Profibrotic role of the SOX9-MMP10-ECM biosynthesis axis in the tracheal fibrosis after injury and repair.

Fibroblast activation and extracellular matrix (ECM) deposition play an important role in the tracheal abnormal repair process and fibrosis. As a transcription factor, SOX9 is involved in fibroblast activation and ECM deposition. However, the mechanism of how SOX9 regulates fibrosis after tracheal injury remains unclear.

Gene Expression, Morphology, and Electrophysiology During the Dynamic Development of Human Induced Pluripotent Stem Cell-Derived Atrial- and Ventricular-Like Cardiomyocytes.

Background And Objectives: Gene expression, morphology, and electrophysiological combination are essential for assessing the dynamic development of human induced pluripotent stem cell-derived atrial- and ventricular-like cardiomyocytes (iPS-AM and iPS-VM, respectively).

Methods: For iPS-AM/VM differentiation, we performed the small molecule-based temporal modulation of the retinoic acid and bone morphogenetic protein signaling pathways. We investigated the gene expression and morphology using immunofluorescence, quantitative real-time polymerase chain reaction, flow cytometry, and transmission electron microscopy as well as registered electrophysiological functions using a whole-cell patch clamp on days 20, 30, and 60 post-differentiations.

Icariin inhibits chondrocyte ferroptosis and alleviates osteoarthritis by enhancing the SLC7A11/GPX4 signaling.

Background: Chondrocyte ferroptosis plays a critical role in the pathogenesis of osteoarthritis (OA), regulated by the SLC7A11/GPX4 signaling pathway. Icariin (ICA), a flavonoid glycoside, exhibits strong anti-inflammatory and antioxidant activities. This study investigated whether ICA could modulate the SLC7A11/GPX4 signaling to inhibit chondrocyte ferroptosis and alleviate OA.

Recombinant Slit2 attenuates tracheal fibroblast activation in benign central airway obstruction by inhibiting the TGF-β1/Smad3 signaling pathway.

Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2-roundabout guidance receptor 1 (Slit2-Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported.

Mitochondrial dysfunction is associated with hypertrophic cardiomyopathy in Pompe disease-specific induced pluripotent stem cell-derived cardiomyocytes.

Pompe disease (PD) is a rare autosomal recessive disorder that presents with progressive hypertrophic cardiomyopathy. However, the detailed mechanism remains clarified. Herein, PD patient-specific induced pluripotent stem cells were differentiated into cardiomyocytes (PD-iCMs) that exhibited cardiomyopathic features of PD, including decreased acid alpha-glucosidase activity, lysosomal glycogen accumulation and hypertrophy.

GATA6 promotes fibrotic repair of tracheal injury through NLRP3 inflammasome-mediated epithelial pyroptosis.

Tracheal injury is a challenging emergency condition that is characterized by the abnormal repair of the trachea. GATA6, a well-established transcription factor, plays a crucial role in tissue injury and epithelial regenerative repair. This study aims to evaluate the role of GATA6 in NF-κB-mediated NLRP3 inflammasome activation and pyroptosis after tracheal injury.

Patient-specific induced pluripotent stem cell properties implicate Ca-homeostasis in clinical arrhythmia associated with combined heterozygous and variants.

We illustrate use of induced pluripotent stem cells (iPSCs) as platforms for investigating cardiomyocyte phenotypes in a human family pedigree exemplified by novel heterozygous RYR2-A1855D and SCN10A-Q1362H variants occurring alone and in combination. The proband, a four-month-old boy, presented with polymorphic ventricular tachycardia. Genetic tests revealed double novel heterozygous RYR2-A1855D and SCN10A-Q1362H variants inherited from his father (F) and mother (M), respectively.

IL-11 drives the phenotypic transformation of tracheal epithelial cells and fibroblasts to enhance abnormal repair after tracheal injury.

Tracheal stenosis (TS) is a multifactorial and heterogeneous disease that can easily lead to respiratory failure and even death. Interleukin-11 (IL-11) has recently received increased attention as a fibrogenic factor, but its function in TS is uncertain. This study aimed to investigate the role of IL-11 in TS regulation based on clinical samples from patients with TS and a rat model of TS produced by nylon brush scraping.

