Immunomodulation by mesenchymal stem cells in treating human autoimmune disease-associated lung fibrosis.

Background: Interstitial pneumonia in connective tissue diseases (CTD-IP) featuring inflammation and fibrosis is a leading cause of death in CTD-IP patients. The related autoimmune lung injury and disturbed self-healing process make conventional anti-inflammatory drugs ineffective. Equipped with unique immunoregulatory and regenerative properties, mesenchymal stem cells (MSCs) may represent a promising therapeutic agent in CTD-IP.

Neonatal colonization of mice with LGG promotes intestinal development and decreases susceptibility to colitis in adulthood.

Development of the intestinal microbiota during early life serves as a key regulatory stage in establishing the host-microbial relationship. This symbiotic relationship contributes to developing host immunity and maintaining health throughout the life span. This study was to develop an approach to colonize conventionally raised mice with a model probiotic bacterium, Lactobacillus rhamnosus GG (LGG), and to determine the effects of LGG colonization on intestinal development and prevention of colitis in adulthood.

Preserving viability of Lactobacillus rhamnosus GG in vitro and in vivo by a new encapsulation system.

Probiotics have shown beneficial effects on health and prevention of diseases in humans. However, a concern for application of probiotics is the loss of viability during storage and gastrointestinal transit. The aim of this study was to develop an encapsulation system to preserve viability of probiotics when they are administrated orally and apply Lactobacillus rhamnosus GG (LGG) as a probiotic model to evaluate the effectiveness of this approach using in vitro and in vivo experiments.

Keloid-derived, plasma/fibrin-based skin equivalents generate de novo dermal and epidermal pathology of keloid fibrosis in a mouse model.

Keloids are wounding-induced tumor-like human scars. Unclear etiology and lack of animal models to reveal disease mechanisms and invent therapies deepen the grievous health and psychosocial state of vulnerable individuals. Epitomizing the injury-repair environment which triggers and fosters keloid formation and essential dermal/epidermal interactions in disease development, the novel animal model was established by implanting porous polyethylene ring-supported plasma/fibrin-based epidermal-dermal skin constructs on the dorsum of athymic NU/J mice.

Benefits and barriers to participating in longitudinal research of youth-onset type 2 diabetes: Results from the TODAY retention survey.

Background/aims: Conducting longitudinal research related to chronic illness in adolescents is inherently challenging due to developmental changes and psychosocial stressors. Participants in the Treatment Options for type 2 Diabetes in Adolescents and Youth clinical trial were socioeconomically disadvantaged as well. This study assessed attitudes and beliefs about retention in Treatment Options for type 2 Diabetes in Adolescents and Youth to shed light on the factors that potentially promote and detract from the likelihood of sustained participation.

Evidence for the involvement of fibroblast growth factor 10 in lipofibroblast formation during embryonic lung development.

Lipid-containing alveolar interstitial fibroblasts (lipofibroblasts) are increasingly recognized as an important component of the epithelial stem cell niche in the rodent lung. Although lipofibroblasts were initially believed merely to assist type 2 alveolar epithelial cells in surfactant production during neonatal life, recent evidence suggests that these cells are indispensable for survival and growth of epithelial stem cells during adulthood. Despite increasing interest in lipofibroblast biology, little is known about their cellular origin or the molecular pathways controlling their formation during embryonic development.

Phosphoflow-Based Evaluation of Mek Inhibitors as Small-Molecule Therapeutics for B-Cell Precursor Acute Lymphoblastic Leukemia.

Upstream mutations that lead to constitutive activation of Erk in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are relatively common. In the era of personalized medicine, flow cytometry could be used as a rapid method for selection of optimal therapies, which may include drugs that target the Erk pathway. Here, we evaluated the utility of phospho-flow, compared to Western blotting, to monitor Erk pathway activation and its inhibition by targeted Mek kinase inhibitors in human BCP ALL.

