The efficacy of hemiepiphysiodesis for idiopathic knee coronal angular deformity by reconstruction plate and screw: A pilot study.

Background: Angular deformities of the lower extremities are among the most common findings in pediatric orthopedics. Alteration of the mechanical axis in the lower extremity affects the cosmetic appearance and may lead to gait disturbances, knee discomfort, patellar maltracking with or without pain, and early joint osteoarthritis. In the current study, we aimed to investigate the efficacy of 3-hole 3.5 mm reconstruction plates in tension-band temporary hemiepiphysiodesis for correcting idiopathic knee coronal angular deformities. Methods: The surgical procedure was performed using an extraperiosteal tension band plate (a 3-hole reconstruction plate) and two 3.5 mm cortical screws to treat idiopathic knee coronal angular deformity in children. The location of the hemiepiphysiodesis was determined based on the type of angular deformity present. Postoperative follow-ups were conducted through x-rays to measure the medial proximal tibial angle and lateral distal femoral angle of the limbs. Statistical analysis was then performed to evaluate the efficacy of the surgical treatment based on the rate of alignment change exhibited. Results: The study included 14 patients (25 limbs) with genu valgum deformity who underwent temporary hemiepiphysiodesis on both the distal femur and proximal tibia, with 16 proximal tibias and 15 distal femurs being corrected. The correction rate for genu valgum was found to be 0.59° per month for both proximal tibial and distal femoral hemiepiphysiodesis. Six patients (12 limbs) were also identified with genu varum deformity, and the correction rates for proximal tibial lateral hemiepiphysiodesis and distal femoral lateral hemiepiphysiodesis were 0.85° and 0.15° per month, respectively. During a mean follow-up duration of 11 ± 5.7 months, only one case of physeal plate closure was observed, and there were no other significant complications. Conclusion: Temporary hemiepiphysiodesis with a 3-hole R-plate and two cortical screws takes advantage of physiological physeal growth to successfully treat idiopathic angular deformities with low complication rates.

Cancer combination therapies by silencing of CTLA-4, PD-L1, and TIM3 in osteosarcoma.

Osteosarcoma (OS) is the most common orthopedic neoplasm, with a high metastasis rate and a dismal prognosis despite surgery and chemotherapy. Immunotherapies have offered cancer patients a ray of optimism, but their impact on OS has been disappointing. The objective of this study is to assess the effect of mono, dual, and triple combinations of CTLA-4, PD-L1, and TIM3 blockade on OS cell viability, apoptosis, and migration. The MG-63 and U-2 OS cell lines were transfected with mono, dual, and triple combinations of siRNAs specific for CTLA-4, PD-L1, and TIM3. After evaluation for transfection efficacy by qRT-PCR, MTT assay and flow cytometry were applied to assess cell viability and apoptosis rate in siRNA-transfected cells, respectively. Ultimately, the migration of transfected cells was measured by wound-healing assay. First, the qRT-PCR analysis revealed that in siRNA-transfected OS cells, CTLA-4, PD-L1, and TIM3 were downregulated. The MTT assay and flow cytometry results confirmed that silencing of these immune checkpoints in dual or triple combinations, but not in the single-agent blockade, significantly decreases cell viability and increases apoptosis, respectively. These effects were more significant when triple silencing was performed. Finally, the wound-healing assay revealed that dual and triple silencing of immune checkpoints significantly inhibits cell migration, with triple silencing exhibiting a greater effect. Our findings suggest that triple blockade of CTLA-4, PD-L1, and TIM3 is an effective strategy for inhibiting tumor cell progression and migration in OS, which requires large-scale clinical investigations to be translated into broad therapeutic applicability for OS patients.

Prognostic significance and therapeutic potentials of immune checkpoints in osteosarcoma.

Although there exist manifold strategies for cancer treatment, researchers are obliged to develop novel treatments based on the challenges that arise. One of these recent treatment approaches is cancer immunotherapy, which enjoys various types of strategies itself. However, one of the most significant methods, in this regard, is employing immune checkpoint proteins (ICPs). Bone sarcomas have several subtypes, with the most common ones being chordoma, chondrosarcoma, Ewing sarcoma, and osteosarcoma. Although many aggressive treatment approaches, including radiotherapy, chemotherapy, and surgical resection, have been employed over the last decades, significantly improved outcomes have not been observed for Ewing sarcoma or osteosarcoma patients. Additionally, chordoma and chdrosarcoma resist against both radiation and chemotherapy. Accordingly, elucidating how recent therapies could affect bone sarcomas is necessary. Checkpoint inhibitors have attracted great attention for the treatment of several cancer types, including bone sarcoma. Herein, the recent advances of current immune checkpoint targets, such as anti-PD-1/PD-L1 and anti-CTLA-4 blockade, for the treatment of bone sarcoma have been reviewed.

Platelet lysate: a promising candidate in regenerative medicine.

