Reactive Organic Suspensions Comprising ZnO, TiO2, and Zeolite Nanosized Adsorbents: Evaluation of Decontamination Efficiency on Soman and Sulfur Mustard

This paper comprises an extensive study on the evaluation of decontamination efficiency of three types of reactive organic suspensions (based on nanosized adsorbents) on two real chemical warfare agents: soman (GD) and sulfur mustard (HD). Three types of nanoparticles (ZnO, TiO2, and zeolite) were employed in the decontamination formulations, for enhancing the degradation of the toxic agents. The efficacy of each decontamination solution was investigated by means of GC-MS analysis, considering the initial concentration of toxic agent and the residual toxic concentration, measured at different time intervals, until the completion of the decontamination process. The conversion of the two chemical warfare agents (HD and GD) into their decontamination products was also monitored for 24 h.

Effects of Lead Nitrate Induced Histological Changes in Liver of Male Sprague Dawley Rats

Lead is a highly toxic agent and a potent risk factor for various diseases as its quantity in an environment is increasing day by day. Aim: To observe and analyze the lead nitrate induced histomorphological changes in the liver of Sprague Dawley rats. Study Design: Experimental Study. Methodology: Animals of group A (control) were fed on normal diet but the animals of group B were given 50mg/kg of lead nitrate dissolved in 10ml of distilled water through oral gavage for 14 days daily. SPSS version 22 was used for data analysis. All the quantitative data was expressed as means ± SD. One Way ANOVA followed by Post Hoc Tukey test was applied. Results: Degenerative effects were noted. The number of Inflammatory and Kupfffer cells is increased with decreased in the body weight. Steatosis and central vein congestion were also present. Conclusion: It was concluded that degenerative effects histologically may be due to oxidative stress produced by formation of free radicals and denaturation of proteins by lead nitrate. Keywords: Lead, Liver, Central Vein Congestion, Oxidative Stress and Free Radicals.

Histopathological and biochemical effect of quercetin on monosodium glutamate supplementation-induced testicular toxicity

Background Despite the wide usage of monosodium glutamate (MSG) as a flavor enhancer in many types of food, it has been reported as a toxic agent to humans and experimental animals. It also adversely influences male fertility. Several research studies attributed detrimental effects of MSG on reproductive organs to oxidative stress. The current study investigated the effects of MSG on testis and the potential role of quercetin in attenuating them. Results MSG-treated rats showed a considerable elevation in lipid peroxidation level and reduction in glutathione concentration, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in the homogenate of testis tissues. Treatment with quercetin in combination with MSG provided significant protection. When QU was used, the toxic side effects were significantly reduced, with a considerable reduction in lipid peroxidation and an increase in SOD and GPx activities, and glutathione concentration. Conclusions Quercetin may be used in combination with MSG to improve the histopathological, ultrastructure, oxidative stress, and biochemical parameters of testicular toxicity induced by MSG due to its antioxidant effects. Graphical abstract

Inhibition of NHE-1 Increases Smoke-Induced Proliferative Activity of Barrett’s Esophageal Cell Line

Several clinical studies indicate that smoking predisposes its consumers to esophageal inflammatory and malignant diseases, but the cellular mechanism is not clear. Ion transporters protect esophageal epithelial cells by maintaining intracellular pH at normal levels. In this study, we hypothesized that smoking affects the function of ion transporters, thus playing a role in the development of smoking-induced esophageal diseases. Esophageal cell lines were treated with cigarettesmoke extract (CSE), and the viability and proliferation of the cells, as well as the activity, mRNA and protein expression of the Na+/H+ exchanger-1 (NHE-1), were studied. NHE-1 expression was also investigated in human samples. For chronic treatment, guinea pigs were exposed to tobacco smoke, and NHE-1 activity was measured. Silencing of NHE-1 was performed by using specific siRNA. CSE treatment increased the activity and protein expression of NHE-1 in the metaplastic cells and decreased the rate of proliferation in a NHE-1-dependent manner. In contrast, CSE increased the proliferation of dysplastic cells independently of NHE-1. In the normal cells, the expression and activity of NHE-1 decreased due to in vitro and in vivo smoke exposure. Smoking enhances the function of NHE-1 in Barrett’s esophagus, and this is presumably a compensatory mechanism against this toxic agent.

A Glyphosate-Based Formulation but Not Glyphosate Alone Alters Human Placental Integrity

Glyphosate (G)-based herbicidal formulations, such as the most commonly used one, Roundup (R), are major pesticides used worldwide on food and feed. Pregnant women may be frequently exposed to R compounds. These are composed of G, which is declared as the active principle, and other products contained in formulations, named formulants, which have been declared as inerts and diluents by the manufacturers. These formulants have, in fact, been demonstrated to be much more toxic than G, in particular to placental and embryonic human cells. In this work, we thus compared the effect of G and a GT+ formulation named R, using placental perfusion ex vivo. R, but not G alone, was demonstrated to alter the placental permeability of a known small model molecule, antipyrine. Similar results were observed for the fetal venous flow rate. The transfer of G alone increases with time, but is significantly decreased in presence of its formulants. The perfusion of R provokes a destruction of fetal vessels, as demonstrated by immunohistochemistry. Formulants obviously alter the fetal-placental circulation and placental integrity according to time of exposure. Therefore, G does not appear to be the main toxic agent of R. Formulants, although undeclared, include polyoxyethanolamines, PAHs, or heavy metals, and may be responsible for this toxicity. These compounds are also present in other pesticides. The progressive blood flow reduction due to the toxic compounds of formulations may diminish the nutrient supply to the fetus, alter the development, and may enhance the poisoning effects. Although these are preliminary results, they could at least partially explain some adverse pregnancy outcomes in mothers exposed to pesticides or other environmental pollutants. The debate on glyphosate alone is proven insufficient for the understanding of the toxicity.

