Regenerative potential of mesenchymal stromal cells in wound healing: unveiling the influence of normoxic and hypoxic environments

The innate and adaptive immune systems rely on the skin for various purposes, serving as the primary defense against harmful environmental elements. However, skin lesions may lead to undesirable consequences such as scarring, accelerated skin aging, functional impairment, and psychological effects over time. The rising popularity of mesenchymal stromal cells (MSCs) for skin wound treatment is due to their potential as a promising therapeutic option. MSCs offer advantages in terms of differentiation capacity, accessibility, low immunogenicity, and their central role in natural wound-healing processes. To accelerate the healing process, MSCs promote cell migration, angiogenesis, epithelialization, and granulation tissue development. Oxygen plays a critical role in the formation and expansion of mammalian cells. The term “normoxia” refers to the usual oxygen levels, defined at 20.21 percent oxygen (160 mm of mercury), while “hypoxia” denotes oxygen levels of 2.91 percent or less. Notably, the ambient O2 content (20%) in the lab significantly differs from the 2%–9% O2 concentration in their natural habitat. Oxygen regulation of hypoxia-inducible factor-1 (HIF-1) mediated expression of multiple genes plays a crucial role in sustaining stem cell destiny concerning proliferation and differentiation. This study aims to elucidate the impact of normoxia and hypoxia on MSC biology and draw comparisons between the two. The findings suggest that expanding MSC-based regenerative treatments in a hypoxic environment can enhance their growth kinetics, genetic stability, and expression of chemokine receptors, ultimately increasing their effectiveness

Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes Can Alleviate the Proctitis Model Through TLR4/NF-Κb Pathway

Background: Proctitis is a significant concern of inflammatory bowel diseases, especially ulcerative colitis. Exosomes are a new method for treating many diseases by their immunosuppressive and tissue-repairing potential. Here, we tried Mesenchymal stem cells (MSCs)-derived Exosomes for treating the proctitis model of rats. Materials and Methods: Rats were assigned into four groups: sham, control group, rectal, and intraperitoneal exosome injection. The proctitis model was induced by rectal administration of 4% acetic acid. The exosome was derived from human MSCs isolated from human umbilical cords. After seven days, rectum samples were assessed for histopathological, IHC, and PCR analysis. Results: The histopathologic scores, collagen deposition, and the expression of NF-κB, TLR4, TNFα, IL-6, and TGFβ were decreased in intraperitoneal exosome compared to controls. The result was not promising for the rectal administration of exosomes. Conclusion: Exosomes can suppress the inflammatory response in the proctitis model and improve the rectum's healing process. Exosomes can inhabit the NF-κB/TLR4 pathway and downstream pro-inflammatory cytokines. This study implicates the therapeutic benefits of exomes in treating proctitis

The clinical impact of mRNA therapeutics in the treatment of cancers, infections, genetic disorders, and autoimmune diseases

mRNA-based therapeutics have revolutionized medicine and the pharmaceutical industry. The recent progress in the optimization and formulation of mRNAs has led to the development of a new therapeutic platform with a broad range of applications. With a growing body of evidence supporting the use of mRNA-based drugs for precision medicine and personalized treatments, including cancer immunotherapy, genetic disorders, and autoimmune diseases, this emerging technology offers a rapidly expanding category of therapeutic options. Furthermore, the development and deployment of mRNA vaccines have facilitated a prompt and flexible response to medical emergencies, exemplified by the COVID-19 outbreak. The establishment of stable and safe mRNA molecules carried by efficient delivery systems is now available through recent advances in molecular biology and nanotechnology. This review aims to elucidate the advancements in the clinical applications of mRNAs for addressing significant health-related challenges such as cancer, autoimmune diseases, genetic disorders, and infections and provide insights into the efficacy and safety of mRNA therapeutics in recent clinical trials

Advances in novel strategies for isolation, characterization, and analysis of CTCs and ctDNA

Over the past decade, the detection and analysis of liquid biopsy biomarkers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have advanced significantly. They have received recognition for their clinical usefulness in detecting cancer at an early stage, monitoring disease, and evaluating treatment response. The emergence of liquid biopsy has been a helpful development, as it offers a minimally invasive, rapid, real-time monitoring, and possible alternative to traditional tissue biopsies. In resource-limited settings, the ideal platform for liquid biopsy should not only extract more CTCs or ctDNA from a minimal sample volume but also accurately represent the molecular heterogeneity of the patient’s disease. This review covers novel strategies and advancements in CTC and ctDNA-based liquid biopsy platforms, including microfluidic applications and comprehensive analysis of molecular complexity. We discuss these systems’ operational principles and performance efficiencies, as well as future opportunities and challenges for their implementation in clinical settings. In addition, we emphasize the importance of integrated platforms that incorporate machine learning and artificial intelligence in accurate liquid biopsy detection systems, which can greatly improve cancer management and enable precision diagnostics

