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151.
Persistent quadriceps strength deficits in individuals with anterior cruciate ligament reconstruction (ACLr) have been attributed to arthrogenic muscle inhibition (AMI). The purpose of the present study was to investigate the effect of vibration-induced hamstrings fatigue on AMI in patients with ACLr. Eight participants with unilateral ACLr (post-surgery time: M = 46.5, SD = 23.5 months; age: M = 21.4, SD = 1.4 years) and eight individuals with no previous history of knee injury (age: M = 22.5, SD = 2.5 years) were recruited. A fatigue protocol, consisting of 10 min of prolonged local hamstrings vibration, was applied to both the ACLr and control groups. The central activation ratio (CAR) of the quadriceps was measured with a superimposed burst of electrical stimulation, and hamstrings/quadriceps coactivation was assessed using electromyography (EMG) during isometric knee extension exercises, both before and after prolonged local vibration. For the ACLr group, the hamstrings strength, measured by a load cell on a purpose-built chair, was significantly (P = 0.016) reduced about 14.5%, indicating fatigue was actually induced in the hamstrings. At baseline, the ACLr group showed a trend (P = 0.051) toward a lower quadriceps CAR (M = 93.2%, SD = 6.2% versus M = 98.1%, SD = 1.1%) and significantly (P = 0.001) higher hamstrings/quadriceps coactivation (M = 15.1%, SD = 6.2% versus M = 7.5%, SD = 4.0%) during knee extension compared to the control group. The fatigue protocol significantly (P = 0.001) increased quadriceps CAR (from M = 93.2%, SD = 6.2% to M = 97.9%, SD = 2.8%) and significantly (P = 0.006) decreased hamstrings/quadriceps coactivation during knee extension (from M = 15.1%, SD = 6.2% to M = 9.5%, SD = 4.5%) in the ACLr group. In conclusion, vibration-induced hamstrings fatigue can alleviate AMI of the quadriceps in patients with ACLr. This finding has clinical implications in the management of recovery for ACLr patients with quadriceps strength deficits and dysfunction.  相似文献   
152.
Failed oocyte activation has been observed in unexplained infertile (UI) and asthenoteratozoospermic (AT) men. The deficiency of phospholipase C‐zeta (PLCζ) could be a possible reason for such failures and has not been studied yet. We investigated the expression and localization of PLCζ protein in the sperms of patients with UI and AT conditions. The relationships between PLCζ‐related parameters with male age, sperm characteristics, DNA integrity, and cellular maturity were assessed. Semen samples were collected from fertile (n = 40), UI (n = 40), and AT (n = 40) men. Subsequently, semen analysis, DNA fragmentation, hyaluronic acid‐binding ability, and PLCζ level along with its distribution were evaluated using computer‐assisted sperm analyzer, sperm chromatin structure assay (SCSA), hyaluronic acid‐binding assay (HBA), western blot analysis and immunofluorescence microscopy, respectively. Unlike SCSA, the values of HBA, and PLCζ expression were significantly reduced in UI and AT patients compared to fertile men, whereas no significant differences were observed among the experimental groups in terms of PLCζ localization patterns. The regression analysis also showed that HBA is the only variable associated with PLCζ levels. Furthermore, the correlation of male age with PLCζ localization in postacrosomal, equatorial, and acrosomal+postacrosomal+equatorial (A+PA+E) patterns, as well as the relation of normal morphology, with the (A+PA+E) pattern, remained in the regression model. Our findings indicated that reduced PLCζ level along with the increased DNA fragmentation and impaired maturation may be possible etiologies of decreased fertilization in the studied subjects.  相似文献   
153.
