Biology-Basel最新文献

This study investigates the role of NIK in activating specific inflammatory genes in macrophages, focusing on the effect of a mutation in NIK found in alymphoplasia (aly/aly) mice. Mouse peritoneal macrophages from aly/aly mice showed a severe defect in the production of some pro-inflammatory cytokines, such as IL-12. This effect seemed to take place at the transcriptional level, as shown by the reduced transcription of Il12b and Il12a in aly/aly macrophages after exposure to the TLR4 agonist LPS. Immunoprecipitation studies showed that the binding of NIK to c-Rel was not efficient in RAW 264.7 cells over-expressing the aly/aly mutation. In addition, the shuttling of c-Rel to the nucleus was shown to be impaired in aly/aly macrophages in response to LPS. When looking more specifically at the regulation of the Il12b promoter, we found that c-Rel bound to the NF-kB consensus sequence in macrophages from WT mice 1 hr. after LPS challenge, whereas in aly/aly macrophages, the transcription factor bound to the promoter was p65. These findings indicate that NIK is essential for efficient c-Rel activation and proper inflammatory responses. NIK dysfunction could lead to weakened immune responses, and targeting this pathway may help in developing therapies for immune-related conditions.

As the population ages and differences among sexes and age groups become more pronounced, the research on bone healing and damage mechanisms continues to advance, with evaluation conducted in both pre-clinical and clinical settings [...].

Urinary incontinence is a widespread issue, particularly among women, with effective treatments remaining elusive. The pig, and especially the female pig, stands as a promising animal model for the study of this condition, due to its anatomical similarities to humans. The aim of this study was to explore the largely uncharted muscular structure of the female pig urethra, linking urethral muscle dysfunction to incontinence. We examined histological sections from the urethras of six sows using Hematoxylin-Eosin and Masson's trichrome staining for morphometric analysis. The statistical significance of cellular disposition was determined through analysis of variance (ANOVA), followed by a Tukey post hoc test to elucidate specific inter-group differences. Our analysis revealed segment-specific epithelial differences, including variations in cell layers, sparse acinar glands, rich vasculature, and distinct muscle fibers with diverse regional distributions. Notably, significant differences in muscular area and tissue distribution were identified between the proximal, middle, and distal segments of the urethra (p < 0.001). The observed anatomical variations, along with the cellular similarities between pigs and humans, establish the female pig as a crucial translational model for advancing urological research. Specifically, these findings provide a foundation for the development of innovative therapeutic strategies and surgical techniques that can be directly applied to improve outcomes in human urological conditions.

Intestinal health is vital for poultry production, and protein plays a key role in intestinal nutrition. The present study used 16S rRNA gene sequencing and serum metabolomics to investigate the effect of CAP on the cecal microflora structure and serum metabolites in 42-day-old broiler chickens. A total of 480 one-day-old Arbor Acres broiler chickens were randomly divided into four treatments with twelve replicates comprising 10 chickens each, evenly divided by sex. The four groups were basal diet group (CAP0), treatment group 1 (CAP2), treatment group 2 (CAP3), and treatment group 3 (CAP4). The broilers in the CAP0 group were fed a basal diet (without CAP), while those in the CAP2, CAP3, and CAP4 groups received diets containing 2%, 3%, and 4% CAP, respectively. Growth performance results showed that dietary CAP supplementation significantly ameliorated the feed conversion rate (FCR) of broilers at 42 days in the CAP3 and CAP4 groups (p < 0.05). Microbial results revealed that CAP did not alter the dominant microorganisms in the cecum at the phylum, family, and genus levels. LEfSe analysis showed significantly higher relative abundances of p_Desulfobacterota, f_Desulfovibrionaceae, and g_Ruminococcus in the CAP3 group compared to the CAP0 and CAP4 groups. Metabolomic analyses indicated that the effect of incorporating CAP into the diet on serum metabolites primarily focused on organic acids and their derivatives, small peptides, amino acid derivatives, and oxidized lipids. The addition of 3% or 4% CAP to the diet can enhance metabolic pathways such as the citrate cycle (TCA cycle) and arginine and proline metabolism. In summary, incorporating CAP into the diet can increase the relative abundance of beneficial bacteria in the cecum and improve the feed conversion efficiency of broilers by enhancing amino acid and energy metabolism.

The formation of animal breeds usually begins with a small subsample from their ancestral population. Deleterious mutations accumulate in the population under genetic drift, inbreeding, and artificial selection during the development and maintenance of traits desired by humans. White raccoon dogs are among the most popular breeds of farmed raccoon dogs, but white raccoon dogs are more susceptible to disease and have a lower reproductive ability. However, the accumulation of deleterious mutations in this white breed is largely unknown. By analyzing and comparing whole-genome sequencing data from 20 white raccoon dogs and 38 normal raccoon dogs, we detected an increased occurrence of loss-of-function (LoF) mutations in white raccoon dogs compared with normal raccoon dogs. With the finding of a significantly higher dosage of homozygous missense mutations in the white raccoon dog genome, we detected a greater fitness cost in white raccoon dogs. Although a much higher FROH level for ROH fragments longer than 1 Mb has been reported in white raccoon dogs, we did not detect a genetic signal of genetic purging in white raccoon dogs. This study provides valuable genomic resources and new insights into the accumulation of mutation loads in farmed raccoon dogs.

