Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury

xlomafota13 shared this article with you from Inoreader Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):711. doi: 10.3892/etm.2021.10143. Epub 2021 May 3. ABSTRACT STAT3 is expressed in neural stem cells (NSCs), where a number of studies have previously shown that STAT3 is involved in regulating NSC differentiation. However, the possible molecular mechanism and role of STAT3 in spinal cord injury (SCI) remain unclear. In the present study, the potential effect of STAT3 in NSCs was first investigated by using short hairpin RNA (shRNA)-mediated STAT3 knockdown in rat NSCs in vitro. Immunofluorescence of β3-tubulin and glial fibrillary acidic protein staining and western blotting showed that knocking down STAT3 expression promoted NSC neuronal differentiation, where the activity of mTOR was upregulated. Subsequently, rats underwent laminectomy and complete spinal cord transection followed by transplantation of NSCs transfected with control-shRNA or STAT3-shRNA at the injured site in vivo. Spinal c ord-evoked potentials and the Basso-Beattie-Bresnahan scores were used to examine functional recovery. In addition, axonal regeneration and tissue repair were assessed using retrograde tracing with FluoroGold, hematoxylin and eosin, Nissl and immunofluorescence staining of β3-tubulin, glial fibrillary acidic protein and microtubule-associated protein 2 following SCI. The results showed that transplantation with NSCs transfected with STAT3-RNA enhanced functional recovery following SCI and promoted tissue repair in rats, in addition to improving neuronal differentiation of the transplanted NSCs in the injury site. Taken together, in vitro and in vivo evidence that inhibiting STAT3 could promote NSC neuronal differentiation was demonstrated in the present study. Therefore, transplantation with NSCs with STAT3 expression knocked down appears to hold promising potential for enhancing the benefit of NSC-mediated regenerative cell therapy for SCI. PMID:34007320 | PMC:PMC8120646 | DOI:10.3892/etm.2021.10143 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy of percutaneous vertebroplasty for the relief of osteoblastic spinal metastasis pain

xlomafota13 shared this article with you from Inoreader Efficacy of percutaneous vertebroplasty for the relief of osteoblastic spinal metastasis pain Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):727. doi: 10.3892/etm.2021.10159. Epub 2021 May 4. ABSTRACT The aim of the present manuscript was to retrospectively evaluate the efficacy of fluoroscopy-guided percutaneous vertebroplasty (PVP) for the relief of osteoblastic spinal metastases pain. PVP was performed in 39 consecutive patients with 82 osteoblastic metastatic spinal vertebras. 19 vertebras had pathologic compressive fracture and the other 63 vertebras had no compressive fracture with obvious imaging abnormalities. The ages of the patients ranged from 40 to 77 years with a mean age of 58.5±9.0 years. Visual analog scale (VAS) and QLQ-BM22 score were used to evaluate pain and quality of life at 2 days pre-operation and at 1 week and 3 months post-operation. Among all 82 vertebras, 35 vertebras had been injected bilaterally and the other 47 vertebras unilaterally. The amount of cement injected per lesion ranged from 0.5 to 4.5 ml with a mean v olume of 1.6±0.8 ml. Cement deposition in all lesions was uniform. The patients were followed up from 3 to 15.5 months with a mean follow up time of 5.6±3.4 months. Mean VAS score declined significantly from preoperative 4.3±2.4 to postoperative 3.0±1.7 at 1 week and 2.4±2.0 at 3 months after the procedure (P=0.001). Mean QLQ-BM22 score declined significantly from preoperative 49.1±12.3 to postoperative 42.4±9.5 at 1 week and 39.6±10.4 at 3 months after the procedure (P<0.001). Extraosseous cement leakage occurred in 21 vertebras of 13 cases and in 1 case into the thoracic vertebra canal without causing any clinical complications. No further procedures were performed after leakage. PVP is an effective treatment for painful osteoblastic spinal metastases. It can relieve pain, reduce disability and improve function. The main complications are bone cement leakage and incomplete pain relief. PMID:34007336 | PMC:PMC8120652 | DOI:10.3892/etm.2021.10159 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

