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Pharmacological intervention for chronic phase of spinal cord injury

Neural Regeneration Research 2025年第5期20卷 1377-1389页

作者： Chihiro Tohda section of Neuromedical Science Institute of Natural MedicineUniversity of ToyamaToyamaJapan

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidat

关键词： axonal growth chronic phase clinical study pharmacotherapy spinal cord injury

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Role of copper chelating agents: between old applications and new perspectives in neuroscience

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Neural Regeneration Research 2025年第3期20卷 751-762页

作者： Rosalba Leuci Leonardo Brunetti Vincenzo Tufarelli Marco Cerini Marco Paparella Nikola Puvača Luca Piemontese Department of Pharmacy-Pharmaceutical Science University of Bari Aldo MoroBariItaly Department of Precision and Regenerative Medicine and Jonian Area(DiMePRe-J) Section of Veterinary Science and Animal ProductionUniversity of Bari Aldo MoroBariItaly Department of Engineering Management in Biotechnology Faculty of Economics and Engineering Management in Novi SadUniversity Business Academy in Novi SadNovi SadSerbia

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

关键词： agriculture Alzheimer's disease chelators copper feed supplements multi-target

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Fine Mapping QTLs Affecting Milk Production Traits on BTA6 in Chinese Holstein with SNP Markers

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Journal of Integrative Agriculture 2013年第1期12卷 110-117页

作者： LIU Rui SUN Dong-xiao WANG Ya-chun YU Ying ZHANG Yi CHEN Hui-yong ZHANG Qin ZHANG Sheng-li ZHANG Yuan College of animal Science and Technology/Key Laboratory of animal genetics and Breeding Ministry of Agriculture/National Engineering Laboratory of Animal Genetics/China Agricultural University Sichuan animal Science Academy

Our previous studies demonstrated that the region around markers BMS470 and BMS1242 on BTA6 showed a linkage to 305-d milk yield and composition traits in the Chinese Holstein population. We herein focused on such narrow region to fine map milk production QTLs with 15 SNPs across 25 Mb with each SNP in 1 Mb within most regions in a Chinese Holstein population with daughter design. 1 449 Holstein cows and 11 sires were genotyped for such SNPs by using TaqMan probe and RFLP assays. Multipoint linkage analysis across family revealed a QTL affecting milk yield between PPARGC1A C4075T and SLC34A2 T1713C. Meanwhile, within family analysis found three milk yield QTLs （two in CR T60984131G-CEP135 C501T and one in PDLIM5 A106C-OPN T3907, a fat yield QTLin UGDH T1670C-CR T60984131G region, and two protein yield QTLs in TBC1D1 G501C-UGDH T1670C and PPARGC1A C4075T-SLC34A2 T1713C, respectively. Associations between aforementioned significant SNP markers and milk production traits were further implemented. We found significant associations of PPARGC1A C4075T, SLC34A2 T1713C with milk yield （P0.05, P0.01, P0.01）, UGDH T1670C, and CR T60984131G with fat yield （P0.01, P0.01）, and PPARGC1A C4075T, SLC34A2 T1713C, UGDH T1670C and OPN T3907 with protein yield （P0.01, P0.01, P0.01, P0.01）. Our findings implied that QTLs affecting milk production traits on BTA6 were pleictropism or multigenic effect and PPARGC1A and OPN may be the causal mutations behind milk production QTLs on BTA6 in the Chinese Holstein population.

关键词： fine mapping milk production trait SNP BTA6 Chinese Holstein

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Dosage Effects of Fadrozole on Growth and Development of Sex-Reversed Genetic Female Chickens

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Journal of Integrative Agriculture 2013年第6期12卷 1049-1053页

作者： YANG Xiu-rong JIANG He-sheng ZHENG Jiang-xia QU Lu-jiang CHEN Si-rui LI Jun-ying XU Gui- yun YANG Ning Department of animal genetics and Breeding Guangxi University Department of animal genetics and Breeding National Engineering Laboratory for Animal Breeding China Agricultural University

