Excess weight, which is seen as the background cause of most diseases, is gradually becoming the most important problem in the world. The cafeteria diet is robust diet that mimics the western diet and provides rapid weight gain associated with the obesity, diabetes, and cancer. The relationship between obesity and cancer is well known. For this reason, it is of great importance to reveal the first molecular and metabolic alterations that occur before entering the obesity process with any factor to understand the pathology of many diseases and to treat them in the early period. The beneficial effects of probiotics are attributed to their metabolite content with antioxidant properties or the postbiotic metabolites produced by them. In this study, the effects of different dietary practices on the hepatic antioxidant system of rats in developmental period were investigated by real-time PCR, enzyme activity measurements, and quantitative measurements of metabolites. After all, it was observed that CAF caused serious impairments by affecting the hepatic antioxidant system at gene and protein levels, and these impairments were relatively reversed with SCD Probiotics supplementation. In addition, regardless of the CAF diet, the regulatory effect of SCD Probiotics supplementation on the hepatic antioxidant system is remarkable.

ObjectivesAbrus precatorius (AP) is a medicinal plant seldomly studied for its beneficial effects and as such significant gap exists in understanding the basis by which AP leaf bioactives (APLBs) elicit beneficial effects against diabetes mellitus (DM) type-1. MethodsWe estimated DM type-1 related parameters - total protein (TP), direct bilirubin (DB), urea, creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and serum glucose (SG) after treatment with methanol extracts of AP leaves (APMLE) for 21 days followed by histopathological analysis of kidney and liver sections. APLBs were collected from GCMS fractions, database and literature searches and common targets were cross-intersected with annotated DM type-1 genes from experimental GSE14503 microarray dataset and genecard database. Overlapping differentially expressed genes were collected, their protein-protein interaction network was constructed and analyzed using various bioinformatics tools: Enrichr, SRplot, GSEA, Cytoscape, PyRx, and Discovery Studio to provide insight into the potential molecular basis of APLBs in DM-type-1.Results 15 compounds were identified from GCMS analysis of APMLE. Antidiabetic potential of APMLE was observed with significant (p <0.05) normalization of SG, TP, DB, ALT, AST, ALP, urea & creatinine while hepatorenal photomicrographs indicated moderate safety of use. Erucic acid, oleic acid, phytol and stigmasterol interact with 25 type-1 DM biomarkers revealed to be enriched in lipid and prostaglandin metabolic processes, neuroactive ligand receptor interaction, PPAR signaling pathway, diabetic cardiomyopathy, and cAMP signaling pathway. Furthermore, PPARalpha (peroxisome proliferator-activated alpha) and SCD (stearoyl-coenzyme A desaturase) were revealed as core biotargets interacting with APLBs via hydrogen bond, hydrophobic interaction and van der Waals forces from docking study. ConclusionThis study demonstrated the potency of APLBs in vivo against type-1 DM. The potential basis of action has been studied from computational perspective. Future interests may provide additional experimental data into mechanisms by which APLBs elicit this remarkable ability.

The search of DNA polymorphisms useful for the genetic improvement of dairy farm animals lasts more than 40 years with relevant findings in cattle for milk traits, where the best combination of alleles for dairy processing have been found in casein genes and in the DGAT1. Nowadays, similar results are not reached yet in river buffaloes despite advanced genomic technologies and accurate phenotype records are available. The aim of the present study was to investigate and validate in a larger buffalo population the effect on six milk traits of four single nucleotide polymorphisms (SNP) in the CSN1S1, CSN3, SCD and LPL genes, previously reported to be associated with or affect dairy traits in smaller populations often belonging to one farm. A total of 800 buffaloes were genotyped. Daily milk yield (dMY, kg), protein yield (dPY, kg) and fat yields (dFY, kg), fat and protein contents (dFP, % and dPP, %), somatic cell count (SCC, 103cell/ml) and urea (mg/dl) were individually recorded in each month for the whole lactation from 2010 to 2021. A total of 15,742 individual milk test day records (2,496 lactations) were available on 680 buffalo cows with 3.6±1.7 parity (from 1 to 13) and 6.1±1.2 test day records per lactation on average. Three out four SNP in CSN1S1, CSN3 and LPL were associated with at least one of analyzed traits. In particular, the CSN1S1 (AJ005430:c.578C&gt;T) gave favorable associations with all yield traits (dMY, p=0.022; dPY, p=0.014 ; dFY, p=0.029) and SCS (p=0.032), whereas the CSN3 (HQ677596: c.536C&gt;T) positively associated with SCS (p=0.005) and milk urea (p=0.04). Favorable effect on dMY (p=0.028), dFP (p=0.027) and dPP (p=0.050) were observed for the LPL. Conversely, SCD did not show any association with milk traits. This is the first example of confirmation study carried out in the Mediterranean river buffalo for genes of economic interest in dairy field and it represents a very important indication for the preselection of young bulls destined to breeding programs in the view of a more sustainable dairy production.

