Preparation and Characterization of Self-Emulsified Docetaxel

The aim of this paper was to prepare a self-microemulsifying docetaxel (Dtx) using PLGA, Tetraglycol, Labrasol, and Cremophor ELP. The prepared Dtx-loaded self-microemulsifying system (SMES) showed the initial size of the range of 80–100 nm with narrow size distribution and the negative zeta-potential values. Its morphology was a spherical shape by atomic force microscopy. In experiment of stability, Dtx-loaded SMES prepared in DW and BSA condition showed good stability at 37∘C for 7 days. The viability of the B16F10 cells incubated with Dtx-loaded SMES, Dtx-solution, and Taxol were decreased as a function of incubation time. In conclusion, we confirmed that Dtx-loaded SMES showed an inhibitory effect for proliferation of B16F10 melanoma cells

Redox-regulation and life-history trade-offs: scavenging mitochondrial ROS improves growth in a wild bird

It has been proposed that animals usually restrain their growth because fast growth leads to an increased production of mitochondrial reactive oxygen species (mtROS), which can damage mitochondrial DNA and promote mitochondrial dysfunction. Here, we explicitly test whether this occurs in a wild bird by supplementing chicks with a mitochondria-targeted ROS scavenger, mitoubiquinone (mitoQ), and examining growth rates and mtDNA damage. In the yellow-legged gull Larus michahellis, mitoQ supplementation increased the early growth rate of chicks but did not reduce mtDNA damage. The level of mtDNA damage was negatively correlated with chick mass, but this relationship was not affected by the mitoQ treatment. We also found that chick growth was positively correlated with both mtDNA copy number and the mitochondrial enzymatic activity of citrate synthase, suggesting a link between mitochondrial content and growth. Additionally, we found that MitoQ supplementation increased mitochondrial content (in males), altered the relationship between mtDNA copy number and damage, and downregulated some transcriptional pathways related to cell rejuvenation, suggesting that scavenging mtROS during development enhanced growth rates but at the expense of cellular turnover. Our study confirms the central role of mitochondria modulating life-history trade-offs during development by other mechanisms than mtROS-inflicted damage.Ministerio de Economía y Competitividad | Ref. CGL2015-69338-C2-1-

Maternal effect senescence via reduced DNA repair ability in the three‐spined stickleback

Maternal effect senescence, a decline in offspring viability with maternal age, has been documented across diverse animals, but its mechanisms remain largely unknown. Here, we test maternal effect senescence and explore its possible molecular mechanisms in a fish. We compared the levels of maternal mRNA transcripts of DNA repair genes and mtDNA copies in eggs and the levels of DNA damage in somatic and germline tissues between young and old female sticklebacks. We also tested, in an in vitro fertilization experiment, whether maternal age and sperm DNA damage level interactively influence the expression of DNA repair genes in early embryos. Old females transferred less mRNA transcripts of DNA repair genes into their eggs than did young females, but maternal age did not influence egg mtDNA density. Despite a higher level of oxidative DNA damage in the skeletal muscle, old females had a similar level of damage in the gonad to young females, suggesting the prioritization for germline maintenance during ageing. The embryos of both old and young mothers increased the expression of DNA repair genes in response to an increased level of oxidative DNA damage in sperm used for their fertilization. The offspring of old mothers showed higher rates of hatching, morphological deformity and post‐hatching mortality and had smaller body size at maturity. These results suggest that maternal effect senescence may be mediated by reduced capacity of eggs to detect and repair DNA damages, especially prior to the embryonic genomic activation.Agencia Estatal de Investigación | Ref. PGC2018-095412-B-I00Universidade de Vigo/CISU

Acute respiratory distress after metofluthrin insecticide ingestion in a 19-month-old girl

Metofluthrin is a volatile pyrethroid insecticide. Despite being widely used as a safe household insecticide, it could cause severe systemic symptoms. A 19-month-old girl was taken to the emergency department after ingesting 1 mL of a mosquito repellent containing metofluthrin. After the arrival, the girl developed respiratory distress, which worsened progressively despite the administration of oxygen with nebulized salbutamol and budesonide. Additionally, she underwent application of high-flow nasal cannula, and administration of activated charcoal and systemic steroids. Her dyspnea gradually improved, and she was thus discharged on day 4 with oral prednisolone. All medications were discontinued 10 days after the discharge without any complication. Respiratory distress can develop after the ingestion of even a small amount of metofluthrin. Symptomatic and adjunctive steroid therapies can be effective therapeutic options

Biocontrol potential of Chitinophaga flava HK235 producing antifungal-related peptide chitinocin

Botrytis cinerea is a necrotrophic fungal pathogen with an extremely broad host range, causing significant economic losses in agricultural production. In this study, we discovered a culture filtrate of bacterial strain HK235, which was identified as Chitinophaga flava, exhibiting high levels of antifungal activity against B. cinerea. From the HK235 culture filtrate, we isolated a new antimicrobial peptide molecule designated as chitinocin based on activity-guided fractionation followed by characterization of the amino acid composition and spectroscopic analyses. The HK235 culture filtrate and chitinocin completely inhibited both conidial germination and mycelial growth of B. cinerea at a concentration of 20% and 200 μg/mL, respectively. In addition to antibiosis against B. cinerea, the active compound chitinocin had a broad antifungal and antibacterial activity in vitro. When tomato plants were treated with the culture filtrate and chitinocin, the treatment strongly reduced the development of gray mold disease in a concentration-dependent manner compared to the untreated control. Here, considering the potent antifungal property in vitro and in vivo, we present the biocontrol potential of C. flava HK235 for the first time

