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Abnormalities of several oncogenes and tumor suppressor genes have been identified in carcinomas during the last decade and of pathological warfare and physiological traits, and multiple genetic changes have been demonstrated in individual carcinomas. We conducted a systematic review of studies enrolling adolescents and adults with Carcinoma, every type in which a cancer intervention was randomized, or all study designs in which there was a primary or secondary outcome. We searched Ovid MEDLINE, EMBASE, and Evidence-Based Medicine Reviews from 1990 to June 2015. Two reviewers evaluated study eligibility and abstracted data. In total, 67 studies were included and consisted of 62 randomized trials, reviews, and 5 studies. None of the studies (0/81) provided a definition. Only one randomized trial provided a definition. We were unable to identify any definitions used in studies of adolescents and adults with Carcinoma. Given that a proportion of this population may receive intensive treatment, there is an urgent need for consensus-based definitions of use across trials and review systematic & and meta-analysis.

AbstractGraphene oxide (GO) is widely used in bone tissue engineering due to its good biocompatibility and proliferation, and is often used in combination with other hydrogels, which not only reduces the cytotoxicity of GO but also improves the mechanical properties of the hydrogels. We developed injectable carboxymethyl chitosan (CMC)/hydroxyethyl cellulose (HEC)/β-tricalcium phosphate (β-TCP)/GO hydrogel via hydrogen bonding cross-linked between (CMC) and (HEC), also, calcium cross-linked by β-TCP was also involved to further improvement of mechanical properties of the hydrogel, and incorporate different concentration of GO in these hydrogel systems. The characterization of the novel hydrogel was tested by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). The swelling ratio and mechanical properties were investigated, the results showed that the addition of GO was able to reduce the swelling rate of hydrogels and improve their mechanical properties, with the best effect in the case of 1 mg/mL content. In vivo experimental studies showed that the hydrogel significantly promoted the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), with the best effect at a concentration of 2 mg/mL. The results of the cellular experiments were similar. Therefore, the novel environment-friendly and non-toxic injectable CMC/HEC/β-TCP/GO hydrogel system may have potential applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Stem cell-derived exosomes exert comparable therapeutic effects to those of their parental stem cells without causing immunogenic, tumorigenic, and ethical disadvantages. Their therapeutic advantages are manifested in the management of a broad spectrum of diseases, and their dosing versatility are exemplified by systemic administration and local delivery. Furthermore, the activation and regulation of various signaling cascades have provided foundation for the claimed curative effects of exosomal therapy. Unlike other relevant reviews focusing on the upstream aspects (e.g., yield, isolation, modification), and downstream aspects (e.g. phenotypic changes, tissue response, cellular behavior) of stem cell-derived exosome therapy, this unique review endeavors to focus on various affected signaling pathways. After meticulous dissection of relevant literature from the past five years, we present this comprehensive, up-to-date, disease-specific, and pathway-oriented review. Exosomes sourced from various types of stem cells can regulate major signaling pathways (e.g., the PTEN/PI3K/Akt/mTOR, NF-κB, TGF-β, HIF-1α, Wnt, MAPK, JAK-STAT, Hippo, and Notch signaling cascades) and minor pathways during the treatment of numerous diseases encountered in orthopedic surgery, neurosurgery, cardiothoracic surgery, plastic surgery, general surgery, and other specialties. We provide a novel perspective in future exosome research through bridging the gap between signaling pathways and surgical indications when designing further preclinical studies and clinical trials. [ABSTRACT FROM AUTHOR]

Salt stress represses the growth and development of plants that mainly depend on the continual propagation and differentiation of stem cells. WUSCHEL (WUS)/WUSCHEL-RELATED HOMEOBOX (WOX) family proteins determine stem cell fate in plants under ever-changing environments. It is not yet known how plant stem cell homeostasis is regulated under salt stress. Methionine synthase catalyzes the formation of methionine by methylating homocysteine in the one-carbon metabolism pathway. In this work, we investigated the role of Arabidopsis METHIONINE SYNTHASE 2 (AtMS2) in stem cell homeostasis under salt stress. The results showed that AtMS2 represses the stem cell maintenance of Arabidopsis in response to salt stress. Under normal growth conditions, AtMS2 is mainly localized in the cytoplasm. However, under salt stress, it exhibits significant accumulation in the nucleus. AtMS2 interacts with the WUS/WOX protein, and, together, they repress WUS/WOX expression by binding to its promoter. The mutation in AtMS2 resulted in enhanced salt tolerance. Therefore, AtMS2 might act as a key negative regulator to repress the stem cell maintenance and growth of Arabidopsis under salt stress. [ABSTRACT FROM AUTHOR]

The liver is the most important metabolic organ in the body. While mouse models and cell lines have further deepened our understanding of liver biology and related diseases, they are flawed in replicating key aspects of human liver tissue, particularly its complex structure and metabolic functions. The organoid model represents a major breakthrough in cell biology that revolutionized biomedical research. Organoids are in vitro three-dimensional (3D) physiological structures that recapitulate the morphological and functional characteristics of tissues in vivo, and have significant advantages over traditional cell culture methods. In this review, we discuss the generation strategies and current advances in the field focusing on their application in regenerative medicine, drug discovery and modeling diseases. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. Methods: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. Results: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. Conclusions: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a huge burden on the health care system worldwide. Although traditional therapy and targeted cartilage cell therapy have made significant progress in the treatment of OA and cartilage regeneration, there are still many problems. Mesenchymal stem cells from various tissues are the most studied cell type and have been used in preclinical and clinical studies of OA, because they are more widely available, have a greater capacity for in vitro expansion, and have anti‐inflammatory and immunomodulatory properties compared to autologous chondrocytes. This article will systematically review the latest developments in these areas. It may provide new insights for improving OA and cartilage regeneration. [ABSTRACT FROM AUTHOR]

Background: Lower lip avulsion is a separation between the lip and the associated soft tissue from the mandible. The degree of these types of injuries varies and heavily affects the outcome of the case. Case Description: This study reported an extensive lower lip avulsion managed by surgery and stem cell metabolite preparation. A one year and nine month-old domestic cats was referred for lower lip avulsion surgery to the Veterinary Teaching Hospital Airlangga University. Owing to the limited amount of tissue, immediate successful results cannot be achieved after the first surgery. Furthermore, tissue necrosis and lack of physical restraint to the cat at home contributed to the delayed union between the soft tissue and mandible, resulting in repeated surgery. Stem cell metabolites preparation was applied at the surgical site and was incorporated into the therapy to support tissue growth. Conclusion: The combination of surgical treatment and stem cell metabolite preparation resulted in good wound healing in the present case. [ABSTRACT FROM AUTHOR]

Summary: Secondary xylem and phloem originate from a lateral meristem called the vascular cambium that consists of one to several layers of meristematic cells. Recent lineage tracing studies have shown that only one of the cambial cells in each radial cell file functions as the stem cell, capable of producing both secondary xylem and phloem. Here, we first review how phytohormones and signalling peptides regulate vascular cambium formation and activity. We then propose how the stem cell concept, familiar from apical meristems, could be applied to cambium studies. Finally, we discuss how this concept could set the basis for future research. [ABSTRACT FROM AUTHOR]

Various groups including animal protection organizations, medical organizations, research centers, and even federal agencies such as the U.S. Food and Drug Administration, are working to minimize animal use in scientific experiments. This movement primarily stems from animal welfare and ethical concerns. However, recent advances in technology and new studies in medicine have contributed to an increase in animal experiments throughout the years. With the rapid increase in animal testing, concerns arise including ethical issues, high cost, complex procedures, and potential inaccuracies. Alternative solutions have recently been investigated to address the problems of animal testing. Some of these technologies are related to stem cell technologies, such as organ-on-a-chip, organoids, and induced pluripotent stem cell models. The aim of the review is to focus on stem cell related methodologies, such as organoids, that can serve as an alternative to animal testing and discuss its advantages and limitations, alongside regulatory considerations. Although stem cell related methodologies has shortcomings, it has potential to replace animal testing. Achieving this requires further research on stem cells, with potential societal and technological benefits. [ABSTRACT FROM AUTHOR]

