Search Results (17,930)

Background: Pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) face several risk factors influencing transplantation success, including nutritional status as measured by body mass index (BMI). Methods: This study analyzed BMI data collected from patients transplanted between 2003 and 2023, and aimed to evaluate whether deviations from normal BMI are associated with poorer clinical outcomes. BMI levels assessed before and after first-line treatment and pre-transplantation were analyzed retrospectively to determine a correlation with survival and post-transplant complications. Results: Underweight patients had significantly lower 12- and 36-month overall survival rates compared to normal-weight and overweight patients (p = 1.22 × 10⁻⁸ and p = 8.88 × 10⁻⁸, respectively). Event-free survival was also lower for underweight patients at all time points. A higher pre-transplant BMI increases the risk of acute graft-versus-host disease (GVHD, p = 0.00068). Otherwise, pre-transplant BMI was not significantly correlated with early TRCs and cGVHD. As secondary objectives, this study identified differences in BMI across primary disease groups, with solid tumor patients having the highest BMI and myelodysplastic syndrome patients having the lowest. BMI cut-offs were identified to predict or protect against serious outcomes, including delayed engraftment, TRCs, and acute and chronic GVHD. Conclusions: This study highlights the importance of nutritional assessment and management in pediatric patients undergoing allo-HSCT to optimize post-transplant outcomes, as deviations from a normal BMI can significantly impact post-transplant health. These findings underscore the importance of integrating BMI assessment throughout the entire pre-HSCT therapeutic course to identify patients at higher risk for complications and to define more effective nutritional management strategies. Full article

Oxytocin (OXT) is a neurohypophysial nonapeptide that exerts its effects mainly through the oxytocin receptor (OXTR). Several studies have pointed out the role of OXT in the modulation of stem cell (SC) fate and properties. SCs are undifferentiated cells characterized by a remarkable ability to self-renew and differentiate into various cell types of the body. In this review, we focused on the role of OXT in SC differentiation. Specifically, we summarize and discuss the scientific research examining the effects of OXT on mesodermal SC-derived lineages, including cardiac, myogenic, adipogenic, osteogenic, and chondrogenic differentiation. The available studies related to the effects of OXT on SC differentiation provide little insights about the molecular mechanism mediated by the OXT–OXTR pathway. Further research is needed to fully elucidate these pathways to effectively modulate SC differentiation and develop potential therapeutic applications in regenerative medicine. Full article

Background: Glioblastoma (GBM) is an extremely aggressive brain tumor that has few available treatment options and a dismal prognosis. Recent research has highlighted the potential of extracellular vesicles (MSC-EVs) produced from mesenchymal stem cells as a potential treatment approach for GBM. MSC-EVs, including exosomes, microvesicles, and apoptotic bodies, perform a significant function in cellular communication and have shown promise in mediating anti-tumor effects. Purpose: This systematic literature review aims to consolidate current findings on the therapeutic potential of MSC-EVs in GBM treatment. Methods: A systematic search was conducted across major medical databases (PubMed, Web of Science, and Scopus) up to September 2024 to identify studies investigating the use of MSC-derived EVs in GBM therapy. Keywords included “extracellular vesicles”, “mesenchymal stem cells”, “targeted therapies”, “outcomes”, “adverse events”, “glioblastoma”, and “exosomes”. Inclusion criteria were studies published in English involving GBM models both in vivo and in vitro and those reporting on therapeutic outcomes of MSC-EVs. Data were extracted and analyzed based on EV characteristics, mechanisms of action, and therapeutic efficacy. Results: The review identified several key studies demonstrating the anti-tumor effects of MSC-EVs in GBM models. A total of three studies were included, focusing on studies conducted between 2021 and 2023. The review included three studies that collectively enrolled a total of 18 patients. These studies were distributed across two years, with two trials published in 2023 (66.7%) and one in 2021 (33.3%). The mean age of the participants ranged from 37 to 57 years. In terms of gender distribution, males were the predominant group in all studies. Prior to receiving MSC-EV therapy, all patients had undergone standard treatments for GBM, including surgery, chemotherapy (CT), and, in some cases, radiation therapy (RT). In all three studies, the targeted treatment involved the administration of herpes simplex virus thymidine kinase (HSVtk) gene therapy delivered to the tumor site, then 14 days of ganciclovir treatment. Outcomes across the studies indicated varying levels of efficacy for the MSC-EV-based therapy. The larger 2023 study reported fewer encouraging outcomes, with a median PFS of 11.0 months (95% CI: 8.3–13.7) and a median OS of 16.0 months (95% CI: 14.3–17.7). Adverse effects were reported in only one of the studies, the 2021 trial, where patients experienced mild-to-moderate side effects, including fever, headache, and cerebrospinal fluid leukocytosis. A total of 11 studies on preclinical trials, using in vitro and in vivo models, were included, covering publications from 2010 to 2024. The studies utilized MSCs as delivery systems for various therapeutic agents (interleukin 12, interleukin 7, doxorubicin, paclitaxel), reflecting the versatility of these cells in targeted cancer therapies. Conclusions: MSC-derived EVs represent a promising therapeutic approach for GBM, offering multiple mechanisms to inhibit tumor growth and enhance treatment efficacy. Their ability to deliver bioactive molecules and modulate the tumor microenvironment underscores their potential as a novel, cell-free therapeutic strategy. Future studies should optimize EV production and delivery methods and fully understand their long-term effects in clinical settings to harness their therapeutic potential in GBM treatment. Full article

