Simultaneous Replacement Research Articles

Bilateral total knee arthroplasty-analysis of risk factors for blood loss and blood transfusion

Background: Total knee arthroplasty in general is a safe and successful surgical procedure for end stage arthritis of the knee joint to relieve pain, correct the deformity and restore function in the joint. However, it is often associated with significant blood loss. In such cases, blood transfusion is not uncommon. Methods: 100 patients who underwent simultaneous bilateral TKA from April 2022 to December 2022 at Sant Parmanand Hospital, New Delhi were taken up for the study. Results: In this study among 100 patients who underwent simultaneous bilateral total knee replacement, 9% of the cases required blood transfusion. Preoperative haemoglobin (<12.64 gm/dl) continues to be a predictor in blood transfusions. A haemoglobin level of less than 10.34 gm/dl preoperatively, a postoperative haemoglobin day 1 level of less than 8.56gm/dl and a postoperative day 3 level of less than 7.49 gm/dl increases the necessity for blood transfusion in simultaneously performed bilateral TKAs. Conclusions: Asthma, Diabetes mellitus and patients on blood thinners are three major comorbidities than can cause increased blood loss. Age, gender, BMI and comorbidities are not related to the need for blood transfusion. Patients on blood thinners are at an increased risk for blood transfusion if they have a lower preoperative haemoglobin. Checking haemoglobin values on postoperative day 1 and day 3 are significant in terms of the need for blood transfusion.

Water-soluble neutral octahedral chalcogenide tungsten and molybdenum {M6Q8} clusters with P(C2H4CONH2)3 ligand

Developing the chemistry of octahedral chalcogenide molybdenum and tungsten cluster complexes in the context of applications in biology and medicine, in this work a series of water-soluble neutral cluster complexes [{M6Q8}(P(C2H4CONH2)3)6] (M = Mo, W; Q = S, Se) have been obtained by simultaneous replacement of inner and terminal halide ligands in [{M6I8}I6]2− with chalcogenide and organic phosphine ligands and characterized by single-crystal X-ray diffraction analysis, 1H and 31P NMR spectroscopies, elemental analysis, and UV–vis spectroscopy. The amide groups of the organic ligands, on the one hand, contribute to the solubility of the resulting clusters in water and, on the other hand, are able to form an extensive network of hydrogen bonds, leading to the crystallization of the complexes from aqueous solutions. Despite this fact, the complexes have sufficient solubility and stability in aqueous solutions, which made it possible to demonstrate their low cytotoxicity on Hep-2 cells (IC50 were not reached even at concentration up to 4 mM). The resulting clusters are among the most biocompatible of the octahedral clusters studied to date and are the starting point for the development of a new family of X-ray contrast agents.

Simultaneous beating-heart mitral valve replacement and aortic repair following Bentall procedure via double right mini-thoracotomies: a case report

BackgroundRedo mitral valve surgery by re-sternotomy approach has challenges such as bleeding and organ injury due to adhesion dissection, sternal bone infection, and poor field of view of mitral valve. On the other hand, redo mitral valve surgery via a right mini-thoracotomy approach appears to address these challenges. We successfully performed a double right mini-thoracotomies approach for mitral valve replacement and pseudoaneurysm repair under the beating-heart condition. Herein, we report the effectiveness and the safety of this technique and detailed procedure.Case presentation.The patient is a 71-year-old man with a history of Bentall procedure using a mechanical valve at another hospital 30 years ago. He developed acute heart failure due to severe mitral valve regurgitation. After medication, he was referred to our department for the purpose of surgery for mitral valve regurgitation. Preoperative transesophageal echocardiography showed extensive degenerative change of the both leaflets and chordae tendineae rupture at the P3 segment. Both left atrium and ventricle dilated, and left ventricle contractility reduced. Aortic mechanical valve had no problem. In addition, preoperative contrast enhanced computed tomography revealed a pseudoaneurysm at the distal anastomotic site of Bentall procedure. We performed mitral valve replacement by mechanical valve and repair of distal anastomotic cite under beating heart condition, utilizing a double right mini-thoracotomies approach for mitral valve and ascending aortic pseudoaneurysm respectively. The postoperative course was uneventful, the patient was discharged without complications.ConclusionThe right mini-thoracotomies approach efficiently accessed mitral valve and ascending aorta in reoperations, reducing the adhesion dissection risks and ensuring clear exposure. Moreover, concomitant use of beating-heart technique minimized adhesion dissection for aortic cross-clamp, preserved cardiac function.

