Research Progress and Applications of Bovine Genome in the Tribe Bovini.

Various bovine species have been domesticated and bred for thousands of years, and they provide adequate animal-derived products, including meat, milk, and leather, to meet human requirements. Despite the review studies on economic traits in cattle, the genetic basis of traits has only been partially explained by phenotype and pedigree breeding methods, due to the complexity of genomic regulation during animal development and growth. With the advent of next-generation sequencing technology, genomics projects, such as the 1000 Bull Genomes Project, Functional Annotation of Animal Genomes project, and Bovine Pangenome Consortium, have advanced bovine genomic research. These large-scale genomics projects gave us a comprehensive concept, technology, and public resources. In this review, we summarize the genomics research progress of the main bovine species during the past decade, including cattle (Bos taurus), yak (Bos grunniens), water buffalo (Bubalus bubalis), zebu (Bos indicus), and gayal (Bos frontalis). We mainly discuss the development of genome sequencing and functional annotation, focusing on how genomic analysis reveals genetic variation and its impact on phenotypes in several bovine species.

Zein-Based Triple-Drug Nanoparticles to Promote Anti-Inflammatory Responses for Nerve Regeneration after Spinal Cord Injury.

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem is developed to deliver autophagy-promoting, anti-inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor are combined into the zein-based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles are internalized by BV2 microglia and SH-SY5Y neuron-like cells in culture; they inhibit the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protect SH-SY5Y cells from the toxicity of H2O2. In a rat model of spinal cord injury, the nanoparticles mitigate inflammation and promote spinal cord repair. In the in vitro and in vivo experiments, the complete nanoparticles function better than the free drugs or nanoparticles containing only one or two drugs. These results suggest that the triple-drug nanoparticles show promise for treating spinal cord injury.

Injectable Hydrogel To Deliver Bone Mesenchymal Stem Cells Preloaded with Azithromycin To Promote Spinal Cord Repair.

Spinal cord injury is a disease that causes severe damage to the central nervous system. Currently, there is no cure for spinal cord injury. Azithromycin is commonly used as an antibiotic, but it can also exert anti-inflammatory effects by down-regulating M1-type macrophage genes and up-regulating M2-type macrophage genes, which may make it effective for treating spinal cord injury. Bone mesenchymal stem cells possess tissue regenerative capabilities that may help promote the repair of the injured spinal cord. In this study, our objective was to explore the potential of promoting repair in the injured spinal cord by delivering bone mesenchymal stem cells that had internalized nanoparticles preloaded with azithromycin. To achieve this objective, we formulated azithromycin into nanoparticles along with a trans-activating transcriptional activator, which should enhance nanoparticle uptake by bone mesenchymal stem cells. These stem cells were then incorporated into an injectable hydrogel. The therapeutic effects of this formulation were analyzed in vitro using a mouse microglial cell line and a human neuroblastoma cell line, as well as in vivo using a rat model of spinal cord injury. The results showed that the formulation exhibited anti-inflammatory and neuroprotective effects in vitro as well as therapeutic effects in vivo. These results highlight the potential of a hydrogel containing bone mesenchymal stem cells preloaded with azithromycin and trans-activating transcriptional activator to mitigate spinal cord injury and promote tissue repair.

CAQK modification enhances the targeted accumulation of metformin-loaded nanoparticles in rats with spinal cord injury.

Spinal cord injury (SCI) often causes neuronal membrane rupture and immediate death of neurons, followed by complicated secondary injuries. Treatment of SCI still remains a major challenge in clinical practice; thus, a great advance is urgently needed in this field. Metformin (MET) has anti-oxidant, anti-inflammatory, anti-apoptotic and neuroprotective properties, which may exert a potential therapeutic effect on SCI. In this study, we established a zein-based MET-loaded nanodrug system (CAQK-MET-NPs) for the targeted drug delivery for SCI. The results showed that MET could be effectively encapsulated into zein to obtain the zein-based spherical nanoparticles. Pharmacokinetic analysis indicated that CAQK-MET-NPs exhibited sustained-release and long-term therapeutic effects. The fluorescence imaging and tissue distribution experiments showed that CAQK-MET-NPs could efficiently accumulate at the lesion site of SCI rats. In conclusion, CAQK-MET-NPs may be a promising nanodrug for the treatment of SCI.

TAT-modified tetramethylpyrazine-loaded nanoparticles for targeted treatment of spinal cord injury.

