Anti-Apoptosis Effect of Astragaloside Iv on Alzheimer's Disease Rat Model via Enhancing the Expression of Bcl-2 And Bcl-Xl

The aim is to explore the protective effect of Astragaloside IV on Alzheimer’s disease (AD) in rats induced  by amyloid-ß peptide (Aß1-42) and its potential therapeutic mechanism. Methods: 50 Male Sprague Dawley  rats were divided into five groups (10 rats for each): control group, model group, treatment groups 1~3.  10μg Aß1-42 was injected bilaterally into the dorsal dentate gyrus of the hippocampus of rats in the model  and treatment groups to prepare the AD models. 24h after modeling, Astragaloside IV administration, with  different drug dosages of 20mg/(kg•day), 40mg/(kg•day) and 60mg/(kg•day), was performed by gastric  perfusion for rats in the treatment group 1~3. Later on, the cognitive ability of rats was examined by a series  of behavioral tests, and the expression of Bcl-2 and Bcl-xl in the hippocampus of rats was detected by the  fluorescein based Quantitative RT-PCR. Results: The spontaneous alternation test in a Y maze and Morris  water maze task have demonstrated that the repeated daily administration of Astragaloside IV at the doses  of 20mg/kg bw/day) (p<0.05), 40mg/kg bw/day) (p<0.01), and 60mg/kg bw/day) (p<0.01) significantly  ameliorated the impairment of performance caused by Aß1–42. Furthermore, Astragaloside IV also enhanced  the expression of Bcl-2 and Bcl-xl in hippocampal neurons of rats in a dosage-dependent manner. Conclusion:  These findings suggest that Astragaloside IV could alleviate cognitive impairment and enhance the  expression of Bcl-2 and Bcl-xl in hippocampus of rat models with AD.

Photodynamic therapy with light-emitting diode arrays producing different light fields induces apoptosis and necrosis in gastrointestinal cancer

IntroductionLight-emitting diodes (LEDs) have become a new light source for photodynamic therapy (PDT) because of their excellent optical properties, small size, and low cost. LED arrays have so far been designed to meet the need for accurate illumination of irregular lesions. However, LED arrays determine not only the shape of the illuminated spot but also the light field, which has a significant impact on the efficacy of PDT.MethodsWe designed three types of LED arrays producing different light fields, namely an intensive LED array for a uniform light field, a sparse LED array for a non-uniform light field, and a point LED array for a Gaussian-like light field, and investigated the effect and mechanism of these light fields on PDT for gastrointestinal cancer both in vitro and in vivo.ResultsWe found that intensive LED-PDT induced earlier and more serious cell death, including apoptosis and necrosis, than sparse LED-PDT and point LED-PDT. Among the three LED arrays, the intensive LED array induced cells to produce more differential proteins (DEPs), mainly related to mitochondria, ribosomes, and nucleic acids. DEPs in cells subjected to sparse LED- and point LED-PDT were mainly involved in extracellular activities. For MGC-803 tumor-bearing mice, intensive LED-PDT and point LED-PDT had better tumor ablation effect than sparse LED-PDT. Notably, recurrence was observed on day 7 after sparse LED-PDT. VCAM-1 and ICAM-1 were highly expressed in sparse LEDs-PDT treated tumor tissues and were associated tumor angiogenesis, which in turn lead to poor tumor suppression.ConclusionsTherefore, the type of LED array significantly affected the performance of PDT for gastrointestinal cancer. Uniform light field with low power densities work better than non-uniform and Gaussian-like light fields

Hypermethylation of SOX2 Promoter in Endometrial Carcinogenesis

This paper aimed at investigating the expression and methylation profiles of SOX2, a gene coding for the stem cell-related transcription factor SOX2, in endometrial carcinomas. By methylation-specific polymerase chain reaction (MS-PCR), the methylation status of SOX2 promoter region in 72 endometrial carcinomas and 12 normal endometrial samples was examined. Methylated allele was found in 37.5% (27/72) of endometrial carcinomas but only in 8.3% (1/12) of normal endometrial, significantly more frequent in cancers (P = .0472). SOX2 mRNA level was significantly reduced in endometrial carcinoma compared with nonneoplastic endometrium (P = .045). A significant correlation between SOX2 mRNA expression and hypermethylation of SOX2 was found (P = .024). Hypermethylation of SOX2 tended to be more frequently found in type II serous or clear cell adenocarcinoma. SOX2 methylation was also significantly correlated with shorter survival of patients (P = .046). In conclusion, epigenetic mechanisms may play a crucial role on the transcriptional regulation of SOX2 and loss of SOX2 expression may be related to endometrial carcinogenesis