GATA6 triggers fibroblast activation and tracheal fibrosis through the Wnt/β-catenin pathway.

Tracheal fibrosis is a key abnormal repair process leading to fatal stenosis, characterized by excessive fibroblast activation and extracellular matrix (ECM) deposition. GATA6, a zinc finger-containing transcription factor, is involved in fibroblast activation, while its role in tracheal fibrosis remains obscure. The present study investigated the potential role of GATA6 as a novel regulator of tracheal fibrosis.

Celastrol promotes apoptotic cell death in children neuroblastoma cells through caspases dependent pathway.

Objective: To investigate the in-depth pharma-cological mechanisms of celastrol in children neuro-blastoma treatment.

Methods: In the current study, we examined the effects of celastrol on children neuroblastoma cells viability and proliferation by cell counting kit-8 assay and colony formation assay. Annexin V-FTIC and PI staining were applied to determine cell apoptosis after celastrol treatment.

GDF15 alleviates the progression of benign tracheobronchial stenosis by inhibiting epithelial-mesenchymal transition and inactivating fibroblasts.

Benign tracheobronchial stenosis (BTS) is a fatal and incurable disease. Epithelial repair and matrix reconstruction play an important role in the wound repair process. If the interstitial context is not restored and stabilized in time, it can lead to pathological fibrosis.

Knockdown of SOX9 alleviates tracheal fibrosis through the Wnt/β-catenin signaling pathway.

Trachealfibrosis is an important cause of tracheal stenosis without effective treatments, and new drug targets need to be developed. The role of SOX9 in the injury and repair of the trachea is unknown; this study aims to investigate the role of SOX9 in the regulation of tracheal fibrosis based on clinical samples from patients with tracheal injury and a model of tracheal fibrosis produced by tracheal brushing in rats. The results showed that the expressions of SOX9 and mesenchymal and ECM-related indicators were increased in the injury and fibrosis of the trachea in patients and rats.

Trifluoperazine Synergistically Potentiates Bortezomib-Induced Anti-Cancer Effect in Multiple Myeloma via Inhibiting P38 MAPK/NUPR1.

Multiple myeloma (MM) is a common hematological malignancy. Bortezomib (BTZ) is a traditional medicine for MM treatment, but there are limitations for current treatment methods. Trifluoperazine (TFP) is a clinical drug for acute and chronic psychosis therapy.

Estradiol inhibits autophagy of ‑infected 16HBE cells and controls the proliferation of intracellular .

Tracheobronchial tuberculosis (TBTB) is most common in young, middle‑aged females. Despite adequate anti‑tuberculosis therapy, >90% of patients develop tracheobronchial stenosis, which has a high rate of resulting in disability. The present study aimed to explore the effect of estradiol on the development of TBTB.

Establishment of iPSC line from a Chinese infant (XACHi012-A) with Jervell and Lange-Nielsen syndrome carrying combined KCNQ1 frameshift c.431delC(p.I145Sfs*92) and nonsense c.1175G > A (p.W392X) variants and two iPSC lines from the parents (XACHi013-A, XACHi014-A).

Induced pluripotent stem cell lines (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from the peripheral blood of a two month-old boy and the parents. Jervell and Lange-Nielsen syndrome (JLNS) was diagnosed in the boy carrying combined KCNQ1 frameshift c.431delC (p.

microRNA-637 promotes apoptosis and suppresses proliferation and autophagy in multiple myeloma cell lines via NUPR1.

Multiple myeloma (MM) is a heterogeneous disease with poor prognosis. Increasing evidence has revealed that microRNAs (miRNAs) are strongly associated with the pathogenesis and progression of MM. Here, we investigated the role of microRNA-637 (miR-637) in MM to identify potential therapeutic targets.

Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma.

