Translational research : the journal of laboratory and clinical medicine
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Cell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases, including emphysema, pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune responses in mouse lung disease models. ⋯ In parallel, the identity and role of endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular reference to animal models.
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We studied the genetic and clinical features of diabetic subjects in a 5-generation Michigan-Kentucky pedigree ascertained through a proband with pancreatic agenesis and homozygous for the IPF1 mutation Pro63fsx60. Diabetic and nondiabetic family members were genotyped and phenotyped. We also carried out genetic studies to determine the history of the IPF1 mutation in the Michigan-Kentucky family and a Virginia family with the same mutation. ⋯ Obesity and hyperinsulinemia have been observed occasionally in other subtypes of MODY, which suggests that hyperinsulinemia may be a general phenomenon when obesity occurs in MODY subjects. Hypoinsulinemia in nonobese MODY subjects seems to be caused by a functional defect in the beta cell. Genetic testing should be considered in multigenerational obese diabetic subjects, particularly when such families contain young diabetic members.
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Toona sinensis (TS), which is also known as Cedrela sinensis, belongs to Meliaceae family, the compounds identified from this TS leaves possess a wide range of biologic functions, such as hypoglycemic effects, anti-LDL glycative activity, antioxidant activities, and inhibition of sudden acute respiratory syndrome (SARS) coronavirus replication. However, their effect against cancer cells is not well explored. In this study, to understand the cytotoxic effect and molecular mechanism stimulated by TSL-1 (TS leaf extract fraction) we employed three different non-small-cell lung cancer (NSCLC) cell lines: H441 cells (lung adenocarcinoma), H661 cells (lung large cell carcinoma) and H520 cells (lung squamous cell carcinoma). ⋯ The decreased Bcl2 protein level was concurrent with an increased Bax protein level in all 3 cell lines. Additionally, the tumoricidal effect of TSL-1 was measured using a xenograft model, after 5 weeks of TSL-1 treatment by various regimen caused regression of tumor. Taken together both these in vitro and in vivo studies revealed that TSL-1 is a potent inhibitor against NSCLC growth and our provoking result suggest that TSL-1 can be a better nutriceutical as a singlet or along with doublet agents (taxane, vinorelbine, and gemcitabine) for treating NSCLC.
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Apelin and ghrelin have emerged as novel adipokines, but their role in coronary artery disease (CAD) remains obscure. In the present study, we analyzed their serum levels in patients with acute coronary syndromes (ACS) or established asymptomatic CAD. A total of 355 participants were enrolled. ⋯ Besides this result, apelin showed an inverse relationship with ACS incidence and a Gensini score independent of other cardiovascular risk factors (P < 0.05). In conclusion, CAD seemed to correlate with low serum apelin and ghrelin levels. Moreover, apelin concentrations inversely were associated with the severity and the acute phase of CAD, which suggests its involvement in the progression and destabilization of coronary atherosclerotic plaques.
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The technique of conducting high tidal volume (TV) ventilation-induced lung inflammation including remote organs is still open to discussion, and our aim is to investigate this issue in isolated ventilated rat lungs perfused with salt solution. Selective right lung (RL) hyperventilation (TV of 15 mL/kg with air containing 5% CO(2) on zero or 2.5 cm H(2)0 end expiratory pressure [ZEEP or PEEP] in addition to left lung (LL) on 2.5 cm H(2)0 continuous positive airway pressure (CPAP) for 60 min, was realized after 30 min both lungs ventilation by occluding the left main bronchus, and it was allocated to the following 5 groups: groups 1 and 2 underwent hyperventilation under ZEEP, groups 3 and 4 underwent hyper ventilation under PEEP with recirculation or nonrecirculation (R-ZEEP or NR-ZEEP and R-PEEP or NR-PEEP), and group 5 served as the control group. Recirculation means the same perfusate recirculates the system throughout the procedure. ⋯ PEEP prevented these injuries. Lung injury was also demonstrated in the recirculated LL compared with the nonrecirculated LL (Prot-BALF, TNF-alpha and interleukin-1beta [IL-1beta] mRNAs: the LL of the R-ZEEP is greater than the LL of NR-ZEEP by P < 0.01). Unilateral hyperventilated lungs with ZEEP induced TNF-alpha, increased permeability, and injured the control lung via perfusion.