Tetramethylpyrazine (TMP) has been effectively used for treating spinal cord injury (SCI) due to its anti-inflammatory, antioxidant, and neuroprotective activity. However, its clinical application is limited due to poor water solubility and insufficient spinal cord targeting through the traditional dosage forms. Given that intravascular neutrophils are quickly recruited to the injury site as part of the inflammatory response in SCI, we conjugated the cell-penetrating HIV trans-activator of transcription (TAT) peptide to human serum albumin nanoparticles (NPs) to make a TMP delivery system (TAT-TMP-NPs) that could be internalized by neutrophils and delivered to SCI lesions. Results found that in SCI rats TAT-TMP-NPs promoted the recovery of locomotor function and the lesion area, while reducing the levels of inflammatory cytokines and oxidative stress-related factors. Safety evaluation and in vivo small-animal imaging showed that the cell-penetrating peptide TAT could enhance the uptake of TAT-TMP-NPs by neutrophils without being toxic to the body. TAT-TMP-NPs may overcome the poor water solubility and low bioavailability of TMP, showing promise for the clinical treatment of SCI.

TAT-modified serum albumin nanoparticles for sustained-release of tetramethylpyrazine and improved targeting to spinal cord injury.

BACKGROUND: Spinal Cord injury (SCI) is a kind of severe traumatic disease. The inflammatory response is a significant feature after SCI. Tetramethylpyrazine (TMP), a perennial herb of umbelliferae, is an alkaloid extracted from ligustici. TMP can inhibit the production of nitric oxide and reduce the inflammatory response in peripheral tissues. It can be seen that the therapeutic effect of TMP on SCI is worthy of affirmation. TMP has defects such as short half-life and poor water-solubility. In addition, the commonly used dosage forms of TMP include tablets, dropping pills, injections, etc., and its tissue and organ targeting is still a difficult problem to solve. To improve the solubility and targeting of TMP, here, we developed a nanotechnology-based drug delivery system, TMP-loaded nanoparticles modified with HIV trans-activator of transcription (TAT-TMP-NPs). RESULTS: The nanoparticles prepared in this study has integrated structure. The hemolysis rate of each group is less than 5%, indicating that the target drug delivery system has good safety. The results of in vivo pharmacokinetic studies show that TAT-TMP-NPs improves the bioavailability of TMP. The quantitative results of drug distribution in vivo show that TAT-TMP-NPs is more distributed in spinal cord tissue and had higher tissue targeting ability compared with other treatment groups. CONCLUSIONS: The target drug delivery system can overcome the defect of low solubility of TMP, achieve the targeting ability, and show the further clinical application prospect.

Treatment of Rheumatoid Arthritis by Serum Albumin Nanoparticles Coated with Mannose to Target Neutrophils.

Rheumatoid arthritis (RA) is an angiogenic and chronic inflammatory disease. One of the most extensively used first-line drugs against RA is methotrexate (MTX), but it shows poor solubility, short in vivo circulation, and off-target binding, leading to strong toxicity. To overcome these shortcomings, the present study loaded MTX into nanoparticles of human serum albumin modified with mannose (MTX-M-NPs) to target the drug to neutrophils. MTX-M-NPs were prepared, and their uptake by neutrophils was studied using laser confocal microscopy and flow cytometry. A chick chorioallantoic membrane assay was used to assess their ability to inhibit angiogenesis. The pharmacokinetics and tissue distribution of MTX-M-NPs were investigated using fluorescence microscopy and high-performance liquid chromatography. Their pharmacodynamics was evaluated in a rat model with arthritis induced by collagen. Neutrophils took up MTX-M-NPs significantly better than the same nanoparticles (NPs) without mannose. MTX-M-NPs markedly suppressed angiogenesis in chick embryos, and the MTX circulation was significantly longer when it was delivered as MTX-M-NPs than as a free drug. MTX-M-NPs accumulated mainly in arthritic joints. The retention of NPs was promoted by mannose-derived coating in arthritic joints. Serum levels of inflammatory cytokines, joint swelling, and bone erosion were significantly decreased by MTX-M-NPs. In conclusion, these NPs can prolong the in vivo circulation of MTX and target it to the sites of inflammation in RA, reducing drug toxicity. MTX-M-NPs allow the drug to exert its intrinsic anti-inflammatory, antiangiogenic, and analgesic properties, making it a useful drug delivery system in RA.