Generation and Validation of miR-142 Knock Out Mice.

microRNA-142 (miR-142) is an important regulator of many biological processes and associated signaling pathways during embryonic development, homeostasis and disease. The miR-142 hairpin gives rise to the "guide strand" miR-142-3p and the sister "passenger" strand miR-142-5p. miR-142-3p has been shown to play critical, non-redundant functions in the development of the hematopoietic lineage.

Alpha7 nicotinic acetylcholine receptor is required for blood-brain barrier injury-related CNS disorders caused by Cryptococcus neoformans and HIV-1 associated comorbidity factors.

Background: Cryptococcal meningitis is the most common fungal infection of the central nervous system (CNS) in HIV/AIDS. HIV-1 virotoxins (e.g.

Non-canonical WNT signalling in the lung.

The role of WNT signalling in metazoan organogenesis has been a topic of widespread interest. In the lung, while the role of canonical WNT signalling has been examined in some detail by multiple studies, the non-canonical WNT signalling has received limited attention. Reliable evidence shows that this important signalling mechanism constitutes a major regulatory pathway in lung development.

Plasminogen Activator Inhibitor-1 in Cancer: Rationale and Insight for Future Therapeutic Testing.

Despite its function as an inhibitor of urokinase and tissue-type plasminogen activator (PA), PA inhibitor-1 (PAI-1) has a paradoxical protumorigenic role in cancer, promoting angiogenesis and tumor cell survival. In this review, we summarize preclinical evidence in support of the protumorigenic function of PAI-1 that has led to the testing of small-molecule PAI-1 inhibitors, initially developed as antithrombotic agents, in animal models of cancer. The review discusses the challenges and the opportunities that lay ahead to the development of efficacious and nontoxic PAI-1 inhibitors as anticancer agents.

Increased FGF1-FGFRc expression in idiopathic pulmonary fibrosis.

Background: Recent clinical studies show that tyrosine kinase inhibitors slow the rate of lung function decline and decrease the number of acute exacerbations in patients with Idiopathic Pulmonary Fibrosis (IPF). However, in the murine bleomycin model of fibrosis, not all tyrosine kinase signaling is detrimental. Exogenous ligands Fibroblast Growth Factor (FGF) 7 and 10 improve murine lung repair and increase survival after injury via tyrosine kinase FGF receptor 2b-signaling.

Lower Preprandial Insulin and Altered Fuel Use in HIV/Antiretroviral-Exposed Infants in Cameroon.

Context: Intrauterine HIV/antiretroviral (ARV) and postnatal ARVs are known to perturb energy metabolism and could have permanent effects on future metabolic health. Such maladaptive effects could be mediated by changes in mitochondrial function and intermediary metabolism due to fetal and early-life ARV exposure in HIV/ARV-exposed uninfected (HEU) infants.

Objective: The objective of the study was to understand the relationship(s) between mitochondrial fuel use (assessed via acylcarnitines and branched chain amino acids) and preprandial insulin in infants exposed to in utero HIV/ARV plus postnatal zidovudine or nevirapine compared with HIV/ARV-unexposed uninfected (HUU) infants.

Chemokine-guided angiogenesis directs coronary vasculature formation in zebrafish.

Interruption of the coronary blood supply severely impairs heart function with often fatal consequences for patients. However, the formation and maturation of these coronary vessels is not fully understood. Here we provide a detailed analysis of coronary vessel development in zebrafish.

Repositioning of Memantine as a Potential Novel Therapeutic Agent against Meningitic E. coli-Induced Pathogenicities through Disease-Associated Alpha7 Cholinergic Pathway and RNA Sequencing-Based Transcriptome Analysis of Host Inflammatory Responses.

Neonatal sepsis and meningitis (NSM) remains a leading cause worldwide of mortality and morbidity in newborn infants despite the availability of antibiotics over the last several decades. E. coli is the most common gram-negative pathogen causing NSM.

Potential of autologous NK cell therapy to eradicate leukemia: "Education is [not] the best provision for old age" -Aristotle.

