesis/signaling or tryptophan metabolism remains unknown. The goal of this study was to determine the effects of exposure to naphthenic acid (NA), a key toxicant found in wastewater from bitumen (thick crude oil present in oil sands deposits) extraction on the enzymes involved in tryptophan metabolism and serotonin production. Methods: McA-RH7777 rat hepatoma cells, were exposed to a technical NA mixture for 48 hours at concentrations within the reported range of NA found in wastewaters from oil extraction. We assessed mRNA expression for key rate-limiting enzymes involved in tryptophan metabolism that lead to either serotonin [Tph1] and/or kynurenine [Ido2 and Tdo2] production, as well as downstream enzymes in the kynurenine pathway [Afmid, Kyat1, Aadat, Kyat3, Kmo, Haao, Acmsd, Qprt]. We also examined the effects of NA on prostaglandin synthesis [Ptgs1, Ptgs2, Ptges] and signalling [Ptger2, Ptger4] as prostaglandins have been shown to be induced by serotonin and are linked to hepatic fat accumulation. Results: NA treatment significantly increased Tph1 and Ido2 expression; this occurred in association with a significant increase in the expression of the inducible prostaglandin synthase Ptgs2 (COX-2), prostaglandin E synthase Ptges, and prostaglandin receptors Ptger2 and Ptger4. Acmsd was the only downstream enzyme in the kynurenine pathway that was significantly altered by NA treatment. Conclusion: These results provide proof-of-concept that compounds associated with oil sands extraction have the potential to perturb key components of serotonin synthesis (Tph1) and tryptophan metabolism (Ido2, Acmsd). Furthermore, we found that the increase in Tph1 expression paralleled expression of Ptgs2. As increased prostaglandin production has been reported in association with nonalcoholic steatohepatitis, these data provide a potential mechanism by which exposure to NA and other petroleum-based compounds may increase the risk of metabolic disease.

Exposure to xenobiotic estrogens has the potential to induce estrogen activity that may contribute to a range of undesired physiological effects including the stimulation of estrogen responsive tumors. We have previously determined that extracts of OTC medications containing the stimulant laxative bisacodyl induce estrogenic activity in tissue culture bioassays. In this study, we tested the hypothesis that bisacodyl is responsible for the estrogen activity of these extracts and then characterized these effects. Ethanol extracts and dilutions were prepared from OTC medications containing Bisacodyl (1 gm:1 ml). The estrogen agonist and antagonist activity of each extract, as well as bisacodyl and then metabolite DA-bisacodyl was determined using the T47dkbluc estrogen reporter gene and the MCF-7 E3 estrogen responsive proliferation assays. LC-MS analysis was used to determine bisacodyl and DA-bisacodyl concentration in extracts as well as to trace the metabolism of bisacodyl to DA-bisacodyl in the cell culture bioassays. Molecular modeling “docking” simulations of the interactions of bisacodyl and the metabolite DA-bisacodyl with the estrogen receptor (ER) ligand binding domain was performed using MOE from Chemical Computing Group. Bisacodyl and the metabolite DA-bisacodyl induced mixed agonist/antagonist activity in MCF-7 E3 estrogen responsive proliferation assay similar to 4OH-tamoxifen. At the same time, both compounds stimulated only minimal estrogen activity in the T47dkbluc estrogen reporter gene assay. LC-MS analysis determinations identified that almost all bisacodyl was converted to the dihydroxy metabolite DA-bisacodyl in cell culture bioassays. Molecular modeling “docking” simulations determined that while bisacodyl does not fit into the agonist (estradiol) or antagonist (4OH-tamoxifen) conformations of the estrogen receptor ligand binding site, the metabolite DA-bisacodyl may fit into the antagonist induced binding pocket of the ER in a reasonable way. This study characterizes the observed estrogen activity of extracts from OTC medications containing bisacodyl as resulting from the bisacodyl metabolite DA-bisacodyl interacting with the estrogen receptor. Thus, bisacodyl is an OTC medication active ingredient that has potential to induce side effects and or toxicity involving estrogen signalling. The capacity for medications containing bisacodyl or other estrogenic substances to induce estrogen activity in patients is unclear. At the same time, consumers and practitioners should be aware of the potential estrogen activity of bisacodyl containing products.

