Comparison of the mesodermal differentiation potential between embryonic stem cells and scalable induced pluripotent stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) have promising potential in clinical application, whereas their limited amount and sources hinder their bioavailability. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have become prominent options in regenerative medicine as both possess the ability to differentiate into MSCs. METHODS: Recently, our research team has successfully developed human leukocyte antigen (HLA)-homozygous iPSC cell lines with high immune compatibility, covering 13.5% of the Taiwanese population. As we deepen our understanding of the differences between these ESCs and HLA-homozygous iPSCs, our study focused on morphological observations and flow cytometry analysis of specific surface marker proteins during the differentiation of ESCs and iPSCs into MSCs. RESULTS: The results showed no significant differences between the two pluripotent stem cells, and both of them demonstrated the equivalent ability to further differentiate into adipose, cartilage, and bone cells. CONCLUSION: Our research revealed that these iPSCs with high immune compatibility exhibit the same differentiation potential as ESCs, enhancing the future applicability of highly immune-compatible iPSCs.

Dysregulation of the circRNA_0087207/miR-548c-3p/PLSR1-TGFB2 axis in Leber hereditary optic neuropathy in vitro.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is mainly the degeneration of retinal ganglion cells (RGCs) associated with high apoptosis and reactive oxygen species (ROS) levels, which is accepted to be caused by the mutations in the subunits of complex I of the mitochondrial electron transport chain. The treatment is still infant while efforts of correcting genes or using antioxidants do not bring good and consistent results. Unaffected carrier carries LHON mutation but shows normal phenotype, suggesting that the disease's pathogenesis is complex, in which secondary factors exist and cooperate with the primary complex I dysfunction. METHODS: Using LHON patient-specific induced pluripotent stem cells (iPSCs) as the in vitro disease model, we previously demonstrated that circRNA_0087207 had the most significantly higher expression level in the LHON patient-iPSC-derived RGCs compared with the unaffected carrier-iPSC-derived RGCs. To elaborate the underlying pathologies regulated by circRNA_008720 mechanistically, bioinformatics analysis was conducted and elucidated that circRNA_0087207 could act as a sponge of miR-548c-3p and modulate PLSCR1/TGFB2 levels in ND4 mutation-carrying LHON patient-iPSC-derived RGCs. RESULTS: Using LHON iPSC-derived RGCs as the disease-based platform, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on targeted mRNA of miR-548c-3p showed the connection with apoptosis, suggesting downregulation of miR548c-3p contributes to the apoptosis of LHON patient RGCs. CONCLUSION: We showed that the downregulation of miR548c-3p plays a critical role in modulating cellular dysfunction and the apoptotic program of RGCs in LHON.

n-3 polyunsaturated fatty acids delay intervertebral disc degeneration by inhibiting nuclear receptor coactivator 4-mediated iron overload.

n-3 polyunsaturated fatty acids (PUFAs) are closely related to the progression of numerous chronic inflammatory diseases, but the role of n-3 PUFAs in the intervertebral disc degeneration (IVDD) remains unclear. In this study, male C57BL/6 wildtype mice (WT group, n = 30) and fat-1 transgenic mice (TG group, n = 30) were randomly selected to construct the IVDD model. The results demonstrated that the optimized composition of PUFAs in the TG mice had a significant impact on delaying IVDD and cellular senescence of intervertebral disc (IVD). Mechanismly, n-3 PUFAs inhibited IVD senescence by alleviating NCOA4-mediated iron overload. NCOA4 overexpression promoted iron overload and weakened the pro-proliferation and anti-senescence effect of DHA on the IVD cells. Furthermore, this study futher revealed n-3 PUFAs downregulated NCOA4 expression by inactiviting the LGR5/ß-catenin signaling pathway. This study provides an important theoretical basis for preventing and treating IVDD and low back pain.

Efficient induction of pluripotent stem cells differentiated into mesenchymal stem cell lineages.

