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1.
Int J Mol Sci ; 23(17)2022 Aug 29.
Article in English | MEDLINE | ID: mdl-36077191

ABSTRACT

Phosphatidic acid (PA) is an important signal molecule in various biological processes including osmotic stress. Lysophosphatidic acid acyltransferase (LPAT) acylates the sn-2 position of the glycerol backbone of lysophosphatidic acid (LPA) to produce PA. The role of LPAT2 and its PA in osmotic stress response remains elusive in plants. Here we showed that LPAT2-derived PA is important for salt and drought stress tolerance in rice. Rice LPAT2 was localized to the endoplasmic reticulum (ER) to catalyze the PA synthesis. The LPAT2 transcript was induced by osmotic stress such as high salinity and water deficit. To reveal its role in osmotic stress response, an LPAT2 knockdown mutant, designated lpat2, was isolated from rice, which contained a reduced PA level relative to wild type (WT) plants under salt stress and water deficit. The lpat2 mutant was more susceptible to osmotic stress and less sensitive to abscisic acid (ABA) than that of WT, which was recovered by either PA supplementation or genetic LPAT2 complementation. Moreover, suppressed LPAT2 also led to a large number of differentially expressed genes (DEGs) involved in diverse processes, particularly, in ABA response, kinase signaling, and ion homeostasis in response to salt stress. Together, LPAT2-produced PA plays a positive role in osmotic tolerance through mediating ABA response, which leads to transcriptional alteration of genes related to ABA response, protein kinase signaling, and ion homeostasis.


Subject(s)
Oryza , Abscisic Acid/metabolism , Abscisic Acid/pharmacology , Acyltransferases , Droughts , Gene Expression Regulation, Plant , Oryza/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/metabolism , Stress, Physiological , Water/metabolism
3.
Biomed Pharmacother ; 103: 869-878, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29710503

ABSTRACT

Cardiovascular dysfunction is a major complication associated with sepsis induced mortality. Cardiac fibrosis plays a critical role in sepsis induced cardiac dysfunction. The mechanisms of the activation of cardiac fibrosis is unclarified. In this study, we found that microRNA-23b (miR-23b) was up-regulated in heart tissue during cecal ligation and puncture (CLP)-induced sepsis and transfection of miR-23b inhibitor improved survival in late sepsis. Inhibition of miR-23b in the myocardium protected against cardiac output and enhanced left ventricular systolic function. miR-23b inhibitor also alleviated cardiac fibrosis in late sepsis. MiR-23b mediates the activation of TGF-ß1/Smad2/3 signaling to promote the differentiation of cardiac fibroblasts through suppression of 5'TG3'-interacting factor 1 (TGIF1). MiR-23b also induces AKT/N-Cadherin signaling to contribute to the deposition of extracellular matrix by inhibiting phosphatase and tensin homologue (PTEN). TGIF1 and PTEN were confirmed as the targets of miR-23b in vitro by Dual-Glo Luciferase assay. miR-23b inhibitor blocked the activation of adhesive molecules and restored the imbalance of pro-fibrotic and anti-fibrotic factors. These data provide direct evidence that miR-23b is a critical contributor to the activation of cardiac fibrosis to mediate the development of myocardial dysfunction in late sepsis. Blockade of miR-23b expression may be an effective approach for prevention sepsis-induced cardiac dysfunction.


Subject(s)
Heart/physiopathology , Homeodomain Proteins/metabolism , MicroRNAs/genetics , Myocardium/pathology , PTEN Phosphohydrolase/metabolism , Repressor Proteins/metabolism , Sepsis/genetics , Animals , Fibrosis , HEK293 Cells , Heart Function Tests , Humans , Mice, Inbred C57BL , MicroRNAs/antagonists & inhibitors , Sepsis/pathology , Survival Analysis
4.
J Infect Dis ; 218(2): 300-311, 2018 06 20.
Article in English | MEDLINE | ID: mdl-29506272

ABSTRACT

Background: microRNA-23b (miR-23b) is a multiple functional miRNA. We hypothesize that miR-23b plays a role in the pathogenesis of sepsis. Our study investigated the effect of miR-23b on sepsis-induced immunosuppression. Methods: Mice were treated with miR-23b inhibitors by tail vein injection 2 days after cecal ligation puncture (CLP)-induced sepsis. Apoptosis in spleens and apoptotic signals were investigated, and survival was monitored. T-cell immunoreactivities were examined during late sepsis. Nuclear factor κB (NF-κB)-inducing kinase (NIK), tumor necrosis factor (TNF)-receptor associated factor 1 (TRAF1), and X-linked inhibitor of apoptosis protein (XIAP), the putative targets of miR-23b, were identified by a dual-luciferase reporter assay. Results: miR-23b expression is upregulated and sustained during sepsis. The activation of the TLR4/TLR9/p38 MAPK/STAT3 signal pathway contributes to the production of miR-23b in CLP-induced sepsis. miR-23b inhibitor decreased the number of spleen cells positive by terminal deoxynucleotidyl transferase dUTP nick-end labeling and improved survival. miR-23b inhibitor restored the immunoreactivity by alleviating the development of T-cell exhaustion and producing smaller amounts of immunosuppressive interleukin 10 and interleukin 4 during late sepsis. We demonstrated that miR-23b mediated immunosuppression during late sepsis by inhibiting the noncanonical NF-κB signal and promoting the proapoptotic signal pathway by targeting NIK, TRAF1, and XIAP. Conclusions: Inhibition of miR-23b reduces late-sepsis-induced immunosuppression and improves survival. miR-23b might be a target for immunosuppression.


