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1.
J Nanobiotechnology ; 22(1): 74, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395929

RESUMO

Due to its unique structure, articular cartilage has limited abilities to undergo self-repair after injury. Additionally, the repair of articular cartilage after injury has always been a difficult problem in the field of sports medicine. Previous studies have shown that the therapeutic use of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) has great potential for promoting cartilage repair. Recent studies have demonstrated that most transplanted stem cells undergo apoptosis in vivo, and the apoptotic EVs (ApoEVs) that are subsequently generated play crucial roles in tissue repair. Additionally, MSCs are known to exist under low-oxygen conditions in the physiological environment, and these hypoxic conditions can alter the functional and secretory properties of MSCs as well as their secretomes. This study aimed to investigate whether ApoEVs that are isolated from adipose-derived MSCs cultured under hypoxic conditions (hypoxic apoptotic EVs [H-ApoEVs]) exert greater effects on cartilage repair than those that are isolated from cells cultured under normoxic conditions. Through in vitro cell proliferation and migration experiments, we demonstrated that H-ApoEVs exerted enhanced effects on stem cell proliferation, stem cell migration, and bone marrow derived macrophages (BMDMs) M2 polarization compared to ApoEVs. Furthermore, we utilized a modified gelatine matrix/3D-printed extracellular matrix (ECM) scaffold complex as a carrier to deliver H-ApoEVs into the joint cavity, thus establishing a cartilage regeneration system. The 3D-printed ECM scaffold provided mechanical support and created a microenvironment that was conducive to cartilage regeneration, and the H-ApoEVs further enhanced the regenerative capacity of endogenous stem cells and the immunomodulatory microenvironment of the joint cavity; thus, this approach significantly promoted cartilage repair. In conclusion, this study confirmed that a ApoEVs delivery system based on a modified gelatine matrix/3D-printed ECM scaffold together with hypoxic preconditioning enhances the functionality of stem cell-derived ApoEVs and represents a promising approach for promoting cartilage regeneration.


Assuntos
Cartilagem Articular , Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Hidrogéis , Tecidos Suporte/química , Gelatina , Células-Tronco , Hipóxia
2.
Orthop Surg ; 16(4): 989-997, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38389215

RESUMO

OBJECTIVE: Closed reduction of pelvic injuries is a prerequisite and critical step in minimally invasive treatment. Achieving non-invasive closed reduction of pelvic injuries is a challenging clinical problem. This study demonstrated a non-invasive traction technique for closed reduction called countertraction closed reduction technique (CCRT) and evaluated its effectiveness for type C pelvic ring injuries. METHOD: The data of patients with unstable pelvic fractures treated with CCRT and minimally invasive fixation were retrospectively reviewed from January 2017 to February 2022. Sacroiliac screws were placed to fix the posterior pelvic ring, and internal or external fixation was used to fix the anterior pelvic ring. Operation time, intraoperative blood loss, duration of hospital stay, fracture union and postoperative complications were recorded. Fracture reduction quality was evaluated using the Matta scoring criteria. Functional recovery and general quality of life were evaluated using the Majeed functional scoring criteria. RESULTS: Thirteen patients (nine males and four females), with an average age of 49.6 years were treated with CCRT and followed up for a mean of 18.5 months. The average operation time was 137.2 minutes (range 92-195 minutes), the average intraoperative blood loss was 31.2 mL (range 10-120 mL) and the average duration of hospital stay was 14.3 days (range 4-32 days). All patients achieved bony union with an average union time of 11.9 weeks (range 10-16 weeks). According to the Matta radiographic criteria, the quality of fracture reduction was excellent in eight patients, good in four, and fair in one. The average Majeed functional score was 89.7 (range 78-100). The functional evaluation revealed that the outcomes were excellent in nine patients, and good in four patients. Complications included incision fat liquefaction in one patient, and heterotopic ossification in another patient. There were no surgical complications as a result of CCRT. CONCLUSION: CCRT is a non-invasive closed reduction method for minimally invasive fixation of fresh Tile C1 and C2 pelvic fractures. The advantages of CCRT combined with minimally invasive treatment include a small surgical incision, reduced intraoperative bleeding, satisfactory fracture reduction, bone healing and functional recovery.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Fixação Interna de Fraturas/métodos , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Qualidade de Vida , Fraturas Ósseas/cirurgia , Ossos Pélvicos/cirurgia , Ossos Pélvicos/lesões , Resultado do Tratamento
3.
IEEE Trans Cybern ; PP2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408005

