ABSTRACT
Cytokines have attracted sustained attention due to their multi-functional cellular response in immunotherapy. However, their application was limited to their short half-time, narrow therapeutic window, and undesired side effects. To address this issue, we developed a portable smart blue-light controlled (PSLC) device based on optogenetic technology. By combining this PSLC device with blue-light controlled gene modules, we successfully achieved the targeted regulation of cytokine expression within the tumor microenvironment. To alter the tumor microenvironment of solid tumors, pro-inflammatory cytokines were selected as blue-light controlled molecules. The results show that blue-light effectively regulates the expression of pro-inflammatory cytokines both in vitro and in vivo. This strategy leads to enhanced and activated tumor-infiltrating immune cells, which facilitated to overcome the immunosuppressive microenvironment, resulting in significant tumor shrinkage in tumor-bearing mice. Hence, our study offers a unique strategy for cytokine therapy and a convenient device for animal studies in optogenetic immunotherapy.
Subject(s)
Cytokines , Light , Optogenetics , Tumor Microenvironment , Animals , Cytokines/metabolism , Mice , Optogenetics/methods , Optogenetics/instrumentation , Humans , Cell Line, Tumor , Immunotherapy/methods , Female , Gene Expression Regulation, Neoplastic , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/metabolismABSTRACT
One of the most frequent malignancies in the head and neck is nasopharyngeal carcinoma (NPC). MicroRNAs, a kind of tiny noncoding RNA molecule, have been used as negative regulators in different types of cancer therapy in recent decades by downregulating their targets. Recent research suggests that microRNAs play an important role in cancer's epithelial-to-mesenchymal transition (EMT), supporting or inhibiting EMT development. The epithelial-to-mesenchymal transition (EMT) is linked to a variety of cancer-related activities, including growth, metastasis, and invasion. Previous research has linked EMT to cancer stem-like characteristics as well as treatment resistance. Moreover, since microRNAs (miRNAs) are important regulators of the EMT phenotype, certain miRNAs have an effect on cancer stemness and treatment resistance. As a result, both fundamental research and clinical therapy benefit from knowing the connection between EMT-associated miRNAs and cancer stemness/drug resistance. As a result, we looked at the different functions that EMT-associated miRNAs (miR-137) play in the stem-like characteristics of malignant cells in this article. Then we looked at how EMT-associated miRNAs interact with nasopharyngeal cancer's drug-resistant complex signaling pathways. Using qRT-PCR, we evaluated the performance of several micro RNAs with the proposed miR-137 for inhibiting invasion, metastasis, and the EMT process. In conclusion, our findings showed that miR-137 acted as a tumor suppressor gene in controlling NPC EMT and metastasis and that it may be a new therapeutic strategy and prognosis marker for the disease.
ABSTRACT
Four pairs of novel meroterpenoid dimers, (±)-applandimeric acids A-D (1-4) with an unprecedented spiro[furo[3,2-b]benzofuran-3,2'-indene] core were isolated from the fruiting bodies of Ganoderma applanatum. Their planar structures were unambiguously determined via extensive spectroscopic analysis. Their relative and absolute configurations were confirmed through calculated internuclear distance, coupling constant, 13C NMR with DP4 + analysis and electronic circular dichroism (ECD). Furthermore, the molecular docking-based method was used to evaluate their interaction with formyl peptide receptor 2 (FPR2) associated with inflammation. Interestingly, (±)-applandimeric acid D (4) can bond with FPR2 by some key hydrogen bonds. Furthermore, an in vitro bioassay verified that 4 can inhibit the expression of FPR2 with IC50 value of 7.93 µM. In addition, compared to the positive control LiCl (20 mM), 4 showed comparable anti-lipogenesis activity at the concentration of 20 µM. Meanwhile, 4 can suppress the protein levels of peroxisome proliferators-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-ß (C/EBP-ß), adipocyte fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS) through activating AMP-activated protein kinase (AMPK) signaling pathway. Thus, our findings indicate that compound 4 could be a lead compound to treat obesity and obesity-related diseases by inhibiting lipid accumulation in adipocyte and alleviating inflammation.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Ganoderma/chemistry , Lipogenesis/drug effects , Receptors, Formyl Peptide/antagonists & inhibitors , Receptors, Lipoxin/antagonists & inhibitors , Terpenes/pharmacology , 3T3-L1 Cells , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , HEK293 Cells , Humans , Mice , Molecular Dynamics Simulation , Molecular Structure , PPAR gamma/antagonists & inhibitors , PPAR gamma/metabolism , Receptors, Formyl Peptide/genetics , Receptors, Formyl Peptide/metabolism , Receptors, Lipoxin/genetics , Receptors, Lipoxin/metabolism , Structure-Activity Relationship , Terpenes/chemistry , Terpenes/isolation & purificationABSTRACT
