Molecular Characterization and Toxicity of Heavy Metal Quinary Mixtures on Enterobacter cloacae Isolate from Nworie River

The molecular characterization and toxicity of Cadmium (Cd), Lead (Pb), Zinc (Zn), Chromium (Cr) and Copper (Cu) quinary mixtures on Enterobacter cloacae isolate from Nworie River was investigated. Quinary mixtures of the heavy metals were compounded using fixed ratio (%); and inhibitory effect assessed using inhibition of total dehydrogenase as toxicity response. The mixtures consisted of five heavy metals in the ratios: Pb (20%) + Cr (20%) + Cd (20%) + Zn (20%) + Cu (20%), Pb (30%) + Cr (20%) + Cd (10%) + Zn (30%) + Cu (10%). Pb (10%) + Cr (10%) + Cd (30%) + Zn (40%) + Cu (10%), Pb (15%) + Cr (25%) + Cd (25%) + Zn (15%) + Cu (20%), Pb (40%) + Cr (15%) + Cd (5%) + Zn (20%) + Cu(20%). Result obtained showed that toxicity of the metals against the bacterium ranked in the order Cu > Cr >Zn > Pb > Cd. The quinary mixtures Pb (20%) + Cr (20%) + Cd (20%) + Zn (20%) + Cu (20%), Pb (30%) + Cr (20%) + Cd (10%) + Zn (30%) + Cu (10%) and 10%Pb + 10%Cr + 30%Cd + 40%Zn + 10%Cu showed synergistic interaction, while 15%Pb + 25%Cr + 25%Cd + 15%Zn + 20%Cu and 40%Pb + 15%Cr + 5%Cd + 20%Zn + 20%Cu mixtures were antagonistic and additive respectively. Threshold inhibitory concentration (IC50) of the quinary mixtures was 0.054 ± 0.005mM, 0.053 ± 0.002 mM, 0.038 ± 0.002 mM, 0.077 ± 0.007 mM and 0.058 ± 0.006 mM for the respective mixtures. The toxic index values evaluated for the mixtures exhibited antagonistic, synergistic and additive interaction in the various ratios. The 16S rRNA and ITSF1 sequences obtained of the isolate showed the phylogenetic placement of the 16S rRNA of the isolate was closely related to Enterobacter cloacae strain DL01 (MH168084). The heavy metals mixtures demonstrated diverse toxicity interaction on the isolate depending on their relative composition, thus poses a threat to aquatic microbial diversity.

Establishment of porcine and monkey colonic organoids for drug toxicity study

Pig and monkey are widely used models for exploration of human diseases and evaluation of drug efficiency and toxicity, but high cost limits their uses. Organoids have been shown to be promising models for drug test as they reasonably preserve tissue structure and functions. However, colonic organoids of pig and monkey are not yet established. Here, we report a culture medium to support the growth of porcine and monkey colonic organoids. Wnt signaling and PGE2 are important for long-term expansion of the organoids, and their withdrawal results in lineage differentiation to mature cells. Furthermore, we observe that porcine colonic organoids are closer to human colonic organoids in terms of drug toxicity response. Successful establishment of porcine and monkey colonic organoids would facilitate the mechanistic investigation of the homeostatic regulation of the intestine of these animals and is useful for drug development and toxicity studies.

A MARINE ALGA EXHIBITS ANTI-TOXICITY POTENTIAL ON THYROID GLAND OF ALBINO RATS

Seaweed is the familiar name for immeasurable species of marine algae that grow in the Ocean. Many types of seaweed contain anti-inflammatory and anti-microbial agents and also possess powerful cancer fighting agents that ultimately prove in the treatment of malignant tumours and leukaemia in people. The purpose of the present work was to determine the anti-toxicity response of seaweed Sargassum wightii against on thyroid gland of cadmium treated Rats. An extract prepared from S.wightii was treated orally every day at a dose level of 200mg/kg of body weight to the rats exposed to 50ppm cadmium for 30 days. Histopathological analysis of thyroid gland showed that an administration of S.wightii treatment reduced the histopathological inflictions and enhancing endocrine functioning in cadmium treated rats.