RESUMO

Image compressed sensing (ICS) has been extensively applied in various imaging domains due to its capability to sample and reconstruct images at subNyquist sampling rates. The current predominant approaches in ICS, specifically pure convolutional networks (ConvNets)-based ICS methods, have demonstrated their effectiveness in capturing local features for image recovery. Simultaneously, the Transformer architecture has gained significant attention due to its capability to model global correlations among image features. Motivated by these insights, we propose a novel hybrid network for ICS, named MTC-CSNet, which effectively combines the strengths of both ConvNets and Transformer architectures in capturing local and global image features to achieve high-quality image recovery. Particularly, MTC-CSNet is a dual-path framework that consists of a ConvNets-based recovery branch and a Transformer-based recovery branch. Along the ConvNets-based recovery branch, we design a lightweight scheme to capture the local features in natural images. Meanwhile, we implement a Transformer-based recovery branch to iteratively model the global dependencies among image patches. Ultimately, the ConvNets-based and Transformer-based recovery branches collaborate through a bridging unit, facilitating the adaptive transmission and fusion of informative features for image reconstruction. Extensive experimental results demonstrate that our proposed MTC-CSNet surpasses the state-of-the-art methods on various public datasets. The code and models are publicly available at MTC-CSNet.

4.
J Appl Toxicol ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409892

RESUMO

Machine learning (ML) has shown a great promise in predicting toxicity of small molecules. However, the availability of data for such predictions is often limited. Because of the unsatisfactory performance of models trained on a single toxicity endpoint, we collected toxic small molecules with multiple toxicity endpoints from previous study. The dataset comprises 27 toxic endpoints categorized into seven toxicity classes, namely, carcinogenicity and mutagenicity, acute oral toxicity, respiratory toxicity, irritation and corrosion, cardiotoxicity, CYP450, and endocrine disruption. In addition, a binary classification Common-Toxicity task was added based on the aforementioned dataset. To improve the performance of the models, we added marketed drugs as negative samples. This study presents a toxicity predictive model, ToxMPNN, based on the message passing neural network (MPNN) architecture, aiming to predict the toxicity of small molecules. The results demonstrate that ToxMPNN outperforms other models in capturing toxic features within the molecular structure, resulting in more precise predictions with the ROC_AUC testing score of 0.886 for the Toxicity_drug dataset. Furthermore, it was observed that adding marketed drugs as negative samples not only improves the predictive performance of the binary classification Common-Toxicity task but also enhances the stability of the model prediction. It shows that the graph-based deep learning (DL) algorithms in this study can be used as a trustworthy and effective tool to assess small molecule toxicity in the development of new drugs.

5.
Vet Sci ; 11(2)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38393094

RESUMO

Copy number variation (CNV), as an essential source of genetic variation, can have an impact on gene expression, genetic diversity, disease susceptibility, and species evolution in animals. To better understand the weight and egg quality traits of chickens, this paper aimed to detect CNVs in Wenshui green shell-laying chickens and conduct a copy number variation regions (CNVRs)-based genome-wide association study (GWAS) to identify variants and candidate genes associated with their weight and egg quality traits to support related breeding efforts. In our paper, we identified 11,035 CNVRs in Wenshui green shell-laying chickens, which collectively spanned a length of 13.1 Mb, representing approximately 1.4% of its autosomal genome. Out of these CNVRs, there were 10,446 loss types, 491 gain types, and 98 mixed types. Notably, two CNVRs showed significant correlations with egg quality, while four CNVRs exhibited significant associations with body weight. These significant CNVRs are located on chromosome 4. Further analysis identified potential candidate genes that influence weight and egg quality traits, including FAM184B, MED28, LAP3, ATOH8, ST3GAL5, LDB2, and SORCS2. In this paper, the CNV map of the Wenshui green shell-laying chicken genome was constructed for the first time through population genotyping. Additionally, CNVRs can be employed as molecular markers to genetically improve chickens' weight and egg quality traits.