Multiple myeloma (MM) is the second most common hematologic malignancy of immunoglobulin-secreting plasma cells. Recent modern combination therapies have improved survival rates, but many patients develop resistance to novel drugs, leading to relapse. Trifluoperazine (TFP), a typical antipsychotic drug, has been reported to exert antitumor effects by targeting various pathways.

Generation of two induced pluripotent stem cell lines (XACHi0010-A, XACHi0011-A) from a Chinese family with combined oxidative phosphorylation deficiency carrying homozygous and heterozygous C1QBP-L275F mutation.

Induced pluripotent stem cell lines (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from the peripheral blood of a 14 year-old boy and his mother using same protocols. Diagnosis of combined oxidative phosphorylation deficiency (COXPD) was established after identifying a homozygous c.823C > T(p.

NUPR1 Silencing Induces Autophagy-Mediated Apoptosis in Multiple Myeloma Cells Through the PI3K/AKT/mTOR Pathway.

Nuclear protein 1 (NUPR1) is a stress-related small molecule and plays important roles in various tumors, including multiple myeloma (MM). Autophagy is essential for maintaining cellular homoeostasis in response to stress and, together with apoptosis, determines cell fate. Previous studies indicate that NUPR1 is involved in cancer progression of MM, but the underlying mechanisms have not been elucidated.

Generation of induced pluripotent stem cells (iPSCs) from an infant with Pompe disease carrying with compound mutations of R608X and E888X in GAA gene.

Induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from the peripheral blood of a five months-old boy with glycogen storage disease type II(GSD II, also known as Pompe disease, PD) carries compound mutations R608X E888X in GAA gene. PBMCs were reprogrammed using non-integrative Sendai viral vectors containing reprogramming factors OCT4, SOX2, KLF4 and C-MYC. iPSCs were shown to express pluripotent markers, have trilineage differentiation potential, carry GAA-R608X and GAA-E888X compound mutations, have a normal karyotype.

Generation of induced pluripotent stem cells (iPSCs) from an infant with catecholaminergic polymorphic ventricular tachycardia carrying the double heterozygous mutations A1855D in RyR2 and Q1362H in SCN10A.

Induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from the peripheral blood of a 4 month-old boy with catecholaminergic polymorphic ventricular tachycardia carrying the double heterozygous mutations RyR2-A1855D and SCN10A-Q1362H. PBMCs were reprogrammed using non-integrative Sendai viral vectors containing reprogramming factors OCT4, SOX2, KLF4 and C-MYC. The iPSCs were shown to express pluripotent markers, have trilineage differentiation potential, carry RyR2-A1855D and SCN10A-Q1362H mutations and have a normal karyotype.

Knockdown of NUPR1 inhibits the growth of U266 and RPMI8226 multiple myeloma cell lines via activating PTEN and caspase activation‑dependent apoptosis.

Nuclear protein‑1 (NUPR1) is a stress response factor that is important in the development of several human malignant tumor cells. However, the role of NUPR1 in multiple myeloma (MM) remains to be fully elucidated. In the present study, it was found that the mRNA levels of NUPR1 were significantly higher in specimens from patients with MM and MM cell lines (U266 and RPMI8226) than in cells of normal human bone marrow.

Altered amygdala-related structural covariance and resting-state functional connectivity in end-stage renal disease patients.

Depression and cognitive control deficits were frequently reported in concurrent end-stage renal disease (ESRD) patients. Neuroimaging studies indicated depression could be a risk factor for cognitive control deficits, and amygdala-related circuitry may play a critical role in this abnormal interaction. To investigate the potential relationship between depressive symptoms and cognitive control reduction in ESRD patients, T1-weighted and resting fMRI images were obtained in 29 ESRD patients and 29 healthy controls.

Abnormal interaction between cognitive control network and affective network in patients with end-stage renal disease.

End-stage renal disease (ESRD) is a common complicated disorder that is generally associated with an altered central nervous system and cognitive impairment. Neuroimaging studies have recorded aberrant brain circuits in patients with ESRD that were closely associated with abnormal clinical manifestations. However, whether the altered interaction was within and/or between these circuits is largely unclear.