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1.
Cells ; 13(17)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39273017

RESUMO

PAK4 and PD-L1 have been suggested as novel therapeutic targets in human cancers. Moreover, PAK4 has been suggested to be a molecule closely related to the immune evasion of cancers. Therefore, this study evaluated the roles of PAK4 and PD-L1 in the progression of osteosarcomas in 32 osteosarcomas and osteosarcoma cells. In human osteosarcomas, immunohistochemical positivity for the expression of PAK4 (overall survival, p = 0.028) and PD-L1 (relapse-free survival, p = 0.002) were independent indicators for the survival of patients in a multivariate analysis. In osteosarcoma cells, the overexpression of PAK4 increased proliferation and invasiveness, while the knockdown of PAK4 suppressed proliferation and invasiveness. The expression of PAK4 was associated with the expression of the molecules related to cell cycle regulation, invasion, and apoptosis. PAK4 was involved in resistance to apoptosis under a treatment regime with doxorubicin for osteosarcoma. In U2OS cells, PAK4 was involved in the stabilization of PD-L1 from ubiquitin-mediated proteasomal degradation and the in vivo infiltration of immune cells such as regulatory T cells and PD1-, CD4-, and CD8-positive cells in mice tumors. In conclusion, this study suggests that PAK4 is involved in the progression of osteosarcoma by promoting proliferation, invasion, and resistance to doxorubicin and stabilized PD-L1 from proteasomal degradation.


Assuntos
Antígeno B7-H1 , Proliferação de Células , Doxorrubicina , Resistencia a Medicamentos Antineoplásicos , Osteossarcoma , Quinases Ativadas por p21 , Osteossarcoma/patologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Osteossarcoma/genética , Humanos , Antígeno B7-H1/metabolismo , Feminino , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Animais , Quinases Ativadas por p21/metabolismo , Quinases Ativadas por p21/genética , Masculino , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Camundongos , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Adulto , Adolescente , Estabilidade Proteica/efeitos dos fármacos , Camundongos Nus , Adulto Jovem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Invasividade Neoplásica
2.
J Orthop Translat ; 47: 191-206, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39040489

RESUMO

The regenerative capacity of bone is indispensable for growth, given that accidental injury is almost inevitable. Bone regenerative capacity is relevant for the aging population globally and for the repair of large bone defects after osteotomy (e.g., following removal of malignant bone tumours). Among the many therapeutic modalities proposed to bone regeneration, electrical stimulation has attracted significant attention owing to its economic convenience and exceptional curative effects, and various electroactive biomaterials have emerged. This review summarizes the current knowledge and progress regarding electrical stimulation strategies for improving bone repair. Such strategies range from traditional methods of delivering electrical stimulation via electroconductive materials using external power sources to self-powered biomaterials, such as piezoelectric materials and nanogenerators. Electrical stimulation and osteogenesis are related via bone piezoelectricity. This review examines cell behaviour and the potential mechanisms of electrostimulation via electroactive biomaterials in bone healing, aiming to provide new insights regarding the mechanisms of bone regeneration using electroactive biomaterials. The translational potential of this article: This review examines the roles of electroactive biomaterials in rehabilitating the electrical microenvironment to facilitate bone regeneration, addressing current progress in electrical biomaterials and the mechanisms whereby electrical cues mediate bone regeneration. Interactions between osteogenesis-related cells and electroactive biomaterials are summarized, leading to proposals regarding the use of electrical stimulation-based therapies to accelerate bone healing.