In recent years, ellagic acid (EA), a naturally-occurring phenolic compound richly contained in some of the human food sources such as Longan and Litchi, was reported to have a number of biological effects. Based on our earlier 3D-QSAR/CoMFA models for cyclooxygenase (COX) I and II, we hypothesize that EA may have the potential to modulate the catalytic activity of COX enzymes, and this hypothesis is examined in the present study. The results from both in vitro and in vivo experiments show that EA is an activator of COX enzyme-catalyzed production of prostaglandin E2, a representative prostaglandin tested. Mechanistically, EA can activate the peroxidase active site of COX enzymes by serving as a co-substrate, presumably for the reduction of protoporphorin IX with FeIV inside. The effect of EA is abrogated by the co-presence of galangin, which is known to bind to COX's peroxidase active site and thereby blocks the effect of the reducing co-substrates. In view of the known physiological functions of COX enzymes in the body, it is suggested that some of the pharmacological and/or toxicological effects of EA may result from an increased production of certain prostaglandins and their related derivatives in the body.
ABSTRACT
BACKGROUND: The differential diagnosis of general paresis (GP) and non-neurosyphilis (NS) dementia is not clearly defined. The present study examined the differences in clinical and laboratory features of GP and non-NS dementia. MATERIALS AND METHODS: We retrospectively examined clinical and laboratory features of 85 GP patients and 196 non-NS dementia patients. Data were collected from Zhongshan Hospital between June 2005 and June 2014. RESULTS: The GP group had a higher percentage of males (83.53%, 71/85) and younger median age ([52 [interquartile range 47.0-61.0] vs. 76 [68.3-82.0] years) than the non-NS dementia group. GP have higher Mini-Mental State Examination (MMSE; Z = -5.809; p = 0.000) than non-NS dementia. Distribution of CDR scores were significantly higher in the non-NS group than GP group (χ2 = 29.153; p = 0.000). The laboratory findings showed signiï¬cantly different total cholesterol (CH), low-density lipoprotein CH and homocysteine levels between the 2 groups. Serologic testing for syphilis revealed that the GP group had higher seropositive rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) rates than the non-NS dementia group (96.47% [82/85] vs. 0.51% [1/196], Z = -2.663, p = 0.008; 100% [85/85] vs. 1.02% [2/196], Z = -2.663, p = 0.008). Interestingly, cerebrospinal fluid (CSF) biochemical indices, including pleocytosis rates, increased protein levels, and positive RPR and TPPA rates in the GP group were higher than that in the non-NS dementia group. CONCLUSIONS: Based on these preliminary data, patients with clinically evident symptoms of dementia, especially middle-aged males, should undergo blood tests for syphilis. All patients with positive serology results should undergo CSF examinations to diagnose GP dementia before further pharmaceutical and behavioral interventions.
Subject(s)
Dementia/diagnosis , Neurosyphilis/diagnosis , Adult , Aged , Aged, 80 and over , Dementia/blood , Dementia/cerebrospinal fluid , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Neurosyphilis/blood , Neurosyphilis/cerebrospinal fluid , Retrospective Studies , Serologic Tests , Treponema pallidumABSTRACT
Ethyl gallate is a phenolic compound richly contained in Longan. In traditional Chinese medicine, Longan is widely known as a fruit with "hot" properties, with a tendency to promote inflammatory and certain other responses. The mechanism for its proinflammatory as well as health beneficial effects is poorly understood. Based on our earlier observation that certain natural phenolic compounds can serve as reducing cosubstrates for cyclooxygenases (COXs), we sought to test a hypothesis that ethyl gallate may activate the catalytic activity of the COX enzymes. Results from studies using cultured cells and animals show that ethyl gallate can activate the production of prostaglandin E2, a representative prostaglandin tested in this study. Computational analysis indicates that ethyl gallate can activate the peroxidase active sites of COX-1 and COX-2 by serving as a reducing cosubstrate. The effect of ethyl gallate is abrogated by galangin, which is known to bind to the same peroxidase active sites of COX-1 and COX-2 as a competitive inhibitor. The findings of this study offer support for a novel hypothesis that the proinflammatory as well as health beneficial effects of Longan may partly attributable to the activation of COX-1 and COX-2 by ethyl gallate.
