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Testicular tumors (TTs) are rare in children, posing diagnostic and therapeutic challenges. This retrospective study evaluates the diagnostic and prognostic utility of SALL4 and OCT3/4 in pediatric TTs. We analyzed 18 cases of different types of TTs using immunohistochemistry (IHC) to assess SALL4 (Spalt-like transcription factor 4) and OCT3/4 (Octamer binding transcription factor 3/4) expression. SALL4 was positive in 83.3% of tumors, while OCT3/4 was positive in 38.9% of tumors, with a significantly higher prevalence in patients aged 12-18 years compared to those aged 0-11 years (p = 0.013). Mixed germinal cell tumors were significantly more frequently associated with OCT3/4 (p = 0.003), and a high immunostaining expression for SALL4 was observed primarily in yolk sac tumors and embryonal carcinoma. Our findings suggest that SALL4 and OCT3/4 immunostaining can aid in accurate diagnosis and treatment planning, and underscores the importance of OCT3/4 as a predictive factor in pediatric testicular tumors, highlighting its substantial correlation with tumor type and its impact on treatment response. These markers may guide personalized therapeutic strategies, potentially improving patient outcomes.
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Pediatric ovarian tumors exhibit unique diagnostic and therapeutic challenges. This study evaluates the expression of SALL4 and OCT3/4 biomarkers in pediatric ovarian tumors and their associations with tumor subtype, stage, and clinical outcome. A retrospective analysis was conducted on 64 patients under 18 years old, examining demographic data, tumor characteristics, immunohistochemical staining, and clinical outcomes. Our results show that SALL4 was significantly expressed in adenocarcinoma, dysgerminoma (DSG), mixed germ cell tumors (GCTs), and immature teratoma, while OCT3/4 was highly expressed in DSG and mixed GCTs. Both markers are associated with a higher tumor grade and stage, indicating a more aggressive disease. The SALL4 positivity expression was correlated with high alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) levels, while OCT3/4 positivity significantly predicted the risk of subsequent metastasis. The mean progression-free survival (PFS) was notably shorter in patients with positive markers. These findings underscore the diagnostic and prognostic value of SALL4 and OCT3/4 in pediatric ovarian tumors, aligning with previous research and supporting their use in clinical practice for better disease management and patient outcomes.
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Biomarcadores Tumorais , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Biomarcadores Tumorais/metabolismo , Criança , Adolescente , Pré-Escolar , Estudos Retrospectivos , Prognóstico , Fator 3 de Transcrição de Octâmero/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Romênia/epidemiologia , Lactente , Fatores de Transcrição/metabolismo , Teratoma/metabolismo , Teratoma/diagnóstico , Teratoma/patologia , Teratoma/genéticaRESUMO
Although CAR-T cell therapy has emerged as a game-changer in cancer immunotherapy several bottlenecks limit its widespread use as a front-line therapy. Current protocols for the production of CAR-T cells rely mainly on the use of lentiviral/retroviral vectors. Nevertheless, according to the safety concerns around the use of viral vectors, there are several regulatory hurdles to their clinical use. Large-scale production of viral vectors under "Current Good Manufacturing Practice" (cGMP) involves rigorous quality control assessments and regulatory requirements that impose exorbitant costs on suppliers and as a result, lead to a significant increase in the cost of treatment. Pursuing an efficient non-viral method for genetic modification of immune cells is a hot topic in cell-based gene therapy. This study aims to investigate the current state-of-the-art in non-viral methods of CAR-T cell manufacturing. In the first part of this study, after reviewing the advantages and disadvantages of the clinical use of viral vectors, different non-viral vectors and the path of their clinical translation are discussed. These vectors include transposons (sleeping beauty, piggyBac, Tol2, and Tc Buster), programmable nucleases (ZFNs, TALENs, and CRISPR/Cas9), mRNA, plasmids, minicircles, and nanoplasmids. Afterward, various methods for efficient delivery of non-viral vectors into the cells are reviewed.
