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Mesenchymal Stem Cell-Derived Exosomes Improve Aging-Related Changes in Liver Lipid Metabolism by Enhancing Autophagy.

Health problems associated with aging have become increasingly severe in recent years. For example, hepatic lipid metabolism declines as the body ages, leading to lipid metabolic disorders. Although exosomes have been explored for treating metabolic diseases, there is currently a paucity of research regarding aging-related changes in hepatic lipid metabolism. Herein, we cultured human umbilical cord mesenchymal stem cells (HucMSCs), from which we extracted HucMSC-derived exosomes (HucMDEs). We then established a natural aging mouse model in vivo and a palmitic acid-induced AML12 cell model in 

Connexin 43-dependent mesenchymal stem cell mitochondrial transfer activates PGC1α disrupting oxidative-inflammation axis in ischemia-reperfusion injury.

Ischemia-Reperfusion Injury-related Acute Kidney Injury (IRI-AKI) is a significant clinical challenge. Despite extensive research into the underlying mechanism for IRI-AKI, the development of effective therapeutic interventions remains challenging due to self-perpetuating positive-feedback loops between oxidative stress and inflammation pathways. Mitochondrial dysfunction has been acknowledged as a significant player in the early stages of IRI in causing cellular damage. However, antioxidant therapy has only yielded modest improvements in outcomes. Interestingly, Mesenchymal Stem/Stromal Cells

Innervation of Human Intestinal Organoids.

The complexity of intestinal cytoarchitecture and function poses significant challenges for the creation of the bioengineered small intestine. Techniques for generating human intestinal organoids (HIOs) resembling human small intestine have been previously reported. HIOs contain epithelium and mesenchyme but lack other critical components of functional intestine such as the enteric nervous system (ENS), immune cells, vasculature, and microbiome. Two independent research groups have published distinct methods to innervate HIOs with an ENS. Here we discuss a unique method of incorporating the EN

Human blood preconditioned porcine arteries as potential conduits for human transplantation: Proof of concept in rabbit.

Tissue-engineered arteries using natural scaffolds could overcome the drawbacks of autografts or artificial conduits used in the repair of many congenital cardiac defects and coronary artery bypass grafts. In this study, we present a novel approach based on the use of decellularized xenogeneic matrix scaffolds preconditioned with human peripheral blood stem cells for future cardiovascular therapy. Cellular components of porcine carotid arteries (n = 40) were removed with physical, chemical and enzymatic means. The decellularized arteries were preconditioned by perfusion with human peripheral b

Advancements in Spinal Cord Injury Treatment: Integrating Drug Delivery, Biophysical Stimulation, Cell-Based Therapies, and Tissue Engineering Approaches.

Spinal cord injuries, whether resulting from traumatic or nontraumatic events, have severe and lasting detrimental effects on individuals, significantly impacting their overall health, mobility, and quality of life. The limited regenerative capacity of the spinal cord is mainly due to neuronal damage, the presence of inhibitory molecules, an impaired immune response, and the formation of glial scars, all of which create a hostile environment for neural repair and functional recovery. The majority of SCIs are caused by traffic accidents and falling objects. The current global treatments used fo

Generation and characterization of two induced pluripotent stem cell lines (ICGi052-A and ICGi052-B) from a patient with frontotemporal dementia with parkinsonism-17 associated with the pathological variant c.2013T>G in the MAPT gene.

Frontotemporal dementia with parkinsonism-17 is a neurodegenerative disease characterised by pathological aggregation of the tau protein with the formation of neurofibrillary tangles and subsequent neuronal death. The inherited form of frontotemporal dementia can be caused by mutations in several genes, including the MAPT gene on chromosome 17, which encodes the tau protein. As there are currently no medically approved treatments for frontotemporal dementia, there is an urgent need for research using in vitro cell models to understand the molecular genetic mechanisms that lead to the developme

Procyanidin B2 targeted CCR7 expression to inhibit the senescence-associated secretory phenotype through the NF-κB pathway to promote osteogenic differentiation of periodontal ligament stem cells in periodontitis.