Subject(s)
Dinoprostone/biosynthesis , Gallic Acid/analogs & derivatives , Sapindaceae/chemistry , Animals , Cyclooxygenase 1/chemistry , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Gallic Acid/metabolism , Gallic Acid/pharmacology , Male , Mice , Molecular Docking Simulation , Protein Conformation , RAW 264.7 Cells , Rats , Rats, Sprague-DawleyABSTRACT
NIR technology is a rapid, nondestructive and user-friendly method ideally suited for Qualitative analysis. In this paper the authors present the use of discriminant partial least Squares (DPLS)-based linear discriminant analysis (LDA) in corn qualitative near infrared spectroscopy analysis. Firstly, a training set including 30 corn varieties (each variety has 20 samples) was used to build the DPLS regression model, and 28 principal components (DPLS-PCs) were obtained from original spectrum. Secondly, the DPLS-PCs scores of the training set were extracted as DPLS features. Thirdly, LDA was applied to the DPLS features, determining 26 principal components (LDA-PCs). A test sample was first projected onto the DPLS-PCs and then onto the LDA-PCs, and finally 26 DPLS+LDA features were obtained. The recognition results were obtained by minimum distance classifier. DPLS+LDA method achieved 96.18% recognition rate, while traditional DPLS regression method and DPLS feature extraction method only achieved 85.38% and 95.76% recognition rate respectively. The experiment results indicated that DPLS +LDA method is with better generalization ability compared with traditional DPLS regression method and NIRS analysis by DPLS+LDA method is an efficient way to discriminate corn species.
Subject(s)
Spectroscopy, Near-Infrared , Zea mays/classification , Discriminant Analysis , Least-Squares AnalysisABSTRACT
A new method for the fast discrimination of varieties of corn based on near-infrared spectroscopy using genetic algorithm and linear discriminant analysis (LDA) was proposed. First, data of NIS of 37 varieties of corn was collected, second, genetic algorithm used for choosing the feature band of spectrum, then PCA and LDA were used to extract features, and finally corn seeds were classified. The result showed that GA could remove noise band effectively and improve the generalization ability of LDA. A large number of redundant data was removed to simplify the computing, which resulted in the data dimension reduction from 2075 to 233. For the 300 samples of test set one, the average correct recognition rate and average correct rejection rate attained 99.30% for both, and the average correct recognition rate of 73.33% varieties of corn attained for 100%. For the 175 samples of test set 2 (all of whose varieties had not been trained), the average correct recognition rate attained 99.65%. The run time is shorter and the correct rate is higher compared to the common method of PCA.
Subject(s)
Seeds/chemistry , Spectroscopy, Near-Infrared/methods , Zea mays/chemistry , Algorithms , Discriminant Analysis , Principal Component AnalysisABSTRACT
In HIV-1 epidemics in China, HIV-1 subtype B' is the most predominant subtype circulating in intravenous drug users. In this study, we constructed an HIV-1 full-length infectious molecular clone based on the primary virus LWJ, which was isolated from an HIV-infected patient in Fujian Province, China. Phylogenetic and bootscanning analysis of the viral sequence revealed that the isolate LWJ belonged to HIV-1 subtype B'. The infectious clone was designated as "pLWJ". The virus (LWJ-c) produced from this infectious clone by in vitro transfection of 293T cells could infect both human peripheral blood mononuclear cells (PBMCs) and human the T cell line MT4. Interestingly, the cloned LWJ-c virus utilized CXCR4 as its co-receptor and could replicate in vitro with similar efficiency and kinetics compared to its parental primary isolate LWJ as well as the clade B reference virus NL4-3. The LWJ-c virus could also cause cytopathic effects in both PBMCs and MT cells. Sequence analysis of the envelope glycoprotein of pLWJ showed that a conserved GPGR motif and an arginine at position 11 were present in the V3 loop, which was consistent with previous reports regarding CXCR4 co-receptor usage and syncytium-inducing (SI) phenotype. Thus, the infectious clone represents a fast-replicating, high-producing, CXCR4-tropic and syncytium-inducing isolate. Given the prevalence of HIV-1 subtype B' in China, this infectious clone can be a very useful tool to provide a versatile molecular model for research focusing on the biological properties of this subtype.