3.
Reprod Domest Anim ; 59(7): e14661, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38979950

RESUMO

Spermatogonial stem cells (SSCs) comprise the foundation of spermatogenesis and hence have great potential for fertility preservation of rare or endangered species and the development of transgenic animals and birds. Yet, developing optimal conditions for the isolation, culture, and maintenance of SSCs in vitro remains challenging, especially for chicken. The objectives of this study were to (1) find the optimal age for SSC isolation in Huaixiang chicken, (2) develop efficient protocols for the isolation, (3) enrichment, and (4) culture of isolated SSCs. In the present study, we first compared the efficiency of SSC isolation using 11 different age groups (8-79 days of age) of Huaixiang chicken. We found that the testes of 21-day-old chicken yielded the highest cell viability. Next, we compared two different enzymatic combinations for isolating SSCs and found that 0.125% trypsin and 0.02 g/L EDTA supported the highest number and viability of SSCs. This was followed by investigating optimal conditions for the enrichment of SSCs, where we observed that differential plating had the highest enrichment efficiency compared to the Percoll gradient and magnetic-activated cell sorting methods. Lastly, to find the optimal culture conditions of SSCs, we compared adding different concentrations of foetal bovine serum (FBS; 2%, 5%, 7%, and 10%) and different concentrations of GDNF, bFGF, or LIF (5, 10, 20, or 30 ng/mL). We found that a combination of 2% FBS and individual growth factors, including GDNF (20 ng/mL), bFGF (30 ng/mL), or LIF (5 ng/mL), best supported the proliferation and colony formation of SSCs. In conclusion, SSCs can be optimally isolated through enzymatic digestion from testes of 21-day-old chicken, followed by enrichment using differential plating. Furthermore, adding 2% FBS and optimized concentrations of GFNF, bFGF, or LIF in the culture promotes the proliferation of chicken SSCs.


Assuntos
Células-Tronco Germinativas Adultas , Técnicas de Cultura de Células , Separação Celular , Galinhas , Animais , Masculino , Técnicas de Cultura de Células/veterinária , Separação Celular/métodos , Separação Celular/veterinária , Testículo/citologia , Espermatogônias/citologia , Sobrevivência Celular , Células Cultivadas
4.
Exp Cell Res ; 440(1): 114115, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38844260

RESUMO

The process of aging is characterized by structural degeneration and functional decline, as well as diminished adaptability and resistance. The aging kidney exhibits a variety of structural and functional impairments. In aging mice, thinning and graying of fur were observed, along with a significant increase in kidney indices compared to young mice. Biochemical indicators revealed elevated levels of creatinine, urea nitrogen and serum uric acid, suggesting impaired kidney function. Histological analysis unveiled glomerular enlargement and sclerosis, severe hyaline degeneration, capillary occlusion, lymphocyte infiltration, tubular and glomerular fibrosis, and increased collagen deposition. Observations under electron microscopy showed thickened basement membranes, altered foot processes, and increased mesangium and mesangial matrix. Molecular marker analysis indicated upregulation of aging-related ß-galactosidase, p16-INK4A, and the DNA damage marker γH2AX in the kidneys of aged mice. In metabolomics, a total of 62 significantly different metabolites were identified, and 10 pathways were enriched. We propose that citrulline, dopamine, and indoxyl sulfate have the potential to serve as markers of kidney damage related to aging in the future. Phosphoproteomics analysis identified 6656 phosphosites across 1555 proteins, annotated to 62 pathways, and indicated increased phosphorylation at the Ser27 site of Minichromosome maintenance complex component 2 (Mcm2) and decreased at the Ser284 site of heterogeneous nuclear ribonucleoprotein K (hnRNP K), with these modifications being confirmed by western blotting. The phosphorylation changes in these molecules may contribute to aging by affecting genome stability. Eleven common pathways were detected in both omics, including arginine biosynthesis, purine metabolism and biosynthesis of unsaturated fatty acids, etc., which are closely associated with aging and renal insufficiency.


Assuntos
Envelhecimento , Instabilidade Genômica , Rim , Componente 2 do Complexo de Manutenção de Minicromossomo , Animais , Envelhecimento/metabolismo , Envelhecimento/genética , Envelhecimento/patologia , Instabilidade Genômica/genética , Camundongos , Fosforilação , Rim/metabolismo , Rim/patologia , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Camundongos Endogâmicos C57BL , Masculino , Metabolômica/métodos , Dano ao DNA , Multiômica
5.
Complement Ther Med ; 82: 103038, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582375

