Rheumatic diseases are chronic immune-mediated disorders affecting multiple organ systems and significantly impairing patients' quality of life. Current treatments primarily provide symptomatic relief without offering a cure. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their ability to differentiate into various cell types and their immunomodulatory, anti-inflammatory, and regenerative properties. This review aims to summarize the clinical progress of MSC therapy in rheumatic diseases, highlight key findings from preclinical and clinical studies, and discuss challenges and future directions.

Neuroblastoma (NB), the common extracranial solid tumor in children, is associated with a poor prognosis, particularly in high-risk patients. MYCN amplification stands as the most prominent molecular hallmark within this high-risk subgroup. However, MYCN protein is considered "undruggable" due to its lack of a conventional enzymatic binding pocket and its predominant nuclear localization, which precludes targeting by standard small-molecule inhibitors or antibody-based therapeutics. Consequently, current therapeutic strategies have achieved limited efficacy against MYCN-driven NB. Notably, MYCN not only orchestrates diverse metabolic reprogramming pathways in tumors but also exerts a pivotal influence on cellular differentiation. To overcome this therapeutic barrier, we seek to elucidate the contribution of purine metabolism to stemness maintenance in MYCN-amplified NBs and to discover novel small-molecule inhibitors capable of inducing differentiation in high-risk NBs.

This research aimed to investigate the potential of Pogostemon cablin Benth's ethanolic extract (PCEE) as an antiaging agent.

Non-obstructive azoospermia (NOA) represents a severe form of male infertility, characterized by the absence of sperm in the ejaculate due to impaired spermatogenesis. Spermatogonial stem cells (SSCs), which ensure continuous sperm production, are critical for maintaining male fertility. Despite their importance, the molecular mechanisms governing SSC fate determination and their role in NOA pathogenesis remain incompletely understood. This study investigates the regulatory networks underlying SSC dysfunction in NOA patients.

Royal jelly (RJ), a honeybee product, is used as a cosmetic and food ingredient to improve skin condition. However, the influences of RJ on hair growth remain unclear. In this study, we investigated whether RJ regulates hair follicle development, hair shaft formation, and proliferation of hair follicle stem cells (HFSCs) using a gentle anagen induction model by shaving the back skin and a forced anagen induction model by depilating the back skin in mice. The results showed that topical application of RJ on depilated skin induced thinning of the hair shaft and smaller hair bulb formation during the anagen phase. In addition, RJ suppressed the proliferation of CK15-positive HFSCs in hair follicles at the early and middle anagen stages of shaved back skin. RJ suppressed the proliferation of cultured HFSCs in vitro. These findings suggested that RJ induces the formation of thin hair shafts by suppressing the HFSC proliferation.

Macrophage migration inhibitory factor (MIF) is a key modulator of innate and adaptive immunity that has been extensively reported to promote tumor cell survival, proliferation, and metastasis. A recent study focusing on the microenvironment of acute myeloid leukemia (AML) showed that pharmacological inhibition of MIF signaling, in vitro as well as in vivo, reduces AML cell survival. Such data highlights the crucial role of MIF in AML pathogenesis and support the efforts for developing selective MIF modulators. Here, we report the identification and crystallographic characterization of a MIF inhibitor (compound 1) with an allosteric binding motif. Single point screening of 1 against a panel of National Cancer Institute (NCI) 60 human tumor cell lines revealed a selective antitumor activity for the AML cell line HL-60. After confirming the protein's expression in multiple AML cell lines, we utilized 1 to extract mechanistic insights into MIF action. Our findings demonstrate that AML cells utilize an MIF-dependent proliferation mechanism, which upon inhibition triggers a G0/G1 cell cycle arrest of the malignant cells. Complementary analysis of the MIF receptors utilizing neutralizing antibodies and selective small molecule antagonists associates this effect with inhibition of CD74 activation. The collection of data presented herein highlights the important role of MIF in proliferation of AML cells and points to the need of developing small molecule anticancer therapeutics that target MIF signaling.

Prostate cancer (PC) is the most frequently diagnosed cancer and the second leading cause of cancer deaths in American men. While localized cases can be cured through surgery or local radiation, metastatic PC lacks curative therapy. The challenges to the success of treating advanced PC include the adverse effects of current treatment strategies, the continuous generation of cancer cells by cancer stem cells, and tumor heterogeneity. To overcome these challenges, researchers have explored the prodrug approach for targeted, combination drug delivery or release of cytotoxic agents specifically to sites of metastatic PC to improve therapeutic efficacy while decreasing systemic toxicity. The objective of this study is to develop a dual drug conjugate with a prostate-specific antigen (PSA) peptide recognition sequence for PC-specific combination SN-38 and cabazitaxel delivery in the treatment of advanced PC. To achieve this, His-Ser-Ser-Lys-Leu-Glu terminated with the dibenzocyclooctyne (DBCO) functional group conjugated to SN-38 via a leucine spacer was synthesized. Similarly, His-Ser-Ser-Lys-Leu-Glu terminated with azido poly(ethylene glycol) conjugated to cabazitaxel via a leucine spacer was synthesized. The conjugates were linked together via click chemistry to synthesize a dual drug conjugate. In vitro exposure to exogenous PSA was found to trigger the release of cytotoxic drugs. The dual drug conjugate exhibited time- and concentration-dependent cytotoxicity in PC-3 and LNCaP PC cells. The observed cytotoxicity was also dependent on PSA expression in the cellular models tested. This study demonstrates the potential of peptide-drug conjugates for the delivery of combination chemotherapeutics for selective cytotoxicity to PC cells.

Understanding the biology of implant-associated infections is essential in order to provide adequate detection, prevention and therapeutic strategies. Advanced 3D in vitro models offer valuable insights into the complex interactions between cells and bacteria in the presence of implant materials. This review aims to give a comprehensive overview of current 3D in vitro models that mimic implant-associated infections.

Umbilical cord mesenchymal stem cell-derived (UCMSC-derived) secretome is anti- apoptotic, anti-inflammatory, antifibrotic, angiogenic, and tissue-regenerating. Thus, it may treat systemic lupus erythematosus (SLE). The aim of this study was to investigate the impact of the UCMSC-derived secretome on SLE patients' disease activity, using Mexican systemic lupus erythematosus disease activity index (MEX-SLEDAI) score, complement (C3 and C4) levels, tumor necrosis factor-alpha (TNF-α), anti-double-stranded DNA (anti-dsDNA), and interleukin-6 (IL-6) levels. This double-blind randomized controlled trial investigated the efficacy and safety of UCMSC-derived secretome in SLE patients with moderate disease activity. A total of 29 female patients were randomized into two groups to receive weekly 1.5 cc intramuscular injections of UCMSC-derived secretome or placebo (0.9% NaCl) for six weeks. Disease activity was assessed using the MEX-SLEDAI score, C3 and C4 levels, pro-inflammatory cytokines (IL- 6 and TNF-α), and anti-dsDNA antibodies at baseline, Day 22, and Day 43. Results showed a significant reduction in MEX-SLEDAI scores in the secretome group compared to the placebo group (p < 0.05). Complement C3 levels significantly increased in the secretome group on Day 43, indicating improved immune homeostasis, while C4 levels did not show significant differences between groups. IL-6 and TNF-α levels showed decreasing trends in the secretome group. Anti-dsDNA levels exhibited a decreasing trend in the secretome group, though not statistically significant. Importantly, no severe adverse events were observed, underscoring the safety of the intervention. UCMSC-derived secretome demonstrated immunomodulatory and anti-inflammatory effects, reducing disease activity in SLE patients. These findings suggest its potential as a safe and effective adjunct therapy for SLE, although further studies with larger sample sizes and extended follow-up periods are needed to validate these results.