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Vetores Genéticos , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Animais , Linfócitos T/imunologia , Terapia Genética/métodos , Neoplasias/terapiaRESUMO
Introduction: Intra-abdominal cystic formations represent heterogeneous pathologies with varied localization and clinical manifestation. The first challenge of a giant intra-abdominal cystic lesion is identifying the organ of origin. The clinical presentation of intra-abdominal cystic lesions varies from acute manifestations to non-specific symptoms or accidental discovery. Case presentation: A 2-year-old girl presents to the emergency unit with a fever of 38.5 Celsius, loss of appetite, and apathy. The investigations showed a gigantic intra-abdominal mass whose organ belonging could not be specified. Postoperatively, a giant mesenteric lymphangioma was evident, which was completely excised. Discussion: Giant cystic formations modify the anatomical reports and become space-replacing formations, and the starting point is even more challenging to assess preoperatively. Nevertheless, the careful evaluation of the characteristics of the formation, the effect on the adjacent organs, the age of the patient, and the clinical picture can provide elements of differential diagnosis. The stated purpose of this work is to systematize intra-abdominal lesions according to the organ of origin and to make the preoperative diagnosis of an intra-abdominal cystic lesion in the pediatric patient easy to perform starting from the presented case.
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BACKGROUND: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there have been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. MATERIALS AND METHODS: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study, with data collected over a span of eight years, and with the aim of analyzing the types of injury and treatment methods in relation to age and sex, while also focusing on the duration of hospitalization and the occurrence of complications. RESULTS: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (COVID-19), the cases underwent a substantial decline of approximately 60%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 17.3% of the total cases experienced complications. CONCLUSIONS: According to our findings, age has a significant effect on the type of accident (p < 0.05). Complications occurred in 17.3% of patients, most commonly surgical (24 cases, 38.7%), orthopedic (17 cases, 27.4%), and neurological (15 cases, 24.2%).
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Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell-cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC.
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Neoplasias Colorretais , Exossomos , Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Comunicação Celular , Microambiente TumoralRESUMO
Cystic fibrosis (CF) is primarily known for its pulmonary consequences, which are extensively explored in the existing literature. However, it is noteworthy that individuals with CF commonly display gastrointestinal (G-I) manifestations due to the substantial presence of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the intestinal tract. Recognized as pivotal nonpulmonary aspects of CF, G-I manifestations exhibit a diverse spectrum. Identifying and effectively managing these manifestations are crucial for sustaining health and influencing the overall quality of life for CF patients. This review aims to synthesize existing knowledge, providing a comprehensive overview of the G-I manifestations associated with CF. Each specific G-I manifestation, along with the diagnostic methodologies and therapeutic approaches, is delineated, encompassing the impact of innovative treatments targeting the fundamental effects of CF on the G-I tract. The findings underscore the imperative for prompt diagnosis and meticulous management of G-I manifestations, necessitating a multidisciplinary team approach for optimal care and enhancement of the quality of life for affected individuals. In conclusion, the authors emphasize the urgency for further clinical studies to establish a more robust evidence base for managing G-I symptoms within the context of this chronic disease. Such endeavors are deemed essential for advancing understanding and refining the clinical care of CF patients with G-I manifestations.
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Exosomes are nanometric membrane vesicles of late endosomal origin that are released by most, if not all, cell types as a sophisticated means of intercellular communication. They play an essential role in the movement of materials and information between cells, transport a variety of proteins, lipids, RNA, and other vital data, and over time, they become an essential part of the drug delivery system and a marker for the early detection of many diseases. Dendritic cells have generated interest in cancer immunotherapy due to their ability to initiate and modify effective immune responses. Apart from their cytokine release and direct interactions with other cell types, DCs also emit nanovesicles, such as exosomes, that contribute to their overall activity. Numerous studies have demonstrated exosomes to mediate and regulate immune responses against cancers. Dendritic cell-derived exosomes (DCs) have attracted a lot of attention as immunotherapeutic anti-cancer treatments since it was found that they contain functional MHC-peptide complexes along with a variety of other immune-stimulating components that together enable immune cell-dependent tumor rejection. By enhancing tumor and immunosuppressive immune cells or changing a pro-inflammatory milieu to inhibit tumor advancement, exosomes generated from dendritic cells can initiate and support tumor growth. This study reviewed the immunogenicity of dendritic cell-derived exosomes and strategies for expanding their immunogenic potential as novel and effective anti-cancer therapies.
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Exossomos , Neoplasias , Humanos , Exossomos/genética , Células Dendríticas , Neoplasias/patologia , Imunidade , ImunoterapiaRESUMO
In the immunological surveillance against cancer, natural killer (NK) cells are essential effectors that help eradicate altered cells. The complex interactions that occur between NK cells and the tumor microenvironment (TME) are thoroughly examined in this review. The review examines how cytokine stimulation affects NK cell activation, focusing on the dynamic modulation of NK cell function within the TME. It looks at NK cell-related biomarkers such as PD-1/PD-L1, methylation HOXA9 (Homeobox A9), Stroma AReactive Invasion Front Areas (SARIFA), and NKG2A/HLA-E, providing critical information about prognosis and treatment outcomes. The changing landscape of immunotherapies-including checkpoint inhibitors, CAR-NK cells, and cytokine-based interventions-is examined in the context of enhancing NK cell activity. The review highlights the potential pathways for precision medicine going forward, focusing on customized immunotherapies based on unique biomarker profiles and investigating combination medicines to produce more robust anti-tumor responses.
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Neoplasias , Microambiente Tumoral , Humanos , Vigilância Imunológica , Células Matadoras Naturais , Neoplasias/patologia , Citocinas/metabolismoRESUMO
It is becoming more and more apparent that many of the genetic alterations associated with cancer are located in areas that do not encode proteins. lncRNAs are a class of RNAs that do not code for proteins but play a crucial role in maintaining cell function and regulating various cellular processes. By doing this, they have recently introduced what may be a brand-new and essential layer of biological control. These have more than 200 nucleotides and are linked to several diseases; as a result, they have become potential tools for therapeutic intervention. Emerging technologies suggest the presence of mutations on genomic loci that give rise to lncRNAs rather than proteins in a disease as complex as cancer. These lncRNAs play essential parts in gene regulation, which impacts several cellular homeostasis processes, including proliferation, survival, migration, and genomic stability. The leading cause of death in the world today is cancer. Delays in diagnosis and a lack of standard and efficient treatments are the leading causes of the high death rate. Clinically, surgery is frequently used successfully to remove cancers that have not spread, but it is less successful in treating metastatic cancer, which has a drastically lower chance of survival. Chemotherapeutic drugs are a typical therapy to treat the cancer that has spread to other organs. Drug resistance to chemotherapy, however, presents a significant challenge to achieving positive outcomes and is frequently the cause of treatment failure. A substantial barrier to progress in medical oncology is cancer drug resistance. Resistance can develop clinically either before or after cancer treatment. According to this study, lncRNAs influence drug resistance through several different methods. LncRNAs often impact drug resistance by controlling the expression of a few intermediary regulatory variables rather than by directly affecting drug resistance. Additionally, lncRNAs have a variety of roles in cancer medication resistance. Most lncRNAs induce drug resistance when overexpressed; however, other lncRNAs have inhibitory effects. This study provides an overview of the current understanding of lncRNAs, relevance to cancer, and potential therapeutic applications.
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Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Transdução de Sinais/genéticaRESUMO
Traffic accidents involving children and adolescents present complex challenges from both the medico-legal and orthopedic standpoints. Despite the implementation of road traffic safety laws, pediatric road traffic injuries continue to be a significant contributor to mortality rates, physical harm, and hospitalization on a global scale. For children and young people, automobile accidents are considered to be the primary culprit of mortality in developed nations. Even in highly developed nations, trauma is a significant factor in infant mortality. Each age category, from childhood to young adulthood, has its fracture patterns, as their skeletons are considerably different from those of adults. The consequences of traffic accidents extend beyond the immediate physical trauma. The medico-legal aspects surrounding these incidents add another layer of complexity, as legal repercussions may affect the responsible adult or parent, particularly in cases involving child fatalities. To effectively address traffic accidents in children and adolescents, a comprehensive approach is necessary. This approach should involve not only medical professionals but also legal experts and policymakers. Collaboration between orthopedic specialists, medico-legal professionals, law enforcement agencies, and relevant government bodies can facilitate the development and implementation of strategies aimed at prevention, education, the enforcement of traffic laws, and improved infrastructure. By addressing both the medical and legal aspects, it is possible to enhance road safety for children and adolescents, reducing the incidence of injuries and their associated long-term consequences. In this review, we aimed to summarize traffic accidents in children and adolescents from a complex orthopedic and medico-legal approach.