Assessing the suitability of older adults with acute myeloid leukemia (AML) for intensive chemotherapy or stem cell transplantation remains a long-standing challenge. Geriatric assessment, which involves the evaluation of multiple dimensions of health, may influence a patient’s ability to tolerate intensive or mild-intensity approaches, including treatment-related mortality. Prospective studies are required to validate different fitness criteria, in addition to making it possible to compare the effectiveness of geriatric assessment-based fitness against other criteria, in order to identify which aspects of geriatric assessment are linked to treatment tolerance. It is hoped that validation studies will include different groups of patients receiving either intensive or lower-intensity chemotherapy. At a minimum, geriatric assessment should involve the measurement of the comorbidity burden, cognition, physical function, and emotional health—factors previously associated with mortality in AML. These assessments should be conducted before starting chemotherapy in order to minimize the treatment’s impact on the results. While treatment tolerance has traditionally been evaluated through toxicity rates in solid tumor patients, AML treatment often results in high toxicity rates regardless of the intensity. Therefore, early mortality should be the primary endpoint for assessing treatment tolerance, given its significant and clear implications. Other important endpoints might include declines in functional status and quality of life and treatment adjustments or discontinuation due to toxicity. Validating these fitness criteria is essential for guiding treatment choices, improving supportive care, determining trial eligibility, interpreting study outcomes, and informing drug labeling. Full article

The dysregulated NF-κB basal activity is a common feature of human thyroid carcinomas, especially in poorly differentiated or undifferentiated forms that, even if rare, are often resistant to standard therapies, and, therefore, are uncurable. Despite the molecular mechanisms leading to NF-κB activation in thyroid cancer being only partially understood, during the last few years, it has become clear that NF-κB contributes in different ways to the oncogenic potential of thyroid neoplastic cells. Indeed, it enhances their proliferation and viability, promotes their migration to and colonization of distant organs, and fuels their microenvironment. In addition, NF-κB signaling plays an important role in cancer stem cells from more aggressive thyroid carcinomas. Interfering with the different upstream and/or downstream pathways that drive NF-κB activity in thyroid neoplastic cells is an attractive strategy for the development of novel therapeutic drugs capable of overcoming the therapy resistance of advanced thyroid carcinomas. This review focuses on the recent findings about the key functions of NF-κB in thyroid cancer and discusses the potential implications of targeting NF-κB in advanced thyroid carcinomas. Full article