BACKGROUND: Mesenchymal stem cells (MSCs) have garnered significant attention in the field of cell-based therapy owing to their remarkable capabilities for differentiation and self-renewal. However, primary tissue-derived MSCs are plagued by various limitations, including constrained tissue sources, arduous and invasive retrieval procedures, heterogeneous cell populations, diminished purity, cellular senescence, and a decline in self-renewal and proliferative capacities after extended expansion. Addressing these challenges, our study focuses on establishing a robust differentiation platform to generate mesenchymal stem cells derived from induced pluripotent stem cells (iMSCs). METHODS: To achieve this, we used a comprehensive methodology involving the differentiation of induced pluripotent stem cells into MSCss. The process was meticulously designed to ensure the expression of key MSC positive markers (CD73, CD90, and CD105) at elevated levels, coupled with the minimal expression of negative markers (CD34, CD45, CD11b, CD19, and HLA-DR). Moreover, the stability of these characteristics was evaluated across 10th generations. RESULTS: Our findings attest to the success of this endeavor. iMSCs exhibited robust expression of positive markers and limited expression of negative markers, confirming their MSC identity. Importantly, these characteristics remained stable even up to the 10th generation, signifying the potential for sustained use in therapeutic applications. Furthermore, our study demonstrated the successful differentiation of iMSCs into osteocytes, chondrocytes, and adipocytes, showcasing their multilineage potential. CONCLUSION: In conclusion, the establishment of induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) presents a significant advancement in overcoming the limitations associated with primary tissue-derived MSCs. The remarkable stability and multilineage differentiation potential exhibited by iMSCs offer a strong foundation for their application in regenerative medicine and tissue engineering. This breakthrough paves the way for further research and development in harnessing the full therapeutic potential of iMSCs.

Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation.

DNA cytosine methylation plays a vital role in repressing retrotransposons, and such derepression is linked with developmental failure, tumorigenesis and aging. DNA methylation patterns are formed by precisely regulated actions of DNA methylation writers (DNA methyltransferases) and erasers (TET, ten-eleven translocation dioxygenases). However, the mechanisms underlying target-specific oxidation of 5mC by TET dioxygenases remain largely unexplored. Here we show that a large low-complexity domain (LCD), located in the catalytic part of Tet enzymes, negatively regulates the dioxygenase activity. Recombinant Tet3 lacking LCD is shown to be hyperactive in converting 5mC into oxidized species in vitro. Endogenous expression of the hyperactive Tet3 mutant in mouse oocytes results in genome-wide 5mC oxidation. Notably, the occurrence of aberrant 5mC oxidation correlates with a consequent loss of the repressive histone mark H3K9me3 at ERVK retrotransposons. The erosion of both 5mC and H3K9me3 causes ERVK derepression along with upregulation of their neighboring genes, potentially leading to the impairment of oocyte development. These findings suggest that Tet dioxygenases use an intrinsic auto-regulatory mechanism to tightly regulate their enzymatic activity, thus achieving spatiotemporal specificity of methylome reprogramming, and highlight the importance of methylome integrity for development.

Leber's hereditary optic neuropathy: Update on the novel genes and therapeutic options.

A maternal inheritance disorder called Leber's hereditary optic neuropathy (LHON) is the most common primary mitochondrial deoxyribonucleic acid (DNA) disorder. In most studies, there are more male patients than female patients, which contradicts the usual pattern in mitochondrial hereditary diseases. This suggests that nuclear DNA (nDNA) may influence the degeneration of retinal ganglion cells (RGCs) in LHON. The primary cause of this is dysfunction in complex I of the electron transport chain, leading to ineffective adenosine triphosphate (ATP) production. In addition to MT-ND4 or MT-ND1 mutations, genes such as PRICKLE3 , YARS2 , and DNAJC30 , which come from nDNA, also play a role in LHON. These three genes affect the electron chain transport differently. PRICKLE3 interacts with ATP synthase (complex V) at Xp11.23, while YARS2 is a tyrosyl-tRNA synthetase 2 involved in mitochondria . DNAJC30 mutations result in autosomal recessive LHON (arLHON). Understanding how genes impact the disease is crucial for developing new treatments. Idebenone has been approved for treating LHON and has shown safety and efficacy in clinical trials. Mesenchymal stem cell-based therapy has also emerged as a potential treatment for LHON by transferring mitochondria into target cells. Gene therapy research focuses on specific gene mutations, and the wild-type ND4 gene target in the adeno-associated viruses (AAV) vector has shown promise in clinical trials as a potential treatment for LHON.