Fadrozole, an aromatase inhibitor, can masculinize genetic female chickens and high-dose decreases the hatchability. Therefore, it is important to study the growth and development of sex-reversed females after hatch. Chick embryos from a population of CAU3 egg-type were treated with different concentrations of Fadrozole prior to the sexual differentiation at E3.0 （st18）. At hatch, the phenotypic sex and genetic sex were identified by vent sexing and genetic diagnosis with CHD1, respectively. Body weight and shank length of sex reversal were tested at 8 and 20 wk, respectively. Testicular development, oviduct and ovarian degeneration were observed and serum concentration of estradiol and testosterone were tested with radioimmunoassay （RIA） at 30 wk. The results showed that body weight and shank length of sex- reversed females were not significantly different between low-dose groups （0.1, 0.3, and 0.5 mg for F1, F2, and F3, respectively） and high-dose groups （1.0 and 1.3 mg for F4 and F5, respectively）（P〉0.05）. Left and right testes or ovotestes in F2, F3, F4, and F5 groups were heavier than that of in F1 group （P〈0.05）. While the gonad weight of treatment groups were less than that in male control （P〈0.05）, oviduct weight in F2, F3, F4, and F5 groups were significant differences compared with female control and F1 group （P〈0.05）. Egg number from onset of laying egg to 30 wk in F4 and F5 groups were less than in female control, F1 and F2 groups （P〈0.05）. Serum testosterone level in F5 group was significant higher compared with female control, F1, F2, F3, and F4 groups （P〈0.05）, but significant lower compared with male control （P〈0.05）. While concentration of serum estradiol in F5 group was significant lower compared with female control, F1, F2, and F4 groups （P〈0.05）. In conclusion, the concentration of Fadrozole do not affect postnatal growth of sex-reversed female chicken and the degree of sex-reversed females elevate with the increase of Fadrozole concentration at

关键词： chicken Fadrozole growth and development reproductive system sex reversals

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Mapping QTLs Affecting Economic Traits on BTA3 in Chinese Holstein with Microsatellite Markers

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Journal of Integrative Agriculture 2014年第9期13卷 1999-2004页

作者： QIN Chun-hua CHU Qin CHU Gui-yan ZHANG Yi ZHANG Qin ZHANG Sheng-li SUN Dong-xiao College of animal Science and Technology/Key Laboratory of animal genetics and Breeding Ministry of Agriculture/National Engineering Laboratory of Animal Genetics China Agricultural University

It had been demonstrated that the strong and highly significant quantitative trait locus（QTL） can affect protein percentage on Bos Taurus Autosome 3（BTA3） at the position 52 cM, near the microsatellite DIK4353, with the 95% confidence interval spanning from 25 to 57 cM in Chinese Holstein population using QTL-express, MQREML, and GRIDQTL softwares. This study herein focused on such region of fine mapping QTLs for milk production and functional traits with 16 microsatellite markers with coverage of 33 cM between the markers BMS2904 and MB099 on BTA3 in a daughter-designed Chinese Holstein population. A total of 1 298 Holstein cows and 7 sires were genotyped for 16 microsatellites with ABI 3700 DNA sequencer. The variance components QTL linkage analysis（LA） and linkage-disequilibrium（LD） analysis（LA/LD） was performed to map QTLs for 7 traits, i.e., 305-d milk yield, fat yield, protein yield, fat percentage, protein percentage, somatic cell score and persistency of milk yield. Four strong and highly significant QTLs were detected for fat yield, fat percentage, protein percentage and somatic cell score at the position 40, 30, 27 and 26 cM, respectively. Two minor QTLs for milk yield and persistency of milk yield were identified at 42 and 46 cM, respectively. These findings provided a general idea for the fine mapping of the causal mutation for milk production and functional traits on BTA3 in the future.

