Autophagy, a cellular process of "self-eating" by which intracellular components are degraded within the lysosome, is an evolutionarily conserved response to various stresses. Autophagy is associated with numerous patho-physiological conditions, and dysregulation of autophagy contributes to the pathogenesis of a variety of human diseases including cancer. Depending on context, activation of autophagy may promote either cell survival or death, two major events that determine pathological process of many illnesses. Importantly, the activity of autophagy is often associated with apoptosis, another critical cellular process determining cellular fate. A better understanding of biology of autophagy and its implication in human health and disorder, as well as the relationship between autophagy and apoptosis, has the potential of facilitating the development of autophagy-based therapeutic interventions for human diseases such as cancer.
Apoptosis ; Autophagy ; Cell Death ; Cell Survival ; Humans ; Neoplasms ; pathology

Acupuncture Therapy ; Adult ; Colitis, Ulcerative ; drug therapy ; therapy ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Young Adult

For the purpose of expanding the analysis scope of medicines,a RPHPLC assay procedure has been established for quantitative analysis of indomethacin in human plasma.Analytical column was YWG C18(?4 6 mm?200mm).Mobile phase was methanol water acetic acid solution(67∶33∶0 1)(v/v) and wavelength of detector was 254nm.The linear relationship,precision,method of extraction and recovery were comparatively investigated by standard blank human plasma spiked with indomethacin.Indomethacin leved in the blood of the healthy volunteers was detected by using this method.The linear range of the method was 0 1～5 0?g?ml -1 .The calibration curve was linear (?=0 9995). The detection limit was 0 02?g?ml -1 (S/N≥3) and the recovery of indomethacin in human blood was between 97 5%～104 2%. Intra and inter day prccision of the mothod were(1 1?0 2)%(n=4) and(2 7?0 6)%(n=4)respectively.The CV% were no more than 3 0% (n=4).The method shows a high sensitivity,precision,fast and excellent selectivity.Thus it is suitable for investigation of the indomethacin in human blood and its toxicological analysis as well as the pharmacokinetic study.

Objective Investigation and analysis of intelligence and psychomotor function in children born after implementingt universal salt iodization(USI). Methods Historical serious illness areas of water iodine below 10μg/L were selected as study sites, water iodine in 50 - 100 μg/L in the historical non-endemic areas were as control points in Henan, 2008. Cluster sampling was used to select children aged 6 - 15 years as observing subjects,IQ were measured with CRT- Man Test(CRT-C2). A "Tianjin Medical psychomotor test battery" (JPB) was carry out to test psychomotor function. Results In IDD regions 230 children were surveyed post-USI and 1284 children preUSI. The IQs post and pre USI were 99.3 and 99.9, respectively, and the proportion of IQ ≤69 were 2.17%(6/230) and 2.80%(36/1284), respectively. In non-IDD regions 650 children were surveyed post-USI and 2079children pre-USI. The IQs post and pre USI were 95.3 and 93.8, respectively, and the proportion of IQ ≤ 69 were 2.31%(15/650) and 3.37%(70/2079), respectively. In IDD regions, the abnormal rate of T scores and damage index post USI were 3.6%(2/56), 5.3%(3/56), respectively, significantly lower than pre USI [18.1%(29/160),18.1%(29/160), x2 = 7.54, 6.86, all P ＜ 0.01]. Conclusions USI could increase the IQs of children and decrease the positive rate of JPB, and significantly improve the quality of whole nation and persistently eliminating IDD.

Drug therapy is one of the efficient methods for prostate cancer treatment. However, drug resistance greatly hindered the treatment of prostate cancer patients. Herein, the mechanisms of drug resistance in prostate cancer have been exhaustively reviewed, and that can provide an alternative strategy and new targets for anti-prostate cancer therapy.
Drug Resistance, Neoplasm ; Humans ; Male ; Prostatic Neoplasms ; drug therapy

The up-regulation mechanism of membrane type I matrix metalloproteinase (MT1-MMP) in macrophages stimulated by silica in vitro and the contribution of early growth response 1 (Egr-1) transcription factor in the gene expression pathway were investigated. Macrophages stimulated by silica were treated with Egr-1 antibody or Egr-1 decoy oligodeoxynucleotides (ODN). The levels of MT1-MMP proteins were determined by Western blot and the expression of MT1-MMP mRNAs was detected by RT-PCR. The results showed as compared with control macrophages, silica-stimulated group showed up-regulated gene expression of MT1-MMP via Egr-1 (P<0.01). Compared with silica-stimulated macrophages untreated with antibody, the cells treated with 5 microg/mL Egr-1 antibody were associated with reduced expression of MT1-MMP protein (P<0.01) and mRNA (P<0.01). Compared with silica-stimulated untransfected group, the Egr-1 "decoy" ODN group was associated with reduction in the expression of MT1-MMP protein and mRNA (P<0.01). It was concluded gene expression of MT1-MMP which may play a critical role in silicosis was up-regulated by silica in macrophages. Egr-1 participated in the expression of MT1-MMP and positively regulated the expression. Both Egr-1 antibody and Egr-1 decoy ODN suppressed the expression of MT1-MMP through the Egr-1 pathway and may become a potential therapeutic tool in the management of silicosis in the future.