CRISETR: an efficient technology for multiplexed refactoring of biosynthetic gene clusters.

The efficient refactoring of natural product biosynthetic gene clusters (BGCs) for activating silent BGCs is a central challenge for the discovery of new bioactive natural products. Herein, we have developed a simple and robust CRISETR (CRISPR/Cas9 and RecET-mediated Refactoring) technique, combining clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9 and RecET, for the multiplexed refactoring of natural product BGCs. By this approach, natural product BGCs can be refactored through the synergistic interaction between RecET-mediated efficient homologous recombination and the CRISPR/Cas9 system. We firstperformed a proof-of-concept validation of the ability of CRISETR, and CRISETR can achieve simultaneous replacement of four promoter sites and marker-free replacement of single promoter site in natural product BGCs. Subsequently, we applied CRISETR to the promoter engineering of the 74-kb daptomycin BGC containing a large number of direct repeat sequences forenhancingthe heterologous production of daptomycin. We used combinatorial design to build multiple refactored daptomycin BGCs with diverse combinations of promoters different in transcriptional strengths, and the yield of daptomycin was improved 20.4-fold in heterologous host Streptomyces coelicolor A3(2). In general, CRISETR exhibits enhanced tolerance to repetitive sequences within gene clusters, enabling efficient refactoring of diverse and complex BGCs, which would greatly accelerate discovery of novel bioactive metabolites present in microorganism.

Functional and Radiological Outcome of Simultaneous Bilateral Total Knee Replacement in a Tertiary Care Centre : A Quasi-prospective Study.

Osteoarthritis (OA) is the most frequent joint disease with a prevalence of 5313 per 100,000 persons in India. OA of the knee is a major contributor to mobility impairment, particularly among women. In these patients, total knee replacement (TKR) is widely accepted as the gold standard treatment for pain relief and restoration of function. Now, patients have the option of undergoing either a simultaneous bilateral TKR or a staged TKR. The former has shown significant advantages such as shorter rehabilitation, cost efficacy and shorter hospital stay. This study aimed to assess the functional and radiological outcome of simultaneous bilateral TKR in a tertiary care centre. 30 adult patients above the age of 55 years with severe OA knee who underwent simultaneous bilateral TKR between 2022-2023 were included in this prospective study. Preoperatively, they were assessed with radiographs including full length scannograms. Mean Anatomical Axis, Mean Mechanical Axis and Mechanical Axis Deviation (Varus) were calculated based on the scannograms by a single observer. The same observer administered the oxford knee score (OKS) preoperatively to all patients. Regular clinical and radiological follow up was done. After 1 year follow up, the same observer administered the Oxford Knee Score (OKS) to the operated knee. With a female preponderance among the study subjects (56.7%), the majority of the cases in our cohort were characterised as Grade IV Kellgren-Lawrence radiological grade of Osteoarthritis (76.66%) and were found to have tricompartmental involvement (70%). The mean anatomical axis for the right and left lower limb were 4.56±5.17 and 9.68±1.72 respectively. The mean mechanical axis deviation (Varus) for the right and left lower limb were 31.6±15.1 and 52.0±13.9 respectively. Preoperatively, mean mechanical axis for the right and left lower limb were 9.95±4.31 and 14.2 ±0.67 respectively. Postoperatively, mechanical axis was restored to near-normal values (3-5 degrees). Significant improvement in mean OKS from a preoperative value of 18.30 ± 3.46 to postoperative value of 33.50 ± 5.32 was noted at 1 year. Treatment of severe bilateral OA knee with simultaneous single staged bilateral TKR ensures good functional outcome , early mobility with minimal complications.