RESUMO

OBJECTIVE: An increasing body of evidence suggests a positive role of chiropractic in the treatment of neuro-musculoskeletal disorders. This study aims to explore current research hotspots and trends, providing insights into the broad prospects of this field. METHODS: A bibliometric review was conducted on all chiropractic articles included in the Web of Science Core Collection before December 31, 2023. RESULTS: Over the past century, the volume of research in the field of chiropractic has been fluctuating annually, with four peaks observed in total. The United States, Canada, Australia, and the United Kingdom are leading countries. Chu, Eric Chun-Pu is the author with the most publications, while Bronfort, Gert has the highest total citation count. The University of Southern Denmark has produced the most publications, while Queens University - Canada is the most central institution. The Journal of Manipulative and Physiological Therapeutics is the journal with the most publications and citations, while the Journal of the American Medical Association is the most central journal. The two most-cited articles were both authored by Eisenberg DM. Emerging keywords include "chronic pain" and "skills". The theoretical mechanisms and scientific basis of chiropractic, its clinical practice and safety, education and training, integration with other disciplines, and patient experiences and satisfaction are the frontiers and hotspots of research. CONCLUSION: This study integrates bibliometric analysis to summarize the current state of research and global network centers in the field of chiropractic, further highlighting the hotspots and trends in this field. However, Individual and national rankings should be interpreted with caution due to our focus on Web of Science rather than PubMed.


Assuntos
Bibliometria , Quiroprática , Humanos , Pesquisa Biomédica , História do Século XX , História do Século XXI
7.
Heliyon ; 9(11): e21011, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37920504

RESUMO

Aging is associated with gradual changes in liver structure, altered metabolites and other physiological/pathological functions in hepatic cells. However, its characterized phenotypes based on altered metabolites and the underlying biological mechanism are unclear. Advancements in high-throughput omics technology provide new opportunities to understand the pathological process of aging. Here, in our present study, both metabolomics and phosphoproteomics were applied to identify the altered metabolites and phosphorylated proteins in liver of young (the WTY group) and naturally aged (the WTA group) mice, to find novel biomarkers and pathways, and uncover the biological mechanism. Analysis showed that the body weights, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the WTA group. The grips decreased with age, while the triglyceride (TG) and cholesterol (TC) did not change significantly. The increase of fibrosis, accumulation of inflammatory cells, hepatocytes degeneration, the deposition of lipid droplets and glycogen, the damaged mitochondria, and deduction of endoplasmic reticulum were observed in the aging liver under optical and electron microscopes. In addition, a network of metabolites and phosphorylated proteomes of the aging liver was established. Metabolomics detected 970 metabolites in the positive ion mode and 778 metabolites in the negative ion mode. A total of 150 pathways were pooled. Phosphoproteomics identified 2618 proteins which contained 16621 phosphosites. A total of 164 pathways were detected. 65 common pathways were detected in two omics. Phosphorylated protein heat shock protein HSP 90-alpha (HSP90A) and v-raf murine viral oncogene homolog B1(BRAF), related to cancer pathway, were significantly upregulated in aged mice liver. Western blot verified that protein expression of MEK and ERK, downstream of BRAF pathway were elevated in the liver of aging mice. However, the protein expression of BRAF was not a significant difference. Overall, these findings revealed a close link between aging and cancer and contributed to our understanding of the multi-omics changes in natural aging.

8.
Regen Biomater ; 10: rbad083, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37808955

RESUMO

In recent decades, bone tissue engineering, which is supported by scaffold, seed cells and bioactive molecules (BMs), has provided new hope and direction for treating bone defects. In terms of seed cells, compared to bone marrow mesenchymal stem cells, which were widely utilized in previous years, adipose-derived stem cells (ADSCs) are becoming increasingly favored by researchers due to their abundant sources, easy availability and multi-differentiation potentials. However, there is no systematic theoretical basis for selecting appropriate biomaterials loaded with ADSCs. In this review, the regulatory effects of various biomaterials on the behavior of ADSCs are summarized from four perspectives, including biocompatibility, inflammation regulation, angiogenesis and osteogenesis, to illustrate the potential of combining various materials with ADSCs for the treatment of bone defects. In addition, we conclude the influence of additional application of various BMs on the bone repair effect of ADSCs, in order to provide more evidences and support for the selection or preparation of suitable biomaterials and BMs to work with ADSCs. More importantly, the associated clinical case reports and experiments are generalized to provide additional ideas for the clinical transformation and application of bone tissue engineering loaded with ADSCs.

9.
Mol Cell Proteomics ; 22(11): 100659, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37805038

RESUMO

Aging is widely accepted as an independent risk factor for cardiovascular disease (CVD), which contributes to increasing morbidity and mortality in the elderly population. Lysine ß-hydroxybutyrylation (Kbhb) is a novel post-translational modification (PTM), wherein ß-hydroxybutyrate is covalently attached to lysine ε-amino groups. Recent studies have revealed that histone Kbhb contributes to tumor progression, diabetic cardiomyopathy progression, and postnatal heart development. However, no studies have yet reported a global analysis of Kbhb proteins in aging hearts or elucidated the mechanisms underlying this modification in the process. Herein, we conducted quantitative proteomics and Kbhb PTM omics to comprehensively elucidate the alterations of global proteome and Kbhb modification in the hearts of aged mice. The results revealed a decline in grip strength and cardiac diastolic function in 22-month-old aged mice compared to 3-month-old young mice. High-throughput liquid chromatogram-mass spectrometry analysis identified 1710 ß-hydroxybutyrylated lysine sites in 641 proteins in the cardiac tissue of young and aged mice. Additionally, 183 Kbhb sites identified in 134 proteins exhibited significant differential modification in aged hearts (fold change (FC) > 1.5 or <1/1.5, p < 0.05). Notably, the Kbhb-modified proteins were primarily detected in energy metabolism pathways, such as fatty acid elongation, glyoxylate and dicarboxylate metabolism, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, these Kbhb-modified proteins were predominantly localized in the mitochondria. The present study, for the first time, provides a global proteomic profile and Kbhb modification landscape of cardiomyocytes in aged hearts. These findings put forth novel possibilities for treating cardiac aging and aging-related CVDs by reversing abnormal Kbhb modifications.


Assuntos
Lisina , Proteômica , Humanos , Idoso , Camundongos , Animais , Lactente , Lisina/metabolismo , Proteômica/métodos , Histonas/metabolismo , Envelhecimento/metabolismo , Processamento de Proteína Pós-Traducional
10.
Natl Sci Rev ; 10(6): nwac213, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37425654

RESUMO

SARS-CoV and SARS-CoV-2 have been thought to originate from bats. In this study, we screened pharyngeal and anal swabs from 13 064 bats collected between 2016 and 2021 at 703 locations across China for sarbecoviruses, covering almost all known southern hotspots, and found 146 new bat sarbecoviruses. Phylogenetic analyses of all available sarbecoviruses show that there are three different lineages-L1 as SARS-CoV-related CoVs (SARSr-CoVs), L2 as SARS-CoV-2-related CoVs (SC2r-CoVs) and novel L-R (recombinants of L1 and L2)-present in Rhinolophus pusillus bats, in the mainland of China. Among the 146 sequences, only four are L-Rs. Importantly, none belong in the L2 lineage, indicating that circulation of SC2r-CoVs in China might be very limited. All remaining 142 sequences belong in the L1 lineage, of which YN2020B-G shares the highest overall sequence identity with SARS-CoV (95.8%). The observation suggests endemic circulations of SARSr-CoVs, but not SC2r-CoVs, in bats in China. Geographic analysis of the collection sites in this study, together with all published reports, indicates that SC2r-CoVs may be mainly present in bats of Southeast Asia, including the southern border of Yunnan province, but absent in all other regions within China. In contrast, SARSr-CoVs appear to have broader geographic distribution, with the highest genetic diversity and sequence identity to human sarbecoviruses along the southwest border of China. Our data provide the rationale for further extensive surveys in broader geographical regions within, and beyond, Southeast Asia in order to find the most recent ancestors of human sarbecoviruses.

11.
Theranostics ; 13(10): 3245-3275, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37351163

RESUMO

Large bone defects are a major global health concern. Bone tissue engineering (BTE) is the most promising alternative to avoid the drawbacks of autograft and allograft bone. Nevertheless, how to precisely control stem cell osteogenic differentiation has been a long-standing puzzle. Compared with biochemical cues, physicomechanical stimuli have been widely studied for their biosafety and stability. The mechanical properties of various biomaterials (polymers, bioceramics, metal and alloys) become the main source of physicomechanical stimuli. By altering the stiffness, viscoelasticity, and topography of materials, mechanical stimuli with different strengths transmit into precise signals that mediate osteogenic differentiation. In addition, externally mechanical forces also play a critical role in promoting osteogenesis, such as compression stress, tensile stress, fluid shear stress and vibration, etc. When exposed to mechanical forces, mesenchymal stem cells (MSCs) differentiate into osteogenic lineages by sensing mechanical stimuli through mechanical sensors, including integrin and focal adhesions (FAs), cytoskeleton, primary cilium, ions channels, gap junction, and activating osteogenic-related mechanotransduction pathways, such as yes associated proteins (YAP)/TAZ, MAPK, Rho-GTPases, Wnt/ß-catenin, TGFß superfamily, Notch signaling. This review summarizes various biomaterials that transmit mechanical signals, physicomechanical stimuli that directly regulate MSCs differentiation, and the mechanical transduction mechanisms of MSCs. This review provides a deep and broad understanding of mechanical transduction mechanisms and discusses the challenges that remained in clinical translocation as well as the outlook for the future improvements.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Osteogênese/fisiologia , Mecanotransdução Celular , Materiais Biocompatíveis , Engenharia Tecidual , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular
12.
Exp Cell Res ; 427(1): 113566, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37004949

RESUMO

BACKGROUND: Aging is characterized by a general decline in cellular function, which ultimately affects whole body homeostasis. This study aimed to investigate the effects and underlying mechanisms of exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-exos) on the livers of naturally aging mice. METHOD: Twenty-two-month-old C57BL6 mice were used as a natural aging animal model, divided into a saline-treated wild-type aged control group (WT-AC) and a hUCMSC-exo-treated group (WT-AEX), and then detected by morphology, metabolomics and phosphoproteomics. RESULTS: Morphological analysis showed that hUCMSC-exos ameliorated structural disorder and decreased markers of senescence and genome instability in aging livers. Metabolomics showed that hUCMSC-exos decreased the contents of saturated glycerophospholipids, palmitoyl-glycerols and eicosanoid derivatives associated with lipotoxicity and inflammation, consistent with the decreased phosphorylation of metabolic enzymes, such as propionate-CoA ligase (Acss2), at S267 detected by phosphoproteomics. Moreover, phosphoproteomics indicated that hUCMSC-exos reduced the phosphorylation of proteins participating in nuclear transport and cancer signaling, such as heat shock protein HSP90-beta (Hsp90ab1) at S226 and nucleoprotein TPR (Tpr) at S453 and S379, while increasing those involved in intracellular communication, such as calnexin (Canx) at S563 and PDZ domain-containing protein 8 (Pdzd8). Finally, phosphorylated HSP90ß and Tpr were verified predominantly in hepatocytes. CONCLUSION: HUCMSC-exos improved metabolic reprogramming and genome stability mainly associated with phosphorylated HSP90ß in hepatocytes in natural aging livers. This work provides a comprehensive resource of biological data by omics to support future investigations of hUCMSC-exos in aging.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Idoso , Lactente , Exossomos/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Envelhecimento , Células-Tronco Mesenquimais/metabolismo , Metabolômica , Cordão Umbilical , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
13.
Mol Cell Proteomics ; 22(2): 100494, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36621768

RESUMO

AMP-activated protein kinase alpha 2 (AMPKα2) regulates energy metabolism, protein synthesis, and glucolipid metabolism myocardial cells. Ketone bodies produced by fatty acid ß-oxidation, especially ß-hydroxybutyrate, are fatty energy-supplying substances for the heart, brain, and other organs during fasting and long-term exercise. They also regulate metabolic signaling for multiple cellular functions. Lysine ß-hydroxybutyrylation (Kbhb) is a ß-hydroxybutyrate-mediated protein posttranslational modification. Histone Kbhb has been identified in yeast, mouse, and human cells. However, whether AMPK regulates protein Kbhb is yet unclear. Hence, the present study explored the changes in proteomics and Kbhb modification omics in the hearts of AMPKα2 knockout mice using a comprehensive quantitative proteomic analysis. Based on mass spectrometry (LC-MS/MS) analysis, the number of 1181 Kbhb modified sites in 455 proteins were quantified between AMPKα2 knockout mice and wildtype mice; 244 Kbhb sites in 142 proteins decreased or increased after AMPKα2 knockout (fold change >1.5 or <1/1.5, p < 0.05). The regulation of Kbhb sites in 26 key enzymes of fatty acid degradation and tricarboxylic acid cycle was noted in AMPKα2 knockout mouse cardiomyocytes. These findings, for the first time, identified proteomic features and Kbhb modification of cardiomyocytes after AMPKα2 knockout, suggesting that AMPKα2 regulates energy metabolism by modifying protein Kbhb.


