A pre-rolling (PR) process with a small pre-strain was applied along the transverse direction (TD) and the extrusion direction (ED) of non-basal and basal textured AZ61 Mg alloys at room temperature ...to investigate the induced twinning behavior. The microstructural evolution of the alloys was used to evaluate the grain-boundary effect in terms of the texture variation. The results demonstrated that {101¯2} extension twinning was introduced by the PR process and that the volume fraction of twins increased with increasing thickness reduction. The subdivision of grains via twinning induced grain reorientation that generated a prominent basal texture with the c-axis parallel to the normal direction (ND) after PR. The textured Mg alloy with this c-axis//TD feature can promote twinning activity. The twinning performance was critical to initiate plastic deformation, therefore to determine deformation behavior at room temperature. The deformation mechanism was also addressed related to the extension twin lamellae.
Display omitted
•Pre-rolling was processed to investigate the induced twinning behavior.•The texture with this c-axis//TD feature can promote twinning activity.•Basal texture with the c-axis oriented to the ND processed by PR.•Twins can control basal texture based on volume fraction of twinned region.
An increasing number of studies have been conducted to apply unilateral balloon kyphoplasty in the treatment of ostroporotic vertebral compression fractures (OVCFs). However, the efficacy and safety ...of unilateral kyphoplasty and whether a unilateral or a bilateral approach is superior is controversial.
The purpose of this study was to evaluate the role of unilateral balloon kyphoplasty and use meta-analysis to compare the efficacy and safety of unilateral and bilateral kyphoplasty in patients with OVCFs.
A systematic literature search was conducted from 1970 to April 2017 using Medline database and the Cochrane Central Register of Controlled Trials. Articles were limited to those published in English. Randomized controlled trials and nonrandomized comparative studies were also included.
The following search terms were used: "osteoporotic vertebral compression fractures," or "OVCF," and "unilateral kyphoplasty," or "unipedicular approach," or "single balloon kyphoplasty," or "one balloon kyphoplasty." A comprehensive search of reference lists of retrieved articles and previous published reviews was also performed to ensure inclusion of all possible studies.
All potential articles were independently reviewed by 2 investigators for inclusion into the final analysis. MINORS score was used for nonrandomized studies, and Detsky quality index was applied for prospective randomized controlled trials. Systematic review and meta-analysis was performed for the included studies.
After unilateral balloon kyphoplasty the mean postoperative visual analog score (VAS) was from 1.74 to 4.77, mean postoperative kyphotic angle was from 5.9º to 11.22º, and complications involving cement leaks was from 6.8 to 21.9% or adjacent level fractures was from 0 to 5.6%). Unilateral kyphoplasty had significantly lower operative time, and less bone cement volume; however, the postoperative VAS, Oswestry Disability Index (ODI), vertebral height restoration rate, and cement leakage and adjacent vertebral fracture rate, were similar to bilateral kyphoplasty.
Only 6 randomized controlled trials and 3 retrospective comparative studies were selected for analysis. Heterogeneity was detected among the studies when we pooled the outcomes.
Based on the available evidence, the clinical and radiological results of unilateral balloon kyphoplasty were as good as those of bilateral balloon kyphoplasty for the treatment of OVCFs. And unilateral kyphoplasty had advantages in terms of operation time, radiation exposure, and cost.
Unilateral balloon kyphoplasty, bilateral balloon kyphoplasty, osteoporotic vertebral compression fractures, complications of balloon kyphoplasty, meta-analysis.
Recently, studies on microRNAs (miRNAs) and their targets and related genes have provided new therapeutic opportunities for controlling intervertebral disc degeneration (IDD). We aimed to investigate ...the effects of miR-148a-3p overexpression on IDD progression.
This study used microRNA microarrays to analyze key regulators of IDD. Q-PCR was used to verify the IL-1β-induced down-regulation of miR-148a-3p expression both in nucleus pulposus (NP) tissues of IDD patients and in degenerated NP cells (NPCs) of rats. Rat NPC micromass cultures and
intervertebral disc (IVD) culture models were established, and histological staining was performed to verify the effect of miR-148a-3p on the general morphology and proteoglycan and collagen contents of IVDs. In addition, q-PCR and western blotting analyses were performed to examine the expression of ECM molecules and matrix-degrading enzymes. A luciferase reporter assay was used to confirm the target genes of miR-148a-3p.
