Candidates for Repurposing as Anti-Virulence Agents Based on the Structural Profile Analysis of Microbial Collagenase Inhibitors

The pharmacological inhibition of the bacterial collagenases (BC) enzymes is considered a promising strategy to block the virulence of the bacteria without targeting the selection mechanism leading to drug resistance. The chemical structures of the Clostridium perfringens collagenase A (ColA) inhibitors were analyzed using Bemis–Murcko skeletons, Murcko frameworks, the type of plain rings, and docking studies. The inhibitors were classified based on their structural architecture and various scoring methods were implemented to predict the probability of new compounds to inhibit ColA and other BC. The analyses indicated that all compounds contain at least one aromatic ring, which is often a nitrobenzene fragment. 2-Nitrobenzene based compounds are, on average, more potent BC inhibitors compared to those derived from 4-nitrobenzene. The molecular descriptors MDEO-11, AATS0s, ASP-0, and MAXDN were determined as filters to identify new BC inhibitors and highlighted the necessity for a compound to contain at least three primary oxygen atoms. The DrugBank database was virtually screened using the developed methods. A total of 100 compounds were identified as potential BC inhibitors, of which, 10 are human approved drugs. Benzthiazide, entacapone, and lodoxamide were chosen as the best candidates for in vitro testing based on their pharmaco-toxicological profile.

Evaluation of toxicological profile of methanol leaf extract of Waltheria indica (Sterculiaceae)

Waltheria indica has been claimed to be used in managing several diseases in traditional medicine, although substantial scientific data are not available as regards its safety despite its pronounced efficacy in management of some ailments. Therefore, methanol leaf extract of W. indica was evaluated for its effects on some toxicological parameters using experimental animals. However, acute and sub-acute toxicity were carried out using experimental animals as described by standard methods. Absence of death reported after 24 hours of single oral administration of W. indica indicated that the crude drug is safe orally and the sample also had no effect on both hematological and biochemical parameters, with mild toxicity observed with some vital enzymes and organs upon continuous oral administration of W. indica for 21 days. However, it can be concluded that prolong usage of the plant for disease management should be discouraged, which implies that usage of the pant for short time usage in disease management.

A Review on Non-target Toxicity of Deltamethrin and Piperonyl Butoxide: Synergist

Deltamethrin and piperonyl butoxide two synthetic pyrethroids, when used in a combination it produces synergistic effect. This two insecticide has found to be widely used in the management of mosquito, housefly and other insects to control the various vector born diseases. In this review we assessed the toxic effect of deltamethrin and piperonyl butoxide on beneficial organisms commonly available in the ecosystem. It was found to be toxic to fish, honey bees the prime pollinators of crop plant; earthworm is also susceptible at a lethal concentration for a particular exposure. As far the birds are concerned, they have a less toxic risk in lower concentration of exposure. The alterations obtained in the hematological, biochemical and histopathological studies, further conclude that it can cause environment hazards and toxic to the non-targeted organisms. This investigation gives an insight into the combined toxicological profile of deltamethrin and PBO for better risk assessment and safe use of pyrethroids and their synergist in non-targeted organisms.

Toxicological Profile of Biological Environment of Two Elastodontic Devices

Malocclusion and teething problems are common health problems globally, affecting people of all ages, especially children and adolescents. In addition to the pathophysiological complications associated with orthodontic problems, they also affect the well-being of the individual. Orthodontic appliances are frequently used, even from an early age, and their activity in different biological environments is very varied and incompletely described. Due to these considerations, the purpose of the study was to evaluate the toxicological profile of the biological environment (saliva at three pH values: 3, 7, and 10) of two elastodontic orthodontic appliances: Myobrace (MB) and LM TrainerTM 2 (LMD). In vitro techniques applied were conducted on human keratinocytes to evaluate cell viability (Alamar blue assay) and gene expression real-time reverse transcription–polymerase chain reaction (RT-PCR technique). In addition, it was assessed the irritating effect on the vascular plexus using as a biological model the chorioallantoic membrane of the hen’s egg by applying the hen’s egg-chorioallantoic membrane (HET-CAM) method. The obtained results showed a decrease in cell viability up to 82% in the case of LMD at pH = 3, a slight increase in mRNA expression for the anti-apoptotic marker (Bcl-2 and Bcl-xL), and a decrease in mRNA expression for the pro-apoptotic marker (Bad), and any type of toxic change at the capillary level (irritation score being below 0.9). Based on the data obtained, it can be stated that MB and LMD biological environments, at different pH values, present a safe toxicological profile.

Declining Carbon Emission/Concentration during COVID-19: A critical review on temporary relief

In December 2019 the deadly pandemic COVID-19 traumatized mankind through its lethal impact. To seize the outbreak, nationwide/region-based lockdown strategies were adopted by most of the COVID-19 affected countries. This in turn resulted in restricted transportation via surface, water, and air, as well as significantly reduced working hours of the industry sectors, so on and so forth. The obvious outcome was a sudden discernible decline in atmospheric adulteration. Accordingly, the anthropogenic emissions at the global and regional/local scales were examined during the lockdown period by several researchers using both or either satellite-based and ground-based monitoring. Among several other air-contaminants, carbon has a dominant toxicological profile causing adverse health effects and thereby attracting researches interest in carbon-release probing during the systematic confinement period imposed by the ruling authorities across the globe. The results of those studies indicated a confirmed decline in carbon emission/concentration making the air more breathable for the period. In this review, the studies related to anthropogenic emissions of carbon during the lockdown period are accounted for by compiling the recently reported data from published articles.