The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of "super-enhancer omics", inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs. [ABSTRACT FROM AUTHOR]

Precise regulation of stem cell quiescence is essential for tissue development and homeostasis. Therefore, its aberrant regulation is intimately correlated with various human diseases. However, the detailed mechanisms of stem cell quiescence and its specific role in the pathogenesis of various diseases remain to be determined. Recent studies have revealed that the intrinsic and microenvironmental factors are the potential candidates responsible for the orderly switch between the dormant and activated states of stem cells. In addition, defects in signaling pathways related to internal and external factors of stem cells might contribute to the initiation and development of diseases by altering the dormancy of stem cells. In this review, we focus on the mechanisms underlying stem cell quiescence, especially the involvement of intrinsic and microenvironmental factors. In addition, we discuss the relationship between the anomalies of stem cell quiescence and related diseases, hopefully providing therapeutic insights for developing novel treatments. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is a major cause of cervical cancer. As the natural history of HPV‐associated cervical lesions is HPV genotype‐dependent, it is important to understand the characteristics of these genotypes and to manage them accordingly. Among high‐risk HPVs, HPV16 and 18 are particularly aggressive, together accounting for 70% of HPV genotypes detected in cervical cancer. Other than HPV16 and 18, HPV31, 33, 35, 45, 52, and 58 are also at a high risk of progression to cervical intraepithelial neoplasia (CIN)3 or higher. Recent studies have shown that the natural history of HPV16, 18, 52, and 58, which are frequently detected in Japan, depends on the HPV genotype. For example, HPV16 tends to progress in a stepwise fashion from CIN1 to CIN3, while HPV52 and 58 are more likely to persist in the CIN1 to CIN2 state. Among the high‐risk HPVs, HPV18 has some peculiar characteristics different from those of other high‐risk HPV types; the detection rate in precancerous lesions is much lower than those of other high‐risk HPVs, and it is frequently detected in highly malignant adenocarcinoma and small cell carcinoma. Recent findings demonstrate that HPV18 may be characterized by latent infection and carcinogenesis in stem cell‐like cells. In this context, this review outlines the natural history of HPV‐infected cervical lesions and the characteristics of each HPV genotype. [ABSTRACT FROM AUTHOR]

This study investigates whether hAFSCs can improve bladder function in partial bladder outlet obstruction (pBOO) rats by targeting specific cellular pathways. Thirty-six female rats were divided into sham and pBOO groups with and without hAFSCs single injection into the bladder wall. Cystometry, inflammation/hypoxia, collagen/fibrosis/gap junction proteins, and smooth muscle myosin/muscarinic receptors were examined at 2 and 6 weeks after pBOO or sham operation. In pBOO bladders, significant increases in peak voiding pressure and residual volume stimulated a significant upregulation of inflammatory and hypoxic factors, TGF-β1 and Smad2/3. Collagen deposition proteins, collagen 1 and 3, were significantly increased, but bladder fibrosis markers, caveolin 1 and 3, were significantly decreased. Gap junction intercellular communication protein, connexin 43, was significantly increased, but the number of caveolae was significantly decreased. Markers for the smooth muscle phenotype, myosin heavy chain 11 and guanylate-dependent protein kinase, as well as M2 muscarinic receptors, were significantly increased in cultured detrusor cells. However, hAFSCs treatment could significantly ameliorate bladder dysfunction by inactivating the TGFβ-Smad signaling pathway, reducing collagen deposition, disrupting gap junctional intercellular communication, and modifying the expressions of smooth muscle myosin and caveolae/caveolin proteins. The results support the potential value of hAFSCs-based treatment of bladder dysfunction in BOO patients. [ABSTRACT FROM AUTHOR]

Background. The purpose of the present study was to investigate the effect of aerobic)resistance training on the population of cardiac multipotent cells, thickness, and diameter of the ventricular through the C-Kit pathway of male rats during the growth stages. Methods. Overall, 30 male Wistar rats in three age groups of 2 (n = 10), 8 (n = 10), and 96 (n = 10) weeks were accidentally divided into exercise and control groups. Resistance training programs (resistance ladder, 3 days a week) and aerobics (treadmill running, 3 days a week) were performed for 6 weeks. Hematoxylin-Eosin staining was done the heart tissue and histological images were prepared. Afterward, C-Kit gene expression was examined by the real-time polymerase chain reaction method. The statistical method of one-way analysis of variance (P ≥ 0.05) and Tukey’s test were used at a significant level (P ≥ 0.01). Results. The trained neonatal group had higher values in heart weight to body weight index, and the trained neonatal and trained young adult groups had higher values in left ventricular thickness (P ≥ 0.01). The decrease in left ventricular internal diameter in the trained young adult group was significant compared to the control group (P ≥ 0.01). There was a significant increase in C-Kit gene expression in trained young adult and trained old groups (P ≥ 0.01). Conclusion. Aerobic-resistance training can be an effective stimulus for increasing the number of cardiac stem cells and creating structural adaptations of the heart, including increasing thickness and ventricular diameter in neonatal and young adult groups. Practical Implications. Participation in aerobic-resistance training programs leads to the improvement of the cardiac structure and an increase in cardiac stem cells. [ABSTRACT FROM AUTHOR]

Companion animals in veterinary medicine develop multiple naturally occurring diseases analogous to human conditions. We previously reported a comprehensive review on the feasibility, safety, and biologic activity of using novel stem cell therapies to treat a variety of inflammatory conditions in dogs and cats (2008-2015) [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models. Stem Cells. 2016;34(7):1709-1729. https://doi.org/10.1002/stem.2377]. The purpose of this review is to provide an updated summary of current studies in companion animal disease models that have evaluated stem cell therapeutics that are relevant to human disease. Here we have reviewed the literature from 2015 to 2023 for publications on stem cell therapies that have been evaluated in companion animals, including dogs, cats, and horses. The review excluded case reports or studies performed in experimentally induced models of disease, studies involving cancer, or studies in purpose-bred laboratory species such as rodents. We identified 45 manuscripts meeting these criteria, an increase from 19 that were described in the previous review [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models. Stem Cells. 2016;34(7):1709-1729. https://doi.org/10.1002/stem.2377]. The majority of studies were performed in dogs (n  = 28), with additional studies in horses (n  = 9) and cats (n  = 8). Disease models included those related to musculoskeletal disease (osteoarthritis and tendon/ligament injury), neurologic disease (canine cognitive dysfunction, intervertebral disc disease, spinal cord injury) gingival/dental disease (gingivostomatitis), dermatologic disease (atopic dermatitis), chronic multi-drug resistant infections, ophthalmic disease (keratoconjunctivitis sicca, eosinophilic keratitis, immune-mediated keratitis), cardiopulmonary disease (asthma, degenerative valve disease, dilated cardiomyopathy), gastrointestinal disease (inflammatory bowel disease, chronic enteropathy), and renal disease (chronic kidney disease). The majority of studies reported beneficial responses to stem cell treatment, with the exception of those related to more chronic processes such as spinal cord injury and chronic kidney disease. However, it should also be noted that 22 studies were open-label, baseline-controlled trials and only 12 studies were randomized and controlled, making overall study interpretation difficult. As noted in the previous review, improved regulatory oversight and consistency in manufacturing of stem cell therapies are needed. Enhanced understanding of the temporal course of disease processes using advanced-omics approaches may further inform mechanisms of action and help define appropriate timing of interventions. Future directions of stem-cell-based therapies could include use of stem-cell-derived extracellular vesicles, or cell conditioning approaches to direct cells to specific pathways that are tailored to individual disease processes and stages of illness. [ABSTRACT FROM AUTHOR]