B-precursor acute lymphoblastic leukemia (BP-ALL) patients are immunocompromised. We recently reported that functional natural killer (NK) cells can be grown from patient bone marrow and blood samples at diagnosis. Surprisingly, such NK cells exhibit cytotoxicity against autologous BP-ALL cells.

B-cell precursor acute lymphoblastic leukemia and stromal cells communicate through Galectin-3.

The molecular interactions between B-cell precursor acute lymphoblastic leukemia (pre-B ALL) cells and stromal cells in the bone marrow that provide microenvironmentally-mediated protection against therapeutic drugs are not well-defined. Galectin-3 (Lgals3) is a multifunctional galactose-binding lectin with reported location in the nucleus, cytoplasm and extracellular space in different cell types. We previously reported that ALL cells co-cultured with stroma contain high levels of Galectin-3.

Attenuating endogenous Fgfr2b ligands during bleomycin-induced lung fibrosis does not compromise murine lung repair.

Fibroblast growth factors (Fgfs) mediate organ repair. Lung epithelial cell overexpression of Fgf10 postbleomycin injury is both protective and therapeutic, characterized by increased survival and attenuated fibrosis. Exogenous administration of FGF7 (palifermin) also showed prophylactic survival benefits in mice.

Fibroblast growth factor 10 alters the balance between goblet and Paneth cells in the adult mouse small intestine.

Intestinal epithelial cell renewal relies on the right balance of epithelial cell migration, proliferation, differentiation, and apoptosis. Intestinal epithelial cells consist of absorptive and secretory lineage. The latter is comprised of goblet, Paneth, and enteroendocrine cells.

Presentation and effectiveness of early treatment of type 2 diabetes in youth: lessons from the TODAY study.

Objective: The objectives were to (i) describe the characteristics of a large ethnically/racially and geographically diverse population of adolescents with recent-onset type 2 diabetes (T2D), and (ii) assess the effects of short-term diabetes education and treatment with metformin on clinical and biochemical parameters in this cohort.

Research Design And Methods: Descriptive characteristics were determined for subjects screened for Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) who met criteria for diagnosis of T2D (n = 1092). Changes in clinical and biochemical parameters were determined for those who completed at least 8 wk of the run-in phase of the trial, which included standardized diabetes education and treatment with metformin.

Interaction between bone marrow stromal cells and neuroblastoma cells leads to a VEGFA-mediated osteoblastogenesis.

The potential role of osteoblasts in bone and bone marrow (BM) metastases in neuroblastoma (NBL) remains unclear. In this study, we examined the effect of NBL cells on the osteoblastic differentiation of BM-derived mesenchymal stromal cells (BMMSC). We show that the presence of NBL cells enhanced the osteoblastic differentiation of BMMSC driven by bone morphogenetic protein (BMP)-4, in the absence of any effect on NBL cell proliferation.

Differential regenerative capacity of neonatal mouse hearts after cryoinjury.

Neonatal mouse hearts fully regenerate after ventricular resection similar to adult zebrafish. We established cryoinjury models to determine if different types and varying degrees of severity in cardiac injuries trigger different responses in neonatal mouse hearts. In contrast to ventricular resection, neonatal mouse hearts fail to regenerate and show severe impairment of cardiac function post transmural cryoinjury.

Tak1, Smad4 and Trim33 redundantly mediate TGF-β3 signaling during palate development.

Transforming growth factor-beta3 (TGF-β3) plays a critical role in palatal epithelial cells by inducing palatal epithelial fusion, failure of which results in cleft palate, one of the most common birth defects in humans. Recent studies have shown that Smad-dependent and Smad-independent pathways work redundantly to transduce TGF-β3 signaling in palatal epithelial cells. However, detailed mechanisms by which this signaling is mediated still remain to be elucidated.

Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells.

Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects hematopoietic development and therefore is associated with immune deficiencies that can be further exacerbated by chemotherapy. It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytotoxicity (ADCC) can be used for treatment because this depends on the presence of functional effector cells. Here, we used flow cytometry to determine that patient samples at diagnosis, post-induction and relapse contain detectable numbers of CD56+ cells.