Assuntos
Ácido 3-Hidroxibutírico , Proteínas Quinases Ativadas por AMP , Miocárdio , Animais , Humanos , Camundongos , Ácido 3-Hidroxibutírico/química , Ácido 3-Hidroxibutírico/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Cromatografia Líquida , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/metabolismo , Proteômica , Espectrometria de Massas em Tandem
14.
Arch Biochem Biophys ; 731: 109430, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36326546

RESUMO

Diabetic cardiovascular complication is a common systemic disease with high morbidity and mortality worldwide. We hypothesise that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exos) can rescue these disorders and alleviate vascular remodeling in diabetes. Morphological, non-targeted metabolomics and 4D label-free proteomics techniques were used to analyze the aortas of db/m mice as normal control group (NCA), saline treated db/db mice (DMA), and hUCMSCs-exos treated db/db mice (DMTA), and to clarify the molecular mechanism of the protection of hUCMSCs-exos in vascular remodeling from a new point of view. The results showed that 74 metabolites were changed significantly in diabetic aortas, of which 15 were almost restored by hUCMSCs-exos. In proteomics, 30 potential targets such as Stromal cell-derived factor 2-like protein 1, Leukemia inhibitory factor receptor, Peroxisomal membrane protein and E3 ubiquitin-protein ligase MYCBP2 were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis showed that Central carbon metabolism in cancer and Galactose metabolism pathway were up-regulated to near normal by hUCMSCs-exos in metabolomics, with janus associated kinase-signal transducer and activator of transcription (JAK-STAT) pathway displayed in proteomics. According to bioinformatics and integrated analysis, these targeted molecules of hUCMSCs-exos to attenuate the vascular remodeling were mainly associated with regulation of energy metabolism, oxidative stress, inflammation, and cellular communications. This study provided a reference for the therapy of diabetes-induced cardiovascular complications.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Exossomos/metabolismo , Cordão Umbilical , Proteômica , Remodelação Vascular , Células-Tronco Mesenquimais/metabolismo , Aorta
15.
Genes (Basel) ; 13(10)2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36292783

RESUMO

The quality of poultry products depends on genotype, rearing system, and environment. The aim of this study was to investigate the effects of different rearing systems on meat quality, amino acid composition, and breast muscle transcriptome from Lueyang black-bone chickens. Lueyang black-bone chickens (n = 900) were randomly divided into three groups (cage, flat-net, and free-range groups), with three replicates per group (100 chickens per replicate). At 16 weeks, a total of 36 healthy chickens (six males and six females per group) were collected, and their breast muscles were sampled to detect meat quality parameters, amino acid composition, and fatty acid contents. Furthermore, breast muscles from six random hens in each group were used for RNA-seq analysis. The results revealed that the values of pH, shear force, inosine monophosphate (IMP), palmitic acid, and linoleic acid in the free-range group were significantly higher than those in the caged group (p < 0.05). Fat content in the free-range group was significantly lower than in the caged and flat-net groups (p < 0.05). Glutamate (Glu) levels, the amino acid crucial for the umami taste, was significantly higher in the free-range group than in the caged group (p < 0.05). Meanwhile, there was no significant difference between the free-range and flat-net groups (p > 0.05). The breast muscle transcriptome results showed that there were 291, 131, and 387 differently expressed genes (DEGs) among the three comparison groups (caged vs. free-range, flat-net vs. caged, and flat-net vs. free-range, respectively) that were mainly related to muscle development and amino acid metabolism pathways. To validate the accuracy of the transcriptome data, eight genes (GOS2, ASNS, NMRK2, GADL1, SMTNL2, SLC7A5, AMPD1, and GLUL) which relate to fat deposition, skeletal muscle function, and flavor formation were selected for Real-time Quantitative PCR (RT-qPCR) verification. In conclusion, these results suggested that rearing systems significantly influenced the meat quality and gene expression of Lueyang black-bone chickens. All the data proved that free-range and flat-net systems may provide better flavor to consumers by affecting the deposition of flavor substances and the expression of related genes. These findings will provide a valuable theoretical basis for the rearing system selection in the poultry industry.