The limited availability of a healthy donor cornea and the incidence of allograft failure led researchers to seek other corneal substitutes via tissue engineering. Exploring the trend of clinical trials of the cornea with the vision of tissue engineering provides an opportunity to reveal future potential corneal substitutes. The results of this clinical trial are beneficial for future study designs to overcome the limitations of current therapeutic approaches. In this study, registered clinical trials of bio‐based approaches were reviewed for corneal regeneration on March 22, 2024. Among the 3955 registered trials for the cornea, 392 trials were included in this study, which categorized in three main bio‐based scaffolds, stem cells, and bioactive macromolecules. In addition to the acellular cornea and human amniotic membrane, several bio‐based materials have been introduced as corneal substrates such as collagen, fibrin, and agarose. However, some synthetic materials have been introduced in recent studies to improve the desired properties of bio‐based scaffolds for corneal substitutes. Nevertheless, new insights into corneal regenerative medicine have recently emerged from cell sheets with autologous and allogeneic cell sources. In addition, the future perspective of corneal regeneration is described through a literature review of recent experimental models. [ABSTRACT FROM AUTHOR]

Objective: L-arginine is a semi-essential amino acid produced by the body which has an important role in the process of stem cell regeneration. However, under inflammatory conditions, denaturation of pulp amino acids and proteins occurr resulting in a decrease in the ability of stem cells to self-renew. Therefore, in this study, L-arginine was added in vitro to the culture media Dulbecco's Modified Eagle Medium - (DMEM) of human dental pulp stem cells (hDPSCs) to analyse the potential of L-arginine on migration and proliferation by comparing between 3 concentrations, namely 300, 400, 500μmol/L and control group (DMEM), to obtain the most optimal concentration for proliferation and migration. Methods: Serum-starved hDPSCs were divided into four groups: control: hDPSCs in DMEM; hDPSCs in 300 μmol/L of the L-Arginine based culture media group; hDPSCs in 400 µmol/L of the L-Arginine based culture media group; and hDPSCs in 500μmol/L of the L-Arginine based culture media group, which were added in two separate 24-well-plates (5×104 cell/well) for proliferation and migration evaluation. The proliferation of all groups was measured by using a cell count test (haemacytometer and manual checker) after 24 h. The migratory speed rate of all groups was measured by using cell migration assay (scratch wound assay) after 24 h. Cell characteristics were evaluated under microscope that was then evaluated using image-J® interpretation. This image J represented the measurement of migratory speed rate (nm/h) data. Statistical analysis was conducted using one-way ANOVA and post hoc Bonferroni (p<0.05) for proliferation and post hoc LSD (p<0.05) for migration. Results: There was a statistically significant difference in hDPSCs proliferation among various concentration groups of the L-Arginine based solution (300, 400 and 500 µmol/L) compared to the control group (p<0.05). There was a statistically significant difference in the migratory speed rate of hDPSCs at 500 µmol/L of the LArginine based solution group compared to lower concentrations and control group (p<0.05). Conclusion: All three concentrations of L-arginine can induce proliferation of hDPSCs. L-arginine at 500 µmol/L can induce higher hDPSCs proliferation and faster migration at 24 hours compared to lower concentrations and control. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Inorganic Analytical Chemistry / Zhongguo Wuji Fenxi Huaxue is the property of Beijing Research Institute of Mining & Metallurgy Technology Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Asian Journals of Ecotoxicology is the property of Gai Kan Bian Wei Hui and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Many tumours are organised in a hierarchical structure with at its apex a cell that can maintain, establish, and repopulate the tumour—the cancer stem cell. The haematopoietic stem cell (HSC) is the founder cell for all functional blood cells. Like HSCs, the leukaemia stem cells (LSC) are hypothesised to be the leukaemia‐initiating cells, which have features of stemness such as self‐renewal, quiescence, and resistance to cytotoxic drugs. Immunophenotypically, CD34+CD38− defines HSCs by adding lineage negativity and CD90+CD45RA−. At which stage of maturation the further differentiation is blocked, determines the type of leukaemia, and determines the immunophenotype of the LSC specific to the leukaemia type. No apparent LSC phenotype has been described in lymphoid leukaemia, and it is debated if a specific acute lymphocytic leukaemia‐initiating cell is present, as all cells are capable of engraftment in a secondary mouse model. In chronic lymphocytic leukaemia, a B‐cell clone is responsible for uncontrolled proliferation, not a specific LSC. In chronic and acute myeloid leukaemia, LSC is described as CD34+CD38− with the expression of a marker that is aberrantly expressed (LSC marker), such as CD45RA, CD123 or in the case of chronic myeloid leukaemia CD26. In acute myeloid leukaemia, the LSC load had prognostic relevance and might be a biomarker that can be used for monitoring and as an addition to measurable residual disease. However, challenges such as the CD34‐negative immunophenotype need to be explored. [ABSTRACT FROM AUTHOR]

Perivascular adipose tissue (PVAT) regulates vascular function due to its capacity to synthesize vasoactive products and its mechanical properties. PVATs most abundant cells are adipocytes, and their populations are maintained by the maturation of adipocyte progenitor cells (APC), which may play a pivotal role in the pathogenesis of cardiovascular diseases. However, the distribution of APC within PVAT depots, their potential variation in spatial location, and the influence of sex and age on their abundance remain unknown. We hypothesize that APC abundance in PVAT is affected by location, age, sex and that APC subtypes have specific spatial distributions. PVAT from thoracic and abdominal aorta, and mesenteric arteries, and AT from interscapular, gonadal, and subcutaneous depots from 13-week and 30-week-old females and males Pdgfrα-CreERT2 x LSLtdTomato mice (n = 28) were analyzed. Abdominal aorta PVAT had fewer progenitors than mesenteric PVAT and gonadal AT. Aging reduced the abundance of APC in the thoracic aorta but increased their numbers in mesenteric PVAT. Females had more APC than males in mesenteric PVAT and gonadal AT depots. APC exhibited unique spatial distribution in the aorta and mesenteric PVAT where they localized neighboring vasa vasorum and arteries. APC subtypes (APC1, APC2, APC3, diff APC) were identified in all PVAT depots. Thoracic aorta PVAT APC3 were located in the adventitia while diff APC were in the parenchyma. This study identified variability in APC populations based on depot, age, and sex. The distinctive spatial distribution and the presence of diverse APC subtypes suggest that they may contribute differently to cardiovascular diseases-induced PVAT remodeling. [ABSTRACT FROM AUTHOR]

Introduction: Salivary gland dysfunction, often resulting from salivary gland obstruction-induced inflammation, is a prevalent condition. Corticosteroid, known for its anti-inflammatory and immunomodulatory properties, is commonly prescribed in clinics. This study investigates the therapeutic implications and potential side effects of dexamethasone on obstructive sialadenitis recovery using duct ligation mice and salivary gland organoid models. Methods: Functional and pathological changes were assessed after administering dexamethasone to the duct following deligation 2 weeks after maintaining ligation of the mouse submandibular duct. Additionally, lipopolysaccharide- and tumor necrosis factor-induced salivary gland organoid inflammation models were established to investigate the effects and underlying mechanisms of action of dexamethasone. Results: Dexamethasone administration facilitated SG function restoration, by increasing salivary gland weight and saliva volume while reducing saliva lag time. Histological evaluation revealed, reduced acinar cell atrophy and fibrosis with dexamethasone treatment. Additionally, dexamethasone suppressed proinflammatory cytokines IL-1β and TNF expression. In a model of inflammation in salivary gland organoids induced by inflammatory substances, dexamethasone restored acinar markers such as AQP5 gene expression levels, while inhibiting pro-inflammatory cytokines TNF and IL6, as well as chemokines CCL2, CXCL5, and CXCL12 induction. Macrophages cultured in inflammatory substancetreated media from salivary gland organoid cultures exhibited proinflammatory polarization. However, treatment with dexamethasone shifted them towards an anti-inflammatory phenotype by reducing M1 markers (Tnf, Il6, Il1b, and Cd86) and elevating M2 markers (Ym1, Il10, Cd163, and Klf4). However, high-dose or prolonged dexamethasone treatment induced acinoductal metaplasia and had side effects in both in vivo and in vitro models. Conclusions: Our findings suggest the effectiveness of corticosteroids in treating obstructive sialadenitis-induced salivary gland dysfunction by regulating pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