Clinical Applications of the Microbiome in Obstetrics

Human microbiome refers to the genetic material of approximately 1013 microorganisms present in the human body. These microbiomes interact significantly with the physiological, metabolic, and immune systems, particularly during pregnancy. Microbiome dysbiosis in pregnant women and their fetuses is associated with obstetric complications and poor neonatal outcomes. Oral and gut microbiomes can influence the placenta, uterus, and fetus via hematogenous translocation. Through ascending translocation, vaginal microbiota can directly affect the uterine environment. Current research focuses on the presence of the placental microbiome, which is characterized by low biomass. However, more well-controlled studies are required to specifically address the contamination issues. Use of antibiotics during pregnancy and the mode of delivery, specifically cesarean section, have been linked to the establishment of the neonatal gut microbiome. Probiotic supplementation may be beneficial during pregnancy, particularly for women receiving antibiotic treatment

Does Diabetes Mellitus Influence Standardized Uptake Values of Fluorodeoxyglucose Positron Emission Tomography in Colorectal Cancer?

Background/AimsHyperglycemia is associated with decreased 2-18[F]fluoro-2-deoxy-D-glucose (FDG) uptake by tumors assessed by positron emission tomography (PET). In this retrospective study we investigated a comparison of standardized uptake values (SUVs) in patients with primary colorectal cancers who either had diabetes mellitus (DM) or were otherwise healthy.MethodsThe medical records of 397 patients who were diagnosed with colorectal cancer and underwent PET-CT between January 2006 and December 2012 were analyzed. Eighty patients with DM and 317 patients without DM were included. Clinical characteristics were reviewed and maximal standardized uptake values (SUVmax) were calculated in the primary colorectal lesions.ResultsThere was no significant difference between tumor SUVmax in DM patients (10.60±5.78) and those without DM (10.92±5.44). In addition, no significant difference was detected between tumor SUVmax in DM patients with glycated hemoglobin (HbA1c) levels <8% (10.34±5.17) and those with HbA1c levels ≥8% (10.61±7.27). The maximum size of the primary colorectal tumor was associated with SUVmax in a linear regression analysis.ConclusionThe results of this study showed that DM did not influence FDG uptake values in colorectal cancer patients regardless of glucose levels

Formyl-methionine as an N-degron of a eukaryotic N-end rule pathway

In bacteria, nascent proteins bear the pretranslationally generated N-terminal (Nt) formyl-methionine (fMet) residue. Nt-fMet of bacterial proteins is a degradation signal, termed fMet/N-degron. In contrast, proteins synthesized by cytosolic ribosomes of eukaryotes were presumed to bear unformylated Nt-Met. Here we found that the yeast formyltransferase Fmt1, although imported into mitochondria, could also produce Nt-formylated proteins in the cytosol. Nt-formylated proteins were strongly up-regulated in stationary phase or upon starvation for specific amino acids. This up-regulation strictly required the Gcn2 kinase, which phosphorylates Fmt1 and mediates its retention in the cytosol. We also found that the Nt-fMet residues of Nt-formylated proteins act as fMet/N-degrons, and identified the Psh1 ubiquitin ligase as the recognition component of this eukaryotic fMet/N-end rule pathway, which destroys Nt-formylated proteins

Genetic diversity and divergence among Korean cattle breeds assessed using a BovineHD single-nucleotide polymorphism chip

Objective In Korea, there are three main cattle breeds, which are distinguished by coat color: Brown Hanwoo (BH), Brindle Hanwoo (BRH), and Jeju Black (JB). In this study, we sought to compare the genetic diversity and divergence among there Korean cattle breeds using a BovineHD chip genotyping array. Methods Sample data were collected from 168 cattle in three populations of BH (48 cattle), BRH (96 cattle), and JB (24 cattle). The single-nucleotide polymorphism (SNP) genotyping was performed using the Illumina BovineHD SNP 777K Bead chip. Results Heterozygosity, used as a measure of within-breed genetic diversity, was higher in BH (0.293) and BRH (0.296) than in JB (0.266). Linkage disequilibrium decay was more rapid in BH and BRH than in JB, reaching an average r2 value of 0.2 before 26 kb in BH and BRH, whereas the corresponding value was reached before 32 kb in JB. Intra-population, inter-population, and Fst analyses were used to identify candidate signatures of positive selection in the genome of a domestic Korean cattle population and 48, 11, and 11 loci were detected in the genomic region of the BRH breed, respectively. A Neighbor-Joining phylogenetic tree showed two main groups: a group comprising BH and BRH on one side and a group containing JB on the other. The runs of homozygosity analysis between Korean breeds indicated that the BRH and JB breeds have high inbreeding within breeds compared with BH. An analysis of differentiation based on a high-density SNP chip showed differences between Korean cattle breeds and the closeness of breeds corresponding to the geographic regions where they are evolving. Conclusion Our results indicate that although the Korean cattle breeds have common features, they also show reliable breed diversity