6.
Cell Prolif ; : e13605, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38282322

RESUMO

Clinicians and researchers have always faced challenges in performing surgery for rotator cuff tears (RCT) due to the intricate nature of the tendon-bone gradient and the limited long-term effectiveness. At the same time, the occurrence of an inflammatory microenvironment further aggravates tissue damage, which has a negative impact on the regeneration process of mesenchymal stem cells (MSCs) and eventually leads to the production of scar tissue. Tetrahedral framework nucleic acids (tFNAs), novel nanomaterials, have shown great potential in biomedicine due to their strong biocompatibility, excellent cellular internalisation ability, and unparalleled programmability. The objective of this research was to examine if tFNAs have a positive effect on regeneration after RCTs. Experiments conducted in a controlled environment demonstrated that tFNAs hindered the assembly of inflammasomes in macrophages, resulting in a decrease in the release of inflammatory factors. Next, tFNAs were shown to exert a protective effect on the osteogenic and chondrogenic differentiation of bone marrow MSCs under inflammatory conditions. The in vitro results also demonstrated the regulatory effect of tFNAs on tendon-related protein expression levels in tenocytes after inflammatory stimulation. Finally, intra-articular injection of tFNAs into a rat RCT model showed that tFNAs improved tendon-to-bone healing, suggesting that tFNAs may be promising tendon-to-bone protective agents for the treatment of RCTs.

7.
Postgrad Med J ; 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200633

RESUMO

Multidrug-resistant tuberculosis (MDR-TB) has become a critical challenge to public health, and the prevention and treatment of MDR-TB are of great significance in reducing the global burden of tuberculosis. How to improve the effectiveness and safety of chemotherapy for MDR-TB is a pressing issue that needs to be addressed in tuberculosis control efforts. This article provides a comprehensive review of the clinical application of new antituberculosis drugs in MDR-TB, aiming to provide a scientific basis for the prevention and treatment strategy of MDR-TB.

8.
J Mol Model ; 29(12): 385, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-37999816

RESUMO

Aluminized explosive has attracted more and more attention in recent years because of its high explosive heat and high power. Al2O and AlO are indispensable aluminum oxides in the explosion process of aluminized explosives. The study of the physical properties of solid Al2O and AlO under pressure may play an important role in the understanding of the explosion mechanism of aluminized explosives. CONTEXT: The structures, cold-pressed lines and electronic properties of cubic Al2O and AlO are calculated and analyzed based on first-principles calculation in this paper. The optimized structures of Al2O and AlO are in good agreement with those previously studied. The cold pressure line shows that the specific volumes of Al2O and AlO decrease with increasing pressure. The peak values and peak positions of density of state of Al2O and AlO change greatly under pressure. METHODS: The CASTEP code was used to execute these calculations throughout the present work, where the plane-wave basis set and norm conserving pseudopotential were employed.

