Role of STAT3-FOXO3 Signaling in the Modulation of Neuroplasticity by PD-L1-HGF-Decorated Mesenchymal Stem Cell-Derived Exosomes in a Murine Stroke Model.

The limited therapeutic strategies available for stroke leave many patients disabled for life. This study assessed the potential of programmed death-ligand 1 (PD-L1) and hepatocyte growth factor (HGF)-engineered mesenchymal stem cell-derived exosomes (EXO-PD-L1-HGF) in enhancing neurological recovery post-stroke. EXO-PD-L1-HGF, which efficiently endocytosed into target cells, significantly diminishes the HO-induced neurotoxicity and increased the antiapoptotic proteins in vitro.

Novel Programmed Death Ligand 1-AKT-engineered Mesenchymal Stem Cells Promote Neuroplasticity to Target Stroke Therapy.

Although tissue plasminogen activator (t-PA) and endovascular thrombectomy are well-established treatments for acute ischemic stroke, over half of patients with stroke remain disabled for a long time. Thus, a significant unmet need exists to develop an effective strategy for treating acute stroke. We developed a combination of programmed cell death-ligand 1 (PD-L1) and AKT-modified umbilical cord mesenchymal stem cells (UMSC-PD-L1-AKT) implanted through intravenous (IV) and intracarotid (IA) routes to enhance therapeutic efficacy in a murine stroke model for overcoming the hypoxic environment of the ischemic brain, to prolong stem cell survival, and to attenuate systemic inflammation to protect neuroglial cells from ischemic injury.

Spatial and temporal dynamics of ATP synthase from mitochondria toward the cell surface.

Ectopic ATP synthase complex (eATP synthase), located on cancer cell surface, has been reported to possess catalytic activity that facilitates the generation of ATP in the extracellular environment to establish a suitable microenvironment and to be a potential target for cancer therapy. However, the mechanism of intracellular ATP synthase complex transport remains unclear. Using a combination of spatial proteomics, interaction proteomics, and transcriptomics analyses, we find ATP synthase complex is first assembled in the mitochondria and subsequently delivered to the cell surface along the microtubule via the interplay of dynamin-related protein 1 (DRP1) and kinesin family member 5B (KIF5B).

LncRNA SNHG1 regulates neuroblastoma cell fate via interactions with HDAC1/2.

The small nucleolar RNA host gene 1 (SNHG1) is a novel oncogenic long non-coding RNA (lncRNA) aberrantly expressed in different tumor types. We previously found highly expressed SNHG1 was associated with poor prognosis and MYCN status in neuroblastoma (NB). However, the molecular mechanisms of SNHG1 in NB are still unclear.

Quantitative phosphoproteomics reveals ectopic ATP synthase on mesenchymal stem cells to promote tumor progression via ERK/c-Fos pathway activation.

The tumor microenvironment (TME), which comprises cellular and noncellular components, is involved in the complex process of cancer development. Emerging evidence suggests that mesenchymal stem cells (MSCs), one of the vital regulators of the TME, foster tumor progression through paracrine secretion. However, the comprehensive phosphosignaling pathways that are mediated by MSC-secreting factors have not yet been fully established.

Targeting protein interaction networks in mitochondrial dynamics for cancer therapy.

Mitochondria are crucial organelles that provide energy via oxidative phosphorylation in eukaryotic cells and also have critical roles in growth, division, and the cell cycle, as well as the rapid adaptation required to meet the metabolic needs of the cell. Mitochondrial processes are highly dynamic; fusion and fission can vary with cell type, cellular context, and stress levels. Accumulating evidence demonstrates that an imbalance in mitochondrial dynamics leads to death in numerous types of human cancer cells.

Loss of Fis1 impairs proteostasis during skeletal muscle aging in Drosophila.

Increased levels of dysfunctional mitochondria within skeletal muscle are correlated with numerous age-related physiopathological conditions. Improving our understanding of the links between mitochondrial function and muscle proteostasis, and the role played by individual genes and regulatory networks, is essential to develop treatments for these conditions. One potential player is the mitochondrial outer membrane protein Fis1, a crucial fission factor heavily involved in mitochondrial dynamics in yeast but with an unknown role in higher-order organisms.

STAT3 phosphorylation at Ser727 and Tyr705 differentially regulates the EMT-MET switch and cancer metastasis.

Epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET) processes are proposed to be a driving force of cancer metastasis. By studying metastasis in bone marrow-derived mesenchymal stem cell (BM-MSC)-driven lung cancer models, microarray time-series data analysis by systems biology approaches revealed BM-MSC-induced signaling triggers early dissemination of CD133/CD83 cancer stem cells (CSCs) from primary sites shortly after STAT3 activation but promotes proliferation towards secondary sites. The switch from migration to proliferation was regulated by BM-MSC-secreted LIF and activated LIFR/p-ERK/pS727-STAT3 signaling to promote early disseminated cancer cells MET and premetastatic niche formation.

Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and multiple small subcapsular cystic follicles in the ovary during ultrasonography, and affects 5-10% of women of reproductive age. PCOS is frequently associated with insulin resistance (IR) accompanied by compensatory hyperinsulinemia and, therefore, presents an increased risk of type 2 diabetes mellitus (DM). The pathophysiology of PCOS is unclear, and many hypotheses have been proposed.

Multiomics Reveals Ectopic ATP Synthase Blockade Induces Cancer Cell Death via a lncRNA-mediated Phospho-signaling Network.

The EGFR tyrosine kinase inhibitor gefitinib is commonly used for lung cancer patients. However, some patients eventually become resistant to gefitinib and develop progressive disease. Here, we indicate that ecto-ATP synthase, which ectopically translocated from mitochondrial inner membrane to plasma membrane, is considered as a potential therapeutic target for drug-resistant cells.

Cluster validity indices for mixture hazards regression models.

In the analysis of survival data, the problems of competing risks arise frequently in medical applications where individuals fail from multiple causes. Semiparametric mixture regression models have become a prominent approach in competing risks analysis due to their flexibility and easy interpretation of resultant estimates. The literature presents several semiparametric methods on the estimations for mixture Cox proportional hazards models, but fewer works appear on the determination of the number of model components and the estimation of baseline hazard functions using kernel approaches.

Phosphoproteome Analysis Reveals Dynamic Heat Shock Protein 27 Phosphorylation in Tanshinone IIA-Induced Cell Death.

Gastric cancer is one of the most common types of cancer worldwide. Nevertheless, effective therapeutic strategies have not yet been discovered. Several studies have shown that tanshinone IIA (TIIA), which is extracted from the traditional herbal medicine plant Danshen (), has potential activity against many kinds of cancer.

SFRPs Are Biphasic Modulators of Wnt-Signaling-Elicited Cancer Stem Cell Properties beyond Extracellular Control.

Secreted frizzled-related proteins (SFRPs) are mainly known for their role as extracellular modulators and tumor suppressors that downregulate Wnt signaling. Using the established (CRISPR/Cas9 targeting promoters of SFRPs and targeting SFRPs transcript) system, we find that nuclear SFRPs interact with β-catenin and either promote or suppress TCF4 recruitment. SFRPs bind with β-catenin on both their N and C termini, which the repressive effects caused by SFRP-β-catenin-N-terminus binding overpower the promoting effects of their binding at the C terminus.

Outcomes after major surgery in patients with myasthenia gravis: A nationwide matched cohort study.

Objective: To validate the comprehensive features of adverse outcomes after surgery for patients with myasthenia gravis.

Methods: Using reimbursement claims from Taiwan's National Health Insurance Research Database, we analyzed 2290 patients who received major surgery between 2004 and 2010 and were diagnosed with myasthenia gravis preoperatively. Surgical patients without myasthenia gravis (n = 22,900) were randomly selected by matching procedure with propensity score for comparison.

Vaginal birth after cesarean section: 10 years of experience in a tertiary medical center in Taiwan.

Objective: Because of the increased risk of uterine rupture and other morbidities, instances of trial of labor after cesarean (TOLAC) have decreased in number each year. Nevertheless, under careful assessment and advanced medical care, TOLAC is still a safe option for delivery. The objective of this study is to find the factors that impact the success rate for TOLAC and to compare the results with Taiwan national registry data.

NF-κB-driven suppression of FOXO3a contributes to EGFR mutation-independent gefitinib resistance.

Therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib or erlotinib) significantly prolongs survival time for patients with tumors harboring an activated mutation on EGFR; however, up to 40% of lung cancer patients exhibit acquired resistance to EGFR-TKIs with an unknown mechanism. FOXO3a, a transcription factor of the forkhead family, triggers apoptosis, but the mechanistic details involved in EGFR-TKI resistance and cancer stemness remain largely unclear. Here, we observed that a high level of FOXO3a was correlated with EGFR mutation-independent EGFR-TKI sensitivity, the suppression of cancer stemness, and better progression-free survival in lung cancer patients.