Periodontitis is recognized as a chronic inflammatory disease, with aging emerging as a significant risk factor. Cellular senescence plays a crucial role in the biological process of aging. The senescence-associated secretory phenotype (SASP) is characterized by a series of pro-inflammatory factors, chemokines, and proteases, which are hallmark characteristics of senescent cells. These factors collectively alter the local environment, impacting the function of periodontal ligament stem cells (PDLSCs). Procyanidin B2 (PB2), the main dimer of oligomeric procyanidins, possesses antioxidant, anti-

3D printed sodium alginate/gelatin/tannic acid/calcium chloride scaffolds laden bone marrow mesenchymal stem cells to repair defective thyroid cartilage plate.

Due to the absence of blood vessels, cartilage exhibits extremely limited self-repair capacity. Currently, repairing laryngeal cartilage defects, resulting from conditions such as laryngeal tumors, injury, and congenital structural abnormalities, remains a significant challenge in the Department of Otolaryngology, Head and Neck Surgery. Previous research has often focused on enhancing the mechanical properties of synthetic materials. However, their low biological activity and weak cell adhesion necessitate compensatory measures. This study aims to capitalize on the advantages of natural materi

Tirbanibulin (KX2-391) analog KX2-361 inhibits botulinum neurotoxin serotype A mediated SNAP-25 cleavage in pre- and post-intoxication models in cells.

Botulinum neurotoxins (BoNT) inhibit neuroexocytosis, leading to the potentially lethal disease botulism. BoNT serotype A is responsible for most human botulism cases, and there are no approved therapeutics to treat already intoxicated patients. A growing body of research has demonstrated that BoNT/A can escape into the central nervous system, and therefore, identification of BoNT/A inhibitors that can penetrate BBB and neutralize the toxin within intoxicated neurons would be important. We previously identified an FDA-approved, orally bioavailable compound, KX2-391 (Tirbanibulin) that inhibits

Zidovudine and Interferon Alfa based regimens for the treatment of adult T-cell leukemia/lymphoma (ATLL): a systematic review and meta-analysis.

BACKGROUND: ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1 (HTLV-1), is challenging to treat. There is no known treatment for ATLL as of yet. However, it is recommended to use Zidovudine and Interferon Alfa-based regimens (AZT/IFN), chemotherapy, and stem cell transplant. This study aims to review the outcome of patients with different subtypes of ATLL treated with Zidovudine and Interferon Alfa-based regimens. METHODS: A systematic search was carried out for articles evaluatin

Immunomodulatory effect of mushrooms and their bioactive compounds in cancer: A comprehensive review.

Despite enormous development in the field of drug development, cancer still remains elusive. Compromised immunity stands as a roadblock to the successful pharmacological execution of anti-cancer drugs used clinically currently. Recently some breakthrough cancer treatment strategy like nano-formulation, extracellular vesicles treatment, natural antioxidant therapy, targeted immunotherapy, gene therapy, thermal ablation and magnetic hyperthermia, and pathomics and radiomics has been developed and tested pre-clinically as well as clinically. However, clinical efficacy of such therapies is yet to

Beneficial Effect of Human Induced Pluripotent Stem Cell-Derived Neural Precursors in Spinal Cord Injury Repair.

Despite advances in our understanding and research of induced pluripotent stem cells (iPSCs), their use in clinical practice is still limited due to lack of preclinical experiments. Neural precursors (NPs) derived from a clone of human iPSCs (IMR90) were used to treat a rat spinal cord lesion 1 week after induction. Functional recovery was evaluated using the BBB, beam walking, rotarod, and plantar tests. Lesion morphology, endogenous axonal sprouting, graft survival, and iPSC-NP differentiation were analyzed immunohistochemically. Quantitative polymerase chain reaction (qPCR) was used to eval

Fetuin-a in the developing brain.