9.
Regen Biomater ; 10: rbad085, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37814675

RESUMO

The field of regenerative medicine faces a notable challenge in terms of the regeneration of articular cartilage. Without proper treatment, it can lead to osteoarthritis. Based on the research findings, human umbilical cord mesenchymal stem cells (hUMSCs) are considered an excellent choice for regenerating cartilage. However, there is still a lack of suitable biomaterials to control their ability to self-renew and differentiate. To address this issue, in this study using tetrahedral framework nucleic acids (tFNAs) as a new method in an in vitro culture setting to manage the behaviour of hUMSCs was proposed. Then, the influence of tFNAs on hUMSC proliferation, migration and chondrogenic differentiation was explored by combining bioinformatics methods. In addition, a variety of molecular biology techniques have been used to investigate deep molecular mechanisms. Relevant results demonstrated that tFNAs can affect the transcriptome and multiple signalling pathways of hUMSCs, among which the PI3K/Akt pathway is significantly activated. Furthermore, tFNAs can regulate the expression levels of multiple proteins (GSK3ß, RhoA and mTOR) downstream of the PI3K-Akt axis to further enhance cell proliferation, migration and hUMSC chondrogenic differentiation. tFNAs provide new insight into enhancing the chondrogenic potential of hUMSCs, which exhibits promising potential for future utilization within the domains of AC regeneration and clinical treatment.

10.
J Nanobiotechnology ; 21(1): 269, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37574546

RESUMO

Successful biomaterial implantation requires appropriate immune responses. Macrophages are key mediators involved in this process. Currently, exploitation of the intrinsic properties of biomaterials to modulate macrophages and immune responses is appealing. In this study, we prepared hydrophilic nanofibers with an aligned topography by incorporating polyethylene glycol and polycaprolactone using axial electrospinning. We investigated the effect of the nanofibers on macrophage behavior and the underlying mechanisms. With the increase of hydrophilicity of aligned nanofibers, the inflammatory gene expression of macrophages adhering to them was downregulated, and M2 polarization was induced. We further presented clear evidence that the inflammasome NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was the cellular sensor by which macrophages sense the biomaterials, and it acted as a regulator of the macrophage-mediated response to foreign bodies and implant integration. In vivo, we showed that the fibers shaped the implant-related immune microenvironment and ameliorated peritendinous adhesions. In conclusion, our study demonstrated that hydrophilic aligned nanofibers exhibited better biocompatibility and immunological properties.


Assuntos
Inflamassomos , Nanofibras , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Macrófagos/metabolismo , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/metabolismo , Interações Hidrofóbicas e Hidrofílicas
11.
Chem Sci ; 14(28): 7648-7655, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37476717

RESUMO

Pyrroles, furans, and thiophenes are important structural motifs in biologically active substances, pharmaceuticals and functional materials. In this paper, we disclose an efficient synthetic strategy for the rapid construction of multisubstituted pyrroles, furans, and thiophenes via NXS mediated desulfonylative/dehydrogenative cyclization of vinylidenecyclopropanes (VDCPs). The advantages of this method include wide substrate range, high efficiency and synthetic usefulness of the heterocyclic products under metal-free and mild conditions. The derivatization of pyrrole products and the preparation of functional molecules successfully demonstrated the synthetic potential of the products as platform molecules. The reaction mechanism has been investigated on the basis of control experiments and DFT calculations.

12.
ACS Appl Mater Interfaces ; 15(19): 22944-22958, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37134259

RESUMO

The regeneration and reconstruction of articular cartilage (AC) after a defect are often difficult. The key to the treatment of AC defects lies in regeneration of the defect site and regulation of the inflammatory response. In this investigation, a bioactive multifunctional scaffold was formulated using the aptamer Apt19S as a mediator for mesenchymal stem cell (MSC)-specific recruitment and the enhancement of cellular chondrogenic and inflammatory regulation through the incorporation of Mg2+. Apt19S, which can recruit MSCs in vitro and in vivo, was chemically conjugated to a decellularized cartilage extracellular matrix (ECM)-lysed scaffold. The results from in vitro experiments using the resulting scaffold demonstrated that the inclusion of Mg2+ could stimulate not only the chondrogenic differentiation of synovial MSCs but also the increased polarization of macrophages toward the M2 phenotype. Additionally, Mg2+ inhibited NLRP3 inflammasome activation, thereby decreasing chondrocyte pyroptosis. Subsequently, Mg2+ was incorporated into the bioactive multifunctional scaffold, and the resulting scaffold promoted cartilage regeneration in vivo. In conclusion, this study confirms that the combination of Mg2+ and aptamer-functionalized ECM scaffolds is a promising strategy for AC regeneration based on in situ tissue engineering and early inflammatory regulation.


