Oocyte quality following in vitro follicle development

In vitro follicle development (IVFD) is an adequate model to obtain basic knowledge of folliculogenesis and provides a tool for ovarian toxicity screening. IVFD yielding competent oocytes may also offer an option for fertility and species preservation. To promote follicle growth and oocyte maturation in vitro, various culture systems are utilized for IVFD in rodents, domestic animals, wild animals, nonhuman primates, and humans. Follicle culture conditions have been improved by optimizing gonadotropin levels, regulatory factors, nutrient supplements, oxygen concentration, and culture matrices. This review summarizes quality assessment of oocytes generated from in vitro-developed antral follicles from the preantral stage, including oocyte epigenetic and genetic profile, cytoplasmic and nuclear maturation, preimplantation embryonic development following in vitro fertilization, as well as pregnancy and live offspring after embryo transfer. The limitations of oocyte quality evaluation following IVFD and the gaps in our knowledge of IVFD to support proper oocyte development are also discussed. The information may advance our understanding of the requirements for IVFD, with a goal of producing competent oocytes with genetic integrity to sustain embryonic development resulting in healthy offspring.

Sterols from Jatropha tanjorensis leaves exhibit anti-inflammatory potential: in vitro and in silico studies

Background Inflammation has continued to raise global challenges and Jatropha tanrogenesis (JT) is used traditionally for its management. In this study, the in silico and in vitro anti-inflammatory potential of bioactive sterols were investigated. The active compounds of ethanol extract of JT leaves were identified using Gas chromatography-mass spectrometry (GC.MS) followed by molecular docking against COX-1 and COX-2 using maestro Schrödinger and pharmacokinetic profile prediction using webserver tools. The in vitro anti-inflammatory and anti-oxidantive potentials were investigated using standard protocols. Results GC–MS analysis of ethanol extract of JT leaves revealed the presence of eight (8) compounds, the molecular docking analysis of these compounds demonstrated varying degrees of binding affinities against the target proteins. The extract exhibit concentration dependent anti-oxidant activity with IC50 of 106.383 and 6.00 Fe2+E/g for DPPH and FRAP respectively. The extract showed significant (P < 0.05) reduction in percentage inhibition of hemolysis at 200 µg/ml while non-significant (P > 0.05) increase was observed at 600 and 1000 µg/ml compared to 200 µg/ml of diclofenac sodium. At lower concentration of 25 and 50 µg/ml, percentage inhibition of albumin denaturation was significantly (P < 0.05) higher compared to 200 µg/ml of diclofenac sodium. Drug likeness prediction and ADME/toxicity screening showed that the bioactive compounds possess no side effects. Conclusion The results obtained in this study suggested that, JT leaves possess anti-inflammatory activity and could be used as a source of new drug.

Oral Susceptibility to Ivermectin is Over Fifty Times Greater in a Wild Population of Anopheles Albimanus Mosquitoes from Belize than the STECLA Laboratory Reference Strain of A. Albimanus

Background: The STECLA strain of Anopheles albimanus Wiedemann has been in continuous colony for many years and is the reference strain on which genomic studies for the species are based. Recently, the STECLA strain was demonstrated to be much less susceptible to ivermectin ingested in a blood meal (LC 50 of 1468 ng/ml) than all other Anopheles species tested to-date (LC 50 values range from 7 – 56 ng/ml). The ability of A. albimanus to survive ingestion of ivermectin at concentrations far beyond that typically found in the blood of ivermectin-treated people or livestock ( i.e ., 30 – 70 ng/ml) could invalidate the use of ivermectin as a malaria vector control strategy in areas where A. albimanus is a primary vector. Methods: To investigate this, we captured host-seeking A. albimanus in northern Belize and conducted membrane feeding bioassays of ivermectin, using the same methods as described earlier with the STECLA strain. Results: Field-collected A. albimanus in Belize were 55 times more susceptible to ingested ivermectin than were the STECLA reference strain. Oral susceptible to ivermectin in wild A. albimanus from Belize (LC 50 of 26 ng/ml) was equivalent to that of other Anopheles species tested. Conclusion: Contrary to our initial assessment using a highly inbred laboratory strain of mosquito, we show that ivermectin treatment of livestock could reduce A. albimanus populations in areas of Central America and the Caribbean where malaria transmission may occur. Future toxicity screening of ivermectin and other systemic parasiticides for malaria control should consider examining wild populations of the vector species being targeted.

Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids

While pluripotent stem cell-derived kidney organoids represent a promising approach for the study of renal disease, renal physiology and drug screening, the proximal nephron remains immature with limited evidence for key functional solute channels. This may reflect early mispatterning of the nephrogenic mesenchyme or insufficient maturation. In this study, prolonged differentiation and modification of media conditions to enhance metanephric nephron progenitor specification resulted in the induction of nephrons containing elongated and aligned proximal nephron segments together with SLC12A1+ loops of Henle. Nephron proximal segments showed superior HNF4A gene and protein expression, as well as upregulation of key functional transporters, including SLC3A1/2, SLC47A1, and SLC22A2. The striking proximo-distal orientation of nephrons was shown to result from localised WNT antagonism originating from the centre of the organoid. Functionality of such transporters was evidenced by albumin and organic cation uptake, as well as appropriate KIM-1 upregulation in response to the nephrotoxicant, cisplatin. PT-enhanced organoids also possessed improved expression of receptors associated with SARS-CoV2 entry, rendering these organoids susceptible to infection and able to support viral replication without co-location of ACE2 and TMPRSS2. These PT-enhanced organoids provide an accurate model with which to study human proximal tubule maturation, inherited and acquired proximal tubular disease, and drug and viral responses.

AI Informed Toxicity Screening of Amine Chemistries used in the Synthesis of Hybrid Organic-Inorganic Perovskites

This paper describes a machine learning guided framework for screening the potential toxicity impact of amine chemistries used in the synthesis of hybrid organic-inorganic perovskites. Using a combination of a probabilistic molecular fingerprint technique that encodes bond connectivity (MinHash) coupled to non-linear data dimensionality reduction methods (UMAP), we develop an “Amine Atlas’. We show how the Amine Atlas can be used to rapidly screen the relative toxicity levels of amine molecules used in the synthesis of 2D and 3D perovskites and help identify safer alternatives. Our work also serves as a framework for rapidly identifying molecular similarity guided, structure-function relationships for safer materials chemistries that also incorporate sustainability/ toxicity concerns.