Assuntos
Galinhas , Inosina Monofosfato , Animais , Feminino , Masculino , Aminoácidos/genética , Ácidos Graxos , Glutamatos/genética , Inosina Monofosfato/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/genética , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Ácido Linoleico , Carne/análise , Ácido Palmítico , Músculos Peitorais/metabolismo , Transcriptoma
16.
Front Immunol ; 13: 1001526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275667

RESUMO

Ti-5Cu alloy has been proved to have excellent mechanical properties and cell compatibility and has certain antibacterial properties due to the addition of Cu. However, there are few studies on the effects of Ti-5Cu alloy on macrophage polarization and immune-related bone formation. In this study, we prepared Ti-5Cu alloy by three-dimensional printing technology and found that Ti-5Cu alloy presented a much smoother surface compared with Ti. In addition, the CCK-8 results indicated the Ti-5Cu alloy had no cytotoxicity to RAW264.7 cells by co-culture. The results of inductively coupled plasma mass spectrometry showed that the concentration of Cu2+ was 0.133 mg/L after 7 days of co-culture, and the CCK-8 results proved that Cu2+ had no cytotoxicity to RAW264.7 at this concentration. Then, we studied the effects of Ti-5Cu alloy on macrophage polarization; it was shown that the Ti-5Cu alloy is more prone to modulate the RAW264.7 polarization towards the M2 phenotype and the conditioned medium derived from Ti-5Cu alloy significantly promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells. However, when the expression of Oncostatin M (OSM) gene of RAW264.7 was knocked down, the osteogenic differentiation of MC3T3-E1 cells was decreased. This suggests that the OSM secreted by RAW264.7 co-cultured with Ti-5Cu alloy could accelerate the osteogenic differentiation of MC3T3-E1 cells by acting on OSMR/gp130 receptors.


Assuntos
Ligas , Osteogênese , Ligas/farmacologia , Ligas/química , Titânio/farmacologia , Titânio/química , Oncostatina M , Meios de Cultivo Condicionados , Sincalida , Receptor gp130 de Citocina , Macrófagos , Fenótipo , Impressão Tridimensional , Antibacterianos
17.
Front Bioeng Biotechnol ; 10: 888084, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677296

RESUMO

Implant-associated infection (IAI) is one of the major challenges in orthopedic surgery. The development of implants with inherent antibacterial properties is an effective strategy to resolve this issue. In recent years, biodegradable alloy materials have received considerable attention because of their superior comprehensive performance in the field of orthopedic implants. Studies on biodegradable alloy orthopedic implants with antibacterial properties have gradually increased. This review summarizes the recent advances in biodegradable magnesium- (Mg-), iron- (Fe-), and zinc- (Zn-) based alloys with antibacterial properties as orthopedic implant materials. The antibacterial mechanisms of these alloy materials are also outlined, thus providing more basis and insights on the design and application of biodegradable alloys with antibacterial properties as orthopedic implants.

18.
Melanoma Res ; 32(3): 159-165, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35377859

RESUMO

Little is known about the efficacy and safety of angiogenesis inhibitor therapy in patients with melanoma. The objective of this study was to assess the possible benefits and harms of angiogenesis inhibitor therapy in patients with melanoma. Electronic databases of PubMed and Web of Science were searched from inception to January 2020. Randomized controlled trials (RCTs) that investigated the efficacy and safety of angiogenesis inhibitor therapy in patients with melanoma were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS), reported as hazard ratios (HRs). Secondary outcomes were disease control, objective response, and adverse events, reported as odds ratios (ORs), and trial sequential analysis (TSA) was also performed. We identified seven trials with 3185 patients. There was no significant difference in OS [HR, 0.99; 95% confidence interval (CI), 0.90-1.09] or PFS (HR, 0.91; 95% CI, 0.83-1.00) between the treatment groups. No significant effect of angiogenesis inhibitor therapy was identified on disease control (OR, 1.23; 95% CI, 0.97-1.55) or objective response (OR, 1.27; 95% CI, 0.99-1.62). TSA showed that the sample size for analysis of disease control was sufficient. Additionally, angiogenesis inhibitor therapy increased risks of hypertension, neurological symptoms, and diarrhea. Angiogenesis inhibitor therapy makes no significant improvement in OS or PFS in patients with melanoma and even causes an increased risk of important adverse events. Therefore, angiogenesis inhibitor therapy is not recommended for the treatment of melanoma.


