Influence of six digestion methods on the determination of polystyrene microplastics in organisms using the fluorescence intensity

Microplastic pollution has become a global environmental problem and is a cause of great concern. To evaluate the biological effects of microplastics, microplastics in organisms need to be accurately quantified. The quantification of microplastics in organisms using the fluorescence intensity is common; the digestion of biological samples is an important pretreatment method. However, the microplastics may be destroyed by digestion, which affects the fluorescence intensity of the microplastics and results in large deviations between measured and true values. In this study, six commonly used digestive agents were studied: KOH, NaOH, H2O2, HNO3, HNO3: hcl, and HNO3: HClO4. The effect of different digestion methods on the fluorescence intensity and surface morphology of microplastics was studied and the most suitable protocol was selected. The results show that, among the six different digestion methods, KOH digestion(100 g·L-1, 60℃)has the least influence on the fluorescence intensity of the microplastics and does not affect their surface morphology. The other five digestion methods lead to different degrees of reduction of the fluorescence intensity of microplastics and damage the microplastics' surface(aggregation, bubbles, scratches, and depressions). In addition, the KOH digestion method was used to extract microplastics from biological samples. The recovery rate was≥96.3%±0.5%, indicating that the KOH digestion method is suitable for fluorescent microplastics in biological samples

Prostate cancer – a biomarker perspective

Despite early detection and reduced risk of death, prostate cancer still remains the second leading cause of cancer death in American men. There is currently no cure for advanced prostate cancer. The multistage, stochastic and highly heterogeneous nature of prostate cancer, coupled with genetic and epigenetic alterations that occur during disease progression and response to therapy, represent fundamental challenges in our quest to understand and control this complex and prevalent disease. Recent advances in drug development and breakthroughs in omics technologies have renewed our efforts to identify novel biomarkers for prostate cancer prognosis, prediction, and therapeutic response monitoring. In this perspective article, we overview the current status and highlight future prospects of biomarkers for prostate cancer, a disease that affects millions of men worldwide

The Local Linear M

This paper studies the nonparametric regressive function with missing response data. Three local linear M-estimators with the robustness of local linear regression smoothers are presented such that they have the same asymptotic normality and consistency. Then finite-sample performance is examined via simulation studies. Simulations demonstrate that the complete-case data M-estimator is not superior to the other two local linear M-estimators

PD-1 expression on peripheral CD8+ TEM/TEMRA subsets closely correlated with HCV viral load in chronic hepatitis C patients

<p>Abstract</p> <p>Background</p> <p>Tight correlation between host circulating CD8+ T cell-mediated immune response and control of viral replication is classical characteristic of long-term HCV infection. CD8+ T cell maturation/activation markers are expected to be associated with viral replication and disease progression in chronic HCV infection. The aim of the present study was to explore novel markers on CD8+ T cells with ability to evaluate HCV viral replication and disease progression.</p> <p>Methods</p> <p>PBMCs were isolated from 37 chronic HCV-infected patients and 17 healthy controls. Distributed pattern of CD8+ T cells subsets and expression of PD-1, CD38, HLA-DR and CD127 were analyzed by flow cytometry. The correlation between expression of surface markers and HCV viral load or ALT was studied.</p> <p>Results</p> <p>Declined naïve and increased TEMRA CD8+ T subsets were found in HCV-infected individuals compared with healthy controls. Percentage and MFI of PD-1, CD38 and HLA-DR on all CD8+ T cell subsets were higher in HCV-infected patients than healthy controls. In contrast, CD127 expression on CD8+ TCM showed an opposite trend as PD-1, CD38 and HLA-DR did. In chronic HCV infection, MFI of PD-1 on CD8+ TEM (p < 0.0001) and TEMRA (p = 0.0015) was positively correlated with HCV viral load while HLA-DR expression on non-naive CD8+ T cell subsets (p < 0.05) was negatively correlated with HCV viral load.</p> <p>Conclusion</p> <p>PD-1 level on peripheral CD8+ TEM/TEMRA was highly correlated with HCV viral load in chronic HCV-infected patients, which made PD-1 a novel indicator to evaluate HCV replication and disease progression in chronic hepatitis C patients.</p

Probiotics and Postbiotics from Food to Health: Antimicrobial Experimental Confirmation

The field of probiotics is up-and-coming, especially in management of microbial pathogens. Probiotics confer nutritional benefits, reduce inflammation and infection. Probiotics have also shown to be helpful in the management of microbial pathogens, which include bacteria, fungi, and viruses. To ernes this potential maximumly, there is a need for an elaborate screening system for new isolates. This entails; rigorous screening methods and thorough confirmatory systems. There is need also to come up with standard methods used to evaluate the probiotics mechanism of action both in vivo and in vitro. In summary, there is a need for a standard screening process for probiotic microorganisms that is reproducible. The aim is to ensure that, the candidate microbial cultures are not written off without proper investigations. This will also fasten the screening process and save time and resources wasted in pre-screening experiments

Characteristics and PD-1 expression of peripheral CD4+CD127loCD25hiFoxP3+ Treg cells in chronic HCV infected-patients