Overcoming the challenges of scalable iPSC generation in translation medicine.

BACKGROUND: The potential of induced pluripotent stem cells (iPSCs) in revolutionizing regenerative medicine cannot be overstated. iPSCs offer a profound opportunity for therapies involving cell replacement, disease modeling, and cell transplantation. However, the widespread application of iPSC cellular therapy faces hurdles, including the imperative to regulate iPSC differentiation rigorously and the inherent genetic disparities among individuals. To address these challenges, the concept of iPSC super donors emerges, holding exceptional genetic attributes and advantageous traits. These super donors serve as a wellspring of standardized, high-quality cell sources, mitigating inter-individual variations and augmenting the efficacy of therapy. METHODS: In pursuit of this goal, our study embarked on the establishment of iPSC cell lines specifically sourced from donors possessing the HLA type (A33:03-B58:01-DRB1*03:01). The reprogramming process was meticulously executed, resulting in the successful generation of iPSC lines from these carefully selected donors. Subsequently, an extensive characterization was conducted to comprehensively understand the features and attributes of these iPSC lines. RESULTS: The outcomes of our research were highly promising. The reprogramming efforts culminated in the generation of iPSC lines from donors with the specified HLA type. These iPSC lines displayed a range of distinctive characteristics that were thoroughly examined and documented. This successful generation of iPSC lines from super donors possessing advantageous genetic traits represents a significant stride towards the realization of their potential in therapeutic applications. CONCLUSION: In summary, our study marks a crucial milestone in the realm of regenerative medicine. The establishment of iPSC lines from super donors with specific HLA types signifies a paradigm shift in addressing challenges related to iPSC cellular therapy. The standardized and high-quality cell sources derived from these super donors hold immense potential for various therapeutic applications. As we move forward, these findings provide a solid foundation for further research and development, ultimately propelling the field of regenerative medicine toward new horizons of efficacy and accessibility.

HLA-Homozygous iPSC-Derived Mesenchymal Stem Cells Rescue Rotenone-Induced Experimental Leber's Hereditary Optic Neuropathy-like Models In Vitro and In Vivo.

BACKGROUND: Mesenchymal stem cells (MSCs) hold promise for cell-based therapy, yet the sourcing, quality, and invasive methods of MSCs impede their mass production and quality control. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) can be infinitely expanded, providing advantages over conventional MSCs in terms of meeting unmet clinical demands. METHODS: The potential of MSC therapy for Leber's hereditary optic neuropathy (LHON) remains uncertain. In this study, we used HLA-homozygous induced pluripotent stem cells to generate iMSCs using a defined protocol, and we examined their therapeutic potential in rotenone-induced LHON-like models in vitro and in vivo. RESULTS: The iMSCs did not cause any tumorigenic incidence or inflammation-related lesions after intravitreal transplantation, and they remained viable for at least nine days in the mouse recipient's eyes. In addition, iMSCs exhibited significant efficacy in safeguarding retinal ganglion cells (RGCs) from rotenone-induced cytotoxicity in vitro, and they ameliorated CGL+IPL layer thinning and RGC loss in vivo. Optical coherence tomography (OCT) and an electroretinogram demonstrated that iMSCs not only prevented RGC loss and impairments to the retinal architecture, but they also improved retinal electrophysiology performance. CONCLUSION: The generation of iMSCs via the HLA homozygosity of iPSCs offers a compelling avenue for overcoming the current limitations of MSC-based therapies. The results underscore the potential of iMSCs when addressing retinal disorders, and they highlight their clinical significance, offering renewed hope for individuals affected by LHON and other inherited retinal conditions.