In the injured zebrafish retina, Mü ller glial cells (MG) reprogram to adopt retinal stemcell properties and regenerate damaged neurons. The strongest zebrafish reprogramming factors might be good candidates for stimulating a similar regenerative response by mammalian MG. Myc proteins are potent reprogramming factors that can stimulate cellular plasticity in differentiated cells; however, their role in MG reprogramming and retina regeneration remains poorly explored. Here, we report that retinal injury stimulates mycb and mych expression and that, although both Mycb and Mych stimulate MG reprogramming and proliferation, only Mych enhances retinal neuron apoptosis. RNA-sequencing analysis of wild-type, mychmut and mycbmut fish revealed that Mycb and Mych regulate ~40% and ~16%, respectively, of the genes contributing to the regenerationassociated transcriptome of MG. Of these genes, those that are induced are biased towards regulation of ribosome biogenesis, protein synthesis, DNA synthesis, and cell division, which are the top cellular processes affected by retinal injury, suggesting that Mycb and Mych are potent MG reprogramming factors. Consistent with this, forced expression of either of these proteins is sufficient to stimulate MG proliferation in the uninjured retina. [ABSTRACT FROM AUTHOR]

Neural crest cells are a stem cell population unique to vertebrate embryos that retains broad multi-germ layer developmental potential through neurulation. Much remains to be learned about the genetic and epigenetic mechanisms that control the potency of neural crest cells. Here, we examine the role that epigenetic readers of the BET (bromodomain and extra terminal) family play in controlling the potential of pluripotent blastula and neural crest cells. We find that inhibiting BET activity leads to loss of pluripotency at blastula stages and a loss of neural crest at neurula stages. We compare the effects of HDAC (an eraser of acetylation marks) and BET (a reader of acetylation) inhibition and find that they lead to similar cellular outcomes through distinct effects on the transcriptome. Interestingly, loss of BET activity in cells undergoing lineage restriction is coupled to increased expression of genes linked to pluripotency and prolongs the competence of initially pluripotent cells to transit to a neural progenitor state. Together these findings advance our understanding of the epigenetic control of pluripotency and the formation of the vertebrate neural crest. [ABSTRACT FROM AUTHOR]

Cerebellar granule neuron progenitors (GNPs) originate from the upper rhombic lip (URL), a germinative niche in which developmental defects produce human diseases. T-cell factor (TCF) responsiveness and Notch dependence are hallmarks of self-renewal in neural stem cells. TCF activity, together with transcripts encoding proneural gene repressors hairy and enhancer of split (Hes/Hey), are detected in the URL; however, their functions and regulatorymodes are undeciphered. Here, we established amphibian as a pertinent model for studying vertebrate URL development. The amphibian long-lived URL is TCF active, whereas the external granular layer (EGL) is non-proliferative and expresses hes4 and hes5 genes. Using functional and transcriptomic approaches, we show that TCF activity is necessary for URL emergence and maintenance. We establish that the transcription factor Barhl1 controls GNP exit from the URL, acting partly through direct TCF inhibition. Identification of Barhl1 target genes suggests that, besides TCF, Barhl1 inhibits transcription of hes5 genes independently of Notch signaling. Observations in amniotes suggest a conserved role for Barhl in maintenance of the URL and/or EGL via co-regulation of TCF, Hes and Hey genes. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastomas (GBMs) are considered the most lethal cancer in the central nervous system (CNS), whose malignant phenotypes are majorly attributed to glioma stem cells (GSCs). Despite combined surgical radiotherapy with temozolomide chemotherapy and tumor-treating fields (TTFs), the tumor almost always recurs near the resection site. Besides the contribution of GSCs, the tumor microenvironment (TME) also plays an important role in glioma recurrence. Our work has demonstrated that GSC-derived exosomes carry lncRNA NEAT1 to promote the M2 polarization of glioma-associated macrophages (GAMs). Further mechanism exploration indicated that NEAT1 represses the expression of miR-125a in GAMs significantly. The decrease in miR-125a induces the elevation of target gene STAT3, which is required for macrophage M2 polarization. The development of M2-like GAMs contributes to the immunosuppressive microenvironment and glioma progression. Our findings elucidate the functions and mechanisms of the crosstalk between GSCs and GAMs via exosomes, providing new therapeutic targets and strategies for glioma. Glioblastoma (GBM), as the most common primary brain tumor, usually results in an extremely poor prognosis, in which glioma stem cells (GSCs) and their immunosuppressive microenvironment prominently intervene in the resistance to radiotherapy and chemotherapy that directly leads to tumor recurrence and shortened survival time. The specific mechanism through which exosomes generated from GSCs support the creation of an immunosuppressive microenvironment remains unknown, while it is acknowledged to be engaged in intercellular communication and the regulation of the glioma immunosuppressive microenvironment. The elevated expression of LncRNA-NEAT1 was found in glioma cells after radiotherapy, chemotherapy, and DNA damage stimulation, and NEAT1 could promote the malignant biological activities of GSCs. Emerging evidence suggests that lncRNAs may reply to external stimuli or DNA damage by playing a role in modulating different aspects of tumor biology. Our study demonstrated a promotive role of the carried NEAT1 by GSC-derived exosomes in the polarization of M2-like macrophages. Further experiments demonstrated the mediative role of miR-125a and its target gene STAT3 in NEAT1-induced polarization of M2-like macrophages that promote glioma progression. Our findings elucidate the mechanism by which GSCs influence the polarization of M2-like macrophages through exosomes, which may contribute to the formation of immunosuppressive microenvironments. Taken together, our study reveals the miR-125a-STAT3 pathway through which exosomal NEAT1 from treatment-resistant GSCs contributes to M2-like macrophage polarization, indicating the potential of exosomal NEAT1 for treating glioma. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BP) is a recurring psychiatric condition characterized by alternating episodes of low energy (depressions) followed by manias (high energy). Cortical network activity produced by GABAergic interneurons may be critical in maintaining the balance in excitatory/inhibitory activity in the brain during development. Initially, GABAergic signaling is excitatory; with maturation, these cells undergo a functional switch that converts GABAA channels from depolarizing (excitatory) to hyperpolarizing (inhibitory), which is controlled by the intracellular concentration of two chloride transporters. The earliest, NKCC1, promotes chloride entry into the cell and depolarization, while the second (KCC2) stimulates movement of chloride from the neuron, hyperpolarizing it. Perturbations in the timing or expression of NKCC1/KCC2 may affect essential morphogenetic events including cell proliferation, migration, synaptogenesis and plasticity, and thereby the structure and function of the cortex. We derived induced pluripotent stem cells (iPSC) from BP patients and undiagnosed control (C) individuals, then modified a differentiation protocol to form GABAergic interneurons, harvesting cells at sequential stages of differentiation. qRT-PCR and RNA sequencing indicated that after six weeks of differentiation, controls transiently expressed high levels of NKCC1. Using multi-electrode array (MEA) analysis, we observed that BP neurons exhibit increased firing, network bursting and decreased synchrony compared to C. Understanding GABA signaling in differentiation may identify novel approaches and new targets for treatment of neuropsychiatric disorders such as BP. [ABSTRACT FROM AUTHOR]

Acute lung injury is an acute inflammation disorder that disrupts the lung endothelial and epithelial barriers. In this study, we investigated the extracellular vesicles (EVs) obtained via priming inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ on canine adipose mesenchymal stem cells in improving their anti-inflammatory and/or immunosuppressive potential, and/or their ability to alleviate lipopolysaccharide-induced lung injury in vitro. We also explored the correlation between epithelial-to-mesenchymal transition and the inflammatory repressive effect of primed EVs. Using small RNA-Seq, we confirmed that miR-16 and miR-502 significantly increased in EVs from TNF-α and IFN-γ-primed canine adipose mesenchymal stem cells. The pro and anti-inflammatory cytokines were analyzed in a lipopolysaccharideinduced lung injury model and we found that the EV anti-inflammatory effect improved on priming with inflammatory cytokines. EVs obtained from primed stem cells effectively suppress endothelial-to-mesenchymal transition in a lung injury model. Our results suggest a potential therapeutic approach utilizing EVs obtained from adipose mesenchymal stem cells primed with TNF-α and IFN-γ against lung inflammation and endothelial to mesenchymal transition. [ABSTRACT FROM AUTHOR]

