Research Progress of Exosomes and Their Forensic Significance.

Exosomes are membranous tiny vesicles secreted by cells, which are widely found in the extracellular matrix and various body fluids and carry a variety of biologically functional molecules such as proteins, lipids, messenger RNA (mRNA) and microRNA (miRNA). Exosomes not only play important biological roles in the field of immunology and oncology, but also have potential application value in the field of forensic medicine. This article reviews the discovery, production and degeneration mechanism, biological functions, isolation and identification methods of exosomes, summarizes the research on exosomes and their significance in the field of forensic science, and discusses their applications in body fluid identification, individual identification, postmortem interval estimation to provide ideas for the application of exosomes in forensic work.

Mesenchymal stem cells desensitize castration-resistant prostate cancer to docetaxel chemotherapy via inducing TGF-ß1-mediated cell autophagy.

BACKGROUND: Mesenchymal stem cells (MSCs) have been proved to drive castration resistant prostate cancer (CRPC). In this study, we aim to investigate the contribution of MSCs to the development of docetaxel resistance in CRPC cells and its potential mechanisms. METHODS: The effect of MSCs on CRPC cells resistance to docetaxel was determined using in vivo and in vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-ß1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses. RESULTS: MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-ß1 and inhibition of TGF-ß1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel. CONCLUSIONS: These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-ß1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.

Discovering biomarkers in bladder cancer by metabolomics.

It has become increasingly clear that the development of cancer, a multifactorial disease, cannot be explained by a single molecule or gene mutation. As a new discipline, metabolomics focuses on the body's metabolite changes, and attempts to find differences to explain the development of cancer; it has proven to be effective and credible. Metabolic studies of bladder cancer (BCa) lag behind those of other tumors. This review systematically outlines the specific process of metabolomics and the use of metabolomics in BCa studies in recent years. We have reviewed the in vitro cell line, bladder tumor tissue and biofluid (urine, plasma and serum) studies used in metabolomics analyses of BCa. The advantages and drawbacks of the use of different samples were compared. Based on the available studies, we have further described the aberrant metabolic pathways of BCa and have suggested some metabolites that may be potential biomarkers for BCa detection.

Three new benzolactones from Lavandula angustifolia and their bioactivities.

Three new benzolactones (1-3), together with four known ones (4-7), were isolated from the whole herb of Lavandula angustifolia. Their structures were established on the basis of detailed spectroscopic analysis (1D- and 2D-NMR, HRESIMS, UV, and IR) and comparison with data reported in the literature. New compounds were evaluated for their anti-tobacco mosaic virus (TMV) activities and cytotoxic activities. The results revealed that compounds 1-3 showed obvious anti-TMV activities with inhibition rates of 26.9, 30.2, and 28.4%, which were at the same grade as positive control. Compounds 1-3 also showed weak inhibitory activities against some tested human tumor cell lines with IC50 values in the range of 32.1-7.6 µM.

Sesquiterpenoids from Tussilago farfara and their inhibitory effects on nitric oxide production.

Tussilagone (TSL) and its allied sesquiterpenoids were considered as the main active principles of the flower buds of Tussilago farfara, which has been widely used in China as an antitussive herbal medicine. Six new bisabolane-type sesquiterpenoids, tussfararins A-F (1-6), along with 12 known sesquiterpenoids, were isolated from the flower buds of T. farfara. Structures of the new compounds were elucidated by extensive spectroscopic analysis. The biological analysis showed that compounds 1, 3, 6, and 7 inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with IC50 values of 13.6-24.4 µM.

[Determination of chlorogenic acid, rutin, scopoletin and total polyphenol in tobacco by Fourier transform near infrared spectroscopy].

The objective of the present study was to investigate the feasibility of predicting chlorogenic acid, rutin, scopoletin and total polyphenol in tobacco by Fourier transform near-infrared (FT-NIR) spectroscopy. The partial least squares(PLS) regression method, second derivative and Norris derivative filter were applied in the NIR spectroscopy prediction of chlorogenic acid, rutin, scopoletin and total polyphenol in the range of 7 500 to 4 000 cm(-1). For chlorogenic acid, rutin, scopoletin and total polyphenol, the determination coefficients were 0.976 6, 0.941 9, 0.957 1 and 0.966 6, respectively. The SEP/SEC values for them were < 1.2, and the SD/SEP values for them were > 2. The root mean square error of cross validation (RMSECV) of the four calibration models were 1.938 9, 1.046 2, 0.047 9 and 2.745 2, respectively. NIR spectroscopy was compared with the conventional methods. The results show that the two methods showed no significant difference at the significant level of 0.05. NIR spectroscopy technology can accurately analyze chlorogenic acid, rutin, scopoletin and total polyphenol in tobacco.