Hyperactive DNA Cutting for Unbiased UHPLC-MS/MS Quantification of Epigenetic DNA Marks by Engineering DNase I Mutants.

Epigenetic DNA modifications, such as 5-methylcytosine, 5-hydroxymethylcytosine, and 5-formylcytosine, are associated with a variety of diseases and potential biomarkers for cancer diagnosis and therapy. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays are considered to be the gold standard for qualitative and quantitative detection of DNA modifications. DNA digestion for converting long DNA polymer into 2'-deoxynucleosides is an important preprocessing step to achieve sensitive and accurate LC-MS/MS quantification. Here, we showed that, as stimulated by divalent metal ions, Mg2+ and Mn2+, the engineered human DNase I Q9R:E13R:N74K mutant can efficiently digest DNA in the presence of monovalent metal ions at a high concentration (e.g., 1 M NaCl), showing hyperactivity on DNA cutting. We also found that the engineered DNase I mutants display exceptional DNA-cutting activity over a wider pH range (5.5-9.5). Due to their hyperactivity and high salt tolerance, the engineered DNase I mutants cut DNA 5mC and dC efficiently. Benefitting from this DNA-cutting hyperactivity, we demonstrated an LC-MS/MS assay for unbiased and accurate quantification of DNA 5mC.

Rare and misincorporated DNA N6-methyladenine is a hallmark of cytotoxic stresses for selectively stimulating the stemness and proliferation of glioblastoma cells.

The entity of DNA N6-methyladenine (6mA) in mammals remains elusive and subsequently its roles in diseases are poorly understood. Here we exploited a bacterial DNA contamination-free and ultrasensitive UHPLC-MS/MS assay to reassess DNA 6mA in human glioblastomas and unveiled that DNA 6mA (~0.08 ppm) is extremely rare. By the use of two independent heavy stable isotope-labeling strategies, we further prove that the observed 6mA is solely generated by DNA polymerase-mediated misinocorporation. In vitro experiments point toward that the generation of misincorporated DNA 6mA is associated with the cellular stresses-caused release of RNA N6-methyladenine (m6A) nucleoside, which is profoundly inhibited by hypoxia milieu. Consistently, compared with normal brain tissues, DNA 6mA decreases in hypoxic human gliomas. Our data also strongly support that rare DNA 6mA rather than relatively abundant DNA 5-methylcytosine and 5-hydroxymethylcytosine is a hallmark of poor prognosis of IDH1/2 mutation-absent glioblastoma patients, reflecting the incidence of cytotoxic stresses and subsequent release of m6A nucleoside. The released m6A nucleoside may selectively preserve a subset of the glioblastoma cells and stimulate their stemness and proliferation. Noteworthily, demethylation-inhibiting IDH1 mutation increases the DNA 6mA content in human gliomas, but the depletion of the demethylase candidate ALKBH1 fails to do so, together suggesting the presence of other unknown 6mA demethylase for erasing misincorporated DNA 6mA. This is the first report on the identification of the misincorporated 6mA together with its origin and roles in diseases.

Autophagy reprogramming stem cell pluripotency and multiple-lineage differentiation.