<p>Abstract</p> <p>Background</p> <p>Both regulatory T cells (Tregs) and PD-1/PD-L1 pathway were critically involved in HCV viral persistence. However, the association between them was not well investigated. Herein, we aimed to investigate the distributional profiles of Tregs subsets and association between PD-1 expression on these subsets and development of HCV long-term persistence.</p> <p>Methods</p> <p>CD45RA and CD27 were employed to separate peripheral Tregs as naïve/central memory/effector memory/effector subsets. The phenotypic characteristics and PD-1 expression of Tregs were studied by flow cytometry.</p> <p>Results</p> <p>In the present study, the majority of Tregs was identified as central memory phenotype in chronic hepatitis C patients compared with nearly equal contribution of naïve and central memory subsets in healthy individuals. PD-1 expression was elevated in all CD4+ T cell subset in chronic HCV infected patients, including Tregs. Of note, higher level of PD-1 expression was found on TEM- and effector-Treg than naïve- and TCM-Tregs subsets. The ratio of TEM-Tregs/naive-Tregs and TEM-Tregs/TCM-Tregs regarding to PD-1 MFI were significantly lower in CHC patients compared to controls.</p> <p>Conclusions</p> <p>Our study indicated that distinctive characteristics of PD-1 expression on Tregs in HCV infection suggests associated with impaired adaptive immunity as well as viral long-term persistence. The cross talk between Treg cells and PD-1 induced inhibition in chronic HCV infection deserved further exploration for HCV infection associated immune pathogenesis.</p

Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis

To examine the role of hepatitis B virus (HBV) integration in hepatocarcinogenesis, a systematic comparative study of both tumor and their corresponding non-tumor derived tissue has been conducted in a cohort of 60 HBV associated hepatocellular carcinoma (HCC) patients. By using Alu-polymerase chain reaction (PCR) and ligation-mediated PCR, 233 viral-host junctions mapped across all human chromosomes at random, no difference between tumor and non-tumor tissue was observed, with the exception of fragile sites (P = 0.0070). HBV insertions in close proximity to cancer related genes such as hTERT were found in this study, however overall they were rare events. No direct correlation between chromosome aberrations and the number of HBV integration events was found using a sensitive array-based comparative genomic hybridization (aCGH) assay. However, a positive correlation was observed between the status of several tumor suppressor genes (TP53, RB1, CDNK2A and TP73) and the number of chromosome aberrations (r = 0.6625, P = 0.0003). Examination of the viral genome revealed that 43% of inserts were in the preC/C region and 57% were in the HBV X gene. Strikingly, approximately 24% of the integrations examined had a breakpoint in a short 15 nt viral genome region (1820-1834 nt). As a consequence, all of the confirmed X gene insertions were C-terminal truncated, losing their growth-suppressive domain. However, the same pattern of X gene C-terminal truncation was found in both tumor and non-tumor derived samples. Furthermore, the integrated viral sequences in both groups had a similar low frequency of C1653T, T1753V and A1762T/G1764A mutations. The frequency and patterns of HBV insertions were similar between tumor and their adjacent non-tumor samples indicating that the majority of HBV DNA integration events are not associated with hepatocarcinogenesis

GFI1 downregulation promotes inflammation-linked metastasis of colorectal cancer.

Inflammation is frequently associated with initiation, progression, and metastasis of colorectal cancer (CRC). Here, we unveil a CRC-specific metastatic programme that is triggered via the transcriptional repressor, GFI1. Using data from a large cohort of clinical samples including inflammatory bowel disease and CRC, and a cellular model of CRC progression mediated by cross-talk between the cancer cell and the inflammatory microenvironment, we identified GFI1 as a gating regulator responsible for a constitutively activated signalling circuit that renders CRC cells competent for metastatic spread. Further analysis of mouse models with metastatic CRC and human clinical specimens reinforced the influence of GFI1 downregulation in promoting CRC metastatic spread. The novel role of GFI1 is uncovered for the first time in a human solid tumour such as CRC. Our results imply that GFI1 is a potential therapeutic target for interfering with inflammation-induced CRC progression and spread

Chlorpromazine Protects Against Apoptosis Induced by Exogenous Stimuli in the Developing Rat Brain

Background: Chlorpromazine (CPZ), a commonly used antipsychotic drug, was found to play a neuroprotective role in various models of toxicity. However, whether CPZ has the potential to affect brain apoptosis in vivo is still unknown. The purpose of this study was to investigate the potential effect of CPZ on the apoptosis induced by exogenous stimuli. Methodology: The ethanol treated infant rat was utilized as a valid apoptotic model, which is commonly used and could trigger robust apoptosis in brain tissue. Prior to the induction of apoptosis by subcutaneous injection of ethanol, 7-day-old rats were treated with CPZ at several doses (5 mg/kg, 10 mg/kg and 20 mg/kg) by intraperitoneal injection. Apoptotic cells in the brain were measured using TUNEL analysis, and the levels of cleaved caspase-3, cytochrome c, the pro-apoptotic factor Bax and the anti-apoptotic factor Bcl-2 were assessed by immunostaining or western blot. Findings: Compared to the group injected with ethanol only, the brains of the CPZ-pretreated rats had fewer apoptotic cells, lower expression of cleaved caspase-3, cytochrome c and Bax, and higher expression of Bcl-2. These results demonstrate that CPZ could prevent apoptosis in the brain by regulating the mitochondrial pathway. Conclusions: CPZ exerts an inhibitory effect on apoptosis induced by ethanol in the rat brain, intimating that it may offer