Sickle cell disease is characterized by stiff, “sickled” red blood cells that have difficulty moving through the bloodstream and do not efficiently carry oxygen. It is an inherited disease with severely limited treatment options, and is caused by a point mutation. Its prevalence in black and brown communities makes the already limited treatment options even less accessible. Base editing and prime editing are two relatively recent discoveries in the field of genome editing and were developed after the groundbreaking discovery of the CRISPR Cas9 system. While not fully tested, they hold a lot of promise in providing alternative treatment options for sickle cell disease. Both editing systems are able to install individual point mutations in the beta globin gene, which is where the sickle cell mutation occurs, and can thus cure sickle cell disease (in theory). In this paper we outline the mechanisms of CRISPR-Cas9 systems and base and prime editing, and provide insight into how to apply them to treat SCD. Further investigation should be done on specific editing systems and designs to use to ensure optimal treatment of SCD.

We report herein high-resolution x-ray diffraction measurements of basal plane bending of homoepitaxial single-crystal diamond (SCD). The results reveal that growth parameters such as temperature, growth time and basal plane bending of the substrate affect the basal plane bending of SCD. First, the basal plane bending of SCD depends mainly on the substrate itself. The basal plane bending of SCD becomes more severe with increasing basal plane bending of the substrate and this type of basal plane bending cannot be recovered. The SCD growth experiments show that the basal plane bending increases at high temperature and with increasing growth time. Finally, to understand the mechanism behind basal plane bending, we investigate the substrate-surface temperature distribution as a function of basal plane bending of SCD fabricated by chemical vapour deposition (CVD). This allows us to propose a bending model and understand the origin of basal plane bending. The results indicate that an uneven temperature distribution on the substrate surface is the main cause of the CVD diamond base-plane bending.

The life cycle of cancer follows the life cycle of the common ancestor of amoebozoans, metazoans, and fungi (AMF) and its systemic germline, which serves as a blueprint for all germlines capable of asymmetric cell division (ACD) and stem cell differentiation. Consequently, the oxygen sensitivity of the ancient non-gametogenic germline (Urgermline) was inherited by all germ and stem cell lines including the cancer germline. They all respond to Ugermline’s hyperoxia with loss of stemness and ACD ability and a dysregulated phenotype with irreparable DNA defects and defective symmetric cell divisions (DSCD). In protists, defective DSCD cells undergo an ancient MGRS repair program involving cell and nuclear fusion and hyperploid giant nuclei that restores the damaged genome to its former pre-DSCD state, with ACD potential and stemness. Human and metazoan DSCD use the same MGRS repair program inherited from the AMF ancestor. Ectopic DSCDs and DSCD-like phenotypes can survive in humans for many years in suitable niches. Under favorable environmental conditions, they also have access to the ancient MGRS repair mechanism including the ancient gene regulatory network (aGRN) and all other AMF genes. The aGRN takes control of cancer’s hybrid genome and represses human genes. It installs a G+S cancer life cycle of AMF imprinting that shapes the differentiation of naïve cancer stem cells (CSCs). CSCs are deeply homologous to the aGSCs of the AMF ancestor. Reprogramming of the DSCD genome by MGRS paves the way for oncogenesis. In this light, cancer is not a mutational or genetic disease, but a non-mutational genome-altering disease.