Our data revealed that miR-148a-3p was down-regulated in IDD. Overexpression of miR-148a-3p had no effect on ACAN or COL2A1 gene expression but decreased MMP3, MMP13, and ADAMTS5 gene expression. The matrix deposited by miR-148a-3p-overexpressing rat NPCs contained high levels of proteoglycans and collagen. The
experiments verified that agomiR-148a-3p alleviated the NPC matrix degradation induced by IL-1β. A luciferase reporter assay confirmed that miR-148a-3p directly targeted ADAMTS5 and MMP13.
We proved that miR-148a-3p can attenuate ECM loss and protect NP function by inhibiting matrix-degrading enzymes.
Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti‐inflammatory effects, as well as, many other biological activities. Existing evidence has ...aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF‐κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF‐κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL‐1β, FMN inhibited the NF‐κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low‐ and high‐dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high‐dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.
Tetrahydropalmatine (dl-THP) demonstrates an analgesic effect in animal models of neuropathic and inflammatory pain, however, the underlying mechanisms of its pharmacological action within the spinal ...cord remains unclear. Both P2X3 receptor and TRPV1 are associated with the development and progression of such neuropathic and inflammatory pain. Here, we found that both pre-treatment and post-treatment with dl-THP could attenuate Bee Venom (BV)-induced persistent spontaneous pain-related behaviors in rats. Further, the dl-THP also exerted both preventive and therapeutic analgesic effects in BV-induced primary thermal and mechanical pain hypersensitivity as well as in mirror-image thermal pain hypersensitivity. The Rota-Rod treadmill test revealed that the dl-THP administration did not alter the rats' motor coordinating performance. The TRPV1 and P2X3 receptor proteins increased markedly in the spinal cord of the rats following s.c. BV injection, which was significantly suppressed by dl-THP. These results suggest that dl-THP exerts a robust antihyperalgesia effect through down-regulation of P2X3 receptors and TRPV1 in inflammatory pain, providing a scientific basis for the translation of dl-THP treatment in clinics.
This study aimed to conduct a systematic review of literature comparing the clinical effectiveness and safety between anterior reconstruction (AR) and posterior osteotomy (PO) in the treatment of ...Kümmell's disease with neurological deficits.
We systematically reviewed the literature in PubMed, EMBASE, Cochrane Database of Systematic Reviews, and the Web of Science for “spin*,” “surg*,” “Kümmell's disease,” “Kummell's disease,” “Kummell disease,” “vertebral osteonecrosis,” “vertebral pseudarthrosis,” “intravertebral vacuum cleft,” “delayed vertebral collapse,” and “compression fracture nonunion”. Quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation method.
A total of 10 publications involving 268 Kümmell's disease patients with neurological deficits were included in this review, with 7 studies of low- or very low-quality. There were 37.7% and 62.3% of patients receiving AR and PO, respectively. For clinical outcomes, AR group showed no significant differences in pain, neurological dysfunction, and imaging outcome improvements compared with patients who underwent PO. However, the incidence of implant-related complications including loose screw, screw fracture, screw disconnection, and plate dislodgment, was higher in AR group compared with PO group (21.6% vs. 14.3%). As another major complication, AR group more often required a second surgery.
This systematic review demonstrated that both AR and PO could improve pain, neurological dysfunction and imaging outcomes. However, serious comorbidities, multilevel corpectomies and/or severe osteoporosis highly required PO. Design discrepancies were found in the current studies, further higher-quality studies are warranted.
Level III, therapeutic study.