SGLT2 promotes cardiac fibrosis following myocardial infarction and is regulated by miR-141

xlomafota13 shared this article with you from Inoreader SGLT2 promotes cardiac fibrosis following myocardial infarction and is regulated by miR-141 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):715. doi: 10.3892/etm.2021.10147. Epub 2021 May 3. ABSTRACT Cardiac fibrosis is a primary event during myocardial infarction (MI) progression, which impairs cardiac function. The present study aimed to investigate the effect of SGLT2 on cardiac fibrosis following MI. To validate the role of SGLT2 in the regulation of cardiac fibrosis in vivo, an MI rat model was established. Echocardiography was performed to determine cardiac function at 4 weeks post-MI. MI model rats were transfected with short hairpin RNA (sh)-SGLT2 or sh-negative control lentiviruses to investigate the effect of SGLT2 on rat heart function post-MI. Subsequently, the effects of SGLT2 on the cardiac fibrosis of infarcted hearts were assessed by performing Masson's trichrome staining. To further clarify the effect of SGLT2 on cardiac fibroblast proliferation, TGFβ was used to stimulate primary cardiac fibroblasts in vitro. T he results demonstrated that SGLT2 served a key role in cardiac fibrosis. SGLT2 expression levels in infarct tissues were significantly increased at week 1 post-MI compared with the sham group. Compared with the control group, SGLT2 knockdown attenuated cardiac fibrosis by inhibiting the expression of collagen I and collagen III in cardiac fibroblasts in vitro and in vivo. Furthermore, the results indicated that SGLT2 expression was modulated by miR-141 in cardiac fibroblasts. In summary, the present study indicated that upregulated SGLT2 expression in cardiac fibrosis following MI was regulated by miR-141 and SGLT2 that knockdown reduced cardiac fibrosis and improved cardiac function after MI. PMID:34 007324 | PMC:PMC8120516 | DOI:10.3892/etm.2021.10147 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Exogenous BMP9 promotes lung fibroblast HFL-1 cell activation via ALK1/Smad1/5 signaling in vitro

xlomafota13 shared this article with you from Inoreader Exogenous BMP9 promotes lung fibroblast HFL-1 cell activation via ALK1/Smad1/5 signaling <em>in vitro</em> Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):728. doi: 10.3892/etm.2021.10160. Epub 2021 May 4. ABSTRACT Bone morphogenetic protein 9 (BMP9) has recently been described as a crucial regulator in modulating fibroblast-type cell activation. Activin receptor-like kinase 1 (ALK1) is a high affinity receptor for BMP9 that exerts its role via Smad1/5. However, the functional roles of BMP9 in activating lung fibroblasts and the underlying signaling pathway are not completely understood. The present study aimed to explore the effect of exogenous BMP9 on human lung fibroblast HFL-1 cell proliferation and differentiation, as well as the potential role of the ALK1/Smad1/5 signaling pathway. In the present study, fibroblast proliferation was assessed using Cell Counting Kit-8 and colony formation assays, and the mRNA and protein expression of target genes was examined using reverse transcription-quantitative PCR and western blot assays, respectively. Compared wit h the control group, BMP9 treatment increased HFL-1 cell proliferation, mRNA and protein expression of differentiated markers, including α-smooth muscle actin, type I collagen and type III collagen, and the expression of ALK1 and phosphorylated Smad1/5 expression. Furthermore, the effects of BMP9 were partially rescued by dorsomorphin-1, an inhibitor of ALK1. The results indicated that BMP9 may serve as a key inducer of lung fibroblast activation and ALK1/Smad1/5 signaling might be associated with BMP9-mediated effects in HFL-1 cells. Therefore, the present study highlighted that the potential role of the BMP9/ALK1/Smad1/5 signaling pathway in the development of pulmonary fibrosis requires further investigation. PMID:34007337 | PMC:PMC8120641 | DOI:10.3892/etm.2021.10160 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

HMGB1 enhances chemotherapy resistance in multiple myeloma cells by activating the nuclear factor-κB pathway

xlomafota13 shared this article with you from Inoreader HMGB1 enhances chemotherapy resistance in multiple myeloma cells by activating the nuclear factor-κB pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):705. doi: 10.3892/etm.2021.10137. Epub 2021 May 2. ABSTRACT Chemotherapy resistance is a main obstacle in the clinical chemotherapeutic treatment of multiple myeloma (MM). High-mobility group box 1 (HMGB1) has been revealed to be associated with the sensitivity of MM cells to chemotherapy, but how HMGB1 regulates chemotherapy resistance in MM has yet to be fully elucidated. In the present study, the exact molecular mechanism underlying HMGB1-mediated drug resistance in MM was explored using three chemotherapy-resistant MM cells (RPMI8226/ADR, RPMI8226/BOR and RPMI8226/DEX) that were successfully established. Reverse transcription-quantitative polymerase chain reaction revealed that the three chemotherapy-resistant MM cells exhibited a higher release of HMGB1 compared with the parental RPMI8226 cells. Interference with endogenous HMGB1 increased the sensitivity of drug-resistant MM cells to chemotherapy, whi ch was supported by the low IC50 value and the enlargement of cell apoptosis. Furthermore, short hairpin (sh)RNA-transfected MM cells showed an obvious elevation in phosphorylated (p)-IKKα/β, p-IκBα and p-p65 in whole cell lysate and/or nucleus, and treatment of nuclear factor (NF)-κB activator reversed the effect of shHMGB1-mediated cell viability and apoptosis in MM cells. In conclusion, HMGB1 regulates drug resistance in MM cells by regulating NF-κB signaling pathway, suggesting that HMGB1 has the potential to serve as a target for MM treatment. PMID:34007314 | PMC:PMC8120504 | DOI:10.3892/etm.2021.10137 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hedgehog signaling modulates cigarette-induced COPD development