关键词： QTL mapping economic traits microsatellite markers BTA3 Chinese Holstein

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The liver transcriptome of two full-sibling Songliao black pigs with extreme differences in backfat thickness

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Journal of animal Science and Biotechnology 2015年第1期6卷 13-21页

作者： Kai Xing Feng Zhu Liwei Zhai Huijie Liu Zhijun Wang Zhuocheng Hou Chuduan Wang National Engineering Laboratory for animal Breeding and MOA Key Laboratory of animal genetics and Breeding Department of Animal Genetics and BreedingChina Agricultural University Tianjin Ninghe Primary Pig Breeding Farm

Background： Fatness traits in animals are important for their growth, meat quality, reproductive performance, and immunity. The liver is the principal organ of the regulation of lipid metabolism, and this study used massive parallelized high-throughput sequencing technologies to determine the porcine liver tissue transcriptome architecture of two full-sibling Songliao black pigs harboring extremely different phenotypes of backfat thickness. Results： The total number of reads produced for each sample was in the region of 53 million, and 8,226 novel transcripts were detected. Approximately 92 genes were differentially regulated in the liver tissue, while 31 spliced transcripts and 33 primary transcripts showed significantly differential expression between pigs with higher and lower backfat thickness. Genes that were differentially expressed were involved in the metabolism of various substances, smal molecule biochemistry, and molecular transport. Conclusions： Genes involved in the regulation of iipids could play an important role in lipid and fatty acid metabolism in the liver. These results could help us understand how liver metabolism affects the backfat thickness of pigs.

关键词： Backfat thickness Liver Pig RNA-Seq

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Morphological and Hormonal Identifi cation of Porcine Atretic Follicles and Relationship Analysis of Hormone Receptor Levels During Granulosa Cell Apoptosis In vivo

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Journal of Integrative Agriculture 2014年第5期13卷 1058-1064页

作者： YU De-bing YU Min-li LIN Fei JIANG Bao-chun YANG Li-na WANG Si-yu ZHAO Ying WNAG Zheng-chao Department of animal genetics Breeding and Reproduction College of Animal Science and Technology Nanjing Agricultural University

Recent reports have demonstrated that follicular atresia is initiated or caused by granulosa cell apoptosis followed by theca cell degeneration in mammalian ovaries, but the mechanism of follicular atresia is still to be elucidated. Therefore, our present study was designed to examine our hypothesis that the changes of follicular microenvironment induce the granulosa cell apoptosis during pocrine follicular atresia in vivo. We firstly isolated intact porcine antral follicles and identified them into three groups, healthy follicles （HF）, early atretic follicles （EAF） and progressed atretic follicles （PAF） through morphology and histology. To further confirm their status, we detected hormone levels in follicular fluids and the expression level of apoptosis gene Bax in granulosa cells. The rate of progesterone （P） and estradiol （E2） was increased with the expression of Bax, indicating hormone can be used as a marker of granulosa cell apoptosis or follicular atresia. Finally, we analyzed the expression level of hormone receptor genes in granulosa cells and their relationship with follicular atresia. In PAF, the expression of Progesterone receptor （PGR） was increased significantly while estradiol receptor （ER） had no notable changes, which suggesting the increased-PGR accelerated the effect of P-stimulated granulosa cell apoptosis. The dramatic increasing of androgen receptor （AR） expression in PAF and the obvious increase of tumor necrosis factor-u receptor （TNFR） in EAF indicated that there are different pathways regulating granulosa cell apoptosis during follicular atresia. Together, our results suggested that different pathways of granulosa cell apoptosis was induced by changing the follicular microenvironment during follicular atresia.

关键词： granulosa cell apoptosis follicular atresia progesterone estradiol porcine

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Effect of HSPB9 on Apoptosis of DF-1 Cells

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Biomedical and Environmental Sciences 2019年第2期32卷 107-120页

作者： XU Yong Jie HU Mei Ling ZHOU Liang Hui WANG Qi ZHANG Xi Quan LUO Qing Bin Department of animal genetics Breeding and Reproduction College of Animal Science/Key Laboratory of Chicken Genetics Breeding and Reproduction Ministry of Agriculture South China Agricultural University