Relevance of PUFA-derived metabolites in seminal plasma to male infertility

AimThis study aims to investigate the biological effects of polyunsaturated fatty acid (PUFA)-derived metabolites in seminal plasma on male fertility and to evaluate the potential of PUFA as a biomarker for normozoospermic male infertility.MethodsFrom September 2011 to April 2012, We collected semen samples from 564 men aged 18 to 50 years old (mean=32.28 years old)ch., residing in the Sandu County, Guizhou Province, China. The donors included 376 men with normozoospermia (fertile: n=267; infertile: n=109) and 188 men with oligoasthenozoospermia (fertile: n=121; infertile: n=67). The samples thus obtained were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to detect the levels of PUFA-derived metabolites in April 2013. Data were analyzed from December 1, 2020, to May 15, 2022.ResultsOur analysis of propensity score-matched cohorts revealed that the concentrations of 9/26 and 7/26 metabolites differed significantly between fertile and infertile men with normozoospermia and oligoasthenozoospermia, respectively (FDR < 0.05). In men with normozoospermia, higher levels of 7(R)-MaR1 (HR: 0.4 (95% CI [0.24, 0.64]) and 11,12-DHET (0.36 (95% CI [0.21, 0.58]) were significantly associated with a decreased risk of infertility, while higher levels of 17(S)-HDHA (HR: 2.32 (95% CI [1.44, 3.79]), LXA5 (HR: 8.38 (95% CI [4.81, 15.24]), 15d-PGJ2 (HR: 1.71 (95% CI [1.06, 2.76]), and PGJ2 (HR: 2.28 (95% CI [1.42, 3.7]) correlated with an increased risk of infertility. Our ROC model using the differentially expressed metabolites showed the value of the area under the curve to be 0.744.ConclusionThe PUFA-derived metabolites 7(R)-MaR1, 11,12-DHET, 17(S)-HDHA, LXA5, and PGJ2 might be considered as potential diagnostic biomarkers of infertility in normozoospermic men

Mimotope ELISA for Detection of Broad Spectrum Antibody against Avian H5N1 Influenza Virus

Science and Technology Foundation of Fujian Province [2009YZ0002]; National Natural Science Foundation of China [30901077]; National High Technology Research and Development Program [2010AA022801]Background: We have raised a panel of broad spectrum neutralizing monoclonal antibodies against the highly pathogenic H5N1 avian influenza virus, which neutralize the infectivity of, and afford protection against infection by, most of the major genetic groups of the virus evolved since 1997. Peptide mimics reactive with one of these broad spectrum H5N1 neutralizing antibodies, 8H5, were identified from random phage display libraries. Method: The amino acid residues of the most reactive 12mer peptide, p125 (DTPLTTAALRLV), were randomly substituted to improve its mimicry of the natural 8H5 epitope. Result: 133 reactive peptides with unique amino acid sequences were identified from 5 sub-libraries of p125. Four residues (2,4,5.9) of the parental peptide were preserved among all the derived peptides and probably essential for 8H5 binding. These are interspersed among four other residues (1,3,8,10), which exhibit restricted substitution and probably could contribute to binding, and another four (6,7,11,12) which could be randomly substituted and probably are not essential for binding. One peptide, V-1b, derived by substituting 5 of the latter residues is the most reactive and has a binding constant of 3.16x10(-9) M, which is 38 fold higher than the affinity of the parental p125. Immunoassay produced with this peptide is specifically reactive with 8H5 but not also the other related broad spectrum H5N1 avian influenza virus neutralizing antibodies. Serum samples from 29 chickens infected with H5N1 avian influenza virus gave a positive result by this assay and those from 12 uninfected animals gave a negative test result. Conclusion: The immunoassay produced with the 12 mer peptide, V1-b, is specific for the natural 8H5 epitope and can be used for detection of antibody against the broad spectrum neutralization site of H5N1 avian influenza virus

A Systematic Analysis on DNA Methylation and the Expression of Both mRNA and microRNA in Bladder Cancer

Background: DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported. Methodology/Principal Findings: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to "neurogenesis" and "cell differentiation" by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17) by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples. Conclusions/Significance: We characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe