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Tendon injuries present significant medical, social, and economic challenges globally. Despite advancements in tendon injury repair techniques, outcomes remain suboptimal due to inferior tissue quality and functionality. Tissue engineering offers a promising avenue for tendon regeneration, with biocompatible scaffolds playing a crucial role. Ostrich eggshell membrane (ESM), characterized by a strong preferential orientation of calcite crystals, forms a semipermeable polymer network with excellent mechanical properties compared to membranes from other bird species, emerging as a potential natural scaffold candidate. Coupled with platelet-rich plasma (PRP), known for its regenerative properties, ESM holds promise for improving tendon repair. This study aims to evaluate the biocompatibility and efficacy of an ESM-PRP scaffold in treating Achilles tendon ruptures, employing in vitro and in vivo assessments to gauge its potential in tendon regeneration in living organisms. Ostrich ESM was prepared from pathogen-free ostrich eggs, sterilized with UV radiation and prepared in desired dimensions before implantation (1.5 × 1 cm). High-resolution scanning electron microscopy (HRSEM) was utilized to visualize the sample morphology and fiber bonding. In vitro biocompatibility was assessed using the MTT assay and DAPI staining, while in vivo biocompatibility was evaluated in a rat model. For the in vivo Achilles tendinopathy assay, rats were divided into groups and subjected to AT rupture followed by treatment with ESM, PRP, or a combination. SEM was employed to evaluate tendon morphology, and real-time PCR was conducted to analyze gene expression levels. The in vivo assay indicated that the ESM scaffold was safe for an extended period of 8 weeks, showing no signs of inflammation based on histopathological analysis. In the Achilles tendon rupture model, combining ESM with PRP enhanced tendon healing after 14 weeks post-surgery. This finding was supported by histopathological, morphological, and mechanical evaluations of tendon tissues compared to normal tendons, untreated tendinopathy, and injured tendons treated with the ESM scaffold. Gene expression analysis revealed significantly increased expression of Col1a1, Col3a1, bFGF, Scleraxis (Scx), and tenomodulin in the ESM-PRP groups. The findings of our study demonstrate that the combination of Ostrich ESM with PRP significantly enhances AT repair and is a biocompatible scaffold for the application in living organisms., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All experimental protocols were approved by the Institutional Animal Care and the Ethics Committee of the Shiraz University of Medical Science. Also, the study was carried out in compliance in accordance with the relevant guidelines and regulations and the Declaration of Helsinki and also the ARRIVE guidelines., (© 2025. The Author(s).)

Introduction: Tranexamic acid (TXA) has been documented to reduce perioperative blood loss following orthopedic surgeries, such as total hip arthroplasty (THA). Previous studies focused on the best applicable dose and administration method to minimize blood loss. Although the surgical approach is another factor that may influence perioperative bleeding, no previous research has examined its concurrent impact alongside TXA. This meta-analysis investigated the effect of intravenous TXA on perioperative bleeding in primary THA, focusing on the surgical approach used., Method: The authors searched PubMed, Web of Science, Scopus, Embase, and the Cochrane Library through November 2022. Fourteen studies, comprising 1358 patients, were identified as suitable for inclusion in this meta-analysis. To assess perioperative bleeding, hemoglobin (Hb) decline, transfused blood products, total blood loss (TBL), and intraoperative blood loss (IOBL) were recorded., Results: The study showed that the lateral approach (LA) maintains the postoperative Hb level more effectively (WMD = 1.081, 95 % CI: 0.620-1.541). Significantly less IOBL was observed with the posterolateral approach (PLA; WMD = -70.578, 95 % CI: [-130.389] - [-10.766]). The posterior approach (PA) was associated with a reduction in TBL (WMD = -392, 95 % CI: [-474.439] - [-310.231], P-value <0.0001)., Conclusion: The surgical approach plays a significant role in blood management during surgery. Overall, the PLA resulted in the least IOBL, while the LA was associated with the least blood transfusion and a decline in Hb level. Additionally, the PA was linked to the lowest TBL., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Targeting tumor angiogenesis, the formation of new blood vessels supporting cancer growth and spread, has been an intense focus for therapy development. However, benefits from anti-angiogenic drugs like bevacizumab have been limited by resistance stemming from activation of compensatory pathways. Recent immunotherapy advances have sparked interest in novel immunologic approaches that can induce more durable vascular pruning and overcome limitations of existing angiogenesis inhibitors. This review comprehensively examines these emerging strategies, including modulating tumor-associated macrophages, therapeutic cancer vaccines, engineered nanobodies and T cells, anti-angiogenic cytokines/chemokines, and immunomodulatory drugs like thalidomide analogs. For each approach, the molecular mechanisms, preclinical/clinical data, and potential advantages over conventional drugs are discussed. Innovative therapeutic platforms like nanoparticle delivery systems are explored. Moreover, the importance of combining agents with distinct mechanisms to prevent resistance is evaluated. As tumors hijack angiogenesis for growth, harnessing the immune system's specificity to disrupt this process represents a promising anti-cancer strategy covered by this review., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

BACKGROUND Aside from the rarity of mobile spinal schwannomas, the coexistence of these tumors with herniated intervertebral disc is also scarce. Furthermore, cauda equina syndrome (CES), as a manifestation of intraspinal schwannomas has been reported rarely. Described here is a case of simultaneous lumbar disc bulge and mobile spinal schwannoma presented with intermittent symptoms of CES. CASE REPORT A 62-year-old man presented with severe but intermittent leg pain for 2 weeks, which later progressed to an episode of lower extremity weakness and difficulty in urination. Magnetic resonance imaging revealed an intraspinal tumor that moved in position relative to the L1-2 disc bulge on scans 6 h apart, with associated spontaneous regression in symptoms. The tumor was found to be a mobile spinal schwannoma, originated from a nerve root. A standard microdissection technique was used to remove the tumor through a spinous process-sparing unilateral approach, with complete laminectomy of L1. Use of intraoperative ultrasound facilitated the accurate tumor localization. Postoperatively, the patient no longer had symptoms. CONCLUSIONS This report presents a combination of a common spinal pathology, intervertebral disc herniation, alongside a rare condition, mobile spinal schwannoma, whose uncommon clinical manifestations, such as CES can cause irreversible neurological deficits. Surgeons need to remain vigilant of potential atypical scenarios when treating patients. Surgical treatment challenges regarding the mobility of tumors, such as accurate localization, should be addressed using intraoperative imaging to avoid wrong-level surgery. To mitigate the irreversible neurological complications, patients should receive comprehensive information for alarming signs of CES.

Advances in cancer immunotherapy over the last decade have led to the development of several agents that affect immune checkpoints. Inhibitory receptors expressed on T cells that negatively regulate the immune response include cytotoxic T‑lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1), which have been studied more than similar receptors. Inhibition of these proteins and other immune checkpoints can stimulate the immune system to attack cancer cells, and prevent the tumor from escaping the immune response. However, the administration of anti-PD1 and anti-CTLA4 antibodies has been associated with adverse inflammatory responses similar to autoimmune diseases. The current review discussed the role of the NF-κB pathway as a tumor promoter, and how it can govern inflammatory responses and affect various immune checkpoints. More precise knowledge about the communication between immune checkpoints and NF-κB pathways could increase the effectiveness of immunotherapy and reduce the adverse effects of checkpoint inhibitor therapy., (© 2024. The Author(s).)

Colorectal cancer (CRC) and gastric cancer (GC), are the two most common cancers of the gastrointestinal tract, and are serious health concerns worldwide. The discovery of more effective biomarkers for early diagnosis, and improved patient prognosis is important. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), can regulate cellular processes such as apoptosis and the epithelial-mesenchymal transition (EMT) leading to progression and resistance of GC and CRC tumors. Moreover these pathways (apoptosis and EMT) may serve as therapeutic targets, to prevent metastasis, and to overcome drug resistance. A subgroup of ncRNAs is common to both GC and CRC tumors, suggesting that they might be used as biomarkers or therapeutic targets. In this review, we highlight some ncRNAs that can regulate EMT and apoptosis as two opposite mechanisms in cancer progression and metastasis in GC and CRC. A better understanding of the biological role of ncRNAs could open up new avenues for the development of personalized treatment plans for GC and CRC patients.