Assuntos
Cartilagem Articular , Cartilagem Articular/fisiologia , Magnésio/farmacologia , Regeneração/fisiologia , Condrócitos , Engenharia Tecidual/métodos , Oligonucleotídeos , Condrogênese , Matriz Extracelular/metabolismo , Íons/metabolismo , Tecidos Suporte
13.
Signal Transduct Target Ther ; 8(1): 142, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37024477

RESUMO

Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Dysregulation of this process leads to multiple diseases, including osteoporosis. However, the underlying molecular mechanisms are not fully understood. Here, we show that the global and conditional osteoblast knockout of a deubiquitinase Otub1 result in low bone mass and poor bone strength due to defects in osteogenic differentiation and mineralization. Mechanistically, the stability of FGFR2, a crucial regulator of osteogenesis, is maintained by OTUB1. OTUB1 attenuates the E3 ligase SMURF1-mediated FGFR2 ubiquitination by inhibiting SMURF1's E2 binding. In the absence of OTUB1, FGFR2 is ubiquitinated excessively by SMURF1, followed by lysosomal degradation. Consistently, adeno-associated virus serotype 9 (AAV9)-delivered FGFR2 in knee joints rescued the bone mass loss in osteoblast-specific Otub1-deleted mice. Moreover, Otub1 mRNA level was significantly downregulated in bones from osteoporotic mice, and restoring OTUB1 levels through an AAV9-delivered system in ovariectomy-induced osteoporotic mice attenuated osteopenia. Taken together, our results suggest that OTUB1 positively regulates osteogenic differentiation and mineralization in bone homeostasis by controlling FGFR2 stability, which provides an optical therapeutic strategy to alleviate osteoporosis.


Assuntos
Osteogênese , Osteoporose , Animais , Feminino , Camundongos , Osso e Ossos/metabolismo , Osteoblastos/metabolismo , Osteogênese/genética , Osteoporose/genética , Osteoporose/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
14.
Front Bioeng Biotechnol ; 11: 1115312, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36890920

RESUMO

Tendon injuries often result in significant pain and disability and impose severe clinical and financial burdens on our society. Despite considerable achievements in the field of regenerative medicine in the past several decades, effective treatments remain a challenge due to the limited natural healing capacity of tendons caused by poor cell density and vascularization. The development of tissue engineering has provided more promising results in regenerating tendon-like tissues with compositional, structural and functional characteristics comparable to those of native tendon tissues. Tissue engineering is the discipline of regenerative medicine that aims to restore the physiological functions of tissues by using a combination of cells and materials, as well as suitable biochemical and physicochemical factors. In this review, following a discussion of tendon structure, injury and healing, we aim to elucidate the current strategies (biomaterials, scaffold fabrication techniques, cells, biological adjuncts, mechanical loading and bioreactors, and the role of macrophage polarization in tendon regeneration), challenges and future directions in the field of tendon tissue engineering.