B-cell lymphoma/leukemia 11A (BCL11A) is a crucial transcriptional regulator, widely recognized for its role in controlling fetal hemoglobin and its potential as a gene therapy target for inherited hemoglobinopathies. Beyond this, recent studies have also highlighted its key role in the maturation and function of immune cells and erythrocytes, mediated through the regulation of various molecules during hematopoietic development. The dysregulation of BCL11A disrupts downstream molecular pathways, contributing to the development of several hematological malignancies, particularly leukemias. This review provides a comprehensive overview of the role of BCL11A in normal and malignant hematopoiesis, details the hematological disorders associated with its dysregulation and explores the current therapeutic strategies targeting this transcription factor.

The shallow-sea hydrothermal vent at Guishan Islet, located off the coast of Taiwan, serves as a remarkable natural site for studying microbial ecology in extreme environments. In April 2019, we investigated the composition of prokaryotic picoplankton communities, their gene expression profiles, and the dissolved inorganic carbon uptake efficiency. Our results revealed that the chemolithotrophs Thiomicrorhabdus spp. contributed to the majority of primary production in the waters affected by the hydrothermal vent plume. The metatranscriptomic analysis aligned with the primary productivity measurements, indicating the significant gene upregulations associated with carboxysome-mediated carbon fixation in Thiomicrorhabdus. Synechococcus and Prochlorococcus served as the prokaryotic photoautotrophs for primary productivity in the waters with lower influence from hydrothermal vent emissions. Thiomicrorhabdus and picocyanobacteria jointly provided organic carbon for sustaining the shallow-sea hydrothermal vent ecosystem. In addition to the carbon fixation, the upregulation of genes involved in the SOX (sulfur-oxidizing) pathway, and the dissimilatory sulfate reduction indicated that energy generation and detoxification co-occurred in Thiomicrorhabdus. This study improved our understanding of the impacts of shallow-sea hydrothermal vents on the operation of marine ecosystems and biogeochemical cycles.

Exosomes are small extracellular vesicles and are crucial in intercellular communication. Interestingly, tumor-derived exosomes carry oncogenic molecules, such as proteins and microRNAs, which can reprogram recipient cells, promote angiogenesis, and stimulate cancer pre-metastatic niche, supporting cancer growth and metastasis. On the other hand, their biocompatibility, stability, and ability to cross biological barriers make them attractive candidates for drug delivery. Recent advances have shown the potential for exosomes to be used in early disease detection and in targeted drug therapy by delivering therapeutic agents specifically to tumor sites. Despite the promising applications, a number of challenges remain, including exosome isolation and characterization, as well as their inherent heterogeneity. Thus, the current review aims to describe the roles of exosomes in health and disease, and discuss the challenges that hinder their development into becoming useful medical tools.

Background: Antibiotics were extensively used in the pigeon breeding industry previously to promote growth and prevent disease, leading to the spread of antibiotic-resistant genes (ARGs) in gut microbes, which has become a major public health concern.

Methods: A metagenomic analysis was performed to investigate the gut microbial communities and ARGs in young and older pigeons in Nanjing, Jiangsu Province, China.

Results: There were obviously distinct gut microbiota and functional compositions between young and older pigeons. Both Pseudomonadota and Uroviricota were dominant in young and older pigeons. Although sharing 24 gut microbiota phyla between young and older pigeons, Bacillota and Pseudomonadota were the dominant microbial phyla in them, respectively. Besides the shared metabolic pathways and biosynthesis of secondary metabolites, biosynthesis of amino acids was the most abundant Kyoto Encyclopedia of Genes and Genomes (KEGG) function in young pigeons, while microbial metabolism in diverse environments was abundant in older pigeons. A total of 142 ARGs conferring multidrug resistance, tetracycline, and aminoglycoside resistance were identified; the most abundant gene in young pigeons was tetracycline-tetW, while in older pigeons, it was multidrug-acrB.

Conclusions: Our findings revealed significant differences in the gut microbial communities and ARGs between young and older pigeons. This study enhances our understanding of pigeon gut microbiota and antibiotic resistomes, contributing to knowledge-based sustainable pigeon meat production.

Inhibin β-A (INHBA), a TGF-β superfamily member, is crucial for developing follicles. Although miRNAs are essential for post-transcriptional gene regulation, it is not yet known how they affect the expression of INHBA during follicle development. Using bioinformatics analyses, miR-134-3p was found, in this investigation, to be a crucial microRNA that targets INHBA in sheep GCs. Furthermore, when the follicular diameter expanded, there was a discernible decline in miR-134-3p expression. The miR-134-3p overexpression markedly reduced the proliferation of GCs, whereas its knockdown augmented it. Moreover, cell cycle progression was enhanced by miR-134-3p overexpression. Furthermore, miR-134-3p overexpression heightened GC apoptosis, while its knockdown reduced it. Importantly, miR-134-3p overexpression blocked the PI3K/AKT/mTOR axis, whereas its knockdown stimulated it. Overall, the outcomes of transfections with INHBA and miR-134-3p showed that, in sheep GCs, miR-134-3p targets INHBA to control cell proliferation and apoptosis. In summary, these results add to our understanding of the molecular mechanisms involving important miRNAs in ewe fecundity by indicating that miR-134-3p influences cell proliferation, cell apoptosis, and the TGF-β/PI3K/AKT/mTOR axis, which, in turn, influences the follicular development of sheep GCs.