299. SURGICAL STRATEGY FOR THE TREATMENT OF AORTOESOPHAGEAL FISTULA

Abstract Background The number of thoracic endovascular aortic repair (TEVER) and artificial vessel replacement for thoracic aortic aneurysms is increasing. Aortoesophageal fistula (AEF) is one of the problems with long-term outcomes, and management of AEF needs immediate control of hemorrhage and infection. Bleeding control can be performed with artificial vessel replacement, but postoperative graft infection is inevitable in AEF. For infection control, removal of the diseased esophagus should be performed. In this study, we will clarify the surgical outcomes of esophagectomy for AEF. Material and Methods We evaluated 22 patients who underwent artificial vascular replacement and esophagectomy for AEF from 2007 to 2023 at Kobe University Hospital, retrospectively. The surgical approaches for esophagectomy were left open thoracotomy, median sternotomy or minimally invasive esophagectomy (MIE). Results In this study, all patients underwent simultaneous artificial vascular replacement and esophagectomy. According to the surgical approaches, 15 patients underwent left open thoracotomy, 6 patients underwent median sternotomy and 1 patient underwent left open thoracotomy + MIE. The male to female ratio was 15:7, and the median age was 72 (38-85) years. According to the type of reconstruction, 11 patients underwent pediculated jejunum reconstruction and 1 patient underwent ileocolic reconstruction. 12 patients (54.5%) were able to undergo reconstruction, 10 patients (45.5%) were not undergo reconstruction. 4 patients (18.2%) of died in the hospital. Conclusion Esophagectomy simultaneous with artificial vascular replacement could be a feasible treatment for AEF.

Запрет одновременного замещения различных должностей в системе органов публичной власти: проблемы законодательного закрепления и практической реализации

The article considers the prohibition of state and municipal employees to fill state and municipal positions. The author notes the eclecticism of the normative and legal consolidation of this ban in various legislative acts regulating the status of elected officials, persons holding state and municipal positions and regulating the passage of state and municipal service. The exceptions to this prohibition established by the current legislation were analyzed. The author believes that such exceptions are not always advisable from the point of view of its essence. Defects of regulatory support of such exceptions are analyzed. In addition, the work notes the uncertainty of the legal consequences of violating the ban on the simultaneous replacement of state (municipal) posts and positions of the state (municipal) service. Proposals are made to improve legislation in this area.

Characteristics of rehabilitation for patients with severe asymmetric jaw deformities resulting from temporomandibular joint pathology

Relevance. Temporomandibular joint (TMJ) pathology, along with the resultant facial asymmetry, is a common condition within maxillofacial disorders. Addressing the rehabilitation of these patients within specialised medico-social care is a crucial and challenging task.Purpose. To develop a comprehensive rehabilitation protocol for patients with severe asymmetric jaw deformities caused by TMJ pathology.Materials and methods. From 2018 to 2023, ten patients with defects and deformities of the TMJ condylar process, presenting with severe asymmetric jaw deformities, were treated. An assessment of subjective and objective facial aesthetic parameters was conducted based on photographic protocols, as well as 2D and 3D cephalometric facial measurements. Comprehensive preparation for orthognathic surgery with simultaneous endoprosthesis replacement was performed based on the collected data. A regimen of postoperative therapeutic procedures was prescribed following the surgery.Results. All patients achieved the intended statistically significant outcomes: in the sagittal plane, an improvement in facial profile was noted based on the position of the chin (Pog) relative to the true vertical line passing through the subnasale point. In the frontal plane, alignment of the occlusal plane and normalization of the central line of the upper and lower incisors relative to the midline of the face were observed.Conclusion. The algorithm for the comprehensive preparation of patients with asymmetric jaw deformities, developed during growth, prior to performing orthognathic surgery with simultaneous TMJ endoprosthesis replacement should include: orthodontic treatment aimed at aligning teeth position and dental arches, eliminating rotations and pathological inclinations of teeth using a bracket system, fully restoring interocclusal height with temporary implant-supported structures, using occlusal splints and temporary composite restorations, as well as employing separating orthodontic plates. These stages enabled the achievement of good aesthetic results and improved patients' quality of life.