15.
J Dairy Sci ; 106(4): 2535-2550, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36797187

RESUMO

Longitudinal traits, such as milk production traits in dairy cattle, are featured by having phenotypic values at multiple time points, which change dynamically over time. In this study, we first imputed SNP chip (50-100K) data to whole-genome sequence (WGS) data in a Chinese Holstein population consisting of 6,470 cows. The imputation accuracies were 0.88 to 0.97 on average after quality control. We then performed longitudinal GWAS in this population based on a random regression test-day model using the imputed WGS data. The longitudinal GWAS revealed 16, 39, and 75 quantitative trait locus regions associated with milk yield, fat percentage, and protein percentage, respectively. We estimated the 95% confidence intervals (CI) for these quantitative trait locus regions using the logP drop method and identified 581 genes involved in these CI. Further, we focused on the CI that covered or overlapped with only 1 gene or the CI that contained an extremely significant top SNP. Twenty-eight candidate genes were identified in these CI. Most of them have been reported in the literature to be associated with milk production traits, such as DGAT1, HSF1, MGST1, GHR, ABCG2, ADCK5, and CSN1S1. Among the unreported novel genes, some also showed good potential as candidate genes, such as CCSER1, CUX2, SNTB1, RGS7, OSR2, and STK3, and are worth being further investigated. Our study provided not only new insights into the candidate genes for milk production traits, but also a general framework for longitudinal GWAS based on random regression test-day model using WGS data.


Assuntos
Estudo de Associação Genômica Ampla , Leite , Animais , Bovinos/genética , Feminino , Estudo de Associação Genômica Ampla/veterinária , Genótipo , Leite/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Estudos Longitudinais
16.
Biomater Res ; 27(1): 7, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36739446

RESUMO

BACKGROUND: In recent years, there has been significant research progress on in situ articular cartilage (AC) tissue engineering with endogenous stem cells, which uses biological materials or bioactive factors to improve the regeneration microenvironment and recruit more endogenous stem cells from the joint cavity to the defect area to promote cartilage regeneration. METHOD: In this study, we used ECM alone as a bioink in low-temperature deposition manufacturing (LDM) 3D printing and then successfully fabricated a hierarchical porous ECM scaffold incorporating GDF-5. RESULTS: Comparative in vitro experiments showed that the 7% ECM scaffolds had the best biocompatibility. After the addition of GDF-5 protein, the ECM scaffolds significantly improved bone marrow mesenchymal stem cell (BMSC) migration and chondrogenic differentiation. Most importantly, the in vivo results showed that the ECM/GDF-5 scaffold significantly enhanced in situ cartilage repair. CONCLUSION: In conclusion, this study reports the construction of a new scaffold based on the concept of in situ regeneration, and we believe that our findings will provide a new treatment strategy for AC defect repair.

17.
Mater Today Bio ; 19: 100549, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36756208

RESUMO

Improving the poor microenvironment in the joint cavity has potential for treating cartilage injury, and mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos), which can modulate cellular behavior, are becoming a new cell-free therapy for cartilage repair. Here, we used acellular cartilage extracellular matrix (ACECM) to prepare 3D scaffolds and 2D substrates by low-temperature deposition modeling (LDM) and tape casting. We aimed to investigate whether MSC-Exos cultured on scaffolds of different dimensions could improve the poor joint cavity microenvironment caused by cartilage injury and to explore the related mechanisms. In vitro experiments showed that exosomes derived from MSCs cultured on three-dimensional (3D) scaffolds (3D-Exos) had increased efficiency. In short-term animal experiments, compared with exosomes derived from MSCs cultured in a two-dimensional (2D) environment (2D-Exos), 3D-Exos had a stronger ability to regulate the joint cavity microenvironment. Long-term animal studies confirmed the therapeutic efficacy of 3D-Exos over 2D-Exos. Thus, 3D-Exos were applied in the rat knee osteochondral defect model after adsorption in the micropores of the scaffold and combined with subsequent articular cavity injections, and they showed a stronger cartilage repair ability. These findings provide a new strategy for repairing articular cartilage damage. Furthermore, miRNA sequencing indicated that the function of 3D-Exos may be associated with high expression of miRNAs. Thus, our study provides valuable insights for the design of 3D-Exos to promote cartilage regeneration.