The p53 signaling pathway plays a critical role in regulating the cell cycle, apoptosis, and senescence, making it a key target in cancer research. The aim of this study was to investigate the effects of an ethanol extract from the stem of Ziziphus nummularia on the proliferation and expression of genes involved in the p53 pathway in MCF-7 breast cancer cells. To achieve this, real-time quantitative PCR (RT-qPCR) was used to evaluate the mRNA expression of downstream genes linked to cell cycle and senescence, including CycE or CCNEl, RBLl, and E2F1. Molecular docking simulations using Molegro Virtual Docker (MVD) were also performed to assess the potential inhibitory activity of metabolite compounds from Z. nummularia stem against p53-regulating kinase (TP53RK). The results showed that the IC50 value of Z. nummularia stem ethanol extract against MCF-7 cells was 38.27 ± 0.72 μg/mL. The results also revealed a reduction in the expression of downstream genes linked to cell senescence and the cell cycle: CycE or CCNE1 (p = 0.011), RBL1 (p = 0.008), and E2F1 (p = 0.005), which was observed through RT-qPCR analysis of mRNA expression. This fact indicated that the inhibitory effects on proliferation by the ethanol extract of Z. nummularia stem might occur via pathways associated with cell senescence and cell cycle arrest. Molecular docking results of metabolite compounds from Z. nummularia stem suggested that squalene (Rerank score -112.70 kJ/mol), and nummularine B (Rerank score -110.68 kJ/mol) had potential as TP53RK inhibitors. These Rerank scores were smaller compared to the Rerank score of adenyl-imidodiphosphate (AMP-PNP), which was the native ligand of TP53RK, as confirmed by molecular dynamics analysis. These in silico results were confirmed by the decrease in p21 (CDKN1A) mRNA expression. In conclusion, the anti-proliferative effects of the ethanol extract from Z. nummularia stem on breast cancer cells occurred by affecting cell cycle-related genes and inhibiting apoptosis protection mediated by overexpression of p21 (CDKN1A) through p53 activity.

While hematopoietic stem cell transplantation is commonly associated with stem cell procedures in public discourse, "stem cell" remains a broad classification. More precise terminology such as "blood stem cell transplantation", "bone marrow transplantation", or "bone marrow stem cell transplantation" may better characterize hematopoietic stem cell procedures in both public and academic contexts. This study aimed to evaluate public comprehension of these specific terms and to assess awareness and attitudes toward stem cell donation, with particular focus on rural populations.

Recent studies have indicated that assessing the expression levels of cancer stem cell markers is critical in predicting the behavior of these neoplasms. This study aimed to evaluate and compare the expression levels of CD44 and epithelial cell adhesion molecule (EpCAM) markers in pleomorphic adenoma (PA) and mucoepidermoid carcinoma (MEC) using immunohistochemistry.

Hypertrophic scar (HS) is a fibrotic proliferative disorder that arises from an abnormal wound healing process. It is a significant clinical challenge, primarily characterized by the excessive accumulation of extracellular matrix (ECM) and abnormal angiogenesis. This study introduces a novel injectable hydrogel system that integrates sustained-release Exosomes for targeted hypertrophic scar modulation. Exosomes (Exos) from adipose-derived stem cells (ASCs) are emerging as promising treatment for hypertrophic scar inhibition. But when treated independently, it must be applied regularly multiple times to maintain its optimal concentration. Gelatin Methacryloyl (GelMA) hydrogel is an ideal biomaterial candidate for engineering skin tissues because of its similarity to ECM, and importantly GelMA hydrogel can maintain drug concentrations via the encapsulation and sustained release of it, which enhances the potential of clinical applications.