Bilateral simultaneous hip and knee replacement: an epidemiological nationwide study from 2001 to 2016

BackgroundSeveral studies have compared the pros and cons of simultaneous bilateral versus staged bilateral hip and knee replacement but the outcomes of these two surgical options remains a matter of controversy. This study aimed to evaluate demographic features, incidence and hospitalization rates of bilateral one stage total hip and knee arthroplasty in Italy.MethodsThe Italian Ministry of Health’s National Hospital Discharge Reports (SDO) were used to gather data. This study referred to the adult population (+ 20 years of age) from 2001 to 2015 for hip arthroplasty and from 2001 to 2016 for knee arthroplasty.ResultsOverall, 1,544 bilateral simultaneous hip replacement were carried out. The incidence rate was 0.21 cases per 100,000 adult Italian residents. Male/female ratio was 1.1. The average days of hospital stay was 11.7 ± 11.8 days. The main primary codified diagnosis was: osteoarthrosis, localized, primary, pelvic region and thigh (ICD code: 715.15). 2,851 bilateral simultaneous knee replacement were carried out. The incidence rate was 0.37 cases per 100,000 adult Italian residents. Male/female ratio was 0.6. The average days of hospital stay was 7.7 ± 5.8 days. The main primary codified diagnosis was: osteoarthrosis, localized, primary, lower leg (ICD code: 715.16).ConclusionsThe burden of hip and knee osteoarthrosis as a leading cause of bilateral joint replacement is significant in Italy. The national registers’ longitudinal analysis may provide data for establishing international guidelines regarding the appropriate indications for one stage bilateral simultaneous hip or knee replacement versus two stage.

H2 promotes the premature replacement of CH4–CO2 hydrate even when the CH4 gas-phase pressure exceeds the phase equilibrium pressure of CH4 hydrate

Submarine CO2 sequestration via solid hydrate has been considered a promising strategy for controlling greenhouse gas emissions. The simultaneous replacement of CH4 from subsea natural gas hydrates through buried CO2 offers a win-win approach. Utilizing H2 as an enhancer to promote CH4–CO2 hydrate replacement, coupled with integrating the replacement products into CH4 steam reforming for cyclic H2 production, presents a potential pathway for CO2 geological storage and eventual H2 recovery. However, the enhancement mechanism of H2 in the hydrate replacement process remains unclear. Focusing on the critical replacement condition, this study investigates the effects of gas-phase partial pressures on hydrate replacement in CH4-rich systems to elucidate the H2 influence mechanism. Remarkably, the results indicate, for the first time, that H2 induces premature CH4 hydrate dissociation under conditions exceeding the corresponding CH4 gas equilibrium pressure in CO2/CH4/H2 ternary gas systems. The critical condition for hydrate replacement depends on the total system pressure, rather than CO2 gas partial pressure. Additionally, in the CH4-rich systems, the driving force for CH4 hydrate decomposition takes precedence over that for hydrate reformation in controlling replacement. The replacement ratio increases from 16.7 % to 24.5 % as the CH4 partial pressure decreases from 2.01 MPa to 1.11 MPa at 274.15 K, despite simultaneous declines in both CO2 partial pressure and total system pressure from 1.70 MPa to 0.97 MPa and from 6.10 MPa to 3.39 MPa, respectively. These findings can provide insights into the improvement of CH4–CO2/H2 hydrate replacement efficiency and the development of oceanic CO2 sequestration.