Assuntos
Inibidores da Angiogênese , Melanoma , Neoplasias Cutâneas , Inibidores da Angiogênese/efeitos adversos , Humanos , Melanoma/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Cutâneas/tratamento farmacológico
19.
Rev Cardiovasc Med ; 23(3): 89, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35345256

RESUMO

OBJECTIVES: Although injury of myocardium after percutaneous coronary intervention (PCI) has been reported, the mechanism and effect of exogenous phosphocreatine (PCr) supplementation on the injury are yet to be elucidated. Biomarkers, such as interleukin-6 (IL-6) and variations in white blood cells for inflammation, and serum cardiac troponin I (cTnI) for myocardial injury are examined. METHODS: A total of 105 patients undergoing PCI were included and randomly divided into two groups: control (treated with routine hydration therapy) and PCr (treated with additional intravenous infusion of exogenous PCr). The serum levels of biomarkers were detected at administration and 4, 12, 24, and 48 h after PCI, with natural logarithmic (loge) transformation of data when modeling assumptions were not fulfilled. RESULTS: The level of loge-transformed IL-6 increased in both groups, especially at 12 and 24 h after the operation, and that of PCr group was less than the control group at 48 h. The content of loge-transformed cTnI was significantly increased in both groups, while that of the PCr group was markedly lower than the control group at all time points after PCI. Moreover, the ratio of neutrophils was elevated at all time points after PCI, while that of the PCr group was lower at 48 h, and the variations in the ratio of lymphocytes showed opposite results. CONCLUSIONS: Exogenous phosphocreatine reduces stent implantation, triggers inflammation manifested as decreased serum levels of IL-6 and the aggregation of neutrophils, and protects the myocardium of the patients undergoing PCI. These findings provided the potential mechanism and treatment for myocardial injury associated with PCI.


Assuntos
Inflamação , Intervenção Coronária Percutânea , Fosfocreatina , Biomarcadores , Humanos , Inflamação/prevenção & controle , Interleucina-6 , Miocárdio , Intervenção Coronária Percutânea/efeitos adversos , Fosfocreatina/uso terapêutico , Troponina I
20.
J Sport Health Sci ; 11(1): 6-13, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33130094

RESUMO

PURPOSE: The study aimed to conduct a comprehensive systematic review and meta-analysis of injury incidence in professional skiers and snowboarders. METHODS: We systematically searched PubMed, Web of Science, and MEDLINE for studies on injury incidence published from inception to April 2020. Injury data were extracted, alongside information on injury location, severity, type, cause, and sport discipline. Incidence of injuries was presented per 1000 athlete-days, with 95% confidence intervals (95%CIs). RESULTS: The search identified 462 articles, and 22 were included in our review. The overall incidence of injuries among professional skiers and snowboarders was 3.49 per 1000 athlete-days (95%CI: 2.97-4.01). Lower extremity had the highest injury incidence (1.54 per 1000 athlete-days, 95%CI: 1.24-1.84). Incidence rates of slight, mild, moderate, and severe injuries were 0.26, 0.31, 0.57, and 0.59 per 1000 athlete-days, respectively. Contusion had the highest incidence rate (1.82 per 1000 athlete-days, 95%CI: 1.01-2.63). The most common cause of injury was contact trauma (3.20 per 1000 athlete-days, 95%CI: 1.32-5.08). Freestyle skiing had the highest incidence rate (6.83 per 1000 athlete-days, 95%CI: 4.00-9.66), and Nordic skiing had the lowest rate (2.70 per 1000 athlete-days, 95%CI: 1.94-3.46). CONCLUSION: Professional skiers and snowboarders have a substantial risk of sustaining injuries. Our findings can be used to inform the planning and provision of healthcare for elite participants in different snow sports.


Assuntos
Esqui , Humanos , Incidência , Extremidade Inferior , Esqui/lesões
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