Subject(s)
Immune Tolerance , Inhibitor of Apoptosis Proteins/metabolism , MicroRNAs/metabolism , Protein Serine-Threonine Kinases/metabolism , Sepsis/pathology , TNF Receptor-Associated Factor 1/metabolism , Animals , Apoptosis , Artificial Gene Fusion , Disease Models, Animal , Gene Expression Profiling , Genes, Reporter , Inhibitor of Apoptosis Proteins/analysis , Luciferases/analysis , Male , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs/antagonists & inhibitors , Protein Serine-Threonine Kinases/analysis , Spleen/pathology , Survival Analysis , T-Lymphocytes/immunology , TNF Receptor-Associated Factor 1/analysis , NF-kappaB-Inducing Kinase
5.
J Coll Physicians Surg Pak ; 24(5): 369-70, 2014 May.
Article in English | MEDLINE | ID: mdl-24848400

ABSTRACT

This is the first published report of a long-term, fourteen years close annual follow-up of a patient who underwent revision total hip replacement with per-operative anterior cortical perforation of femur while undertaking cemented femoral stem insertion. This patient has complete satisfaction in terms of clinical and radiological outcome. This patient has been walking full weight bearing on her operated leg after 3 months of her surgery. We advocate for the need of paying meticulous attention to observe this complication on operative table and to proceed with controlled stem insertion where doubt exist. Such patients may require a vigilant regular annual follow-up to observe their clinical and radiological status and an expectant approach may be adopted unless patient becomes symptomatic.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Femoral Fractures/etiology , Hip Prosthesis/adverse effects , Prosthesis Failure/etiology , Reoperation , Arthroplasty, Replacement, Hip/methods , Bone Cements , Cementation , Female , Femoral Fractures/diagnostic imaging , Femoral Fractures/surgery , Fracture Fixation, Internal/instrumentation , Fracture Fixation, Internal/methods , Humans , Prosthesis Design , Radiography , Treatment Outcome
6.
BMJ Case Rep ; 20142014 May 13.
Article in English | MEDLINE | ID: mdl-24825555

ABSTRACT

Osteochondral fracture of the lateral femoral condyle can be a real challenging injury to diagnose on initial presentation. The authors report a rare case of bilateral involvement of posterior aspect of lateral femoral condyle osteochondral fracture in a young 15-year-old boy. This was managed with excision of these osteochondral fragments, as the site involved was on the posterior non-weight bearing area of the femur along with chronicity of the injury dictating excision as a reasonable choice of management. Good outcome for such injury is based on an early diagnosis and prompt treatment along with an early rehabilitation for such cases. Our patient has an excellent 2 years outcome with a Knee Society score of 95 after undergoing excision of these osteochondral fragments in both knees in succession.


Subject(s)
Femoral Fractures/surgery , Knee Injuries/surgery , Weight-Bearing , Adolescent , Arthroscopy , Femoral Fractures/diagnosis , Humans , Knee Injuries/diagnosis , Magnetic Resonance Imaging , Male , Treatment Outcome
7.
J Coll Physicians Surg Pak ; 23(2): 162-3, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23374527

ABSTRACT

Knee revision using constrained implants is associated with greater stresses on the implant and interface surfaces. The present report describes a case of failure of the screw coupling between the stem and the femoral component. The cause of the failure is surmised with outline of the treatment in this case with extensive femoral bone loss. Revision implant stability was augmented with the use of a cemented femoral stem, screw fixation and the metaphyseal sleeve of an S-ROM modular hip system (DePuy international Ltd).


Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Femoral Fractures/surgery , Periprosthetic Fractures/surgery , Prosthesis Failure , Aged , Cementation , Femoral Fractures/etiology , Humans , Male , Periprosthetic Fractures/etiology , Reoperation , Treatment Outcome
8.
J Coll Physicians Surg Pak ; 22(3): 182-3, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22414363

ABSTRACT

All limb injuries should be examined with complete documentation of neurovascular assessment as they are often ignored in the busy emergency department setup. This may lead to delay in such diagnosis during the treatment of limb injuries at a follow-up in orthopaedic clinics. Early diagnosis can help orthopaedic team to investigate and start treatment which may help in the recovery of such neurovascular injuries. We report a case of missed neurovascular assessment in the emergency department on a patellar dislocation of a young person leading to foot drop and sensory numbness in the deep peroneal nerve distribution, which improved completely within three and a half months with conservative treatment. This is also the first reported case of foot drop in association with patellar dislocation.


Subject(s)
Knee Injuries/complications , Patella/injuries , Patellar Dislocation/complications , Peroneal Nerve/injuries , Peroneal Neuropathies/etiology , Diagnosis, Differential , Follow-Up Studies , Humans , Knee Injuries/diagnosis , Knee Injuries/therapy , Male , Patellar Dislocation/diagnosis , Patellar Dislocation/therapy , Peroneal Nerve/physiopathology , Peroneal Neuropathies/diagnosis , Peroneal Neuropathies/therapy , Physical Therapy Modalities , Recovery of Function , Young Adult
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