xlomafota13 shared this article with you from Inoreader Hedgehog signaling modulates cigarette-induced COPD development Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):729. doi: 10.3892/etm.2021.10161. Epub 2021 May 4. ABSTRACT Hedgehog (Hh) signaling is involved in early embryogenesis and maintains quiescence in the adult lungs. The interruption of Hh signaling may lead to the development of chronic obstructive pulmonary disease (COPD). The current study aimed to assess whether the Hh pathway affects cigarette-induced emphysema and airway inflammation by regulating inflammatory cytokines. C57BL/6J mice were randomized into control, cigarette smoke (CS) or CS + cyclopamine (CSC) groups. Control mice were exposed to normal room air, CS mice were exposed to tobacco smoke and CSC mice were exposed to CS and received cyclopamine treatment. Histopathological examination of lung tissues was performed, and the expression of sonic hedgehog (HH), glioma-associated oncogene homolog 1 (Gli1), hedgehog-interacting protein (HIP) and several inflammatory mediators (intracellular adhesi on molecule-1, IL-6, IL-8 and TNF-α) were compared using reverse transcription-quantitative PCR and western blotting. The emphysema of lung tissues by histopathological examination demonstrated partial amelioration in the CSC group compared with that in the CS group. Additionally, expression levels of SHH, Gli1 and inflammatory mediators were significantly higher in the CS group compared with the control group but were significantly decreased in the CSC group. The expression of HIP was decreased in the CS group, but significantly increased in the CSC group. Hh signaling may serve an important role in cigarette-induced emphysema and airway inflammation by regulating inflammatory cytokines in animal models. Therefore, diminishing the activation of the Hh signal may serve as a novel therapeutic strategy for patients suffering from smoking-related COPD. PMID:34007338 | PMC:PMC8120645 | DOI:10.3892/etm.2021.10161 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Features of a simvastatin-loaded multi-layered co-electrospun barrier membrane for guided bone regeneration

xlomafota13 shared this article with you from Inoreader Features of a simvastatin-loaded multi-layered co-electrospun barrier membrane for guided bone regeneration Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):713. doi: 10.3892/etm.2021.10145. Epub 2021 May 3. ABSTRACT A novel tri-layer membrane consisting of polycaprolactone (PCL) fibrous sheets and structured nanofibers with a gelatin (Gt) shell and a simvastatin-containing PCL core (PCL-Gt/PCL-simvastatin membrane) was prepared. The soft external layer comprised of Gt/PCL-simvastatin, the external layer of PCL and the middle layer of both microfilaments, interwoven together. The membrane was designed to promote osteoinduction and act as a barrier against cells but not against water and molecules in order to promote guided bone regeneration. The structure of the membrane was characterized by scanning electronic microscopy. The in vitro release rates of simvastatin over 32 days were determined by high-performance liquid chromatography. For in vitro biological assays, bone marrow mesenchymal stem cells and human fibroblasts were cultured on the diff erent surfaces of the membrane. Cell adhesion, proliferation, distribution, and differentiation were examined. For in vivo testing, cranial defects were created in rabbits to assess the amount of new bone formed for each membrane. The results revealed that membranes with multi-layered structures showed good cell viability and effective osteoinductive and barrier properties. These results suggest that the novel multi-layered PCL-Gt/PCL-simvastatin membranes have great potential for bone tissue engineering. PMID:34007322 | PMC:PMC8120663 | DOI:10.3892/etm.2021.10145 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Preclinical study analysis of massive magnesium alloy graft for calcaneal fractures