Subject(s)
Genetic Engineering , HIV-1/growth & development , HIV-1/genetics , Virology/methods , Amino Acid Motifs , Binding Sites , Cells, Cultured , China , Genotype , HIV Infections/virology , HIV-1/classification , HIV-1/isolation & purification , Humans , Leukocytes, Mononuclear/virology , Male , Molecular Sequence Data , RNA, Viral/genetics , Receptors, HIV/physiology , Sequence Analysis, DNA , T-Lymphocytes/virology , Virus Internalization , env Gene Products, Human Immunodeficiency Virus/geneticsABSTRACT
A new method for the discrimination of varieties of corn was proposed based on the data set of near-infrared spectroscopy range from 4 000 to 12 000 cm(-1) of corn seed varieties. Principal component analysis (PCA) method was used to study the feature of the data, and the authors found that the near-infrared spectroscopy of corn seed varieties has a clear feature of zonal distribution, so the correlativity between the change in the distribution of the principal component and the discrimination result was studied, according to which the normalized principal component analysis (NPCA) method was proposed. Besides, principal direction biomimetic pattern recognition (PBPR) was proposed according to the feature, which got a better discrimination result. The average correct recognition rate attained 97.67% for test set I, and the average correct rejection rate attained 98.40%, with 13 of the 30 varieties reaching the correct recognition rate of 100%; The average correct rejection rate attained 98.90% for the test set II , and 11 of the 30 varieties reached the correct rejection rate of 100%. It was proved that the method had a high correct discrimination rate.
Subject(s)
Spectroscopy, Near-Infrared , Zea mays , Principal Component AnalysisABSTRACT
A frequency selection method of NIR spectroscopy was proposed in the present paper for discrimination of maize seed varieties. A criterion function was defined to evaluate the discriminative ability of NIR spectroscopy at different frequencies, and then features of maize seed varieties were extracted accordingly for further processing. By eliminating correlation between features at different frequencies, the selected features are guaranteed to contain as much information of inter-variety difference as possible. Also, features with larger variances are preferred to suppress the impact of noise. Experiment results demonstrate that our frequency selection method can achieve high recognition rate with less spectroscopy features than traditional methods. Specifically, a recognition rate as high as 94.16% can be attained with NIR spectroscopy with only 30 frequencies. Simulation results show that recognition rate of NIR spectroscopy at selected frequencies is stable with small disturbance of frequencies, which verifies the robustness of the authors' method.
Subject(s)
Spectroscopy, Near-Infrared , Zea mays/classification , SeedsABSTRACT
OBJECTIVE: To understand the sero-prevalence of hepatitis E virus (HEV) infection among different populations and animals in Fujian province. METHODS: One thousand one hundred and fifty-one serum samples were collected from 5 species of animals including swine, dog, cow, sheep and rat. A total of 2209 and 1722 serum samples from the general population and from the exposed population were collected. Anti-HEV IgG was detected by ELISA. The general population was composed of healthy blood donors and the individuals who had attended physical examination including farmers, handlers, veterinarians, cooks who worked with pigs or chickens while the poultry wholesale suppliers made up the exposure population. RESULTS: The infection rates of HEV in animals were different between species (chi2 = 406.25, P < 0.01) with the highest seen in the pig group. With pigs being kept at home, the rates were between 70.00% and 94.12% but the rate was 39.77% for those families that keeping the pigs at farms. The infection rate of HEV was 23.3% in the general population and 33.3% in the exposed populations, respectively. A significantly higher infection rate for anti-HEV was found in the exposed population when comparing with general population. The positive rate of anti-HEV IgG was significantly higher in the exposed population that closely having had contact with chickens than those who had contact with pigs. The increasing trend of HEV infection rate with age had been found but there was no significant difference between males and females in the general population. In the exposed population, the infection rate in males was significantly higher than that in females. CONCLUSION: The infection ratse of HEV in pigs and in the exposure population were much higher, especially for those persons in close contact with chickens or pigs, suggesting that the sub-clinical infection for HEV might exist. These data further supported the hypothesis that HEV might have been an zoonotic disease.