ACETABULAR FRACTURES IN OLDER PATIENTS INTERVENTION TRIAL (ACEFIT): A FEASIBILITY TRIPLE-ARM RANDOMIZED CONTROLLED STUDY

Current treatment options for displaced acetabular fractures in elderly patients include non-surgical management, surgical fixation and surgical fixation with simultaneous hip replacement, the so-called “fix-and-replace”™. There remains a paucity of evidence to guide surgeons in decision making for these difficult injuries. The aim of this study was to assess the feasibility of performing an appropriately powered RCT between treatment options for acetabular fractures in older patients.This was an NIHR funded feasibility triple-arm RCT with participation from 7 NHS MTCs. Patients older than 60 were recruited if they had an acetabular fracture deemed sufficiently displaced for the treating surgeon to consider surgical fixation. Randomisation was performed on a 1:1:1 basis. The three treatment arms were non-surgical management, surgical fixation and fix-and-replace. Feasibility was assessed by willingness of patients to participate and clinicians to recruit, drop out rate, estimates of standard deviation to inform the sample size calculation for the full trial and completion rates to inform design of a future definitive trial. EQ-5D was the primary outcome measure at 6 months, OHS and Disability Rating Index were secondary outcome measures.Of 117 eligible patients, 60 were randomised whilst 50 declined study participation. Nine patients did not receive their allocated intervention. Analysis was performed on an intention to treat basis. During the study period 4 patients withdrew before final review, 4 patients died and 1 was lost to follow-up. The estimated sample size for a full scale study was calculated to be 1474 participants for an EQ-5D MCID of 0.06 with a power of 0.8.This feasibility study suggests a full scale trial would require international collaboration. This study also has provided observed safety data regarding mortality and morbidity for the fix-and-replace procedure to aid surgeons in the decision-making process when considering treatment options.

Commentary on the article by S. V. Petrov et al. «Simultaneous replacement of the aortic valve and hip joint in a patient with critical aortic stenosis and femoral neck fracture»

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Commentary on the article by S. V. Petrov et al. «Simultaneous replacement of the aortic valve and hip joint in a patient with critical aortic stenosis and femoral neck fracture»

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A randomized controlled trial comparing carbazochrome sodium sulfonate and tranexamic acid in reducing blood loss and inflammatory response after simultaneous bilateral total hip arthroplasty.

A drug known as carbazochrome sodium sulfonate (CSS) can reduce blood loss. But, it is not known how it can prevent the development of hemostatic and inflammatory conditions in patients who undergo bilateral simultaneous total hip arthroplasty (SBTHA). This study will analyze the safety and effectiveness of combining this drug with SBTHA. The study was conducted on 100 patients who underwent SBTHA with simultaneous total hip replacement. They were split into two groups: group B received TXA with CSS, group A received TXA with no CSS. The main observation of the study was the total blood loss, which is the most common indication of blood loss. Other secondary indicators of the study included hidden blood loss, postoperative blood transfusion rate, level of inflammatory reactants, hip function, pain score, venous thromboembolism (VTE) and the incidence of adverse events. Group B had significantly lower TBL and HBL compared to Group A. Group B showed significant improvement in inflammatory biomarker levels, blood transfusion rate when compared to Group A (p < .05). No thromboembolic complications occurred in either group. There were no significant differences between the two groups in terms of postoperative swelling rate, intraoperative blood loss, visual analog scale pain score, platelet count, discharge motion and average length of stay. As a hemostatic agent, CSS combined with TXA can reduce postoperative blood loss in patients undergoing SBTHA, and is more effective than TXA alone in terms of blood loss and inflammation, and does not increase the incidence of thromboembolic complications.

A simultaneous bilateral total knee replacement: The road to recovery

The patient had suffered from arthritis in both knees for several years. In discussions between the patient and the orthopaedic surgeon the decision was made to carry out a simultaneous bilateral complete knee replacement. Epidural anaesthesia was employed to remove feeling from the lower part of the body. The operation was completed successfully.