Introduction: Hypertrophic and keloid scars are abnormal tissue growth that can be disfiguring, for which the available treatment has not yielded consistent results. Therefore, this study aimed to evaluate the capability of Adipose tissue-derived stem cell (ADSC) therapy in treating these scars. Methods: A literature search was conducted on PubMed, Scopus, Cochrane Library, and Web of Science from inception until July 2022. We included experimental studies that evaluated ADSCs as a therapy for hypertrophic and keloid scars in both in-vivo and in-vitro models. Results: Our findings extracted from 12 included studies demonstrated that ADSCs have a promising potential in reducing collagen deposition, proliferation, and migration rates of fibroblast, decreasing gene/protein expression of scar-related molecules including levels of TGF-β1 and lowering intracellular signal pathway-related molecules of hypertrophic and keloid scars in both models. However, no significant difference (P > .05) was found in the hypertrophic scar in-vitro models in terms of DCN gene expression. Conclusion: Ultimately, the current studies included in this systematic review support the use of ADSCs to alleviate hypertrophic and keloid scars.

Alzheimer's disease (AD) is a common progressive and irreversible neurodegenerative disease. AD accounts for 60%-70% of all dementia cases, ranking as the seventh leading cause of death globally. Human umbilical cord mesenchymal stem cells (hUC-MSCs) characterized by their abundant availability and low immunogenicity, have demonstrated significant therapeutic potential for AD in both preclinical studies and clinical trials. The use of exosomes can help mitigate the issues associated with cellular therapies. However, the clinical application of hUC-MSCs remains challenging due to their inability to effectively traverse the blood-brain barrier (BBB) and reach pathological sites. Therapeutic strategies utilizing exosomes derived from hUC-MSCs (Exos) have emerged as an effective approach for AD intervention.

Diabetic foot ulcers (DFU) represent one of the most common side effects of diabetes, significantly impacting patients' quality of life and imposing considerable financial burdens on families and society at large. Despite advancements in therapies targeting lower limb revascularization and various medications and dressings, outcomes for patients with severe lesions remain limited. A recent breakthrough in DFU treatment stems from the development of mesenchymal stem cells (MSCs). MSCs have shown promising results in treating various diseases and skin wounds due to their ability for multidirectional differentiation and immunomodulation. Recent studies highlight that MSCs primarily repair tissue through their paracrine activities, with exosomes playing a crucial role as the main biologically active components. These exosomes transport proteins, mRNA, DNA, and other substances, facilitating DFU treatment through immunomodulation, antioxidant effects, angiogenesis promotion, endothelial cell migration and proliferation, and collagen remodeling. Mesenchymal stem cell-derived exosomes (MSC-Exo) not only deliver comparable therapeutic effects to MSCs but also mitigate adverse reactions like immune rejection associated with MSCs transplantation. This article provides an overview of DFU pathophysiology and explores the mechanisms and research progress of MSC-Exo in DFU therapy.

Congenital long QT syndrome (LQTS) is a potentially life-threatening hereditary arrhythmia characterized by a prolonged QT interval on electrocardiogram (ECG) due to delayed ventricular repolarization. This condition predisposes individuals to severe arrhythmic events, including ventricular tachycardia and sudden cardiac death. Traditional approaches to LQTS research and treatment are limited by an incomplete understanding of its gene-specific pathophysiology, variable clinical presentation, and the challenges associated with developing effective, personalized therapies. Recent advances in human induced pluripotent stem cell (iPSC) technology have opened new avenues for elucidating LQTS mechanisms and testing therapeutic strategies. By generating cardiomyocytes from patient-specific iPSCs (iPSC-CMs), it is now possible to recreate the patient's genetic context and study LQTS in a controlled environment. This comprehensive review describes how iPSC technology deepens our understanding of LQTS and accelerates the development of tailored treatments, as well as ongoing challenges such as incomplete cell maturation and cellular heterogeneity.

The objective of this study was to investigate the relationship between both short-term and long-term tacrolimus exposure and overall survival after allogeneic stem cell transplantation and to propose individualized tacrolimus dosing based on the population pharmacokinetic model.

Alzheimer's disease (AD), the most common form of dementia, currently has no effective cure. Epimedii Folium (EF), a traditional Chinese medicine known as Yin-yang-huo, has demonstrated significant neuroprotective properties.