Egg activation is the essential process in which mature oocytes gain the competency to proceed into embryonic development. Many events of egg activation are conserved, including an initial rise of intracellular calcium. In some species, such as echinoderms and mammals, changes in the actin cytoskeleton occur around the time of fertilization and egg activation. However, the interplay between calcium and actin during egg activation remains unclear. Here, we use imaging, genetics, pharmacological treatment, and physical manipulation to elucidate the relationship between calcium and actin in living Drosophila eggs. We show that, before egg activation, actin is smoothly distributed between ridges in the cortex of the dehydrated mature oocytes. At the onset of egg activation, we observe actin spreading out as the egg swells though the intake of fluid. We show that a relaxed actin cytoskeleton is required for the intracellular rise of calcium to initiate and propagate. Once the swelling is complete and the calcium wave is traversing the egg, it leads to a reorganization of actin in a wavelike manner. After the calcium wave, the actin cytoskeleton has an even distribution of foci at the cortex. Together, our data show that calcium resets the actin cytoskeleton at egg activation, a model that we propose to be likely conserved in other species.  相似文献   
154.
The aim of this study was to explore the effects of platelet‐rich plasma on gingipain‐caused changes in cell morphology and apoptosis of osteoblasts. Mouse osteoblasts MC3T3‐E1 cells were treated with gingipain extracts from Porphyromonas gingivalis in the presence or absence of platelet‐rich plasma. Apoptosis was detected with terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining. F‐actin was determined by phalloidin‐fluorescent staining and observed under confocal microscopy. Western blot analysis was used to detect integrin β1, F‐actin, and G‐actin protein expressions. A knocking down approach was used to determine the role of integrin β1. The platelet‐rich plasma protected osteoblasts from gingipain‐induced apoptosis in a dose‐dependent manner, accompanied by upregulation of integrin β1. Platelet‐rich plasma reversed the loss of F‐actin integrity and decrease of F‐actin/G‐actin ratio in osteoblasts in the presence of gingipains. By contrast, the effects of platelet‐rich plasma were abrogated by knockdown of integrin β1. The platelet‐rich plasma failed to reduce cell apoptosis and reorganize the cytoskeleton after knockdown of integrin β1. In conclusion, platelet‐rich plasma inhibits gingipain‐induced osteoblast apoptosis and actin cytoskeleton disruption by upregulating integrin β1 expression.  相似文献   
155.
156.
The whooping cough agent Bordetella pertussis secretes an adenylate cyclase toxin (CyaA) that through its large carboxy-proximal Repeat-in-ToXin (RTX) domain binds the complement receptor 3 (CR3). The RTX domain consists of five blocks (I–V) of characteristic glycine and aspartate-rich nonapeptides that fold into five Ca2+-loaded parallel β-rolls. Previous work indicated that the CR3-binding structure comprises the interface of β-rolls II and III. To test if further portions of the RTX domain contribute to CR3 binding, we generated a construct with the RTX block II/III interface (CyaA residues 1132–1294) linked directly to the C-terminal block V fragment bearing the folding scaffold (CyaA residues 1562–1681). Despite deletion of 267 internal residues of the RTX domain, the Ca2+-driven folding of the hybrid block III/V β-roll still supported formation of the CR3-binding structure at the interface of β-rolls II and III. Moreover, upon stabilization by N- and C-terminal flanking segments, the block III/V hybrid-comprising constructs competed with CyaA for CR3 binding and induced formation of CyaA toxin-neutralizing antibodies in mice. Finally, a truncated CyaAΔ1295-1561 toxin bound and penetrated erythrocytes and CR3-expressing cells, showing that the deleted portions of RTX blocks III, IV, and V (residues 1295–1561) were dispensable for CR3 binding and for toxin translocation across the target cell membrane. This suggests that almost a half of the RTX domain of CyaA is not involved in target cell interaction and rather serves the purpose of toxin secretion.  相似文献   
157.
Virologica Sinica - Although antiretroviral treatment lowers the burden of human immunodeficiency virus (HIV)-related disease, it does not always result in immunological recovery. This manifests as...  相似文献   
158.