Bisphenols are Endocrine Disrupting Compounds (EDCs) linked to negative fertility outcomes in humans. The most common one, bisphenol A (BPA) is a plasticizer that acts as an estrogen agonist. Alternatives such as BPS and BPF are becoming widespread and possess similar activities. The oocyte and nearby granulosa cells are particularly vulnerable to EDCs as they are dependent on hormone signaling. Granulosa-Granulosa cell communications are pivotal for proper development and are mediated by gap junction molecules, called connexins (Cxs). Cx37, Cx26, and Cx43 are crucial in follicular communication and are the focus of this study. Bisphenols can alter these genes which directly affects cell-cell communication and in turn proper development. This study uses an in vitro cell culture model of bovine granulosa cells as the bovine species is an excellent translational model for human reproductive toxicology. To determine optimal doses and exposure times, we performed a cytotoxic assay (CCK8) and treated cells with a low dose (0.5 μg/mL), a medium dose (5 μg/mL), the current reported LOAEL (50 μg/mL), and a high dose (0.5 mg/mL) of bisphenols for 1, 6, 12, 24, 48, and 72 hrs. The high dose was lethal at all time points for BPA/BPF, while BPS was toxic from 1 hrs (P=0.0016; n=4). The LOAEL dose was toxic for BPA at 6, 12, 24 hrs (P=0.018, 0.0021, 0.0042 respectively; n=7) and was lethal at 48/72 hrs. BPF at the LOAEL dose showed an increase in cell viability at 6 hrs which was significant at 12hrs (P=0.0119; n=5). This trend declined at 48/72 hrs but was not significant. BPS did not affect cell viability at any other dose and the medium dose did not affect viability for all bisphenols; however, the low dose of BPA/BPF showed a trend towards decreased viability at 48 hrs of treatment. Therefore, we looked at the effects of BPA/S/F at the low and LOAEL doses for 12/48 hrs. We used qPCR and western blotting to quantify transcripts and proteins of the three connexins. Our data show that Cx43 mRNA was significantly increased at the LOAEL dose for BPA/BPF at 12 hrs (p=0.02; n=6). Preliminary data on proteins indicate a decrease and increase in expression at 12hrs for BPA/BPF treatment, respectively, at the LOAEL dose. BPS shows no effect on Cx43. BPS low dose and BPA/BPF LOAEL doses at 12 and 48 hrs increase Cx37 mRNA. Preliminary data on the protein levels show a significant decrease of Cx37 protein at BPA low dose, but no changes after exposure to the other bisphenols. Lastly, Cx26 mRNA is significantly increased after BPA treatment at the LOAEL dose at 12 hrs (P<0.0001; n=5). This novel study investigates the effects of low/high doses and short-term/chronic exposure of bisphenols on cell-cell communication in granulosa cells and provides the basis for future studies on bisphenol toxicity in early development.

Context: Graves’ orbitopathy (GO) an autoimmune disease in orbit, characterized with proptosis due to excessive proliferation, adipogenesis, fibrosis and hyaluronan secretion of orbital fibroblasts (OFs). OFs is potential to be a target for proptosis. But there are few effective therapies. Objectives: Our present purpose was to evaluate the effects of artemisinin (ARS) and the derivatives dihydroartemisinin (DHA), artesunate (ART) on OFs from GO patients in vitro. Design/Setting/Participants: OFs isolated from patients with GO (n = 10) were allowed to proliferate in the proliferation medium (PM); differentiate into adipocytes in the differentiation medium (DM) or differentiate into myofibroblast stimulated by TGF-β (10ng/ml); or produce hyaluronan stimulated by IL-1β (5ng/ml). Different dosages of ARS and the derivatives were administered in the above conditions. Main Outcome Measures: CCK-8 was used to assessed cell viability of OFs, EdU incorporation and flow cytometry were conducted to assess cellular proliferation. Adipogenesis was determined by Western blot and Oil Red O staining. Hyaluronan was quantified by ELISA. Fibrosis was assessed using Western blot. Results: ARS in concentrations lower than 100 μM, DHA < 20 μM and ART < 10 μM are nontoxic for OFs. Cellular proliferation of GO-OFs was halted by ARS and its derivatives at the maximum nontoxic dosage. ARS and its derivatives exerted an inhibitory action on adipogenesis of OFs in a concentration-dependent manner. Moreover, hyaluronan secretion was obviously decreased by ARS and its derivatives. Intriguingly, fibrosis markers were also decreased by the antimalarias in a dosage-dependent way. Conclusions: We elucidated the efficacies of ARS and its derivatives on proliferation, adipogenesis, fibrosis and hyaluronan production of OFs, supporting that ARS-based antimalarials play potential role as a novel therapy for GO from a perspective of in-vitro study.