Incorporation of two‐dimensional nanomaterials into silk fibroin nanofibers for cardiac tissue engineering

info:eu-repo/semantics/publishe

Diagnostic accuracy of ESR1 mutation detection by cell-free DNA in breast cancer: a systematic review and meta-analysis of diagnostic test accuracy

Abstract Background Estrogen receptors express in nearly 70% of breast cancers (ER-positive). Estrogen receptor alpha plays a fundamental role as a significant factor in breast cancer progression for the early selection of therapeutic approaches. Accordingly, there has been a surge of attention to non-invasive techniques, including circulating Cell-free DNA (ccfDNA) or Cell-Free DNA (cfDNA), to detect and track ESR1 genotype. Therefore, this study aimed to examine the diagnosis accuracy of ESR1 mutation detection by cell-free DNA in breast cancer patientsthrough a systematic review and comprehensive meta-analysis. Methods PubMed, Embase, and Web of Science databases were searched up to 6 April 2022. Diagnostic studies on ESR1 measurement by cfDNA, which was confirmed using the tumour tissue biopsy, have been included in the study. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were considered to analyse the data. Results Out of 649 papers, 13 papers with 15 cohorts, including 389 participants, entered the meta-analyses. The comprehensive meta-analysis indicated a high sensitivity (75.52, 95% CI 60.19–90.85), specificity (88.20, 95% CI 80.99–95.40), and high accuracy of 88.96 (95% CI 83.23–94.69) for plasma ESR1. We also found a moderate PPV of 56.94 (95% CI 41.70–72.18) but a high NPV of 88.53 (95% CI 82.61–94.44). We also found an NLR of 0.443 (95% CI 0.09–0.79) and PLR of 1.60 (95% CI 1.20–1.99). Conclusion This systematic review and comprehensive meta-analysis reveal that plasma cfDNA testing exhibits high sensitivity and specificity in detecting ESR1 mutations in breast cancer patients. This suggests that the test could be a valuable diagnostic tool. It may serve as a dependable and non-invasive technique for identifying ESR1 mutations in breast cancer patients. However, more extensive research is needed to confirm its prognostic value

Multifunctional stimuli-responsive niosomal nanoparticles for co-delivery and co-administration of gene and bioactive compound: In vitro and in vivo studies

This study aims to optimize niosomes for carrying and delivering the anticancer agents and genes, simultaneously. We synthesized new cationic niosomal formulations containing Tween 80, Tween 60, cholesterol, and dioleoyl-3-trimethylammonium propane (DOTAP) as a platform to enhance transfection efficacy and stability. Curcumin as an anticancer drug was entrapped with high efficacy inside stable spherical niosomes with sufficient positive charges of about + 27 mV. Loading niosomal curcumins with microRNA-34a (miR-34a) decreased the surface charge to + 15 mV and enhanced the diameter to near 68 nm. The in vitro studies were performed to investigate the cytotoxicity, cellular uptake, and gene expression profiling of normal and cancer cells treated by free curcumin, free miR-34a, niosomal curcumin (NCur), niosomal miR-34a (NmiR), niosomal curcumin + miR-34a (NCur-miR) which is termed as co-delivery, and niosomal curcumin + niosomal miR-34a which is termed as co-administration. Results showed that co-delivery caused more cytotoxicity, uptake, and anticancer activity in cancer cells than in other groups. Most importantly, niosomal and free forms of curcumin and miR-34a showed less toxicity to normal human cells. Besides, the effect of these anticancer agents was studied on the 4 T1 xenografted Balb/C mouse tumor model. Co-delivery of curcumin and miR-34a to cancer models caused a higher tumor inhibition rate than other groups. Thus, a combined therapy of curcumin and miR-34a using the new cationic niosomal delivery can be recognized as a prominent strategy for more effective cancer treatments

Microfluidic-Based Droplets for Advanced Regenerative Medicine: Current Challenges and Future Trends

Microfluidics is a promising approach for the facile and large-scale fabrication of monodispersed droplets for various applications in biomedicine. This technology has demonstrated great potential to address the limitations of regenerative medicine. Microfluidics provides safe, accurate, reliable, and cost-effective methods for encapsulating different stem cells, gametes, biomaterials, biomolecules, reagents, genes, and nanoparticles inside picoliter-sized droplets or droplet-derived microgels for different applications. Moreover, microenvironments made using such droplets can mimic niches of stem cells for cell therapy purposes, simulate native extracellular matrix (ECM) for tissue engineering applications, and remove challenges in cell encapsulation and three-dimensional (3D) culture methods. The fabrication of droplets using microfluidics also provides controllable microenvironments for manipulating gametes, fertilization, and embryo cultures for reproductive medicine. This review focuses on the relevant studies, and the latest progress in applying droplets in stem cell therapy, tissue engineering, reproductive biology, and gene therapy are separately evaluated. In the end, we discuss the challenges ahead in the field of microfluidics-based droplets for advanced regenerative medicine