18.
Anim Biotechnol ; 34(7): 3154-3161, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36282276

RESUMO

Mitochondria are best known for synthesizing ATP through the tricarboxylic acid cycle and oxidative phosphorylation. The cytoplasmic mitochondrial DNA (mtDNA) is important for maintaining the function. This study was designed to reveal the effect of mtDNA on chicken body measurement traits (BMTs). A population of 605 Wenshang Barred chickens were recorded BMTs, including body slope length, keel length, chest width, etc. The single-nucleotide polymorphisms (SNPs) of their mitogenomes were detected by PCR amplification and DNA sequencing. Totally 69 mutations in mitogenome were discovered, including 18 in noncoding region and 51 in coding region. By multi-sequence alignment and haplotype construction, the chickens were clustered into eight haplotypes and further three haplogroups. The association between BMTs and mtDNA SNPs, haplotypes and haplogroups were analyzed in the linear model by ASReml, respectively. Among them, the SNP mt11086 T/C in ND3 was found to significantly affect chest dept (p < .05) and was highly conservative by phylogenetic conservation analyses, which reflected the genetic effect on body size and growth of chickens. No significant association between the mitochondrial haplotypes or haplogroups and BMTs was found. The polymorphic site reflecting body size could be put into chicken breeding programs as the genetic marker.


Assuntos
Galinhas , Genoma Mitocondrial , Animais , Galinhas/genética , Genoma Mitocondrial/genética , Filogenia , Fenótipo , Haplótipos/genética , Polimorfismo de Nucleotídeo Único/genética , DNA Mitocondrial/genética
19.
Biomaterials ; 291: 121888, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36403324

RESUMO

Inferior healing and peritendinous adhesions are the major clinical problems following Achilles tendon injury, leading to impaired motor function and an increased risk of re-rupture. These complications are presumed to be inextricably linked to inflammation and fibroscar formation. Here, microRNA29a is identified as a promising therapeutic target for tendon injury through the cross-regulation of the immune response and matrix remodeling. MiR29a-LNPs were successfully prepared by microfluidic technology. They are then loaded into the core-shell nanofibers to achieve local delivery in the injured tendon, where the shell layer is composed of PELA for anti-adhesion. Our studies reveal that miR29a regulates collagen synthesis and NF-κB activation in tenocytes, and promotes macrophage polarization by inhibiting the inflammasome pathway. In vivo studies of the Achilles tendon-rupture model indicate the best repair in the miR29a group, as evidenced by superior collagen composition and alignment, higher mechanical strength, and better functional recovery. In conclusion, a functionalized anti-adhesive membrane that promotes nascent tendon matrix remodeling and improves the regenerative immune microenvironment is developed for the treatment of tendon injury.


Assuntos
Nanofibras , Traumatismos dos Tendões , Humanos , Tendões , Traumatismos dos Tendões/terapia , Imunidade
20.
J Poult Sci ; 59(4): 323-327, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36382061

RESUMO

Body measurement traits (BMTs), which are classical quantitative traits of vital responses to body growth, have been studied in pigs, cattle, and sheep for several decades. In chickens, BMTs mainly cover body slope length, keel length, chest width, chest depth, tibia length, and tibia diameter; however, their genetic markers are yet to be considered. In this study, the Wenshang Barred chicken, a meat-egg-type native breed in China, was used to investigate the association between BMTs and the expression of growth-related genes, including GH, IGF1, IGF2, GHRL, IGF1R, IGFBP2, GHF-1, and TSHB. The results revealed that the single nucleotide polymorphism (SNP) rs3138025 in GH was significantly associated with keel length (P=0.0455 <0.05), rs313810945 in IGF2 was significantly correlated with chest width (P=0.0454 <0.05) and chest depth (P=0.0259 <0.05), and rs317298536 in TSHB significantly affected chest depth (P=0.0399 <0.05). The SNPs were associated with traits reflecting body size and were potentially involved in bone growth, which was consistent with studies in humans, rodents, and other vertebrate species. In addition, a borderline significant association was found between rs317298536 and body weight (P=0.0604). These polymorphic sites may be treated as candidate genetic markers in breeding programs involving Wenshang Barred chickens.

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