Doping Strategy to Improve the Electrochemical Behavior of Lithium Rich Transition Metal Oxides As Cathodes for Lithium-Ion Batteries

Lithium-rich transition metal oxides are considered a promising cathodic solutions in Li-ion batteries to meet the growing energetic demand, thanks to their high specific capacity and operational voltage [1-2]. Li-rich layered materials have a general stoichiometry Li1+xTM1-xO2, in which TM is a blend of transition metals, as Ni, Mn, Co [2]. They stand out due to their high lithium concentration and specific capacity [1-2]. The higher capacity of Lithium-Rich can be attributed to the specific anionic redox reaction in the bulk at above 4.5 V. Nevertheless, large irreversible capacity loss in the first cycle, poor rate capability, mean working potential decay upon cycling and cobalt content are still major drawbacks that are hindering commercialization. In order to make these materials up scalable to industrial production, it is important to consider the reduction of costs and the toxicity of raw materials, in particular cobalt. Cobalt reduction has been identified as major driver to improve the environmental benignity of batteries and the sustainability of the overall production-consumption-recycling lifecycle. Several efforts to reduce these problems have been made, including the development of different synthetic strategies, doping and surface modification. The most, widely explored, chemical strategy to mitigate the voltage decay and structural degradation in Lithium Rich cathodes is the doping. Elemental doping can be divided into cation and anion doping. As an example, incorporation of redox inactive metals, such as Al, Zr, Ti, has been proposed in order to stabilize the lattice as well as the partial replacement of lithium ions with other alkali cations, e.g. K and Na; or doping the oxygen anion sublattice. In this communication, we present our doping approaches. In particular, the simultaneous replacement of cobalt in the layered structure with aluminum and lithium (over-lithiation). Moreover, we present over-lithiated Co-free materials where the introduction of different amount of iron has been investigated. The characterization of these novel layered materials is reported in terms of composition, structure, morphology and electrochemical performances. These approaches can be applied as a strategy to mitigate the voltage decay and reduce the Cobalt content.[1] Ji, X. et al. Journal of Power Sources 487, (2021).[2] Zhao, S. et al. Angewandte Chemie - International Edition 60, 2208–2220 (2021).

Buried bumper syndrome in percutaneous endoscopic gastrostomy with a jejunal extension tube in patients undergoing levodopa–carbidopa intestinal gel treatment

BackgroundLevodopa–carbidopa intestinal gel (LCIG) treatment is an effective Parkinson’s disease (PD) treatment that requires percutaneous endoscopic gastrostomy with a jejunal extension tube (PEG-J). Buried bumper syndrome (BBS) is an uncommon but significant complication of PEG-J for LCIG.Case presentationA 71-year-old man had been undergoing LCIG therapy for PD since a PEG-J was implemented at our department two years previously. He presented with appetite loss. Computed tomography showed that the gastrostomy bumper was buried in the gastric wall. The patient was surgically treated with the simultaneous removal and replacement of PEG-J. Postoperative gastrocutaneous fistula occurred, which was conservatively treated.ConclusionsNotably, patients and medical staff should be aware that patients with PD on LCIG treatment have a high risk of BBS in PEG-J and that there might be some patients with latent BBS. When simultaneous removal and replacement surgery is performed, establishing a new route at the stomach and abdominal wall is recommended.

Simultaneous replacement of the aortic valve and hip joint in a patient with critical aortic stenosis and femoral neck fracture

Concomitant cardiovascular diseases in elderly patients with a hip fracture significantly increase the risk of developing postoperative complications. Developing the treatment algorithm for a combination of two or more diseases in this category of patients is the main task. The advantages of simultaneous surgery are one-stage repair of two or more surgical diseases, the implementation of one anesthetic procedure, the reduction in the total time of the patient’s stay in the hospital and the reduction in rehabilitation time. This paper presents the clinical observation of simultaneous surgical treatment of severe aortic stenosis and femoral neck fracture in an elderly patient.