The cellular process responsible for the degradation of cytosolic proteins and subcellular organelles in lysosomes was termed "autophagy." This process occurs at a basal level in most tissues as part of tissue homeostasis that redounds to the regular turnover of components inside cytoplasm. The breakthrough in the autophagy field is the identification of key players in the autophagy pathway, compounded under the name "autophagy-related genes" (ATG) encoding for autophagy effector proteins. Generally, the function of autophagy can be classified into two divisions: intracellular clearance of defective macromolecules and organelles and generation of degradation products. Therapeutic strategies using stem cell-based approach come as a promising therapy and develop rapidly recently as stem cells have high self-renewability and differentiation capability as known as mesenchymal stem cells (MSCs). They are defined as adherent fibroblast-like population with the abilities to self-renew and multi-lineage differentiate into osteogenic, adipogenic, and chondrogenic lineage cells. To date, they are the most extensively applied adult stem cells in clinical trials. The properties of MSCs, such as immunomodulation, neuroprotection, and tissue repair pertaining to cell differentiation, processes to replace lost, or damaged cells, for aiding cell repair and revival. Autophagy has been viewed as a remarkable mechanism for maintaining homeostasis, ensuring the adequate function and survival of long-lived stem cells. In addition, authophagy also plays a remarkable role in protecting stem cells against cellular stress when the stem cell regenerative capacity is harmed in aging and cellular degeneration. Understanding the under-explored mechanisms of MSC actions and expanding the spectrum of their clinical applications may improve the utility of the MSC-based therapeutic approach in the future.

Molecular target therapeutics of EGF-TKI and downstream signaling pathways in non-small cell lung cancers.

Lung carcinoma (LC) is the third most common cancer diagnosis and accounted for the most cancer-related mortality worldwide in 2018. Based on the type of cells from which it originates, LC is commonly classified into non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). NSCLC account for the majority of LC and can be further categories into adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. Accurate classification of LC is critical for its adequate treatment and therapeutic outcome. Since NSCLC express more epidermal growth factor receptor (EGFR) with activation mutations, targeted therapy EGFR-tyrosine kinase inhibitors (TKIs) have been considered as primary option of NSCLC patients with activation EGFR mutation. In this review, we present the genetic alterations, reported mutations in EGFR, and TKIs treatment in NSCLC patients with an emphasis on the downstream signaling pathways in NSCLC progression. Among the signaling pathways identified, mitogen activation protein kinase (MAPK), known also as extracellular signal-regulated protein kinase (Erk) pathway, is the most investigated among the related pathways. EGFR activation leads to the autophosphorylation of its kinase domain and subsequent activation of Ras, phosphorylation of Raf and MEK1/2, and the activation of ERK1/2. Phosphatidylinositol 3-kinase (PI3K)/Akt is another signal pathway that regulates cell cycle and has been linked to NSCLC progression. Currently, three generations of EGFR TKIs have been developed as a first-line treatment of NSCLC patients with EGFR activation and mutation in which these treatment options will be further discussed in this review. The Supplementary Appendix for this article is available at http://links.lww.com/JCMA/A138.

Necrosulfonamide Selectively Induces DNA Double-Strand Breaks in Acute Myeloid Leukemia Cells.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy that causes endless pain for patients and accounts for thousands of deaths worldwide. The development of an effective AML treatment is a topic of ongoing interest. Here, we demonstrated that a pyroptosis inhibitor necrosulfonamide (NSA) can selectively induce highly toxic double-strand breaks and kill AML cells. Mechanistically, reactive oxygen species (ROS) were the key effectors mediating the toxicity of NSA. These results probably indicate that NSA is a novel candidate for the treatment of AML.

Predictive and prognostic factors for outcome of microvascular decompression in trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is a disease characterized by recurring, short-lived, electric shock-like pain experienced on one side of the face. Microvascular decompression (MVD) is one of the most effective surgical interventions for resolving TN caused by neurovascular compression. This study aimed to determine the predictive and prognostic factors of surgical outcomes. METHODS: This retrospective cohort study enrolled patients diagnosed with TN who underwent MVD at our hospital during 2013-2019. The demographic information, pain character, peri-operative Barrow Neurological Institute (BNI) scale, medication, operative finding were recorded. And the outcome was Outcomes were divided into drug-free and drug-dependent group. Predisposing factors for each outcome were analyzed by one-way analysis of variance, followed by a Mann-Whitney U test or Kruskal-Wallis test. RESULTS: A total of 104 consecutive patients received MVD to treat TN, and 88 patients were enrolled in this study. The overall postoperative drug-free outcome was 72.7%. A significant difference in drug-free outcomes was observed for patients with typical TN (80.8%) compared with patients with atypical TN (33.33%, p = 0001). When severe venous compression was encountered during MVD, the drug-free outcome fell to 50% (10/20, p = 0.009). The Mann-Whitney U test indicated typical TN as a positive predictive factor of a drug-free outcome, whereas severe venous compression was a negative predictive factor. The patients with preoperative BNI score of 4 had better improvement than others (p = 0.045). Age, onset duration, and arterial loop had no specific difference in this study. CONCLUSION: In our study, atypical TN and severe venous compression were associated with poor outcomes. Regrouping atypical TN into precise diagnosis represents an immediate priority according to our result. The preoperative BNI score could be used as an effective predictive tool for the outcome of MVD surgery.