Background/Objectives: Receptor for hyaluronan-mediated motility (RHAMM) is a hyaluronan (HA) receptor, which exerts diverse biological functions in not only physiological but also pathological conditions in human malignancies, including breast cancer. Although chemoresistance is a significant clinical challenge in breast cancer, a possible contribution of RHAMM and hyaluronan to breast cancer chemoresistance has remained unclear. Methods: We immunolocalized RHAMM and HA in breast carcinoma tissues. Also, we utilized epirubicin-sensitive (parental) and rpirubicin-resistant (EPIR) breast cancer cell lines to explore the role of RHAMMM in breast cancer progression. Results: We found out that RHAMM and HA were cooperatively correlated with breast cancer aggressiveness and recurrence after chemotherapy. In vitro studies demonstrated that RHAMM was overexpressed in EPIR cells compared to parental cells. In addition, the knockdown of RHAMM significantly suppressed proliferation and migration of both parental and EPIR cells. On the other hand, the expression level of cancer stem cell marker CD44, which was overexpressed in M-EPIR (epirubicin-resistant MCF-7 subline) compared to MCF-7, was significantly suppressed by knockdown of RHAMM. In addition, the knockdown of RHAMM significantly altered the expression of N-cadherin and E-cadherin, leading to an epithelial phenotype. Conclusions: Aberrant RHAMM signaling were considered to cause chemoresistance related to cancer stemness and epithelial to mesenchymal transition, and increased cell proliferation and migration of both chemo-sensitive and chemo-resistant breast cancer cells. Full article

Background/Objectives: The therapeutic approach to bone mass loss and bone’s limited self-regeneration is a major focus of research, emphasizing new biomaterials and cell therapy. Tissue bioengineering emerges as a potential alternative to conventional treatments. In this study, an experimental model of a critical bone lesion in rats was used to investigate bone regeneration by treating the defect with biomaterials Evolution^® and Gen-Os^® (OsteoBiol^®, Turín, Italy), with or without mesenchymal stromal cells from dental pulp (DP-MSCs). Methods: Forty-six adult male Wistar rats were subjected to a 5-mm critical bone defect in the right mandible, which does not regenerate without intervention. The rats were randomly assigned to a Simulated Group, Control Group, or two Study Groups (using Evolution^®, Gen-Os^®, and DP-MSCs). The specimens were euthanized at three or six months, and radiological, histological, and ELISA tests were conducted to assess bone regeneration. Results: The radiological results showed that the DP-MSC group achieved uniform radiopacity and continuity in the bone edge, with near-complete structural defect restitution. Histologically, full bone regeneration was observed, with well-organized, vascularized lamellar bone and no lesion edges. These findings were supported by increases in endoglin, transforming growth factor-beta 1 (TGF-β1), protocollagen, parathormone, and calcitonin, indicating a conducive environment for bone regeneration. Conclusions: The use of DP-MSCs combined with biomaterials with appropriate three-dimensional matrices is a promising therapeutic option for further exploration. Full article

Spring low-temperature stress (LTS) has become a major limiting factor for the development of high yield, quality and efficiency in wheat production. It not only affects the function of wheat leaves and the development of spikes but also impacts stem lodging resistance, and may experience elevated risk of stem lodging. This study conducted a field pot experiment to assess the effect of phosphorus fertilizer application mode on wheat stem lodging resistance under spring LTS. Two wheat varieties, Yannong19 (YN19, cold-tolerant variety) and Xinmai26 (XM26, cold-sensitive variety) used as the experiment material. Two phosphorus fertilizer application models including traditional phosphorus application (TPA) and optimized phosphorus application (OPA) were employed. Temperature treatment was conducted at 15 °C (CK) and −4 °C (LT) in a controlled phytotron. Our results showed that spring LTS decreased the stem wall thickness and internode fullness, and altered stem anatomical structure and chemical composition, resulting in a decrease in wheat stem mechanical strength and lodging resistant index. Compared with TPA, the OPA increased the stem wall thickness and internode fullness. The thickness of the stem mechanic tissue layer and parenchymatous tissue, and the area of the large vascular bundle and small vascular bundle were increased by the OPA, which alleviated the damage to stem cell walls caused by spring LTS. At the same time, the OPA also increased the contents of lignin, cellulose, and soluble sugar, improving the C/N ratio in wheat stem. Due to the improved stem morphological characteristics, anatomical structure, and chemical compositions, the wheat stem exhibited enhanced lodging resistance, which increased the lodging resistant index of the 2nd and 3rd internodes of YN19 and XM26 by 27.27%, 11.63% and 14.15%, 15.73% at the dough stage compared with TPA under spring LTS. Meanwhile, OPA could not only alleviate the yield loss caused by spring LTS, but also increase the grain yield without spring LTS. This study indicated that OPA enhances wheat stem lodging resistance under spring LTS, and would be meaningful and practical for improving wheat resistance to low-temperature stress. Full article