The serum protein fetuin-A is essential for mineral homeostasis and shows immunomodulatory functions, for example by binding to TGF superfamily proteins. It proved neuroprotective in a rat stroke model and reduced lethality after systemic lipopolysaccharide challenge in mice. Serum fetuin-A concentrations are highest during intrauterine life. Different species show intrauterine cerebral fetuin-A immunoreactivity, suggesting a contribution to brain development. We therefore aimed at specifying fetuin-A immunoreactivity in brains of newborn rats (age P0-P28) and human neonates (20-40 weeks of ge

Analysis of human auricular cartilage to guide tissue-engineered nanofiber-based chondrogenesis: implications for microtia reconstruction.

OBJECTIVE: Nanofiber-supported, in vitro-generated cartilage may represent an optimal starting material for the development of a cartilage implant for use in microtia reconstruction. To do so, the authors aim to first characterize the molecular composition of endogenous auricular cartilage and determine if human umbilical cord mesenchymal stem cells (hUCMSCs) can be differentiated into cartilage in vitro. STUDY DESIGN: Prospective, controlled. SETTING: Academic research laboratory. SUBJECTS AND METHODS: Human ear cartilage from normal adults, pediatric patients with microtia, and pediatric

Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis.

Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers

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… Characteristic of CSC A landmark discovery in 1997 by Dick and Bonnet significantly advanced the field of stem cell research, as they successfully isolated CSCs with a distinct CD34 + CD38 − phenotype, exhibiting robust proliferative potential in acute myeloid leukemia [ 63 ]. … Unimolecular Self-Assembled Hemicyanine–Oleic Acid Conjugate Acts as a Novel Succinate Dehydrogenase Inhibitor to Amplify Photodynamic Therapy and Eliminate Cancer Stem Cells Research 2023 6 223 10.34133/research.0223 37680304 PMC10482163 14. Chen J. Fan T. Xie Z. Zeng Q. Xue P. Zheng T. Chen Y. …

Evaluation of Safety and Efficacy of Cell Therapy Based on Osteoblasts Derived from Umbilical Cord Mesenchymal Stem Cells for Osteonecrosis of the Femoral Head: Study Protocol for a Single-Center, Open-Label, Phase I Clinical Trial.

Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 ×

Innate immunity and immunotherapy for hemorrhagic shock.

Hemorrhagic shock (HS) is a shock result of hypovolemic injury, in which the innate immune response plays a central role in the pathophysiology ofthe severe complications and organ injury in surviving patients. During the development of HS, innate immunity acts as the first line of defense, mediating a rapid response to pathogens or danger signals through pattern recognition receptors. The early and exaggerated activation of innate immunity, which is widespread in patients with HS, results in systemic inflammation, cytokine storm, and excessive activation of complement factors and innate immun

Downregulated fat mass and obesity-associated protein inhibits bone resorption and osteoclastogenesis by nuclear factor-kappa B inactivation.

During osteoporosis, fat mass and obesity-associated protein (FTO) promotes the shift of bone marrow mesenchymal stem cells to adipocytes and represses osteoblast activity. However, the role and mechanisms of FTO on osteoclast formation and bone resorption remain unknown. In this study, we investigated the effect of FTO on RAW264.7 cells and bone marrow monocytes (BMMs)-derived osteoclasts in vitro and observed the influence of FTO on ovariectomized (OVX) mice model to mimic postmenopausal osteoporosis in vivo. Results found that FTO was up-regulated in BMMs from OVX mice. Double immunofluores

Comparative study on the therapeutic effects of bone marrow mesenchymal stem cells versus platelet rich plasma on the pancreas of adult male albino rats with streptozotocin-induced type 1 diabetes mellitus.

BACKGROUND: The optimal treatment for autoimmune type 1 diabetes mellitus (T1DM) is endogenous regeneration of the pancreatic beta-cell. This can be achieved either by transplanting bone marrow mesenchymal stem cells (BMSCs) or injecting platelet-rich plasma (PRP). Current research reviewed a T1DM model and compared the effect of BMSCs on exocrine and endocrine pancreas portions versus PRP. MATERIALS AND METHODS: Rats were divided into four groups: Control group, Diabetic group (single streptozotocin dose 60 mg/kg IP), Diabetic + PRP group (PRP, 0.5 mL/kg SC twice weekly/4 weeks given to diab