Introduction: In spite of the results of previous studies regarding the benefits of ultrasonography for diagnosis of elbow fractures in children, the exact accuracy of this imaging modality is still under debate. Therefore, in this diagnostic systematic review and meta-analysis, we aimed to investigate the accuracy of ultrasonography in this regard., Methods: Two independent reviewers performed systematic search in Web of Science, Embase, PubMed, Cochrane, and Scopus for studies published from inception of these databases to May 2023. Quality assessment of the included studies was performed using Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). Meta-Disc software version 1.4 and Stata statistical software package version 17.0 were used for statistical analysis., Results: A total of 648 studies with 1000 patients were included in the meta-analysis. The pooled sensitivity and specificity were 0.95 (95% CI: 0.93-0.97) and 0.87 (95% CI: 0.84-0.90), respectively. Pooled positive likelihood ratio (PLR) was 6.71 (95% CI: 3.86-11.67), negative likelihood ratio (NLR) was 0.09 (95% CI: 0.03-0.22), and pooled diagnostic odds ratio (DOR) of ultrasonography in detection of elbow fracture in children was 89.85 (95% CI: 31.56-255.8). The area under the summary receiver operating characteristic (ROC) curve for accuracy of ultrasonography in this regard was 0.93. Egger's and Begg's analyses showed that there is no significant publication bias (P=0.11 and P=0.29, respectively)., Conclusion: Our meta-analysis revealed that ultrasonography is a relatively promising diagnostic imaging modality for identification of elbow fractures in children. However, clinicians employing ultrasonography for diagnosis of elbow fractures should be aware that studies included in this meta-analysis had limitations regarding methodological quality and are subject to risk of bias. Future high-quality studies with standardization of ultrasonography examination protocol are required to thoroughly validate ultrasonography for elbow fractures., Competing Interests: None.

Introduction: Differentiating the soft tissue abscess from other types of skin and soft tissue infections (SSTIs) poses a particular challenge because they have similar physical evaluation findings, but each disease has a different course, outcome, and treatment. This meta-analysis aimed to investigate the diagnostic accuracy of point-of-care ultrasonography for diagnosis of soft tissue abscess in the emergency departments., Methods: A comprehensive literature search of MEDLINE, Scopus, Web of Science, Embase, and Google Scholar, from inception to January 2023, was conducted to identify relevant studies investigating the diagnostic performance of point-of-care ultrasonography for identification of abscess. Methodological quality of the included studies was assessed using a revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2)., Results: The pooled estimates of diagnostic parameters of ultrasonography for diagnosis of abscess were as follows: sensitivity, 0.93 (95% CI: 0.92-0.94); specificity, 0.87 (95% CI: 0.85-0.89), and the area under the summary receiver-operating characteristic (SROC), 0.95. The pooled sensitivity, specificity, and area under the SROC of studies in adult patients were 0.98 (95% CI: 0.92-1), 0.92 (95% CI: 0.86-0.95), and 0.99, respectively. The pooled sensitivity, specificity, and area under the SROC of studies in pediatric patients were 0.9 (95% CI: 0.87-0.92), 0.78 (95% CI: 0.73-0.82), and 0.91, respectively., Conclusion: Our meta-analysis demonstrated that the point-of-care ultrasonography has excellent diagnostic value for the abscess in the emergency department. Furthermore, we found that the diagnostic performance of point-of-care ultrasonography for diagnosis of abscess was higher for adult cases than for pediatric patients., Competing Interests: None.