Inherited heart diseases (IHDs) are caused by genetic mutations that disrupt the physiological structure and function of the heart. Understanding the mechanisms behind these diseases is crucial for developing personalised interventions in cardiovascular medicine. Development of induced pluripotent stem cells, which can then be differentiated to any nucleated adult cell type, has enabled the creation of personalised single-cell and multicellular models, providing unprecedented insights into the pathophysiology of IHDs. This review provides a comprehensive overview of recent advancements in human iPSC models used to dissect the molecular and genetic underpinnings of common IHDs. We examine multicellular models and tissue engineering approaches, such as cardiac organoids, engineered heart tissue, and multicellular co-culture systems, which simulate complex intercellular interactions within heart tissue. Recent advancements in stem cell models offer a more physiologically relevant platform to study disease mechanisms, enabling researchers to observe cellular interactions, study disease progression, and identify therapeutic strategies. By leveraging these innovative models, we can gain deeper insights into the molecular and cellular mechanisms underlying IHDs, ultimately paving the way for more effective diagnostic and therapeutic strategies. Full article

Adenomyosis (AM) is a gynecological disease characterized by the invasion of endometrial glands and stroma within the myometrium. The etiology and pathogenesis of AM remain inadequately understood. Pale cells were identified as a novel cell type characterized by the absence of desmosomal contacts and light-colored cytoplasm. These cells were observed to migrate individually through ultra-micro ruptures in the basal membrane of the endometrial glands, translocating into the stroma and then further into the myometrium. Our study aimed to explore the possible stem cell properties of these pale cells. Forty hysterectomy specimens were analyzed using immunohistochemistry and immunofluorescence to assess negative E-cadherin expression and the positive expression of stem cell markers SSEA-1, MSI-1, and SOX-2. Immunohistochemical analysis revealed the presence of pale cells and occasionally rounded, enlarged E-cadherin-negative cells predominantly in the basal endometrial epithelium. The stem cell marker SSEA-1 was significantly elevated in the basalis epithelium, as well as in the ectopic epithelium. SSEA-1 positive cells were also identified in the stroma and myometrium. Sporadic colocalization of SSEA-1+/E-cadherin– cells was confirmed through immunofluorescence. The positive staining of pale cells for SSEA-1 and MSI-1 was also confirmed at the ultrastructural level by immunoelectron microscopy. These findings indicate that pale cells may possess stem cell characteristics, particularly a positive SSEA-1 profile, warranting further in vitro investigation into their role in the pathogenesis of adenomyosis. Full article

Expansins are known as cell wall loosening proteins and are involved in cell expansion and varieties of plant developmental progresses. However, little is known about their biological functions in alfalfa (Medicago sativa L.). In the present study, 30 MsEXP genes were identified in the alfalfa (cultivar “zhongmu-1”) genome. Phylogenetic analysis revealed that these MsEXP proteins were divided into four subfamilies, including twenty-one MsEXPAs, six MsEXPBs, one MsEXL1 and two MsEXLBs. MsEXP genes were unevenly distributed on eight chromosomes. The gene structures of the MsEXP genes and the motif composition of the MsEXP proteins were inconsistent with the phylogenetic relationship of MsEXPs. Cis-acting elements analysis indicated that MsEXP genes may respond to diverse hormonal signals involved in the developmental progress of plants. Furthermore, expression analysis suggested that MsEXP genes exhibited distinct expression patterns among different tissues of alfalfa. Overexpression of MsEXPA3 or MsEXPA4 promoted the growth of leaves, stems and roots of Arabidopsis, thereby increasing the biomass of plants. Subsequent cell morphological analysis uncovered that overexpression of MsEXPA3 or MsEXPA4 promoted the expansion of cells. Taken together, these findings illustrate the functions of MsEXP proteins in regulating the development of plants. Our results may provide a strong basis for further elucidating the roles of these EXP genes in alfalfa development and valuable genetic resources for future crop improvement. Full article