Introduction: Patients with COVID-19 infection present with a variety of clinical symptoms such as fever, diarrhea, dyspnea, anosmia and various electrolyte abnormalities. Hypokalemia is an important electrolyte abnormality associated with infection due to SARS-CoV-2 as it may be associated with life threatening cardiac abnormalities Objective: To investigate the prevalence and clinical implications of of hypokalemia and its association with disease severity and various laboratory markers of inflammation. Materials and methods-design, setting and participants: This retrospective study was conducted at Peerless Hospital, Kolkata, West Bengal, India, from March 15, 2020, to September 30, 2020. Participants included patients who received a diagnosis of COVID-19 after testing positive by RT-PCR test and were admitted to the hospital. The patients were classified as having severe hypokalemia (plasma potassium <3 mmol/L), hypokalemia (plasma potassium 3-3.5 mmol/L), and normokalemia (plasma potassium >3.5 mmol/L). We categorized patients into 3 groups of disease severity- mild (fever/uncomplicated upper respiratory tract infection without hypoxemia), moderate (pneumonia with no signs of severe disease, respiratory rate > 24/min OR spO2 <94% in room air) and severe (respiratory distress requiring mechanical ventilation- NIV or invasive, respiratory rate > 30/min Or SpO2 <90% in room air). The clinical features, lab and ECG abnormalities, were compared between the 3 groups. Data analysis was conducted in October 2020. Interventions: The patients were given general support and antiviral therapy. Their epidemiological and clinical features were collected. Results: 122 patients(38.4%) had hypokalemia and 58 patients(18.2%) had severe hypokalemia. There was significant association between disease severity and hypokalemia. Fever had significant association with hypokalemia and severe hypokalemia. There was also significant association between dyspnea, anosmia, decreased oxygen saturation, ECG abnormalities and mortality with hypokalemic patients. Also there was significant association between degree of hypokalemia and markers of systemic inflammation such as IL-6 and CRP. Conclusions: The high prevalence of hypokalemia among patients with coronavirus disease 2019 suggests the presence of disordered rennin angiotensin system activity, which is increased as a result of the reduced counteractivity of angiotensin converting enzyme 2, which is bound by severe acute respiratory syndrome coronavirus. The study also indicates the need to monitor this group of patients for cardiac rhythm disturbances, especially when drugs like hydroxychloroquine and azithromycin, which are known to prolong the QTc interval and are known to reduce the rate of cardiac conduction and cause arrythmias, are used off-label to treat COVID-19.

The mammary gland is a hormone sensitive organ that is susceptible to endocrine disrupting chemicals (EDCs) during several vulnerable periods, including pregnancy and lactation. Mammary gland reorganization during pregnancy and lactation is hormone driven and provides long-term protection against breast cancer risk. It is unknown if EDC exposures during these sensitive windows can alter mammary reorganization to either enhance or offset parity-induced protection against breast cancer. Here, we examined effects of propylparaben (PP), a common preservative used in personal care products and foods with estrogen receptor (ER) agonist properties, on the parous mouse mammary gland. Pregnant BALB/c mice were treated with 0, 20, 100, or 10,000 µg/kg/day PP throughout pregnancy and lactation. These doses were selected for their relevance to human exposures. We also included an unexposed nulliparous female group to evaluate the typical changes associated with parity. Five weeks post-involution (and five weeks after the last PP exposure), mammary glands were collected and assessed for changes in histomorphology, hormone receptor expression, immune cell number, and gene expression. We found that PP reduced many of the typical morphological effects of parity on the mammary gland, resulting in intermediate phenotypes for ductal density and total epithelial structures. Notably, we found increased proliferation in PP-treated mammary glands, despite decreased ductal epithelial volume relative to parous controls. Mammary glands from PP-treated females also had alterations in the expression of ERα-mediated genes, including PgR (the gene that encodes progesterone receptor) and Igf1, with expression levels that were intermediate to both nulliparous and parous control mice. Finally, PP reduced the effect of parity on several immune cell types in the mammary gland including B cells, T-cells, and M2 macrophages. These results suggest that PP, at levels relevant to human exposure, can disrupt the normal response to parity in the mouse mammary gland, including persistent alterations to mammary gland structures. Future studies should address whether PP exposures disturb the protective effects of pregnancy on mammary cancer risk.