Effect of Micelle Encapsulation on Toxicity of CdSe/ZnS and Mn-Doped ZnSe Quantum Dots

The optical properties of quantum dots (QD) make them excellent candidates for bioimaging, biosensing, and therapeutic applications. However, conventional QDs are comprised of heavy metals (e.g., cadmium) that pose toxicity challenges in biological systems. Synthesising QDs without heavy metals or introducing thick surface coatings, e.g., by encapsulation in micelles, can reduce toxicity. Here, we examined the toxicity of micelle encapsulated tetrapod-shaped Mn-doped ZnSe QDs, comparing them to 3-mercaptopropionic acid (MPA)-capped Mn-doped ZnSe QDs prepared by ligand exchange and commercial CdSe/ZnS QD systems that were either capped with MPA or encapsulated in micelles. HepG2 cell treatment with MPA-coated CdSe/ZnS QDs resulted in a dose-dependent reduction of viability (MTT assay, treatment at 0–25 μg/mL). Surprisingly, no reactive oxygen species (ROS) or apoptotic signaling was observed, despite evidence of apoptotic behavior in flow cytometry. CdSe/ZnS QD micelles showed minimal toxicity at doses up to 25 μg/mL, suggesting that thicker protective polymer layers reduce cytotoxicity. Despite their shape, neither MPA- nor micelle-coated Mn-doped ZnSe QDs displayed a statistically significant toxicity response over the doses investigated, suggesting these materials as good candidates for bioimaging applications.

Toxicity, response, and survival in older adults with metastatic melanoma treated with checkpoint inhibitors.

9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastatic melanoma. Trials suggest no differences in outcomes between older and younger patients, but only relatively young patients with a good performance status were included in these trials. The aim of this study was to describe treatment patterns and outcomes of older adults with metastatic melanoma, and to identify predictors of outcome. Methods: We included all patients aged ≥65 years with metastatic melanoma between 2013 and 2020 from the Dutch Melanoma Treatment registry (DMTR), in which detailed information on patients, treatments and outcomes is available. We assessed predictors of grade ≥3 toxicity and 6-months response using logistic regression models, and melanoma-specific and overall survival using Cox regression models. Additionally, we described reasons for hospital admissions and treatment discontinuation. Results: A total of 2216 patients were included. Grade ≥3 toxicity did not increase with age, comorbidity or WHO performance status, in patients treated with monotherapy (anti-PD1 or ipilimumab) or combination treatment. However, patients aged ≥75 were admitted more frequently and discontinued treatment due to toxicity more often. Six months-response rates were similar to previous randomized trials (40.3% and 43.6% in patients aged 65-75 and ≥75 respectively for anti-PD1 treatment) and were not affected by age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity, but age, comorbidity and WHO performance status were associated with overall survival in multivariate analyses. Conclusions: Toxicity, response and melanoma-specific survival were not associated with age or comorbidity status. Treatment with immunotherapy should therefore not be omitted solely based on age or comorbidity. However, the impact of grade I-II toxicity in older patients deserves further study as older patients discontinue treatment more frequently and receive less treatment cycles.[Table: see text]

Diurnal Fe(II)/Fe(III) cycling and enhanced O2 production in a simulated Archean marine oxygen oasis

The oxygenation of early Earth’s atmosphere during the Great Oxidation Event, is generally accepted to have been caused by oceanic Cyanobacterial oxygenic photosynthesis. Recent studies suggest that Fe(II) toxicity delayed the Cyanobacterial expansion necessary for the GOE. This study investigates the effects of Fe(II) on two Cyanobacteria, Pseudanabaena sp. PCC7367 and Synechococcus sp. PCC7336, in a simulated shallow-water marine Archean environment. A similar Fe(II) toxicity response was observed as reported for closed batch cultures. This toxicity was not observed in cultures provided with continuous gaseous exchange that showed significantly shorter doubling times than the closed-culture system, even with repeated nocturnal addition of Fe(II) for 12 days. The green rust (GR) formed under high Fe(II) conditions, was not found to be directly toxic to Pseudanabaena sp. PCC7367. In summary, we present evidence of diurnal Fe cycling in a simulated shallow-water marine environment for two ancestral strains of Cyanobacteria, with increased O2 production under anoxic conditions.