Acute myeloid leukemia (AML) is a heterogeneous blood-related neoplasm that predominantly afflicts older adults with a poor prognosis due to their physical condition and the presence of medical accompanying comorbidities, adverse biological disease features, and suitability for induction intensive chemotherapy and allogenic stem cells transplantation. Recent research into the molecular and biological factors contributing to disease development and progression has led to significant advancements in treatment approaches for older patients with AML. This review article discusses the latest biological and therapeutic developments that are transforming the management of AML in older adults. Full article

This study examines the critical role of aquaporins (AQPs) in skin physiology and aging pathophysiology. The skin plays a vital role in maintaining homeostasis by acting as a protective barrier against external pathogens and excessive water loss, while also contributing to the appearance and self-esteem of individuals. Key physiological features, such as elasticity and repair capability, are essential for its proper function. However, with aging, these characteristics deteriorate, reducing the skin’s ability to tolerate environmental stressors which contribute to external aging as well as internal aging processes, which negatively affect barrier function, immune response, and overall well-being. AQPs, primarily known for facilitating water transport, are significant for normal skin functions, including hydration and the movement of molecules like glycerol and hydrogen peroxide, which influence various cellular processes and functions. In this context, we categorized aquaporin dysfunction into several hallmarks of aging, including mitochondrial dysfunction, cellular senescence, stem cell depletion, impaired macroautophagy, dysbiosis, and inflamm-aging. Eight aquaporins (AQP1, 3, 5, 7, 8, 9, 10, and 11) are expressed in various skin cells, regulating essential processes such as cell migration, proliferation, differentiation, and also immune response. Dysregulation or altered expression of these proteins can enhance skin aging and related pathologies by activating these hallmarks. This study provides valuable insights into the potential of targeting aquaporins to mitigate skin aging and improve skin physiologic functions. Full article

Mesenchymal stem cells (MSCs) are capable of differentiating into various cell types and play a crucial role in repairing aging tissues and diseased organs. Aging manifests as a gradual loss of cellular, tissue, and organ function, leading to the progression of pathologies. Exosomes (Exos) are extracellular vesicles secreted by cells, which maintain cellular homeostasis, clear cellular debris, and facilitate communication between cells and organs. This review provides a comprehensive summary of the mechanisms for the synthesis and sorting of MSC–Exo miRNAs and summarizes the current research status of MSCs–Exos in mitigating aging and age-related diseases. It delves into the underlying molecular mechanisms, which encompass antioxidative stress, anti-inflammatory response, and the promotion of angiogenesis. Additionally, this review also discusses potential challenges in and future strategies for advancing MSC–Exo miRNA-based therapies in the treatment of aging and age-related diseases. Full article

Background/objectives: Euchromatic histone lysine methyltransferase 2 (EHMT2, also known as G9a) is a mammalian histone methyltransferase that catalyzes the dimethylation of histone 3 lysine 9 (H3K9). On human chromosome 15, the parental-specific expression of Prader–Willi Syndrome (PWS)-related genes, such as SNRPN and SNORD116, are regulated through the genetic imprinting of the PWS imprinting center (PWS-IC). On the paternal allele, PWS genes are expressed whereas the epigenetic maternal silencing of PWS genes is controlled by the EHMT2-mediated methylation of H3K9 in PWS-IC. Here, we measured the effects of RNA interference of EHMT2 on the maternal expression of genes deficient in PWS in mouse model and patient iPSC-derived cells. Methods: We used small interfering RNA (siRNA) oligonucleotides and lentiviral short harpin RNA (shRNA) to reduce Ehtm2/EHMT2 expression in mouse Snord116 deletion primary neurons, PWS patient-derived induced pluripotent stem cell (iPSC) line and PWS iPSC-derived neurons. We then measured the expression of transcript or protein (if relevant) of PWS genes normally silenced on the maternal allele. Results: With an approximate reduction of 90% in EHMT2 mRNA and more than 80% of the EHMT2 protein, we demonstrated close to a 2-fold increase in the expression of maternal transcripts for SNRPN and SNORD116 in PWS iPSCs treated with siEHMT2 compared to PWS iPSC siControl. A similar increase in SNORD116 and SNRPN RNA expression was observed in PWS iPSC-derived neurons treated with shEHMT2. Conclusions: RNAi reduction in EHMT2 activates maternally silenced PWS genes. Further studies are needed to determine whether the increase is therapeutically relevant. This study confirms the role of EHMT2 in the epigenetic regulation of PWS genes. Full article