Introduction: In order to improve the efficacy of requesting knee radiography and reduce unnecessary radiation exposure, some clinical decision rules have been proposed for the assessment of knee injuries. Among them, the Ottawa Knee Rule (OKR) was considered as one of the best guidelines with several validation studies. Therefore, in this meta-analysis, we aimed to investigate the accuracy of OKR for diagnosis of fracture in patients presenting with knee trauma., Methods: A systematic search was conducted in PubMed, Web of Science, Scopus, Google Scholar, and EBSCO from inception to September 2022. Quality assessment of the included studies was performed using QUADAS-2 tool. Diagnostic accuracy parameters were analyzed using random-effects model. Statistical analysis was performed using Meta-Disc and Stata softwares., Results: The meta-analysis of the 18 included studies (6702 patients) showed that the pooled sensitivity and specificity of OKR for diagnosis of fractures were 0.98 (95% CI: 0.96-0.99) and 0.43 (95% CI: 0.42-0.45), respectively. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 1.56 (95% CI: 1.39-1.75) and 0.12 (95% CI: 0.05-0.26), respectively. The area under curve (AUC) of the hierarchical summary receiver operating characteristic (HSROC) curve was 0.54., Conclusion: This meta-analysis indicates that OKR has a high diagnostic performance for diagnosis of fracture, with a pooled sensitivity of 98% and a pooled specificity of 43%. These results propose potential effects of OKR on reduction of unnecessary radiography, time spent in emergency departments, and direct and indirect costs, which should be confirmed using high-quality studies in the future., Competing Interests: None.

Targeted therapy is a new cancer treatment approach, involving drugs that particularly target specific proteins in cancer cells, such as receptor tyrosine kinases (RTKs) which are involved in promoting growth and proliferation, Therefore inhibiting these proteins could impede cancer progression. An understanding of RTKs and the relevant signaling cascades, has enabled the development of many targeted drug therapies employing RTK inhibitors (RTKIs) some of which have entered clinical application. Here we discuss RTK structures, activation mechanisms and functions. Moreover, we cover the potential effects of combination drug therapy (including chemotherapy or immunotherapy agents with one RTKI or multiple RTKIs) especially for drug resistant cancers., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Exosomes are membranous vesicles with a 30 to 150 nm diameter secreted by mesenchymal stem/stromal cells (MSCs) and other cells, such as immune cells and cancer cells. Exosomes convey proteins, bioactive lipids, and genetic components to recipient cells, such as microRNAs (miRNAs). Consequently, they have been implicated in regulating intercellular communication mediators under physiological and pathological circumstances. Exosomes therapy as a cell-free approach bypasses many concerns regarding the therapeutic application of stem/stromal cells, including undesirable proliferation, heterogeneity, and immunogenic effects. Indeed, exosomes have become a promising strategy to treat human diseases, particularly bone- and joint-associated musculoskeletal disorders, because of their characteristics, such as potentiated stability in circulation, biocompatibility, low immunogenicity, and toxicity. In this light, a diversity of studies have indicated that inhibiting inflammation, inducing angiogenesis, provoking osteoblast and chondrocyte proliferation and migration, and negative regulation of matrix-degrading enzymes result in bone and cartilage recovery upon administration of MSCs-derived exosomes. Notwithstanding, insufficient quantity of isolated exosomes, lack of reliable potency test, and exosomes heterogeneity hurdle their application in clinics. Herein, we will deliver an outline respecting the advantages of MSCs-derived exosomes-based therapy in common bone- and joint-associated musculoskeletal disorders. Moreover, we will have a glimpse the underlying mechanism behind the MSCs-elicited therapeutic merits in these conditions., (© 2023. The Author(s).)