Human platelet lysate has attracted much interest from many researchers as it is growth-factor rich for cell expansion, which is employed as a new therapeutic strategy. Not only are human platelet lysates used for cell therapy, but they are also used for the completion of basal media in mesenchymal stem cell cultures. Due to the presence of a large number of growth factors, platelet lysates have potential roles in wound healing, treatment of ocular graft-versus-host disease, osteoarthritis, Parkinson's disease, tendon regeneration, infertility, androgenetic alopecia, nerve repair and regenerative tissue, such as bone regeneration. In this review, we summarize that platelet lysates could be valuable candidates for the treatment of a variety of diseases in regenerative medicine.

Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers.

Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.

Prospects for the involvement of cancer stem cells in the pathogenesis of osteosarcoma.

Osteosarcoma (OS) is one of the most common bone tumors in children and adolescents that cause a high rate of mortality in this age group and tends to be metastatic, in spite of chemotherapy and surgery. The main reason for this can be returned to a small group of malignant cells called cancer stem cells (CSCs). OS-CSCs play a key role in the resistance to treatment and relapse and metastasis through self-renewal and differentiation abilities. In this review, we intend to go through the different aspects of this malignant disease, including the cancer stem cell-phenotype, methods for isolating CSCs, signaling pathways, and molecular markers in this disease, and drugs showing resistance in treatment efforts of OS.

Implications of exosomes as diagnostic and therapeutic strategies in cancer.

Exosomes offer a new perspective on the biology of cancer with both diagnostic and therapeutic concepts. Due to the cell-to-cell association, exosomes are involved in the progression, metastasis, and therapeutic efficacy of the tumor. They can be isolated from blood and other body fluids to determine the disease progression in the body, including cancer growth. In addition to being reservoirs of biochemical markers of cancer, exomes can be designed to restore tumor immunity. Tumor exosomes interact with different cells in the tumor microenvironment to confer beneficial modulations, responsible for stromal activity, angiogenesis, increased vascular permeability, and immune evasion. Exosomes also contribute to the metastasis with the aim of epithelial transmission to the mesenchyme and the formation of premetastatic niches. Moreover, exosomes protect cells against the cytotoxic effects of chemotherapeutic drugs and prevent the transmission of chemotherapy resistance to adjacent cells. Therefore, exosomes are essential for many fatal cancer agents, and understanding their origins and role in cancer is important. In this article, we attempted to clarify the potential of exosomes for the application in cancer diagnosis and therapy.

Insights into the roles of miRNAs; miR-193 as one of small molecular silencer in osteosarcoma therapy.

Today, cancer is one of the most common causes of death. Osteosarcoma (OS) is a tumor in long bones and its prevalence is high in teenagers and young people. Among the methods that used to treat cancer, one can name chemotherapy, surgery, and radiotherapy. Since these methods have some disadvantages and they are not absolutely successful, the use of microRNAs (miRNAs) is very useful in diagnosis and treatment of OS. MiRNAs are small non-coding RNA molecules, containing 18-25 nucleotides, which are involved in the regulation of gene expression via binding to messenger RNA (mRNA). These RNAs are divided into two classes of suppressors and oncogenes. During OS, there is aberrant expression of several miRNAs. Among these miRNAs are downregulation of miR-193 that has been associated with cancer occurrence. The aim of the current manuscript is to have overview on the treatment approaches of OS with special focus on miR-193.

Prospect of mesenchymal stem cells in therapy of osteoporosis: A review.

Osteoporosis is a systemic skeletal disease associated with reduced bone strong point that results in raised fracture risk, with decreased bone strength, leading to reduced bone mineral density and poor bone quality. It is the most common in older females but some men are also at high risk. Although considered as a predictable result of aging, it is can be avoidable and treatable. The existing treatment of osteoporosis mainly contains antiresorptive and anabolic agents. In spite of these improvements, concerns around unusual side-effects of antiresorptive drugs, and the lack of perfect confirmation in maintenance of their long-standing effectiveness is bring about many patients not receiving these drugs. Over the years, the stem cell-based therapy has attained substantial clinical consideration because of its potential to treat numerous diseases. The stem cell therapy has been recommended as a probable therapeutic approach for patients with osteoporosis. Even though the concept of stem cell-based therapy for osteoporosis has caught substantial attention, no clinical trial has been published on humans. The cell studies based on osteoporosis are primarily focused on osteoclastic activity and bone resorption procedures. Earlier, it was on osteoblastogenesis and in recent times, on the differentiation probable of mesenchymal stem cells. In this review, we have summarized the therapeutic role of stem cell-based strategy in osteoporosis.

Immune checkpoint blockade opens a new way to cancer immunotherapy.

Among the main promising systems to triggering therapeutic antitumor immunity is the blockade of immune checkpoints. Immune checkpoint pathways regulate the control and eradication of infections, malignancies, and resistance against a host of autoantigens. Initiation point of the immune response is T cells, which have a critical role in this pathway. As several immune checkpoints are initiated by ligand-receptor interactions, they can be freely blocked by antibodies or modulated by recombinant forms of ligands or receptors. Antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) were the first immunotherapeutics that achieved the US Food and Drug Administration approval. Preliminary clinical results with the blockers of additional immune checkpoint proteins, such as programmed cell death protein 1 (PD-1) indicate extensive and different chances to boost antitumor immunity with the objective of conferring permanent clinical effects. This study provides an overview of the immune checkpoint pathways, including CTLA-4, PD-1, lymphocyte activation gene 3, T-cell immunoglobulin and mucin domain 3, B7-H3, and diacylglycerol kinase α and implications of their inhibition in the cancer therapy.