Biological versus mechanical SAVR patient's age threshold: PARTNER II study influenced real world practice in a large French cohort

Abstract Background/introduction Published in 2016, PARTNER II study has shown TAVR to be non inferior to SAVR in intermediate risk patients. This result might influence the type of SAVR chosen in patients for whom a redo surgery would surely be a procedure at intermediate risk, based on estimated age at time for redo and taking into account ViV TAVI as a game changer for treating a degenerated biological prosthesis. Purpose To assess the choice of type of valve according to age in aortic position through the French National Database EPICARD before and after the publication of Parter II study. Methods We extracted from EPICARD all valvular patients operated on from 2007 to 2022 in 24 participating public or private centers chosen to represent a balanced representation of center sizes and geographical discrepancies. Patients with associated pathology of the aorta (aneurysm or dissection) and requiring a vascular aortic prosthesis were excluded. Results From the obtained representative study population of 101,070 valvular patients, we studied 72,375 SAVR (mean age 71.4 +/- 12.2). We observed a mechanical versus biological prosthesis ratio (MBPR) of 0.14 for the overall aortic SAVR population. Before 50 y-o, MBPR was &amp;gt;1.3 (p&amp;lt;0.001) while patients above 60 y-o received principally biological SAVR (p&amp;lt;0.0001). Concerning patients between 50-60 y-o patients, MBPR was 1.04 (p=0.03). Patients 50-60 y-o from the first and second quartile (before August 2015) received preferentially mechanical SAVR (p&amp;lt;0.001). We observed a shift towards more biological SAVR (p&amp;lt;0.001) for patients from the third and fourth quartile to reach a MBPR at 0.43 during the last years of the series. Incidentally, the choice of type of SAVR was influenced by associated procedures. Simultaneous mitral valve replacement were more common in case of mechanical SAVR (p&amp;lt;0.0001), while associated CABGs were more frequent in case of biological SAVR (p&amp;lt;0.0001). Conclusion In a large contemporary French patient population, real world practice showed that publication of the PARTNER II study was followed by a shift towards a lower threshold for biological SAVR as compared to ESC Guidelines.

Cooperatively inhibition effect of miR-143-5p and miR-145-5p in tumorigenesis of glioblastoma cells through modulating AKT signaling pathway

Introduction: As the most common aggressive primary brain tumor, glioblastoma is inevitably a recurrent malignancy whose patients’ prognosis is poor. miR-143 and miR-145, as tumor suppressor miRNAs, are downregulated through tumorigenesis of multiple human cancers, including glioblastoma. These two miRNAs regulate numerous cellular processes, such as proliferation and migration. This research was intended to explore the simultaneous replacement effect of miR-143, and miR-145 on in vitro tumorgenicity of U87 glioblastoma cells. Methods: U87 cells were cultured, and transfected with miR-143-5p and miR-145-5p. Afterward, the changes in cell viability, and apoptosis induction were determined by MTT assay and Annexin V/PI staining. The accumulation of cells at the cell cycle phases was assessed using the flow cytometry. Wound healing and colony formation assays were performed to study cell migration. qRT-PCR and western blot techniques were utilized to quantify gene expression levels. Results: Our results showed that miR-143-5p and 145-5p exogenous upregulation cooperatively diminished cell viability, and enhanced U-87 cell apoptosis by modulating Caspase-3/8/9, Bax, and Bcl-2 protein expression. The combination therapy increased accumulation of cells at the sub-G1 phase by modulating CDK1, Cyclin D1, and P53 protein expression. miR-143/145-5p significantly decreased cell migration, and reduced colony formation ability by the downregulation of c-Myc and CD44 gene expression. Furthermore, the results showed the combination therapy of these miRNAs could remarkably downregulate phosphorylated-AKT expression levels. Conclusion: In conclusion, miR-143 and miR-145 were indicated to show cooperative anti- cancer effects on glioblastoma cells via modulating AKT signaling as a new therapeutic approach.