Scaffolds play a key role in cultured meat production by providing an optimal environment for efficient cell attachment, growth, and development. This study investigated the effects of gelatin coating on the adhesion, proliferation, and adipogenic differentiation of adipose tissue-derived stem cells (ADSCs) cultured on soy protein–agarose scaffolds. Gelatin-coated scaffolds were prepared using 0.5% and 1.0% (w/v) gelatin solutions. The microstructure, water absorption rate, mechanical strength, cytotoxicity, cell adhesion, proliferation, and differentiation capabilities of the scaffolds were analyzed. Field emission scanning electron microscopy revealed the porous microstructure of the scaffolds, which was suitable for cell growth. Gelatin-coated scaffolds exhibited a significantly higher water absorption rate than that of non-coated scaffolds, indicating increased hydrophilicity. In addition, gelatin coating increased the mechanical strength of the scaffolds. Gelatin coating did not show cytotoxicity but significantly enhanced cell adhesion and proliferation. The gene expression levels of peroxisome proliferator-activated receptor gamma, CCAT/enhancer-binding protein alpha, and fatty acid-binding protein 4 were upregulated, and lipid accumulation was increased by gelatin coating. These findings suggest that gelatin-coated scaffolds provide a supportive microenvironment for ADSC growth and differentiation, highlighting their potential as a strategy for the improvement of cultured meat production and adipose tissue engineering. [ABSTRACT FROM AUTHOR]

Diabetic wound healing is a serious, complex, and chronic process; one current promising and focusing technology in this area is stem cell treatment. Here, novel porous microneedle (MN) arrays is fabricated, which can highly mimetic stem cell niches, through template filling, and particle etching method. The human adipose‐derived stem cells (ADSCs) are encapsulated in Matrigel then loaded into the porous MN arrays by post‐perfusion. Because of the extracellular matrix‐mimicking, the biocompatible Matrigel offers a bionic microenvironment of stem cell nest suitable for growth. Benefiting from the numerous pore structures of MNs, the loaded ADSCs have enough space to fully absorb nutrients, proliferate greatly and exhibit prompted function. In addition, the cell‐loaded MN arrays have enough mechanical strength to penetrate the skin, allowing the ADSCs to get into the deep wound areas. Based on these features, the performance of the resultant MN arrays in promoting tissue regeneration is demonstrated, collagen deposition and angiogenesis in diabetes wounds of rat models. Thus, it is believe that the bioinspired porous MNs can act as excellent stem cell scaffolds and will find many practical values in clinic wound healing. [ABSTRACT FROM AUTHOR]

• Regenerative cell therapy is efficacious after experimental stroke. • Regenerative cell therapy can act by systemic effects (trophic factors, immunomodulation). • Intracerebral grafts sustained by biomaterials are developed. • Small clinical trials have provided encouraging efficacy results in stroke patients. • Implementation of large trials is limited by huge cost of clinical-grade cell products, and regulation. Stroke is the most common cause of disability. Brain repair mechanisms are often insufficient to allow a full recovery. Stroke damage involve all brain cell type and extracellular matrix which represent the crucial "glio-neurovascular niche" useful for brain plasticity. Regenerative medicine including cell therapies hold great promise to decrease post-stroke disability of many patients, by promoting both neuroprotection and neural repair through direct effects on brain lesion and/or systemic effects such as immunomodulation. Mechanisms of action vary according to each grafted cell type: "peripheral" stem cells, such as mesenchymal stem cells (MSC), can provide paracrine trophic support, and neural stem/progenitor cells (NSC) or neurons can act as direct cells' replacements. Optimal time window, route, and doses are still debated, and may depend on the chosen medicinal product and its expected mechanism such as neuroprotection, delayed brain repair, systemic effects, or graft survival and integration in host network. MSC, mononuclear cells (MNC), umbilical cord stem cells and NSC are the most investigated. Innovative approaches are implemented concerning combinatorial approaches with growth factors and biomaterials such as injectable hydrogels which could protect a cell graft and/or deliver drugs into the post-stroke cavity at chronic stages. Through main publications of the last two decades, we provide in this review concepts and suggestions to improve future translational researches and larger clinical trials of cell therapy in stroke. [ABSTRACT FROM AUTHOR]

BACKGROUND: It was found that the ligands and receptors of Notch are both cell membrane surface proteins, which are important proteins to mediate intercellular communication, and the Notch signaling pathway plays a crucial regulatory role in the proliferation and differentiation of mesenchymal stem cells. OBJECTIVE: To review the regulatory mechanism of the Notch signaling pathway on the proliferation and differentiation of mesenchymal stem cells, summarize and clarify the research advance in how the Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells, and provide theoretical support for the future use of stem cells to treat various related diseases. METHODS: By using the computer, the first author searched the relevant studies involving Notch signaling pathway regulation of mesenchymal stem cell proliferation and differentiation on CNKI, Wanfang, VIP, PubMed, Web of Science, and Nature databases with Chinese search terms “mesenchymal stem cells, Notch, Notch signaling pathway, proliferation, differentiation” and the English search terms “mesenchymal stem cells, MSC, Notch, Notch signaling pathway, proliferation, differentiation”. Part of the literature was searched in combination with the literature tracing method. Finally, 87 articles were included in the review analysis. RESULTS AND CONCLUSION: (1) Notch signaling pathway is a conserved signaling pathway in multicellular organisms, which plays an important role in regulating cell differentiation, proliferation, apoptosis, and the cell cycle by mediating communication between neighboring cells through receptor-ligand binding. (2) Mesenchymal stem cells are a class of adult stem cells with self-proliferative and multi-directional differentiation potential, which can be regulated by external signaling pathways to affect their proliferation and differentiation. Notch signaling pathway, as one of them, when Notch ligands are activated, the Notch proteins will undergo two protein hydrolysis cleavages to release Notch intracellular structural domain NICD, which then enters the nucleus and thus promotes the transcription of target genes to regulate the proliferation and differentiation of mesenchymal stem cells from different sources, such as bone marrow, adipose, and umbilical cord. However, the specific mechanisms that regulate the proliferation and differentiation of mesenchymal stem cells from different tissue sources of the same species are different. (3) The Notch signaling pathway can regulate the differentiation of mesenchymal stem cells into different target cells, but due to different target cells, the expression levels of receptors or ligands in the Notch signaling pathway vary. (4) Clinical targeting of the Notch signaling pathway to promote mesenchymal stem cells for the treatment of various refractory diseases, such as aplastic anemia, severe joint injuries, ischemic strokes, and myocardial infarctions, has a promising application. (5) By exploring the Notch signaling pathway via regulating the expression levels of its receptors and ligands in bone marrow mesenchymal stem cells from rat, mouse, and human, it can be found that the Notch signaling pathway expression levels in the proliferation and differentiation of mesenchymal stem cells from different species origins are also different. (6) The role of mesenchymal stem cells in tissue engineering has been gradually highlighted due to their advantages of safety, low immune rejection, and wide therapeutic prospects. The Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells with a wide range of influencing factors, and subsequent studies should further optimize the influencing factor variables and explore the standardized studies of regulating the proliferation and differentiation of mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exosomes play a role in all stages of wound repair, and there is currently a large body of research on exosomes in skin wound repair, which has been shown to have great potential for clinical applications. OBJECTIVE: To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds, in order to promote the clinical translation of exosomes. METHODS: PubMed, clinicaltrials.gov, China National Knowledge Infrastructure, Food and Drug Administration database, and Chinese Clinical Trial Register were searched from inception to March 2023. The English search terms were “exosomes, wound healing, stem cells, chronic wound, immunoregulation, inflammation, skin, therapeutic use, isolation, characterization, infections”. The Chinese search terms were “exosomes, wound healing, stem cells, immunomodulation, clinical applications”. A total of 79 articles were included for the summary. RESULTS AND CONCLUSION: (1) Exosomes can improve and accelerate wound healing through inflammation regulation, immune protection, angiogenesis, cell proliferation and migration, and collagen remodeling. (2) Exosomes derived from stem cells have mature preparation techniques and related mechanism research, which is currently the mainstream research direction. Non-stem cell-derived exosomes have the advantages of convenience, economy, and easy production, and can be used as a supplement for clinical applications. (3) The clinical application of exosomes is still in its infancy, but has great potential for application. Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research. (4) The clinical translation of exosomes faces many challenges, such as low yield, high heterogeneity, lack of unified standards for isolation, purification, and quality control, and difficulties in storage. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mesenchymal stem cells have great potential in the treatment of ischemia-reperfusion injury of skin flaps. However, their defects and the decline of their role in the treatment of ischemia-reperfusion injury of skin flaps restrict their wide application. OBJECTIVE: To review the strategies for improving the treatment of ischemia-reperfusion injury of skin flaps with mesenchymal stem cells, and provide a reference for its further theoretical research and clinical application. METHODS: Relevant documents included in CNKI, WanFang and PubMed were searched. The Chinese and English search terms were “mesenchymal stem cell, ischemia-reperfusion adjustment of skin flap, mesenchymal stem cells, stem cells, skin flap, ischemia-reperfusion injury, pretreatment, gene modification, biomaterial packaging, joint application”. The relevant documents since 2007 were retrieved, and the documents with little relationship between the research content and the article theme, poor quality and outdated content were eliminated through reading the article, and finally 75 documents were included for summary. RESULTS AND CONCLUSION: (1) Mesenchymal stem cells can inhibit inflammatory reactions, resist oxidative stress and induce angiogenesis, which has great potential in the treatment of skin flap ischemia-reperfusion injury. (2) Although mesenchymal stem cells have shown great potential in the treatment of skin flap ischemia-reperfusion injury, their shortcomings in treatment have limited their widespread clinical application. Through pre-treatment (cytokines, hypoxia, drugs, and other pre-treatment mesenchymal stem cells), gene-modified mesenchymal stem cells, biomaterial encapsulation of mesenchymal stem cells, as well as the combined use of mesenchymal stem cells and other drugs or therapeutic methods, can not only overcome the shortcomings of mesenchymal stem cells in treatment, but also improve their therapeutic effectiveness in skin flap ischemia-reperfusion injury. (3) Therefore, further improving the effectiveness of mesenchymal stem cells in treating skin flap ischemia-reperfusion injury and exploring its therapeutic potential are of great significance for the research of mesenchymal stem cells and the treatment of skin flap ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: The research of dental stem cells in the fields of regenerative medicine and tissue engineering has been deepening, bringing hope for the repair of tooth-related tissues and the treatment of systemic diseases. However, there is a lack of systematic research and analysis on the biological characteristics of dental stem cells in different age groups. OBJECTIVE: To explore the biological characteristics of the human deciduous tooth and permanent tooth pulp stem cells cultured in umbilical cord blood platelet lysate to provide a reliable basis for human platelet lysates to replace fetal bovine serum. METHODS: The pulp tissues of deciduous teeth, juvenile permanent teeth and adult permanent teeth were taken out and cultured in DMEM/F-12 medium supplemented with 10% fetal bovine serum or different concentrations (5%, 10% and 15%) of human platelet lysates. Cell proliferation in the four groups was detected by cytometry. The optimal concentration of human platelet lysates was selected for subsequent experiments. Under the optimal concentration of human platelet lysates, human deciduous tooth and juvenile and adult permanent tooth pulp stem cells were cultured in vitro. The cell growth status was observed under the microscope. The specific antigen on the cell surface was detected by flow cytometry. The cell proliferation ability was tested by the cell counting method and CCK-8 assay. The cell differentiation ability in vitro was observed by a three-line differentiation assay. RESULTS AND CONCLUSION: (1) The cell proliferation rate of the 10% human platelet lysate group was the highest. (2) In all three groups, fusiform fibrous cells grew and expanded from around the tissue block. There was no significant difference between deciduous teeth and juvenile permanent tooth cells, but the adult permanent tooth cells were larger than the deciduous and juvenile permanent tooth cells of the same generation. (3) The results of flow cytometry showed that deciduous teeth, juvenile permanent teeth and adult permanent teeth conformed to the phenotypic characteristics of mesenchymal stem cells. (4) The proliferative capacity of adult permanent dental pulp stem cells was significantly lower than those of deciduous teeth and juvenile permanent dental pulp stem cells (P < 0.01). (5) mRNA expressions of osteoblast-related genes alkaline phosphatase and bone morphogenetic protein 2, lipoprotein lipase and peroxisome proliferator-activated receptor γ2, mRNA expressions of chondroblast related gene type II collagen α1 and cartilage oligomeric matrix protein in adult pulp stem cells of permanent teeth were significantly lower than those of deciduous teeth and juvenile permanent teeth pulp stem cells (P < 0.01). (6) Compared with adult dental pulp stem cells, human deciduous teeth and juvenile permanent teeth dental pulp stem cells have the stronger proliferative capacity and multidirectional differentiation potential, and are more suitable for clinical research and disease treatment. [ABSTRACT FROM AUTHOR]

In order to survive and replicate, Salmonella has evolved mechanisms to gain access to intestinal epithelial cells of the crypt. However, the impact of Salmonella Typhimurium on stem cells and progenitors, which are responsible for the ability of the intestinal epithelium to renew and protect itself, remains unclear. Given that intestinal organoids growth is sustained by stem cells and progenitors activity, we have used this model to document the effects of Salmonella Typhimurium infection on epithelial proliferation and differentiation, and compared it to an in vivo model of Salmonella infection in mice. Among gut segments, the caecum was preferentially targeted by Salmonella. Analysis of infected crypts and organoids demonstrated increased length and size, respectively. mRNA transcription profiles of infected crypts and organoids pointed to upregulated EGFR-dependent signals, associated with a decrease in secretory cell lineage differentiation. To conclude, we show that organoids are suited to mimic the impact of Salmonella on stem cells and progenitors cells, carrying a great potential to drastically reduce the use of animals for scientific studies on that topic. In both models, the EGFR pathway, crucial to stem cells and progenitors proliferation and differentiation, is dysregulated by Salmonella, suggesting that repeated infections might have consequences on crypt integrity and further oncogenesis. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to characterize incidences of CMV reactivations within one year post-allo-SCT and identify risk factors for CMV second reactivation episode in population with high seropositivity where first CMV reactivation episode deemed to be high. Methods: This retrospective cohort study analyzed data from 359 allo-SCT patients aged 14 and older admitted to a tertiary academic hospital. Data on demographic and clinical factors, CMV serostatus, conditioning regimens, graft-versus-host disease prophylaxis, engraftment time, and CMV reactivations were collected. Results: First and second CMV reactivations occurred in 88.9% and 18.4% of post-allo-SCT patients respectively. Patients were stratified into two groups based on primary disease necessitating allo-SCT, patients with malignant (Group 1) and non-malignant (Group 2) hematological disease. Factors associated with the second reactivation included cord blood as a stem cell source, human leukocyte antigen mismatch, acute graft-versus-host disease, and hematological malignancies. Patients with non-malignant hematological disease displayed better outcomes, including a higher rate of spontaneous clearance of first CMV reactivation (70% versus 49.4%) and lower rates of second CMV reactivation (9.6% versus 31%) than those with malignant hematological disease. The one-year overall survival rate was 87.7% (95.5% in non-malignant hematological disease and 78.13% in malignant hematological disease). Conclusion: Our findings are concordant with previous local study in regard to high rate of first CMV reactivation post-allo-SCT. It appears that patients with nonmalignant hematological disease had better outcomes, such as lower second CMV reactivation and higher survival rates compared to patients with malignant hematological disease. Further investigation is needed to identify other factors affecting recurrent CMV reactivations in allo-SCT in patients with malignant hematological disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Uranium, a fuel material widely used for nuclear reaction and a source of nuclear weapons, is an emerging pollutant threatening human health. This study investigates the impact of uranium poisoning on mesenchymal stem cells (MSCs), which are crucial for bone formation and healing. The role of gap junctional intercellular communication (GJIC) in uranium toxicity was also examined. The study found that increasing concentrations of uranyl nitrate led to greater damage to MSCs, as shown by TEM images and confirmed by cellular viability and DSB production. Apoptosis was notably higher at a concentration of 84 μM, causing significant membrane disruption. Interestingly, closely connected cell groups were more resistant to uranium toxicity compared to sparsely grown ones, which were weakened by the use of a GJIC inhibitor. Subsequently, an impairment of wound healing and connexin expression were observed after exposure to uranyl nitrate, which was more remarkable with the increase in concentration. This suggests that GJIC, which is linked to the integrity of cellular membranes, plays a role in the response to uranium toxicity. Bone is a major tissue for uranium deposition in human body. Considering mesenchymal stem cells (MSCs) play a vital role in bone formation and injury recovery, studying the mechanism of MSCs responding to uranium poisoning can benefit the understanding of bone damage and repair after uranium exposure. Cellular structural alterations were analyzed via transmission electron microscopy (TEM). Changes in cellular behaviors were assessed through cellular viability, apoptosis, and the production of DNA double-strand breaks (DSBs). In addition, the influence of gap junctional intercellular communication (GJIC) on uranium toxicity was assessed. The disruption of MSCs was elevated with the increase in uranyl nitrate concentration, as shown by TEM micrograph. This was verified by the results of cellular viability and DSB production. Interestingly, the results of apoptosis assay indicated significant apoptosis occurred, which was accompanied with an obvious disruption of cellular membranes. Furthermore, closely contacted cell confluence groups exhibited resistant to uranium poisoning in contrast to sparse growth groups, which can be eliminated with the pretreatment of a GJIC inhibitor in the close connection group. To verify the association between GJIC and cytotoxic effects of uranyl nitrate, GJIC function was evaluated by wound healing and cellular migration. The results showed an inhibition of the healing ratio and migration ability induced by the exposure of uranyl nitrate. The low transfer efficiency of the dye coupling experiment and depressed expression of gap functional protein connexins confirmed the impairment of GJIC function. These results suggest that uranium toxicity is involved with GJIC dysfunction. [ABSTRACT FROM AUTHOR]