The effects of exogenous p16(ink4a) gene on biological behaviors of human lung cancer cell line with homozygous deletion of p16(ink4a) gene were investigated. Exogenous p16(ink4a) gene was transfected by lipofectin into human lung cell line A549, in which p16(ink4a) gene was homozygously deleted. The expression of p16(ink4a) mRNA and protein was detected by RT-PCR and immunocyto-chemistry, respectively. The changes in the behaviors of the transfected cell lines in vitro and in vivo were observed. In the transfected cell line A549, the exogenous p16(ink4a) gene could be stably expressed. The growth of A549 cells transfected with p16(ink4a) gene was obviously slowed down. Flow cytometry revealed that transfection of the exogenous p16(ink4a) gene resulted in A549 cell lines arrest in G1 phase of cell cycle. The tumorigenicity of these transfected cells in nude mice could be inhibited, and the tumor growth of nude mice was significantly suppressed. It was concluded that exogenous p16(ink4a) gene may be stably expressed in human lung cancer cell line A549. The expression of the introduced p16(ink4a) could block lung cancer cells to entry into S phase of cell cycle and inhibit tumor malignant growth both in vitro and in vivo.

The aim of this paper is to report the synthesis of the mPEG-PCL-g-PEI copolymers as small interfering RNA (siRNA) delivery vector, and exploration of the siRNA delivery potential of mPEG-PCL-g-PEI in vitro. The diblock copolymers mPEG-PCL-OH was prepared through the ring-opening polymerization. Then, the hydroxyl terminal (-OH) of mPEG-PCL-OH was chemically converted into the carboxy (-COOH) and N-hydroxysuccinimide (NHS) in turn to prepare mPEG-PCL-NHS. The branched PEI was reacted with mPEG-PCL-NHS to synthesize the ternary copolymers mPEG-PCL-g-PEI. The structure of mPEG-PCL-g-PEI copolymers was characterized with Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The mPEG-PCL-g-PEI/siRNA nanoparticles were prepared by complex coacervation, and the nanoparticles size and zeta potential were determined, separately. The cytotoxicities of mPEG-PCL-g-PEI/siRNA nanoparticles and PEI/siRNA nanoparticles were compared through cells MTT assays in vitro. The inhibition efficiencies of firefly luciferase gene expression by mPEG-PCL-g-PEI/ siRNA nanoparticle at various N/P ratios were investigated through cell transfection in vitro. The experimental results suggested that the ternary (mPEG5k-PCL(1.2k))1.4-g-PEI(10k) copolymers were successfully synthesized. (mPEG(5k)-PCL(1.2k))1.4-g-PEI(10k) could condense siRNA into nanoparticles (50-200 nm) with positive zeta potential. MTT assay results showed that the cytotoxicity of (mPEG(5k)-PCL(1.2k))1.4-g-PEI(10k)/siRNA nanoparticles was significantly lower than that of PEI(10k)/siRNA nanoparticles (P < 0.05). The expression of firefly luciferase gene could be significantly down-regulated at a range of N/P ratio from 50 to 150 (P < 0.01), and maximally inhibited at the N/P ratio of 125. The mPEG-PCL-g-PEI polymers could delivery siRNA into cells to inhibit the expression of target gene with very low cytotoxicity, which suggested that mPEG-PCL-g-PEI could serve as a new type of siRNA delivery vector.

Adult ; Cardiomyopathy, Hypertrophic ; complications ; pathology ; Humans ; Male ; Myocardium ; pathology

ObjectiveTo observe clinical features and identify causative genes of reticulate pigmented anomaly of the flexures in a pedigree.Methods A survey was conducted in a pedigree with reticulate pigmented anomaly of the flexures.Clinical manifestations were recorded in details for each patient in this pedigree.Tissue specimen was obtained from the proband for histopathological examination and ultrastructural observation.Mutation scanning was carried out by PCR and direct sequencing in 3 patients in the family.ResultsAll the patients in this pedigree presented with reticular pigmentation of the flexures and idiopathic guttate hypomelanosis on the abdomen and back.Histopathological and ultrastructural study revealed epidermal hyperpigmentation with an increase in melanin content in epidermal keratinocytes but no changes in the number of melanocytes.No mutation was found in the KRT5 gene in this family.ConclusionsThis is the first case report of reticulate pigmented anomaly of the flexures associated with idiopathic guttate hypomelanosis.No mutation is identified in the KRT5 gene of patients with reticulate pigmented anomaly of the flexures in this family,indicating the existence of other causative genes.