Subject(s)
Hepatitis E virus/immunology , Hepatitis E/epidemiology , Hepatitis E/veterinary , Animals , Animals, Domestic , Antibodies, Viral/analysis , China/epidemiology , Female , Humans , Immunoglobulin G/analysis , Male , Rats , Seroepidemiologic Studies , ZoonosesABSTRACT
OBJECTIVE: To compare the clinical values of computed tomography (CT) and fluorine-18 fluorodeoxyglucose positron remission tomography (FDG-PET) in diagnosis of mediastinal metastasis of non-small cell lung cancer (NSCLC). METHODS: Sixty patients with respectable NSCLC underwent CT and FDG-PET with an interval of 2 weeks and then underwent thoracotomy for clearance of the lymph nodes or biopsy of the mediastinal lymph nodes via mediastinoscopy. The specimens of mediastinal lymph node underwent HE staining and PCNA/Ki67 immunohistochemical staining. The sensitivity, specificity, accuracy, positive prediction value, and negative prediction value in diagnosis of metastasis of mediastinal lymph nodes of these 2 procedures were compared. RESULTS: The sensitivity, specificity, accuracy, positive prediction value, and negative prediction value in diagnosis of metastasis of mediastinal lymph nodes were 92.3%, 87.5%, 91.2%, 96.0%, and 77.7% respectively for FDG-PET, and were 76.9%, 50.0%, 70.6%, 83.3%, and 40.0% respectively for CT. The sensitivity rate was 98% for CT plus FDG-PET. CONCLUSION: PET is superior to CT in diagnosis of metastasis of NSCLC to mediastinal lymph nodes. PET + CT significantly increases the sensitivity in diagnosis.
Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnosis , Fluorodeoxyglucose F18 , Lung Neoplasms/diagnosis , Lymph Nodes/pathology , Positron-Emission Tomography , Tomography, X-Ray Computed , Aged , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/secondary , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Mediastinum , Middle AgedABSTRACT
OBJECTIVE: To study the seroprevalence of human T-cell leukaemia virus type I/II (HTLV-I/II) infection in adult population in the east coastal areas of Fujian and to explore the possible risk factors of HTLV-I/II. METHODS: A total number of 3259 blood samples from drug users, sexually transmitted disease (STD) patients, prostitutes and blood donors for serologic assays during 1999 to 2002, were collected. All samples were screened for HTLV-I/II antibody, using enzyme linked immunosorbent assay (ELISA) kits. All of the positive samples were confirmed by western blot (WB) kits. Statistical analysis was done by Epi software, and chi(2) test by Fisher's exact test. P value < 0.05 was considered statistically significant. RESULTS: The overall seroprevalence rate of HTLV-I/II in healthy populations was 0.06% including, 0.32% in drug users, 0.58% in STD patients and prostitutes respectively. HTLV-II had not been found. The seropositive rates for HTLV-I in STD patients and prostitutes were significantly higher than the findings among healthy populations (P < 0.05). There were no different seroprevalence rates between drug users and healthy populations (P > 0.05). No significant changes in HTLV-I prevalence rates were found in the different age groups as well as in Fuzhou and Linde cities (P > 0.05). CONCLUSION: The result suggested that in the east coastal areas of Fujian province, HTLV-I was the main prevalent virus. The seroprevalence of HTLV-I was very low, with no HTLV-II. Neither age nor gender seemed to be HTLV-I risk factor in the east coastal areas of Fujian province, but the increase of exposure to sex might be one.