Background: Stress urinary incontinence (SUI) is a common condition with a significant impact on the quality of life of female patients. The limitations of current treatment strategies have prompted the exploration of new effective and minimally invasive alternative approaches, including cell therapy. Methods: A literature search was conducted to update the current clinical status of stem cell therapy in the management of female stress urinary incontinence. Results: Over thirty clinical studies have been designed to assess the feasibility, safety and efficacy of cell therapy for female SUI. Despite differences in cell types and protocols, the overall treatment procedures were similar. Standard subjective and objective assessment tools, and follow-up periods ranged from 6 weeks to 6 years have been used. Cell injection has shown to be a safe therapy in the treatment of female SUI. However, the results from more recent randomized trials have shown less promising results than expected in restoring continence. Heterogeneous research methodologies using different cell types and doses make it difficult to draw conclusions about effectiveness. Several key points remain that need to be further explored in future clinical trials. Conclusion: To advance in the development of cell therapy, it is essential to know the mechanisms involved to be able to direct it properly, its efficacy and the durability of the injected cells. Rigorous and homogenized preclinical and clinical studies that demonstrate its scope and improve its application are necessary for validation in the treatment of female SUI. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic stem cell transplantation (HSCT) is considered as the last treatment option in many life-threatening diseases. The number of donated cells can affect transplantation success. This study attempted to investigate the relationship between the health-promoting lifestyle of allogeneic stem cell donors and the number of donated CD34+ and CD3+ cells. Materials and Methods: The study was a descriptive correlational study in which 100 peripheral blood stem cells donors participated. A demographic form and health-promoting lifestyle profile-II questionnaire were distributed to participants, and then cell separation was started. Afterward, the results of CD34 + and CD3 + cell counts, as well as other clinical parameters of the participants, were recorded. The collected data were analyzed by descriptive and analytical statistical methods . Results: The results showed that the mean total health-promoting lifestyle profile score for hematopoietic stem cell donors was 2.876±0.461. There was no significant relationship between the health- promoting lifestyle score and the number of CD34+, CD3+ cells and CD3+/CD34+ ratio. A positive and significant correlation was found between the weight of the donors and the number of CD34+ (P < 0.001) and CD3+ cells (P = 0.001). The number of CD34+ cells was significantly different between women and men (P = 0.009). Conclusion: Lifestyle had no significant effect on the number of CD3+/CD34+ cells. Moreover, the number of CD34+ cells was significantly higher in men, so males should be preferentially recruited as donors for the HSCT procedure. [ABSTRACT FROM AUTHOR]

Banking of umbilical cord blood (UCB) is performed to collect and store umbilical cord stem cells. Both public and private cord blood banks have been established around the world. The study aimed to determine the level of awareness of UCB banking among pregnant couples and to assess the attitude of the couples toward UCB banking. We also tried to explore the factors influencing the UCB banking donation and the couple's expectations of UCB banking in the future. A prevalidated questionnaire on UCB banking was administered, and the interview was conducted among the same pregnant couples (both husband and wife) attending the obstetrics and gynecology (OBG) outpatient department (OPD). Only 28% (N = 121) of the participants had heard of UCB banking, and only 12% had correct knowledge of UCB banking. Only 4.9% of participants had heard of public or private UCB banks. Only one couple of 121 has stored UCB in their previous pregnancy, and about 36% of couples were willing to store their newborn's UCB in the present pregnancy. Poor understanding continues to be a significant barrier to reaping the benefits of UCB and preservation. Obstetricians and pediatricians should take a more active role in educating patients about the benefits and drawbacks of UCB banking. [ABSTRACT FROM AUTHOR]

Hair is a biofilament with unique multi-dimensional values. In human, in addition to physiologic impacts, hair loss and hair related disorders can affect characteristic features, emotions, and social behaviors. Despite significant advancement, there is a dire need to explore alternative novel therapies with higher efficacy, less side effects and lower cost to promote hair growth to treat hair deficiency. Glucocorticoid-induced leucine zipper (GILZ) is a protein rapidly induced by glucocorticoids. Studies from our group and many others have suggested that a synthetic form of GILZ, TAT-GILZ, a fusion peptide of trans-activator of transcription and GILZ, can function as a potent regulator of inflammatory responses, re-establishing and maintaining the homeostasis. In this study, we investigate whether TAT-GILZ could promote and contribute to hair growth. For our pre-clinical model, we used 9–12 week-old male BALB/c and nude (athymic, nu/J) mice. We applied TAT-GILZ and/or TAT (vehicle) intradermally to depilated/hairless mice. Direct observation, histological examination, and Immunofluorescence imaging were used to assess the effects and compare different treatments. In addition, we tested two current treatment for hair loss/growth, finasteride and minoxidil, for optimal evaluation of TAT-GILZ in a comparative fashion. Our results showed, for the first time, that synthetic TAT-GILZ peptide accelerated hair growth on depilated dorsal skin of BALB/c and induced hair on the skin of athymic mice where hair growth was not expected. In addition, TAT-GILZ was able to enhance hair follicle stem cells and re-established the homeostasis by increasing counter inflammatory signals including higher regulatory T cells and glucocorticoid receptors. In conclusion, our novel findings suggest that reprofiling synthetic TAT-GILZ peptide could promote hair growth by increasing hair follicle stem cells and re-establishing homeostasis. [ABSTRACT FROM AUTHOR]