Objective Our aim was to explore whether heat stress protein(HSP) 9 preferentially expresses under heat stress and affects the expression of other heat stress proteins as well as to explore the effect of HSPB9 overexpression and knockdown on apoptosis in DF-1. Methods We used gene cloning to construct an overexpression vector of the target gene, and synthesized the target gene interference fragment to transfect the chicken fibroblast cell line. Gene and protein expression, as well as apoptosis, were detected by RT-qPCR, Western blot, and flow cytometry. Results Chicken DF-1 cells showed an early state of apoptosis in the early stages of HSPB9 overexpression. In the later stages, as HSPB9 expression increased, the cells showed inhibition of apoptosis. When the cells were under heat stress, HSPB9 expression was much higher and earlier than the expression of HSPB1 and HSPA2. In addition, high expression of HSPB9 had a negative effect on HSPB1 and HSPA2 expression. This negative feedback decreased the percentage of early stages of apoptotic cells and promoted cell survival. Conclusion HSPB9 expression, although rapid, is detrimental to cell survival early during its overexpression. In heat stress, HSPB9 overexpression, while inhibiting the expression of HSPA2 and HSPB1, is beneficial to cell survival.

关键词： Heat stress HSPB9 HSPB1 HSPA2 Apoptosis

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QTL alleles on chromosome 7 from fatty Meishan pigs reduce fat deposition

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Science China(Life Sciences) 2003年第1期46卷 10-17页

作者：岳根华 Petra Beeckmann Gerhard Moser Elisabeth Müller Hans Bartenschlager1 Stanislav Cepica Jaroslav Schrffel Antonin Stratil Hermann Geldermann Department of animal Breeding and Biotechnology University of Hohenheim Institute of animal Physiology and genetics Academy of Sciences of the Czech Republic

For detecting QTL in the whole swine genome,1068 pigs from three F2 populations con-structed by crossing European Wild boar and Pietrain (W譖),Meishan and Pietrain (M譖),and Wild Boar and Meishan (W譓) were genotyped for genetic markers evenly spaced at approximately 20 cM inter-vals. A QTL analysis was performed using a least-squares method. Here the results of the QTL analysis on the porcine chromosome 7 are presented. QTL for carcass composition (*** weight,carcass length,backfat depth,abdominal fat and bacon meat) were mapped in the chromosomal region CYPA/CYPD-TNFB-S0102 in M譖 and W譓,but not in W譖. The QTL was additive. Surprisingly, in contrast to the parental phenotype, the QTL alleles from fatty Meishan were associated with thinner backfat than Pietrain and Wild Boar alleles,suggesting that the genome of the fatty Meishan pig contains genes which can reduce fat content of carcass substantially.

关键词： genomics, pig, SSC7, QTL, backfat.

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Reorganization of 3D genome architecture across wild boar and Bama pig adipose tissues

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Journal of animal Science and Biotechnology 2022年第4期13卷 1011-1027页

作者： Jiaman Zhang Pengliang Liu Mengnan He Yujie Wang Hua Kui Long Jin Diyan Li Mingzhou Li Institute of animal genetics and Breeding College of Animal Science and TechnologySichuan Agricultural UniversityChengdu 611130China

Background:A growing body of evidence has revealed that the mammalian genome is organized into hierarchical layers that are closely correlated with and may even be causally linked with variations in gene *** studies have characterized chromatin organization in various porcine tissues and cell types and compared them among species and during the early development of ***,how chromatin organization differs among pig breeds is poorly ***:In this study,we investigated the 3D genome organization and performed transcriptome characterization of two adipose depots(upper layer of backfat[ULB]and greater omentum[GOM])in wild boars and Bama pigs;the latter is a typical indigenous pig in *** found that over 95%of the A/B compartments and topologically associating domains(TADs)are stable between wild boars and Bama *** contrast,more than 70%of promoterenhancer interactions(PEIs)are dynamic and widespread,involving over a thousand *** in chromatin structure are associated with changes in the expression of genes that are involved in widespread biological functions such as basic cellular functions,endocrine function,energy metabolism and the immune *** 95%and 97%of the genes associated with reorganized A/B compartments and PEIs in the two pig breeds differed between GOM and ULB,***:We reported 3D genome organization in adipose depots from different pig *** a comparison of Bama pigs and wild boar,large-scale compartments and TADs were mostly conserved,while fine-scale PEIs were extensively *** chromatin architecture in these two pig breeds was reorganized in an adipose depotspecific *** results contribute to determining the regulatory mechanism of phenotypic differences between Bama pigs and wild boar.

关键词： 3D genome organization A/B compartments Adipose tissues PEI Pig breeds TAD

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