Colorectal cancer (CRC) is the third cause of cancer death worldwide. Although, in some cases, treatment can increase patient survival and reduce cancer recurrence, in many cases, tumors can develop resistance to therapy leading to recurrence. One of the main reasons for recurrence and therapy resistance is the presence of cancer stem cells (CSCs). CSCs possess a self-renewal ability, and their stemness properties lead to the avoidance of apoptosis, and allow a new clone of cancer cells to emerge. Numerous investigations inidicated the involvment of cellular signaling pathways in embryonic development, and growth, repair, and maintenance of tissue homeostasis, also participate in the generation and maintenance of stemness in colorectal CSCs. This review discusses the role of Wnt, NF-κB, PI3K/AKT/mTOR, Sonic hedgehog, and Notch signaling pathways in colorectal CSCs, and the possible modulating drugs that could be used in treatment for resistant CRC., Competing Interests: Conflicts of interest MRH declares the following potential conflicts of interest. Scientific Advisory Boards: Transdermal Cap Inc, Cleveland, OH; Hologenix Inc. Santa Monica, CA; Vielight, Toronto, Canada; JOOVV Inc, Minneapolis-St. Paul MN; Consulting; USHIO Corp, Japan; Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany. The other authors have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

N6-methyladenosine (m 6 A) modification is the most abundant post-transcriptional regulation of RNAs in eukaryotes. Dysregulation of m 6 A readers, writers, and erasers can significantly promote tumorigenesis by altering the expression of various genes. Wnt/β-catenin is an evolutionarily conserved signaling pathway that has recently been linked to the pathogenesis of many cancers. Given the significance of this pathway in regulating normal tissue homeostasis and stem cell differentiation, a subtle understanding of the molecular mechanism underlying its dysregulation is required for effective targeting. There is mounting evidence that m 6 A regulators are highly implicated in the dysregulation of the Wnt/β-catenin signaling pathway. Since m 6 A regulators can affect Wnt pathway components and dysregulation of either leads to carcinogenesis, this study aims to clarify the relationship between m 6 A regulators and the Wnt/β-catenin signaling pathway to investigate their combined impact on tumorigenesis., Competing Interests: Conflict of interest statement The authors have no conflicts of interest to declare that they are relevant to the content of this article., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Autoimmune disease, caused by unwanted immune responses to self-antigens, affects millions of people each year and poses a great social and economic burden to individuals and communities. In the course of autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and multiple sclerosis, disturbances in the balance between the immune response against harmful agents and tolerance towards self-antigens lead to an immune response against self-tissues. In recent years, various regulatory immune cells have been identified. Disruptions in the quality, quantity, and function of these cells have been implicated in autoimmune disease development. Therefore, targeting or engineering these cells is a promising therapeutic for different autoimmune diseases. Regulatory T cells, regulatory B cells, regulatory dendritic cells, myeloid suppressor cells, and some subsets of innate lymphoid cells are arising as important players among this class of cells. Here, we review the roles of each suppressive cell type in the immune system during homeostasis and in the development of autoimmunity. Moreover, we discuss the current and future therapeutic potential of each one of these cell types for autoimmune diseases., Competing Interests: ARA was employed by Xsphera Biosciences. LF is an inventor in patents and patent applications pertaining to the use of immune regulatory cells for therapy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 Ghobadinezhad, Ebrahimi, Mozaffari, Moradi, Beiranvand, Pournazari, Rezaei-Tazangi, Khorram, Afshinpour, Robino, Aref and Ferreira.)

In the present study, it is attempted to scrutinize the properties of the maghemite nanoparticle as a Carmustine drug delivery system by means of the density functional theory calculations regarding their geometries, adsorption energies, vibrational frequencies, and topological features of the electron density. Based on the density functional theory results, it is found that the interaction between Carmustine drug molecule and maghemite nanoparticle is weak; so that, the adsorption of the Carmustine drug is typically physisorption. It is also found that the intermolecular hydrogen bonds between the drug and the nanoparticle play the significant role in the stability of the physisorption configurations. The nature of the intermolecular interactions has been explored by calculation of the electron densities and their Laplacian at the bond critical points using Atoms-in-Molecule theory. Moreover, natural bond orbital analysis indicates that the Carmustine molecule can be adsorbed on the nanoparticle surface with a charge transfer from the Carmustine drug to the nanoparticle.