xlomafota13 shared this article with you from Inoreader Preclinical study analysis of massive magnesium alloy graft for calcaneal fractures Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):731. doi: 10.3892/etm.2021.10163. Epub 2021 May 7. ABSTRACT The highly comminuted calcaneal fractures represent a challenge for surgeons and require bone grafts for a good clinical outcome. Postoperative results are generally associated with increased morbidity and long periods of inactivity. The biomedical community promotes the use of artificial materials for grafts in order to achieve improved results. In an era when cosmetic concerns as well as the satisfaction of patients are mandatory and the use of autologous bone grafts is not without complications, an artificial replacement appears to be a favorable option. Synthetic bone grafts are known to fail under stress shield or are associated with systemic side effects. The purpose of the present study was to investigate and determine an already commercially available magnesium (Mg) alloy whose design is most suitable for long-term use. The mechanical prope rties of Mg1Ca and MgYREZr compared with normal cortical and cancellous bone were assessed. Another discussed aspect was the influence of the alloy in the graft fixation. The results revealed that Mg1Ca and MgYREZr alloys had a low tensile strength of 75 and 250 MPa, respectively. For this reason, it was surmised that MgYREZr alloy could be an optimal choice with favorable corrosion resistance. Since calcaneal fractures are prone to skin necrosis and septic complications, the need for antibacterial procedures and antibiotic prophylaxis is highlighted. Thus, an in vivo attempt was also made to identify the relationship between Mg alloy products and bacterial load. However, the most important feature of the present study was the creation of a 3D model grafting, with an anti-sliding design, which can be potentially used with the preferred Mg alloy in this type of fractures. In conclusion, artificial materials are the future in medicine, replacing the body-limiting capabilities o f grafts. They are safe and incur less comorbidities. This method could pave the way for reducing patient discomfort and increasing patient satisfaction. Although further testing is required, this research represents a great starting point for calcaneal fractures. PMID:34007339 | PMC:PMC8120552 | DOI:10.3892/etm.2021.10163< /p> View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Dihydroartemisinin inhibits endothelial cell migration via the TGF-β1/ALK5/SMAD2 signaling pathway

xlomafota13 shared this article with you from Inoreader Dihydroartemisinin inhibits endothelial cell migration via the TGF-β1/ALK5/SMAD2 signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):709. doi: 10.3892/etm.2021.10141. Epub 2021 May 3. ABSTRACT Anti-angiogenesis therapy is a novel treatment method for malignant tumors. Endothelial cell (EC) migration is an important part of angiogenesis. Dihydroartemisinin (DHA) exhibits strong anti-angiogenic and anti-EC migration effects; however, the underlying molecular mechanisms are yet to be elucidated. The TGF-β1/activin receptor-like kinase 5 (ALK5)/SMAD2 signaling pathway serves an important role in the regulation of migration. The present study aimed to explore the effects of DHA treatment on EC migration and the TGF-β1/ALK5/SMAD2 signaling pathway. The effects of DHA on human umbilical vein EC migration were assessed using wound healing and Transwell assays. The effects of DHA on the TGF-β1/ALK5/SMAD2 signaling pathway were detected using western blotting. DHA exhibited an inhibitory effect on EC migration in the wound healing and Transwell assays. DHA treatment upregulated the expression levels of ALK5 and increased the phosphorylation of SMAD2 in ECs. SB431542 rescued the inhibitory effect of DHA during EC migration. DHA inhibited EC migration via the TGF-β1/ALK5/SMAD2-dependent signaling pathway, and DHA may be a novel drug for the treatment of patients with malignant tumors. PMID:34007318 | PMC:PMC8120513 | DOI:10.3892/etm.2021.10141 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cis-acting: A pattern of lncRNAs for gene regulation in induced pluripotent stem cells from patients with Down syndrome determined by integrative analysis of lncRNA and mRNA profiling data

xlomafota13 shared this article with you from Inoreader Cis-acting: A pattern of lncRNAs for gene regulation in induced pluripotent stem cells from patients with Down syndrome determined by integrative analysis of lncRNA and mRNA profiling data Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):701. doi: 10.3892/etm.2021.10133. Epub 2021 May 2. ABSTRACT Down syndrome (DS), caused by the trisomy of chromosome 21, is one of the common chromosomal disorders, the main clinical manifestations of which are delayed nervous development and intellectual disability. Long non-coding RNAs (lncRNAs) have critical roles in various biological processes, including cell growth, cell cycle regulation and differentiation. The roles of abnormally expressed lncRNAs have been previously reported; however, the biological functions and regulatory patterns of lncRNAs in DS have remained largely elusive. The aim of the present study was to perform a whole-genome-wide identification of lncRNAs and mRNAs associated with DS. In addition, global expression profiling analysis of DS-induced pluripotent stem cells was performed and differentially expressed (DE) lncRNAs and mRNAs were screened. Furthermore, the target genes and fu nctions of the DE lncRNAs were predicted using Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis. The results revealed that the majority of the lncRNAs exerted functions in DS via cis-acting target genes. In addition, the results of the enrichment analysis indicated that these target genes were mainly involved in nervous and muscle development in DS. In conclusion, this integrative analysis using lncRNA and mRNA profiling provided novel insight into the pathogenesis of DS and it may promote the diagnosis and development of novel therapeutics for this disease. PMID:34007310 | PMC:PMC8120638 | DOI:10.3892/etm.2021.10133 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.