An investigation and pathological analysis of two fatal cases of cadmium poisoning.

Pollution associated with population growth, and with industrial and urban development has led to a serious decline in the water quality of Chinese rivers. Cadmium (Cd) is recognized as one of the most toxic metals and is strongly accumulated by organisms. Humans are exposed to cadmium originating from the environment and from industrial pollution. In spite of thousands of published studies on Cd, there is little information on its pathological features seen in human autopsy. The gross and pathological findings of forensic autopsies of two case of cadmium poisoning are presented and related to an epidemiological investigation. In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets, which is consistent with reports in the literature. In particular, in both cases, transmission electron microscopy revealed a large number of dense lysosomal and phagocytic particles in the cytoplasm near the nucleus, indicating the need for a genotoxic study of cadmium. Our observations provide new clues for the future recognition and prevention of Cd poisoning.

[Forensic analysis of 74 tumor related medical malpractice cases].

OBJECTIVE: To analyze the causes of medical malpractice in patients with tumor, to determine the medical responsibility, and to recommend the related preventions. METHODS: Seventy four medical malpractice cases, which were involved in tumor and collected from 2000 to 2009 in medicolegal expertise center of west China, were analyzed retrospectively. RESULTS: The medical malpractice cases in the patients with tumor showed an increasing tendency in recent years. The main causes are missed diagnosis, misdiagnosis, improper chemotherapy and neglect of complications. The causes of medical malpractice were different in the different levels of medical services. The occurrence of medical malpractice in surgery and OB-GYN showed more frequent than the others. CONCLUSION: Forensic pathology autopsy is important to resolve medical malpractice of tumor patients by finding out the cause of death and clarifying the medical responsibility. The occurrence of medical malpractice could be reduced by the clinical doctors through improving serve consciousness, obtaining the patients' trust, improving the medical treatment, following related laws and rules, fulfiling duty of medical careness.

[The statin dosage for achieving goal of cholesterol-lowering based on risk stratification in patients with ischemic cerebrovascular diseases].

OBJECTIVE: To explore statin dosages for targeting goal of LDL-C lowering on the basis of stroke risk stratification and the dosage-effective relation of statin and LDL-C lowering in Chinese patients with ischemic stroke and transient ischemic attack (TIA). METHODS: This is a prospective and open clinical trial patients with ischemic stroke/TIA within 6 months were enrolled and the dosages of atorvastatin were calculated based on risk stratification according to "Chinese Consensus for Prevention of Ischemic Stroke/TIA with Statin" (Chinese Consensus). A dose of 10 mg of atorvastatin daily to target LDL-C goal was taken as the standard dosage targeting goal (SDTG). Patients taking this dosage of atorvastatin constituted a SDTG group. Those who needed a daily dose of 20 mg or more of atorvastatin were randomized into an intensive dosage targeting goal (IDTG) group (atorvastatin 20 - 80 mg/d) and a standard dosage non-targeting goal (SDNTG) group (atorvastatin 10 mg/d without targeting goal). All patients took atorvastatin for 12 weeks. The primary outcome was the rate of targeting goal for LDL-C lowering at 2, 4 and 12 weeks, respectively and the secondary outcome was the occurence of recurrent stroke and other vascular events within 12 weeks. The main safety endpoint was serial adverse events including symptomatic intracranial hemorrhage. RESULTS: Altogether 102 cases were enrolled and 99 cases were followed up for 12 weeks. According to the Chinese Consensus, the rate of high risk, very high risk-I and very high risk-II was 44%, 28% and 28%, respectively. Targeting rate for LDL-C lowering was 77% - 85% at each time point in the SDTG and IDTG groups, being significantly higher than those in the SDNTG group (12% - 16%, P < 0.01). No significant difference was found concerning the occurrence of recurrent stroke, other vascular events and safety endpoints among the three groups. The amplitude of LDL-C lowering was 32% - 35%, 46% - 49%, 51% - 52% and 60% - 65% with corresponding to daily dosage of 10 mg, 20 mg, 40 mg and 80 mg atorvastatin. CONCLUSIONS: At least more than half of the patients after ischemic stroke/TIA need intensive statin therapy to target the LDL-C lowering goal. The dosage-effective relation of atorvastatin and LDL-C lowering in Chinese is similar to the reported data in other races.