Critical assessment of DNA adenine methylation in eukaryotes using quantitative deconvolution.

The discovery of N6-methyldeoxyadenine (6mA) across eukaryotes led to a search for additional epigenetic mechanisms. However, some studies have highlighted confounding factors that challenge the prevalence of 6mA in eukaryotes. We developed a metagenomic method to quantitatively deconvolve 6mA events from a genomic DNA sample into species of interest, genomic regions, and sources of contamination. Applying this method, we observed high-resolution 6mA deposition in two protozoa. We found that commensal or soil bacteria explained the vast majority of 6mA in insect and plant samples. We found no evidence of high abundance of 6mA in Drosophila, Arabidopsis, or humans. Plasmids used for genetic manipulation, even those from Dam methyltransferase mutant Escherichia coli, could carry abundant 6mA, confounding the evaluation of candidate 6mA methyltransferases and demethylases. On the basis of this work, we advocate for a reassessment of 6mA in eukaryotes.

Detection and Quantification of UV-irradiation-induced DNA Damages by Liquid Chromatography-Mass Spectrometry and Immunoassay.

Solar ultraviolet (UV)-induced DNA lesions are associated with skin carcinogenesis. The detection of these DNA lesions is important to understand their genotoxicity and health effects. However, sunlight exposure-relevant DNA damage measurement is still a challenge. Here, we summarize our recent progresses on the related analytical techniques, including synthesis of dimeric lesions, the optimization of procedures for ultrahigh performance liquid chromatography-coupled mass spectrometry (UHPLC-MS/MS), and the maturation of anti-T(6-4)T photoproduct antibodies and their potential applications for immunoassay.

Evaluating the biocompatibility and biological performance of FePt-decorated nano-epoxy nanoparticles in mesenchymal stem cells.

BACKGROUND: Nanoparticles have wide potential applications in biolabeling, bioimaging, and cell tracking. Development of dual functional nanoparticles increases the versatility. METHODS: We combined the fluorescent property of nano-epoxy (N-Epo) and the magnetic characteristic of FePt to fabricate the FePt-decorated N-Epo (N-Epo-FePt). The size in diameter of N-Epo-FePt (177.38 ± 39.25 nm) was bigger than N-Epo (2.28 ± 1.01 nm), both could be absorbed into mesenchymal stem cells (MSCs) via clathrin-mediated endocytosis and have multiple fluorescent properties (blue, green, and red). RESULTS: N-Epo-FePt prevented N-Epo-induced platelet activation, CD68+-macrophage differentiation in blood, and intracellular ROS generation in MSCs. The induction of apoptosis and the inhibitory effects of N-Epo-FePt on cell migration, MMP-9 activity, and secretion of SDF-1α were less than that of N-Epo in MSCs. CONCLUSION: N-Epo-FePt was more biocompatible without altering biological performance than N-Epo in MSCs. These results suggest that N-Epo-FePt nanoparticle can be used for fluorescence labeling of MSCs and is potential to apply to bioimaging and cell tracking of MSCs in vivo by magnetic resonance imaging or computed tomography.

An Update on Mesoporous Silica Nanoparticle Applications in Nanomedicine.