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BACKGROUND: Pediatric road traffic accidents (RTAs) have a substantial impact on the worldwide youth population, resulting in a considerable burden of disability. According to the World Health Organization's (WHO) Global Status Report on Road Safety, around 1.35 million children die each year in RTAs around the world, having a big effect on health and financial costs. Today's high-income countries like the Netherlands have experienced a decrease in the incidence of fatal traffic accidents (TAs) in children compared to countries with higher-than-average scores, including Romania, where roughly one out of every two minor deaths was a pedestrian; however, there is a lack of comprehensive and up-to-date epidemiological data on non-fatal TAs regarding pediatric patients. The objective of this study is to perform a thorough examination of the epidemiological aspects of Tas in pediatric patients admitted to the Emergency Department (ED) of "St. Mary's" Emergency Clinical Hospital for Children in Iasi, Romania. MATERIALS AND METHODS: A descriptive retrospective research study was conducted at the "St. Mary's" Emergency Clinical Hospital for Children in Iasi, Romania, from January 2015 to December 2022. The research population includes all pediatric trauma patients that were between the age range of 1 month and 18 years who were treated by the trauma department. A total of 358 cases met the inclusion criteria and fulfilled fulfilled fulfilled. Data concerning variables such as accident incidents, types of injuries, and length of hospitalization have been gathered. RESULTS: The average age of the patients was 11.43 ± 4.07 years, with patients of both sexes, the representation of the male sex being 78.5%. The incidence occurred during the summer, representing 15.3% in June. Of the patients admitted to the ED, 55.5% (n = 196) did not require surgery. Most of the patients spent from a minimum of one day to a maximum of 28 days in the hospital, with an average of 8.50 hospital days. The most common injuries were fractures (n = 221), and the most frequent anatomical region affected was the upper limbs (n = 55.2%). CONCLUSION: While the literature on fatal TA cases shows a declining trend, there is a lack of up-to-date information on non-fatal TAs involving children. The results of our study suggest that there is a high incidence of pediatric TAs due to the scale of "St. Mary's" Emergency Clinical Hospital for Children, from Iasi, which provides medical services to a considerable number of patients coming from both rural and urban areas of the seven counties of Moldova region, in Romania.
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Current genome-wide studies have indicated that a great number of long non-coding RNAs (lncRNAs) are transcribed from the human genome and appeared as crucial regulators in a variety of cellular processes. Many studies have displayed a significant function of lncRNAs in the regulation of autophagy. Autophagy is a macromolecular procedure in cells in which intracellular substrates and damaged organelles are broken down and recycled to relieve cell stress resulting from nutritional deprivation, irradiation, hypoxia, and cytotoxic agents. Autophagy can be a double-edged sword and play either a protective or a damaging role in cells depending on its activation status and other cellular situations, and its dysregulation is related to tumorigenesis in various solid tumors. Autophagy induced by various therapies has been shown as a unique mechanism of resistance to anti-cancer drugs. Growing evidence is showing the important role of lncRNAs in modulating drug resistance via the regulation of autophagy in a variety of cancers. The role of lncRNAs in drug resistance of cancers is controversial; they may promote or suppress drug resistance via either activation or inhibition of autophagy. Mechanisms by which lncRNAs regulate autophagy to affect drug resistance are different, mainly mediated by the negative regulation of micro RNAs. In this review, we summarize recent studies that investigated the role of lncRNAs/autophagy axis in drug resistance of different types of solid tumors.