Cyclophilin 1 (TvCyP1), a cyclophilin type peptidyl-prolyl isomerase present in the human parasite Trichomonas vaginalis, interacts with Myb1 and assists in its nuclear translocation. Myb1 regulates ...the expression of ap65-1 gene that encodes for a disease causing cytoadherence enzyme. Here, we determined the crystal structures of TvCyP1 and its complex with the minimum TvCyP1-binding sequence of Myb1 (Myb1
), where TvCyP1 formed a homodimer, unlike other single domain cyclophilins. In the complex structure, one Myb1
peptide was bound to each TvCyP1 protomer, with G106-P107 and Y105 fitting well into the active site and auxiliary S2 pocket, respectively. NMR data further showed that TvCyP1 can catalyze the cis/trans isomerization of P107 in Myb1
. Interestingly, in the well-folded Myb1 protein (Myb1
), the minimum binding sequence adopted a different conformation from that of unstructured Myb1
peptide, that could make P107 binding to the active site of TvCyP1 difficult. However, NMR studies showed that similar to Myb1
peptide, Myb1
also interacted with the active site of TvCyP1 and the dynamics of the Myb1
residues near P107 was reduced upon interaction. Together, the structure of TvCyP1 and detailed structural insights on TvCyP1-Myb1 interaction provided here could pave the way for newer drugs to treat drug-resistant strains.
Vaccinia virus (VACV) belonging to the poxvirus family enters the host cell via two different entry pathways; either endocytosis or virus/host cell membrane fusion. With respect to the virus/host ...cell membrane fusion, there are eleven viral membrane proteins forming a complicated entry-fusion complex (EFC), including A28, A21, A16, F9, G9, G3, H2, J5, L5, L1 and O3, to conduct the fusion function. These EFC components are highly conserved in all poxviruses and each of them is essential and necessary for the fusion activity. So far, with the exceptions of L1 and F9 whose crystal structures were reported, the structural information about other EFC components remains largely unclear. We aim to conduct a structural and functional investigation of VACV virus-entry membrane protein A28. In this work, we expressed and purified a truncated form of A28 (14 kDa; residues 38–146, abbreviated as tA28 hereinafter), with deletion of its transmembrane domain (residues 1–22) and a hydrophobic segment (residues 23–37). And the assignments of its backbone and side chain
1
H,
13
C and
15
N chemical shifts of tA28 are reported. The secondary structure propensity from TALOS+ indicates that tA28 does contain three α-helices, six β-strands and connecting loops. Aside from this, we demonstrated that tA28 does interact with fusion suppressor viral protein A26 (residues 351–500) by the
1
H–
15
N HSQC spectrum. We interpret that A28 binding to A26 deactivates EFC fusion activity. The current study provides a valuable framework towards further structural analyses of this protein and for better understanding virus/host cell membrane fusion mechanism in association with virus entry.
Eukaryotic mRNA biogenesis involves a series of interconnected steps mediated by RNA-binding proteins. The exon junction complex core protein Y14 is required for nonsense-mediated mRNA decay (NMD) ...and promotes translation. Moreover, Y14 binds the cap structure of mRNAs and inhibits the activity of the decapping enzyme Dcp2. In this report, we show that an evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for its binding to the mRNA cap structure. A Trp-73 mutant (W73V) bound weakly to mRNAs and failed to protect them from degradation. However, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NMD activity. In addition, we found that the W73V mutant could not interact with translation initiation factors. Overexpression of W73V suppressed reporter mRNA translation in vitro and in vivo and reduced the level of a set of nascent proteins. These results reveal a residue of Y14 that confers cap-binding activity and is essential for Y14-mediated enhancement of translation. Finally, we demonstrated that Y14 may selectively and differentially modulate protein biosynthesis.
In Trichomonas vaginalis (T. vaginalis), cyclophilins play a vital role in dislodging Myb proteins from the membrane compartment and leading them to nuclear translocation. We previously reported that ...TvCyP1 cyclophilin from T. vaginalis forms a dimer and plays an essential role in moving the Myb1 transcription factor toward the nucleus. In comparison, TvCyP2 containing an extended segment at the N-terminus (N-terminal segment) formed a monomer and showed a different role in regulating protein trafficking. Four X-ray structures of TvCyP2 were determined under various conditions, all showing the N-terminal segment interacting with the active site of a neighboring TvCyP2, an unusual interaction. NMR study revealed that this particular interaction exists in solution as well and also the N-terminal segment seems to interact with the membrane. In vivo study of TvCyP2 and TvCyP2-∆N (TvCyP2 without the N-terminal segment) indicated that both proteins have different subcellular localization. Together, the structural and functional characteristics at the N-terminal segment offer valuable information for insights into the mechanism of how TvCyP2 regulates protein trafficking, which may be applied in drug development to prevent pathogenesis and disease progression in T. vaginalis infection.
PDF