Severe respiratory viral infectious diseases such as influenza and COVID‐19 especially affect the older population. This is partly ascribed to diminished CD8+ T‐cell responses a result of aging. The phenotypical diversity of the CD8+ T‐cell population has made it difficult to identify the impact of aging on CD8+ T‐cell subsets associated with diminished CD8+ T‐cell responses. Here we identify a novel human CD8+ T‐cell subset characterized by expression of Killer‐cell Immunoglobulin‐like Receptors (KIR+) and CD45RA (RA+). These KIR+RA+ T cells accumulated with age in the blood of healthy individuals (20–82 years of age, n = 50), expressed high levels of aging‐related markers of T‐cell regulation, and were functionally capable of suppressing proliferation of other CD8+ T cells. Moreover, KIR+RA+ T cells were a major T‐cell subset becoming activated in older adults suffering from an acute respiratory viral infection (n = 36), including coronavirus and influenza virus infection. In addition, older adults with influenza A infection showed that higher activation status of their KIR+RA+ T cells associated with longer duration of respiratory symptoms. Together, our data indicate that KIR+RA+ T cells are a unique human T‐cell subset with regulatory properties that may explain susceptibility to viral respiratory disease at old age.  相似文献   
159.
Hepatocellular carcinoma (HCC) is one of the most common metastatic tumours. Tumour growth and metastasis depend on the induction of cell proliferation and migration by various mediators. Here, we report that the A Disintegrin and Metalloproteinase (ADAM) 8 is highly expressed in murine HCC tissues as well as in murine and human hepatoma cell lines Hepa1-6 and HepG2, respectively. To establish a dose-dependent role of different ADAM8 expression levels for HCC progression, ADAM8 expression was either reduced via shRNA- or siRNA-mediated knockdown or increased by using a retroviral overexpression vector. These two complementary approaches revealed that ADAM8 expression levels correlated positively with proliferation, clonogenicity, migration and matrix invasion and negatively with apoptosis of hepatoma cells. Furthermore, the analysis of pro-migratory and proliferative signalling pathways revealed that ADAM8 expression level was positively associated with expression of β1 integrin as well as with the activation of focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK), Src kinase and Rho A GTPase. Finally, up-regulation of promigatory signalling and cell migration was also seen with a proteolytically inactive ADAM8 mutant. These findings reveal that ADAM8 is critically up-regulated in hepatoma cells contributes to cell proliferation and survival and furthermore induces pro-migratory signalling pathways independently of its proteolytic activity. By this, ADAM8 can promote cell functions most relevant for HCC growth and metastasis.  相似文献   
160.
骨关节炎(osteoarthritis,OA)是最常见的慢性致残性关节疾患,目前尚无针对病因的有效治疗手段。程序性坏死在多种疾病中扮演关键角色,受体相互作用蛋白质激酶3(receptor-interacting protein kinase 3, RIP3)是程序性坏死进程的关键调控因子。有研究显示,RIP3在人与鼠骨关节炎退变软骨组织中表达水平显著上调,提示程序性坏死的发生,但RIP3在软骨中的具体病生理角色仍不明确。本研究拟对过表达RIP3前后的软骨细胞转录物组进行测序分析,探索RIP3在骨关节炎进程中发挥作用的具体机制。RNA测序结果显示,RIP3的过表达诱发软骨细胞中244个基因表达上调,277个表达下调。通过进一步构建基因间共表达作用网络,筛选出16个候选靶基因在mRNA水平进行验证,证实RIP3对磷脂酰肌醇3激酶调节亚单位5(phosphoinositide-3-kinase, regulatory subunit 5,Pik3r5)、整合素β3(integrin subunit beta 3,Itgb3)及成髓细胞瘤转录因子第2亚型(MYB proto-oncogene like 2,Mybl2)的表达上调作用最为显著。CCK-8以及乳酸脱氢酶活性检测结果表明,利用siRNA沉默Itgb3的表达可显著抑制RIP3诱发的软骨细胞活力下降及程序性坏死,同时也抑制了RIP3对软骨细胞中分解代谢相关基因Mmp1、Mmp13与Il6的表达上调作用,以及其对合成代谢相关基因Acan、Col2a1与Sox9的下调作用。本研究证实,RIP3通过上调软骨细胞中Itgb3的表达诱发软骨细胞坏死与软骨基质代谢紊乱,并最终导致软骨退变,为骨关节炎的临床治疗提供了新靶点,同时进一步明确了程序性坏死的病理生理学意义。  相似文献   
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