The effective treatment of various diseases requires not only medications but also precise delivery methods to the body and specific organs. In this regard, radiology plays a crucial role, acting as the eyes of physicians. In contrast, interventional radiology serves as its hands, acting as one of the most effective drug delivery systems. Among interventional radiology disciplines, arterial drug delivery through arteries holds paramount importance as organs primarily receive nourishment directly from them. Furthermore, regenerative medicine is a burgeoning field dedicated to repairing diverse body tissues without relying on pharmaceutical drugs. Stem cells, inherent in various parts of our bodies, are vital for tissue regeneration and reconstruction. Depending on the treatment approach, stem cells can be sourced from the patient's body (autologous) or another individual (allogeneic). There exist various types of stem cells across species, with regenerative properties observed in animals and even plants. However, targeted cell therapy is preferred over systematic injections throughout the body for better efficacy. This article aims to familiarize interventionalists with stem cells and provide them with a clear and helpful explanation of their functions, mechanisms of action, different sources, and other relevant aspects. This will help them select the most appropriate cells for their therapeutic purposes. By comprehensively understanding the significance of stem cells in interventional radiology, we can implement optimal methodologies to address diverse medical conditions efficiently. [ABSTRACT FROM AUTHOR]

A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells. First, we examine the unique characteristics of differentiated cell division, focusing on why differentiated cells are more susceptible than stem cells to accumulating mutations. Next, we investigate why the evolution of multicellularity in animals likely required plastic differentiated cells that maintain the capacity to return to the cell cycle and required the tumor suppressor p53. Finally, we examine an example of an evolutionarily conserved program for the plasticity of differentiated cells, paligenosis, which helps explain the origins of cancers that arise in adults. Altogether, we highlight new perspectives for understanding the development of cancer and new strategies for preventing carcinogenic cellular transformations from occurring. This review summarises emerging views on how differentiated cells become cancer cells and contribute to malignancies due to accumulating mutations, aberrant tissue repair programs and hijacked cell state plasticity. [ABSTRACT FROM AUTHOR]

Intestinal organoid is a new experimental model and is widely used in research on intestinal diseases and functional changes for its property in mimicking structures and functions of in vivo organs. In recent years, researchers have combined gene ⁃ editing technology with intestinal organoids, offering possibilities for elucidating the mechanisms of diseases and developing targeted therapies for these diseases. This review looks back on the applications of gene ⁃ editing in intestinal organoids and their future perspectives in disease modeling and drug development. [ABSTRACT FROM AUTHOR]

Background: Understanding human stem cell differentiation into osteoblasts and osteoclasts is crucial for bone regeneration and disease modeling. Numerous morphological techniques have been employed to assess this differentiation, but a comprehensive review of their application and effectiveness is lacking. Methods: Guided by the PRISMA framework, we conducted a rigorous search through the PubMed, Web of Science and Scopus databases, analyzing 254 articles. Each article was scrutinized against pre-defined inclusion criteria, yielding a refined selection of 14 studies worthy of in-depth analysis. Results: The trends in using morphological approaches were identified for analyzing osteoblast and osteoclast differentiation. The three most used techniques for osteoblasts were Alizarin Red S (mineralization; six articles), von Kossa (mineralization; three articles) and alkaline phosphatase (ALP; two articles) followed by one article on Giemsa staining (cell morphology) and finally immunochemistry (three articles involved Vinculin, F-actin and Col1 biomarkers). For osteoclasts, tartrate-resistant acid phosphatase (TRAP staining) has the highest number of articles (six articles), followed by two articles on DAPI staining (cell morphology), and immunochemistry (two articles with VNR, Cathepsin K and TROP2. The study involved four stem cell types: peripheral blood monocyte, mesenchymal, dental pulp, and periodontal ligament. Conclusion: This review offers a valuable resource for researchers, with Alizarin Red S and TRAP staining being the most utilized morphological procedures for osteoblasts and osteoclasts, respectively. This understanding provides a foundation for future research in this rapidly changing field. [ABSTRACT FROM AUTHOR]

Cycling myeloid cells (CMCs) are often detected from various tissues using single-cell RNA sequencing (scRNA-seq) datasets, however, their research value was not noticed before. For the first time, our study preliminarily revealed the origin, differentiation, and roles of CMCs in physiological processes. Particularly, subgroup a of cycling myeloid cells (aCMCs) were conclusively identified as belonging to a specific cell type. In an active state, aCMCs rapidly proliferate during the early stages of an embryonic development. With an individual maturing, most aCMCs differentiate into specialized cells, while a small portion of them enter an inactive or dormant state. Under pathological conditions, aCMCs restore their proliferative and differentiation capacities via activation or revival. The present study has set the stage for future research on CMCs by linking them with progenitors of immune cells, and provided a crucial starting point to understand the origin, differentiation, and roles of CMCs in various physiological and pathological processes, particularly those related to traumatic injury, cancer, and pathogen infection, leading to develop targeted therapies or interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Elbow osteoarthritis (OA) is a common cause of pain and lameness in dogs, often resulting from the developmental disorder elbow dysplasia. Currently, there is no effective treatment or cure for this disease. This study aimed to evaluate the effect of treating dogs with OA with stem cells (SVF, stromal vascular fraction) and blood plasma rich in platelets (PRP) derived from the dog's own fat and blood, respectively. The mixture was administered as a single injection into affected elbows. Nineteen dogs with elbow OA were treated with SVF and PRP. Subjective and objective evaluations were performed before treatment, after six months, and after a minimum of one year. A "Symmetry Squares" graphic presentation of objective gait forces (peak force and impulse) was also used to compare changes in gait over time. The results showed that subjective evaluation of clinical lameness was improved at the six-month follow up evaluation and that the peak force was transferred from the hind limbs to the front limbs in the treated dogs after 12 months. However, the treatment failed to show a general evident effect. Further research should be conducted to evaluate whether SVF and PRP treatment should be recommended for dogs with elbow OA. (1) Background: The aim of the current pilot study was to describe the long-term effects of a single intra-articular injection of autologous stromal vascular fraction (SVF) with platelet-rich plasma (PRP) in dogs with confirmed elbow OA, using orthopedic lameness scoring and kinetic and kinematic gait analysis. For comparison of normal long-term variation of gait over time, a group of healthy control dogs (CDs) was also evaluated. (2) Methods: A prospective longitudinal clinical pilot study investigating 19 client-owned dogs with elbow OA (OADs) treated with SVF and PRP and eight CDs not receiving treatment. The OAD and CD groups were evaluated before and after 6 and at least 12 months following treatment with SVF and PRP (OAD group) and twice with a six-month interval (CD group), respectively, through orthopedic examinations, goniometry, and kinetic and kinematic analyses (seven variables). (3) Results: The OAD had an increase in fore–hind peak force symmetry ≥12 months after treatment (p < 0.05), but no other objective variables changed over time. Orthopedic consensus scores had improved at ≥six months follow-up evaluation (p < 0.05). None of the investigated gait variables had changed at ≥six months follow-up evaluation in the CD group. (4) Conclusions: The current study could not confirm a significant benefit from SVF and PRP treatment in OADs, but future studies should be conducted in order to fully evaluate the potential of the treatment. The improvement seen in fore–hindlimb symmetry may represent an improvement in gait or an incidental finding. [ABSTRACT FROM AUTHOR]

Background/Aim: Dermal papilla (DP) stem cells are known for their remarkable regenerative capacity, making them a valuable model for assessing the effects of natural products on cellular processes, including stemness, and autophagy. Materials and Methods: Autophagy and stemness characteristics were assessed using real-time RT-PCR to analyze mRNA levels, along with immunofluorescence and western blot techniques for protein level evaluation. Results: Butterfly Pea, Emblica Fruits, Kaffir Lime, and Thunbergia Laurifolia extracts induced autophagy in DP cells. Kaffir Lime-treated cells exhibited increase in the OCT4, NANOG, and SOX2 mRNA (6-, 5, and 5.5-fold, respectively), and protein levels (4-, 3-, and 1.5-fold, respectively). All extracts activated the survival protein kinase B (Akt) in DP cells. Conclusion: Natural products are a promising source for promoting hair growth by rejuvenating hair stem cells. [ABSTRACT FROM AUTHOR]