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MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Autofagia/genética , Resistência a MedicamentosRESUMO
Developmental dysplasia of the hip (DDH) is a condition that includes a wide spectrum of anomalies ranging from simple instability with ligamentous hyperlaxity to the complete displacement of the femoral head outside the abnormally developed cotyloid cavity. Early detection and initiation of treatment allow "restitutio ad integrum" healing, which has raised the medical community's interest in early diagnosis. However, in countries with limited material resources, where echographic screening is not performed, efforts are being made to increase the sensitivity of clinical screening. Thus, the concept of "hip at risk" is taking shape worldwide. This is the normal clinical hip, but associated with one or more risk factors. We conducted a retrospective study for the period 2010-2015 with patients who presented in the ambulatory clinic of the St. John Children's Clinical Hospital, Galati. The study included 560 patients, who were all examined clinically and sonographically, according to the Graf method, by a senior orthopedic doctor with competence in hip sonography. The data obtained from the anamnesis, clinical examination, and ultrasound examination were recorded in the DDH file. The goal of the statistical analysis of the group of patients was to find a correlation between DDH and the risk factors used in the clinical detection of this pathology. In the studied group, four risk factors were identified that have an increased association with DDH: female sex, pelvic presentation, limitation of coxo-femoral abduction, and congenital clubfoot; thus, the conclusion of the study is that patients who have at least one of the listed risk factors should be examined sonographically as quickly as possible. The early ultrasound examination will allow the identification of the disease and the initiation of treatment.
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Background: Clubfoot is a congenital deformity that can affect one or both of a newborn's lower extremities. The main objective of the study is to evaluate and compare the outcomes of the Ponseti method for the management of different types of clubfoot. Methods: A retrospective analysis of 151 children with 253 clubfeet (idiopathic untreated, idiopathic recurrent, and syndromic) with at least one year of follow-up was conducted in four months after ethical approval. Data were collected with a structured proforma after the consent of the parents. An independent sample t-test was applied to show the comparison between the groups, and a p-value of 0.05 was considered significant. Results: Out of 151 patients, 76% were male and 24% were female. Out of a total of 235 feet, 96 (63%) were idiopathic untreated, 40 (26.5%) were idiopathic recurrent, and 15 (9.5%) were syndromic clubfoot. The average number of casts was higher in syndromic clubfoot (9 casts per foot). There was no significant difference in the baseline Pirani score of the three groups (p-value > 0.05); but after one year of follow-up, there was a significant difference in the Pirani score of idiopathic and syndromic clubfoot (p-value ≤ 0.05) and between recurrent clubfoot and syndromic clubfoot (p-value = 0.01). Conclusions: The aetiology of syndromic clubfoot affects the outcomes of the Ponseti method and leads to relapse. In idiopathic (untreated and recurrent) clubfoot, the Ponseti method does not produce a significant difference in outcome. Poor brace compliance and a lack of tenotomy lead to orthotic (ankle foot orthosis AFO and foot orthosis FO) use in the day time and the recurrence of clubfoot deformity in these three types of clubfoot.
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Objective: The present study aimed to compare electrocardiographic (ECG) parameters of amputee football players (AF) with football players without disability (FP) and sedentary individuals without disability (SI). Methods: A total of 32 participants (AF = 9, FP = 11, SI = 12) were included in the study. ECG parameters including P-wave amplitude, P-wave duration, PR interval, QRS duration, RR interval, QT interval, corrected-QT interval (QTc), ST segment duration, Tp-e duration, Tp-e/QT and Tp-e/QTc ratios were assessed in all the study participants by using a 12-lead ECG device. OneWay ANOVA Test was used for statistical analysis. Results: Of all ECG parameters, P-wave amplitude and QTc were significantly higher in the AF group in comparison to FP and SI groups. QRS duration was found to be lower in the AF group when compared to FP and SI groups. Myocardial repolarization parameters including Tp-e duration, Tp-e/QT and Tp-e/QTc ratios were similar between groups, as were other parameters such as P-wave duration, PR interval, RR interval, QRS duration and QT interval. Conclusion: It was found that some ECG parameters of amputee football players differ from those with non-disabled players and non-disabled sedentary individuals. These different parameters were within normal limits.