The efficient and safe delivery of therapeutic drugs, proteins, and nucleic acids are essential for meaningful therapeutic benefits. The field of nanomedicine shows promising implications in the development of therapeutics by delivering diagnostic and therapeutic compounds. Nanomedicine development has led to significant advances in the design and engineering of nanocarrier systems with supra-molecular structures. Smart mesoporous silica nanoparticles (MSNs), with excellent biocompatibility, tunable physicochemical properties, and site-specific functionalization, offer efficient and high loading capacity as well as robust and targeted delivery of a variety of payloads in a controlled fashion. Such unique nanocarriers should have great potential for challenging biomedical applications, such as tissue engineering, bioimaging techniques, stem cell research, and cancer therapies. However, in vivo applications of these nanocarriers should be further validated before clinical translation. To this end, this review begins with a brief introduction of MSNs properties, targeted drug delivery, and controlled release with a particular emphasis on their most recent diagnostic and therapeutic applications.

Fabrication of hyaluronic acid-gold nanoparticles with chitosan to modulate neural differentiation of mesenchymal stem cells.

BACKGROUND: Chitosan (Chi) is a natural material which has been widely used in neural applications due to possessing better biocompatibility. In this research study, a novel of nanocomposites film based on Chi with hyaluronic acid (HA), combined with varying amounts of gold nanoparticles (AuNPs), was created resulting in pure Chi, Chi-HA, Chi-HA-AuNPs (25 ppm), and Chi-HA-AuNPs (50 ppm). METHODS: This study focused on evaluating their effects on mesenchymal stem cell (MSC) viability, colony formation, and biocompatibility. The surface morphology and chemical position were characterized through UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), SEM, and contact-angle assessment. RESULTS: When seeding MSCs on Chi-HA-AuNPs (50 ppm), the results showed high cell viability, biocompatibility, and the highest colony formation ability. Meanwhile, the evidence showed that Chi-HA-Au nanofilm was able to inhibit nestin and ß-tubulin expression of MSCs, as well as inhibit the ability of neurogenic differentiation. Furthermore, the results of matrix metalloproteinase 2/9 (MMP2/9) expression in MSCs were also significantly higher in the Chi-HA-AuNP (50 ppm) group, guiding with angiogenesis and wound healing abilities. In addition, in our rat model, both capsule thickness and collagen deposition were the lowest in Chi-HA-AuNPs (50 ppm). CONCLUSION: Thus, in view of the in vitro and in vivo results, Chi-HA-AuNPs (50 ppm) could not only maintain the greatest stemness properties and regulate the neurogenic differentiation ability of MSCs, but was able to also induce the least immune response. Herein, Chi-HA-Au 50 ppm nanofilm holds promise as a suitable material for nerve regeneration engineering.

Application of artificial intelligence-driven endoscopic screening and diagnosis of gastric cancer.

The landscape of gastrointestinal endoscopy continues to evolve as new technologies and techniques become available. The advent of image-enhanced and magnifying endoscopies has highlighted the step toward perfecting endoscopic screening and diagnosis of gastric lesions. Simultaneously, with the development of convolutional neural network, artificial intelligence (AI) has made unprecedented breakthroughs in medical imaging, including the ongoing trials of computer-aided detection of colorectal polyps and gastrointestinal bleeding. In the past demi-decade, applications of AI systems in gastric cancer have also emerged. With AI's efficient computational power and learning capacities, endoscopists can improve their diagnostic accuracies and avoid the missing or mischaracterization of gastric neoplastic changes. So far, several AI systems that incorporated both traditional and novel endoscopy technologies have been developed for various purposes, with most systems achieving an accuracy of more than 80%. However, their feasibility, effectiveness, and safety in clinical practice remain to be seen as there have been no clinical trials yet. Nonetheless, AI-assisted endoscopies shed light on more accurate and sensitive ways for early detection, treatment guidance and prognosis prediction of gastric lesions. This review summarizes the current status of various AI applications in gastric cancer and pinpoints directions for future research and clinical practice implementation from a clinical perspective.