In vitro cytotoxic and genotoxic effects of Cissus verticillata and Sphagneticola trilobata used for treatment of Diabetes Mellitus in Brazilian folk medicine

Cissus verticillata and Sphagneticola trilobata have been used in Brazilian folk medicine for Diabetes Mellitus treatment, although their pharmacological and toxicological profile has not been clearly established. Thus, the aim of this study was to evaluate the preclinical toxicity of the aqueous extracts of C. verticillata and S. trilobata. The main groups of secondary metabolites were investigated, and the species differed by the presence of coumarins in C. verticillata and by tannins in S. trilobata extracts. The highest contents of phenolic compounds and flavonoids were quantified in C. verticillata infusion with 2.594 ± 0.04 mg equivalents of gallic acid g-1 of extract and 1.301 ± 0.015 mg equivalents of catechin g-1 of extract, respectively. While the extract of S. trilobata showed minimum values of these compounds, with 0.002 ± 0.001 mg equivalents of gallic acid g-1 extract and 0.005 ± 0.0004 mg equivalents of catechin g-1 of extract, respectively. These differences implied the results of in vitro antioxidant activity evaluated using ferric reducing antioxidant power (FRAP), in which the sample of C. verticillata at 5 mg mL-1 showed a value of 122 µM ferrous sulfate equivalents (FSE), while S. trilobata showed 0.93 µM FSE at the same concentration. With respect to cytotoxic assay with murine fibroblast cell line (3T3) only S. trilobata exhibited cytotoxic effects measured by MTT and Sulforhodamine B assays, evidenced by the cell viability value of approximately 16%, in both tests after 24 and 72 hours of exposure of the cells to 5 mg mL-1 of the extract. Comparatively, at 5 mg mL-1 the C. verticillata extract showed cell viability of 142% and 95%, respectively, after 24 hours of cell exposure. On the other hand, both species showed genotoxic profiles evidenced by chromosomal aberrations by Allium cepa bioassay, observed by the higher percentage values of chromosome bridges, chromosome loss, and disturbed anaphase for all concentrations of both extracts than those of the negative control. The results support the characterization of the toxicological profile for both species and create an alert regarding the use of S. trilobata, which should be avoided.

Biocompatible Silver Nanoparticles: Study of the Chemical and Molecular Structure, and the Ability to Interact with Cadmium and Arsenic in Water and Biological Properties

In the field of research for designing and preparing innovative nanostructured systems, these systems are able to reveal the presence of heavy metals in water samples, and can efficiently and selectively interact with them, allowing for future applications in the field of water remediation. We investigated the electronic and molecular structure, as well as the morphology, of silver nanoparticles stabilized by mixed biocompatible ligands (the amino acid L-cysteine and the organic molecule citrate) in the presence of cadmium and arsenic ions. The molecular, electronic, and local structure at the ligands/silver nanoparticles interface was probed by the complementary synchrotron radiation-induced techniques (SR-XPS, NEXAFS and XAS). The optical absorption (in the UV-Vis range) of the nanosystem was investigated in the presence of Cd(II) and As(III) and the observed behavior suggested a selective interaction with cadmium. In addition, the toxicological profile of the innovative nanosystem was assessed in vitro using a human epithelial cell line HEK293T. We analyzed the viability of the cells treated with silver nanoparticles, as well as the activation of antioxidant response.

A Co-Culture Model of the Human Respiratory Tract to Discriminate the Toxicological Profile of Cationic Nanoparticles According to Their Surface Charge Density

This study aimed at discriminating with sensitivity the toxicological effects of carbon dots (CDs) with various zeta potential (ζ) and charge density (Qek) in different cellular models of the human respiratory tract. One anionic and three cationic CDs were synthetized as follows: CD-COOH (ζ = -43.3 mV); CD-PEI600 (Qek = 4.70 µmol/mg; ζ = +31.8 mV); CD-PEHA (Qek = 3.30 µmol/mg; ζ = +29.2 mV) and CD-DMEDA (Qek = 0.01 µmol/mg; ζ = +11.1 mV). Epithelial cells (A549) and macrophages (THP-1) were seeded alone or as co-cultures with different A549:THP-1 ratios. The obtained models were characterized, and multiple biological responses evoked by CDs were assessed in the mono-cultures and the best co-culture model. With 14% macrophages, the 2:1 ratio co-culture best mimicked the in vivo conditions and responded to lipopolysaccharides. The anionic CD did not induce any effect in the mono-cultures nor in the co-culture. Among the cationic CDs, the one with the highest charge density (CD-PEI600) induced the most pronounced responses whatever the culture model. The cationic CDs of low charge density (CD-PEHA and CD-DMEDA) evoked similar responses in the mono-cultures, whereas in the co-culture, the three cationic CDs ranked according to their charge density (CD-PEI600 > CD-PEHA > CD-DMEDA), when taking into account their inflammatory effect. Thus, the co-culture system developed in this study appears to be a sensitive model for finely discriminating the toxicological profile of cationic nanoparticles differing by the density of their surface charges.