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Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix's structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM. Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions. Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1ß, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1ß, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway. Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression.
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Exosomes are now significant players in both healthy and unhealthy cell-to-cell communication. Exosomes can mediate immune activation or immunosuppression, which can influence the growth of tumors. Exosomes affect the immune responses to malignancies in various ways by interacting with tumor cells and the environment around them. Exosomes made by immune cells can control the growth, metastasis, and even chemosensitivity of tumor cells. In contrast, exosomes produced by cancer cells can encourage immune responses that support the tumor. Exosomes carry circular RNAs, long non-coding RNAs, and microRNAs (miRNAs), all involved in cell-to-cell communication. In this review, we focus on the most recent findings concerning the role of exosomal miRNAs, lncRNAs, and circRNAs in immune modulation and the potential therapeutic implications of these discoveries.
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MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , MicroRNAs/genética , Neoplasias/genética , Neoplasias/terapia , Comunicação Celular , RNA Circular/genética , RNA Longo não Codificante/genéticaRESUMO
Wound healing is a dynamic and complicated process containing overlapping phases. Presently, definitive therapy is not available, and the investigation into optimal wound care is influenced by the efficacy and cost-effectiveness of developing therapies. Accumulating evidence demonstrated the potential role of mesenchymal stem/stromal cell (MSC) therapy in several tissue injuries and diseases due to their high proliferation and differentiation abilities along with an easy collection procedure, low tumorigenesis, and immuno-privileged status. MSCs have also accelerated wound repair in all phases through their advantageous properties, such as accelerating wound closure, improving re-epithelialization, elevating angiogenesis, suppressing inflammation, and modulating extracellular matrix (ECM) remodeling. In addition, the beneficial therapeutic impacts of MSCs are largely associated with their paracrine functions, including extracellular vesicles (EVs). Exosomes and microvesicles are the two main subgroups of EVs. These vesicles are heterogeneous bilayer membrane structures that contain several proteins, lipids, and nucleic acids. EVs have emerged as a promising alternative to stem cell-based therapies because of their lower immunogenicity, tumorigenicity, and ease of management. MSCs from various sources have been widely investigated in skin wound healing and regeneration. Considering these features, in this review, we highlighted recent studies that the investigated therapeutic potential of various MSCs and MSC-EVs in skin damages and wounds.
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Exossomos , Vesículas Extracelulares , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Vesículas Extracelulares/metabolismo , Exossomos/metabolismo , Cicatrização , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
Diamond-Blackfan anemia is a rare (6-7 million live births), inherited condition manifesting as severe anemia due to the impaired bone marrow production of red blood cells. We present the unusual case of a six month old infant with a de novo mutation of the RPS19 gene causing Diamond-Blackfan anemia who additionally suffers from severe sinus bradycardia. The infant was diagnosed with this condition at the age of four months; at the age of 6 months, she presents with severe anemia causing hypoxia which, in turn, caused severe dyspnea and polypnea, which had mixed causes (hypoxic and infectious) as the child was febrile. After correction of the overlapping diarrhea, metabolic acidosis, and severe anemia (hemoglobin < 3 g/dL), she developed severe persistent sinus bradycardia immediately after mild sedation (before central venous catheter insertion), not attributable to any of the more frequent causes, with a heart rate as low as 49 beats/min on 24 h Holter monitoring, less than the first percentile for age, but with a regular QT interval and no arrhythmia. The echocardiogram was unremarkable, showing a small interatrial communication (patent foramen ovale with left-to-right shunting), mild left ventricular hypertrophy, normal systolic and diastolic function, and mild tricuspid regurgitation. After red cell transfusion and appropriate antibiotic and supportive treatment, the child's general condition improved dramatically but the sinus bradycardia persisted. We consider this a case of well-tolerated sinus bradycardia and foresee a good cardiologic prognosis, while the hematologic prognosis remains determined by future corticoid response, treatment-related complications and risk of leukemia.