ABSTRACT
Lung is the largest organ of the respiratory system. During hypoxia, pulmonary cells undergo rapid damage changes and activate the self-rescue pathways, thus leading to complex biomacromolecule modification. Death from mechanical asphyxia refers to death due to acute respiratory disorder caused by mechanical violence. Because of the absence of characteristic signs in corpse, the accurate identification of mechanical asphyxia has always been the difficulty in forensic pathology. This paper reviews the biomacromolecule changes under the pulmonary hypoxia condition and discusses the possibility of application of these changes to accurate identification of death from mechanical asphyxia, aiming to provide new ideas for related research.
Subject(s)
Humans , Asphyxia/pathology , Cause of Death , Hypoxia/pathology , Lung/pathology , Forensic PathologyABSTRACT
Objective To investigate the protective effect of gastrodin (Gas) on the hepatic ischemia-reperfusion injury (HIRI) in mice,and study possible mechanisms.Methods Forty male C57BL/6 mice were randomly divided into sham-operated group (Sham),HIRI group,gastrodin-treated groups with low and high does (Gas-L,Gas-H,respectively),and cobalt protoporphyrin(CoPP) group(n =8).Mice in Gas-L,Gas-H,and CoPP groups were injected intraperitoneally with individual drugs and dose before operation.Except for Sham group,an 70％ volume HIRI model was established by means of 60 minutes ischemia and then 6 hours reperfusion in the other groups.The levels of serum AST and ALT in each group were compared.The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver tissue were measured;The level of TNF-αt,IL-6,IL-10 and heme oxygenase-I (HO-1) mRNA level were detected by real time quantitative PCR.Liver tissue was stained with H&E.The hepatocyte apoptosis was studied by TUNEL.Results Respectively,the serum ALT level in the HIRI,Gas-L,Gas-H and CoPP groups was (5 057.34±290.80)U/L,(3 917.49±198.10) U/L,(3 645.63± 171.10) U/L,(2 977.78± 179.00) U/L,and the ALT level was (5 871.25 ± 819.01) U/L,(4 660.88 ± 505.96) U/L,(4 182.00 ± 507.51) U/L,(3 788.65±462.14)U/L.The serum level of ALT and AST in Gas-L,Gas-H and CoPP groups was lower than HIRI group (P＜ 0.05).The apoptotic index in Gas-L,Gas-H and CoPP groups respectively was (37.89±4.27)％,(32.59±3.78)％,(20.45-±2.49)％,which was lower than group (58.92±3.32)％ (P＜ 0.05).Compared with HIRI group,the TNF-α and IL-6 mRNA level in Gas-L,Gas-H and CoPP groups were decreased,and the levels of IL-10 and HO-1 mRNA were increased.Simultaneously,the activity of SOD was promoted,whereas the levels of MDA was reduced (P＜0.05).Conclusions Gastrodin shows an protective function aganist liver ischemia-reperfusion injury in mice by inhibiting inflammation,oxidative stress and cell apoptosis.The up-regulation of HO-1 by gastrodin may be the possible mechanism.
ABSTRACT
Objective To explore the effect of endoplasmic reticulum stress (ER stress) in uric acid?induced phenotypic change in renal tubular epithelial cells (HK?2). Methods (1) HK?2 cells were cultured with 0, 75, 150, 225, 300 mg/L uric acid for 24 h in vitro. (2) The cells were divided into normal control group, ER stress inhibitor 4?PBA (5 μmol/L) group, uric acid (150 mg/L) group and 4?PBA+uric acid group for 24 h. Morphological changes of HK?2 cells were observed under inverted microscope. MTT assay was used to detect the proliferation of HK?2 cells treated with 150 mg/L uric acid for 24, 48 and 72 h. The protein expressions of α?smooth muscle actin (α?SMA), vimentin, snail, glucose regulated protein 78 (GRP78) and the phosphorylation of eukaryotic initiation factor 2α(p?eIF2α) in HK?2 cells were measured by Western blotting. Results Compared with the control group, HK?2 cells in uric acid groups (150, 225, 300 mg/L) showed fibroblast?like appearance. The protein expressions of α?SMA, vimentin, snail, GRP78 and p?eIF2α in 150 mg/L and 225 mg/L uric acid groups were higher than those in the control group (all P<0.05). The proliferation of HK?2 cells in 150 mg/L uric acid group was lower than that in control group at 48 and 72 h (all P<0.01). Compared with the uric acid group, the cell morphology in 4?PBA+uric acid group was improved, and the protein expressions ofα?SMA, vimentin, snail, GRP78 and p?eIF2α were decreased (all P<0.05). Conclusions Uric acid may induce the phenotype transformation of renal tubular epithelial cell, and ER stress is involved. 4?PBA may inhibit the uric acid?induced ER stress response and phenotypic transformation, and may be beneficial in attenuating uric acid?induced renal tubular damage.
ABSTRACT
Melanoma is the most serious type of skin cancer and one of the most common cancers in the world. Advanced melanoma is often resistant to conventional therapies and has high potential for metastasis and low survival rates. Vemurafenib is a small molecule inhibitor of the BRAF serine-threonine kinase recently approved by the United States Food and Drug Administration to treat patients with metastatic and unresectable melanomas that carry an activating BRAF (V600E) mutation. Many clinical trials evaluating other therapeutic uses of vemurafenib are still ongoing. The ATP-binding cassette (ABC) transporters are membrane proteins with important physiological and pharmacological roles. Collectively, they transport and regulate levels of physiological substrates such as lipids, porphyrins and sterols. Some of them also remove xenobiotics and limit the oral bioavailability and distribution of many chemotherapeutics. The overexpression of three major ABC drug transporters is the most common mechanism for acquired resistance to anticancer drugs. In this review, we highlight some of the recent findings related to the effect of ABC drug transporters such as ABCB1 and ABCG2 on the oral bioavailability of vemurafenib, problems associated with treating melanoma brain metastases and the development of acquired resistance to vemurafenib in cancers harboring the BRAF (V600E) mutation.