Role of miR-142 in the pathogenesis of osteosarcoma and its potential as therapeutic approach.

Osteosarcoma (OS) is the most common primary malignant tumor of the bone with a strong tendency to early metastasis, and occurs in growing bones more commonly in children and adolescents. Considering the limited therapeutic methods and lack of 100% success of these methods, developing innovative therapies with high efficacy and lower side effects is needed. Meanwhile, miRNAs and the studies indicating the involvement of miRNAs in OS development have attracted attentions as a result of the frequent abnormalities in expression of miRNAs in cancer. miRNAs are noncoding short sequences with lengths ranging from 18 to 25 nucleotides that play a very important role in cellular processes, such as proliferation, differentiation, migration, and apoptosis. MiRNAs can have either oncogenic or tumor suppressive role based on cellular function and targets. This review aimed to have overview on miR-142 as a tumor suppressor in OS. Moreover, the genes involved in the disease, such as RAC1, HMAG1, MMP9, MMP2, and E-cadherin, which have irregularities as a result of change in miR-142 expression, and, thereby, result in increasing the proliferation, invasion, and metastasis of the cells in the tissues and OS cells will be discussed.

A Two-Level Scheme for Quality Score Compression.

Previous studies on quality score compression can be classified into two main lines: lossy schemes and lossless schemes. Lossy schemes enable a better management of computational resources. Thus, in practice, and for preliminary analyses, bioinformaticians may prefer to work with a lossy quality score representation. However, the original quality scores might be required for a deeper analysis of the data. Hence, it might be necessary to keep them; in addition to lossy compression this requires lossless compression as well. We developed a space-efficient hierarchical representation of quality scores, QScomp, which allows the users to work with lossy quality scores in routine analysis, without sacrificing the capability of reaching the original quality scores when further investigations are required. Each quality score is represented by a tuple through a novel decomposition. The first and second dimensions of these tuples are separately compressed such that the first-level compression is a lossy scheme. The compressed information of the second dimension allows the users to extract the original quality scores. Experiments on real data reveal that the downstream analysis with the lossy part-spending only 0.49 bits per quality score on average-shows a competitive performance, and that the total space usage with the inclusion of the compressed second dimension is comparable to the performance of competing lossless schemes.

Platelet rich plasma, stromal vascular fraction and autologous conditioned serum in treatment of knee osteoarthritis.

Osteoarthritis (OA) is a multifactorial chronic disease, causing several problems on patients, hygiene and community care systems. Conventional therapies, such as non-pharmacological mediations, systemic drug treatment and intra-articular therapies are applying previously; however, controlling and management approaches of the disease mainly remain insufficient. Injections of intra-articular therapies directly into the joint evade conservative obstacles to joint entry, rise bioavailability and minor systemic toxicity. Current progresses in osteoarthritis management have designed better diversity of treatment approaches. Innovative treatments, such as autologous blood products and mesenchymal stem cells, are in progress. Platelet-rich plasma (PRP) is one of the several novel therapeutic approaches that stay to progress in the field of orthopedic medicine. Stromal vascular fraction (SVF) comprises a lesser amount of mesenchymal stem cells and is a treatment for OA and cartilage damage. Based on novel opinions, an innovative therapy by autologous conditioned serum (ACS) from the whole blood was settled. The inoculation of ACS into tissues has revealed clinical efficacy for the treatment of osteoarthritis and muscle injuries. Here, we make available historical perspective of PRP, SVF, and ACS and the other existing researches on using PRP, SVF and ACS for the treatment of knee OA. In conclusion, in current years, OA stem cell therapy has rapidly progressed, with optimistic consequences in animals and human studies. Additionally, PRP, SVF and ASC injection seem to be accompanied with numerous favorable results for treatment of patients with OA.

Modelling overdispersion in longitudinal count data in clinical trials with application to epileptic data.

A family of multi-level models with different types of random error components in the linear predictor is presented for analysing longitudinal count data in clinical trials. These models account for overdispersion, heterogeneity, serial correlation, and heteroscedasticity. The proposed models are applied to epileptic seizure count data and illustrated in a simulation study. The effects of omitted variables, link function, outliers, and initial conditions on overdispersion are investigated. It has been shown that proper introduction of the error component in the linear predictor overcomes the problem of overdispersion arising from the omitted variables. We use three model checking criteria deviance, variance inflation factor, and global goodness-of-fit tests based on Bayesian probability to identify the best structure of the error term in the linear predictor. Further, Markov Chain Monte Carlo method using Gibbs sampling is used as estimation approach.