Translational research : the journal of laboratory and clinical medicine
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Clinical Trial
Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's disease.
Parkinson's disease (PD) is a progressive neurodegenerative disease for which stem cell research has created hope in the last few years. Seven PD patients aged 22 to 62 years with a mean duration of disease 14.7+/-7.56 years were enrolled to participate in the prospective, uncontrolled, pilot study of single-dose, unilateral transplantation of autologous bone-marrow-derived mesenchymal stem cells (BM-MSCs). The BM-MSCs were transplanted into the sublateral ventricular zone by stereotaxic surgery. ⋯ These results indicate that our protocol seems to be safe, and no serious adverse events occurred after stem-cell transplantation in PD patients. The number of patients recruited and the uncontrolled nature of the trial did not permit demonstration of effectiveness of the treatment involved. However, the results encourage future trials with more patients to demonstrate efficacy.
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The last decade has witnessed a steady embrace of genomic and personalized medicine by senior government officials, industry leadership, health care providers, and the public. Genomic medicine, which is the use of information from genomes and their derivatives (RNA, proteins, and metabolites) to guide medical decision making-is a key component of personalized medicine, which is a rapidly advancing field of health care that is informed by each person's unique clinical, genetic, genomic, and environmental information. As medicine begins to embrace genomic tools that enable more precise prediction and treatment disease, which include "whole genome" interrogation of sequence variation, transcription, proteins, and metabolites, the fundamentals of genomic and personalized medicine will require the development, standardization, and integration of several important tools into health systems and clinical workflows. ⋯ In addition, information from individual genomes, which is a fast-moving area of technological development, is spawning a social and information revolution among consumers that will undoubtedly affect health care decision making. Although these and other scientific findings are making their way from the genome to the clinic, the full application of genomic and personalized medicine in health care will require dramatic changes in regulatory and reimbursement policies as well as legislative protections for privacy for system-wide adoption. Thus, there are challenges from both a scientific and a policy perspective to personalized health care; however, they will be confronted and solved with the certainty that the science behind genomic medicine is sound and the practice of medicine that it informs is evidence based.
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Mounting evidence suggests that all organisms at the cellular level respond to stress by synthesizing heat shock proteins at the expense of other proteins, and the ability of human cells to respond to heat stress decreases with aging. We thus investigate the association of 3 variants (A1267G in HSPA1B, G190C in HSPA1A, and T2437C in HSPA1L) in the heat shock protein 70 (Hsp70) family with natural longevity in a Xinjiang Hetian Uygur population. A case-control study was conducted in 191 healthy individuals greater than 90 years of age, and 53 naturally died persons 65-70 years of age. ⋯ The haplotype results were strengthened by interaction analysis, which suggests an optimal model in which G190C and T2437C exert an interacting effect on longevity. No functional significance was observed between 190G and 190C alleles in both control and heat-inducible A549 cells (P>0.05). Taken together, our findings suggested that common genetic variants in Hsp70 family might contribute interactively to longevity the Xinjiang Hetian Uygur population.
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High-tidal-volume mechanical ventilation and hyperoxia used in patients with acute lung injury (ALI) can induce alveolar coagulopathy and fibrin depositions within the airways. Hyperoxia has been shown to increase ventilator-induced lung injury (VILI), but the mechanisms that regulate interaction between high-tidal-volume mechanical ventilation and hyperoxia are unclear. We hypothesized that mechanical stretch with hyperoxia synergistically augmented neutrophil infiltration and production of plasminogen activator inhibitor-1 (PAI-1) via the nuclear factor-kappaB (NF-kappaB) pathway. ⋯ No statistically significant increase of neutrophil infiltration and inflammatory cytokine production was found in the mice ventilated at 6 mL/kg using hyperoxia. Hyperoxia-induced augmentation of VILI was attenuated in mice with pharmacologic inhibition of NF-kappaB activity by SN-50. We conclude that hyperoxia increased high-tidal-volume-induced cytokine production and neutrophil influx through activation of the NF-kappaB pathway.
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Asthma is a complex respiratory disease whose incidence has increased worldwide in the last decade. Currently there is no cure for asthma. Although bronchodilator and anti-inflammatory medications are effective medicines in some asthmatic patients, it is clear that an unmet therapeutic need persists for a subpopulation of individuals with severe asthma. ⋯ Inhibitors of the mevalonate pathway or statins hold promise for asthma treatment, because they exhibit anti-inflammatory, antimigratory, and antiproliferative effects in preclinical and clinical studies, and they can target the smooth muscle. This review will discuss current knowledge of ASM biology and identify gaps in the field to stimulate future investigations of the cellular mechanisms that control ASM overabundance in asthma. Targeting ASM has the potential to be an innovative venue of treatment for patients with asthma.