A vimentin-targeting oral compound with host-directed antiviral and anti-inflammatory actions addresses multiple features of COVID-19 and related diseases

ABSTRACTDamage in COVID-19 results from both the SARS-CoV-2 virus and its triggered overreactive host immune responses. Therapeutic agents that focus solely on reducing viral load or hyperinflammation fail to provide satisfying outcomes in all cases. Although viral and cellular factors have been extensively profiled to identify potential anti-COVID targets, new drugs with significant efficacy remain to be developed. Here, we report the potent preclinical efficacy of ALD-R491, a vimentin-targeting small molecule compound, in treating COVID-19 through its host-directed antiviral and anti-inflammatory actions. We found that by altering the physical properties of vimentin filaments, ALD-491 affected general cellular processes as well as specific cellular functions relevant to SARS-CoV-2 infection. Specifically, ALD-R491 reduced endocytosis, endosomal trafficking, and exosomal release, thus impeding the entry and egress of the virus; increased the microcidal capacity of macrophages, thus facilitating the pathogen clearance; and enhanced the activity of regulatory T cells, therefore suppressing the overreactive immune responses. In cultured cells, ALD-R491 potently inhibited the SARS-CoV-2 spike protein and human ACE2-mediated pseudoviral infection. In aged mice with ongoing, productive SARS-CoV-2 infection, ALD-R491 reduced disease symptoms as well as lung damage. In rats, ALD-R491 also reduced bleomycin-induced lung injury and fibrosis. Our results indicate a unique mechanism and significant therapeutic potential for ALD-R491 against COVID-19. We anticipate that ALD-R491, an oral, fast-acting, and non-toxic agent targeting the cellular protein with multipart actions, will be convenient, safe, and broadly effective, regardless of viral mutations, for patients with early- or late-stage disease, post-COVID complications and other related diseases.IMPORTANCEWith the Delta variant currently fueling a resurgence of new infections in the fully-vaccinated population, developing an effective therapeutic drug is especially critical and urgent in fighting COVID-19. In contrast to the many efforts to repurpose existing drugs or address only one aspect of COVID-19, we are developing a novel agent with first-in-class mechanism-of-actions that address both the viral infection and the overactive immune system in the pathogenesis of the disease. Unlike virus-directed therapeutics that may lose efficacy due to viral mutations and immunosuppressants that require ideal timing to be effective, this agent, with its unique host-directed antiviral and anti-inflammatory actions, can work against all variants of the virus, be effective during all stages of the disease, and even resolve post-disease damage and complications. A further development of the compound will provide an important tool in the fight against COVID-19, its complications, as well as future outbreaks of new viruses.

Bone morphogenetic protein 4 as a biomarker for cadmium-associated bone damage

Background Cadmium is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. However, only a few studies have addressed the mechanism on cadmium-associated bone damage and none of them has used a panel of sensitive and specific biomarkers for the detection of cadmium-associated bone damage. BMP/SAMD signaling pathway can mediate osteogenic differentiation, but the association between cadmium and BMP/SAMD signaling pathway is yet to be illuminated. Methods We treated human bone marrow mesenchymal stem cells (BMSCs) with CdCl2 in vitro to to detect the expression of BMPs and SAMDs. And we also enrolled 67 cases of bone damage and 67 cases without bone damage. Urinary cadmium concentration and the concentrations of BMP-2 and BMP-4 of subjects were detected. Mediation analyses was used to estimate the influence of urinary cadmium and BMP-4 on bone damage, adjusting for a set of confounders. Results Cd exposure significantly promoted adipogenic differentiation of hBMSCs, and inhibited its' osteogenic differentiation by inhibiting the expression of BMP-2/4, SAMD4, and p-SAMD1/5/9 complex. BMP-4 mediated 22.92% (95%CI 6.37, 46.00) of the total association between cadmium and the risk of osteoporosis. Conclusions We found BMP-4 can be a diagnostic biomarker and therapeutic target of cadmium-associated bone damage.

Exposures and suspected intoxications during SARS-CoV-2 pandemic: preliminary results from an Italian poison control centre

Data on cleaner and disinfectant exposure and misuse-related acute intoxications in Italy during SARS-CoV-2 pandemic are still lacking. The aim of the present study was to analyse and describe cleaner and disinfectant-related intoxications during SARS-CoV-2 pandemic in an Italian poison control centre. Data were obtained from the toxicological consultations requested to the Toxicology Unit and Poison Centre, Careggi University Hospital, Florence (Italy). We compared data from January 1st to April 30th of 2019 and 2020. Data concerning probable or acute intoxication from any causative agent in the general population (all age groups), from private individuals or from Regional and National health structures, were included in the analysis. A toxicological evaluation was also performed to calculate the Poisoning Severity Score.In 2019, 451 phone counselling sessions were performed and compared to a total of 410 calls received during the same period of 2020. In both periods, the majority of events occurred in paediatric (0–17 years) and adult (18–65 years) patients, who were mainly exposed to one toxic agent, and intoxications took place principally at home due to domestic accidents. The oral route of intoxication was the most frequently observed one, followed by inhalation of toxic agents, which increased by 4.7% in 2020. In 2020, sanitizers and cleaners were reported in 21.6% of cases compared to 12.5% in 2019. This is the first study describing cleaner and disinfectant-related intoxications in Italy. Our results suggested a possible misuse of these products during the SARS-CoV-2 pandemic, underling the effects of home isolation on mental health and unintentional toxic exposures.