COVID-19 Vaccination Reporting and Adverse Event Analysis in Taiwan.

The COVID-19 pandemic necessitated an urgent global response in vaccine deployment, achieving over 70.6% global vaccination coverage with at least one dose. This study focuses on Taiwan's vaccine administration and adverse event reporting, set against a global backdrop. Using data from Taiwan's Vaccine Adverse Event Reporting System (VAERS) and global vaccination data, this study investigates vaccine safety and the public health implications of vaccination strategies from local and global perspectives. Taiwan's proactive approach, resulting in high vaccination rates, provides a case study for the monitoring and management of vaccine-related adverse events. This study offers insights into the safety profiles of various COVID-19 vaccines and further explores the implications of adverse event reporting rates for vaccine policy and public health strategies. The comparative analysis reveals that, while vaccination has been effective in controlling the virus's spread, safety monitoring remains critical for maintaining public trust. It underscores the necessity of enhanced surveillance and the importance of transparent and tailored risk communication to support informed public health decisions. The findings aim to contribute to the global dialogue on vaccine safety, equitable distribution, evidence-based policy-making, and development of mitigation measures with consideration of local demographics in the ongoing fight against COVID-19.

Pharmacogenomic Landscape of Ivermectin and Selective Antioxidants: Exploring Gene Interplay in the Context of Long COVID.

COVID-19 pandemic has caused widespread panic and fear among the global population. As such, repurposing drugs are being used as viable therapeutic options due to the limited effective treatments for Long COVID symptoms. Ivermectin is one of the emerging repurposed drugs that has been shown effective to have antiviral effects in clinical trials. In addition, antioxidant compounds are also gaining attention due to their capabilities of reducing inflammation and severity of symptoms. Due to the absence of knowledge in pharmacogenomics and modes of actions in the human body for these compounds, this study aims to provide a pharmacogenomic profile for the combination of ivermectin and six selected antioxidants (epigallocatechin gallate (EGCG), curcumin, sesamin, anthocyanins, quercetin, and N-acetylcysteine (NAC)) as potentially effective regimens for long COVID symptoms. Results showed that there were 12 interacting genes found among the ivermectin, 6 antioxidants, and COVID-19. For network pharmacology, the 12 common interacting genes/proteins had the highest associations with Pertussis pathway, AGE-RAGE signaling pathway in diabetic complications, and colorectal cancer in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Disease analyses also revealed that the top three relevant diseases with COVID-19 infections were diabetes mellitus, ischemia, reperfusion injury. We also identified 6 potential target microRNAs (miRNAs) of the 12 commonly curated genes used as molecular biomarkers for COVID-19 treatments. The established pharmacogenomic network, disease analyses, and identified miRNAs could facilitate developments of effective regimens for chronic sequelae of COVID-19 especially in this post-pandemic era. However, further studies and clinical trials are needed to substantiate the effectiveness and dosages for COVID-19 treatments.

Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics.

Symptom treatments for Coronavirus disease 2019 (COVID-19) infection and Long COVID are one of the most critical issues of the pandemic era. In light of the lack of standardized medications for treating COVID-19 symptoms, traditional Chinese medicine (TCM) has emerged as a potentially viable strategy based on numerous studies and clinical manifestations. Taiwan Chingguan Yihau (NRICM101), a TCM designed based on a medicinal formula with a long history of almost 500 years, has demonstrated its antiviral properties through clinical studies, yet the pharmacogenomic knowledge for this formula remains unclear. The molecular mechanism of NRICM101 was systematically analyzed by using exploratory bioinformatics and pharmacodynamics (PD) approaches. Results showed that there were 434 common interactions found between NRICM101 and COVID-19 related genes/proteins. For the network pharmacology of the NRICM101, the 434 common interacting genes/proteins had the highest associations with the interleukin (IL)-17 signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Moreover, the tumor necrosis factor (TNF) was found to have the highest association with the 30 most frequently curated NRICM101 chemicals. Disease analyses also revealed that the most relevant diseases with COVID-19 infections were pathology, followed by cancer, digestive system disease, and cardiovascular disease. The 30 most frequently curated human genes and 2 microRNAs identified in this study could also be used as molecular biomarkers or therapeutic options for COVID-19 treatments. In addition, dose-response profiles of NRICM101 doses and IL-6 or TNF-α expressions in cell cultures of murine alveolar macrophages were constructed to provide pharmacodynamic (PD) information of NRICM101. The prevalent use of NRICM101 for standardized treatments to attenuate common residual syndromes or chronic sequelae of COVID-19 were also revealed for post-pandemic future.

Minocycline and Doxycycline: More Than Antibiotics.

Minocycline and doxycycline both are second-generation tetracycline antibiotics with similar chemical structures and comparable antibacterial spectrum. Minocycline has also emerged as the tetracycline of choice for multidrug-resistant Acinetobacter baumannii infections, although doxycycline has also shown the activity. Minocycline showed promising results in experimental neurology, which was due to its highly lipophilic nature. It is clinically safe and effective adjunct to antipsychotic medications. The objective of the current review is to provide clinical and preclinical, non-antibiotic uses of minocycline as well as doxycycline. Relevant literature covers antibiotic actions but is more specifically concerned with the non-antibiotic biological aspect of tetracyclines. Non-antibiotic biological effects for both the antibiotics were identified through searching relevant databases including: PubMed, Scopus, and Web of Science up to 2020, using the keywords 'minocycline and doxycycline'. Anti-inflammatory, anti-oxidant, anti-apoptotic neuroprotective, immunomodulatory and the number of other non-antibiotic effects were compiled for minocycline and doxycycline.

ChemiRs: a web application for microRNAs and chemicals.

BACKGROUND: MicroRNAs (miRNAs) are about 22 nucleotides, non-coding RNAs that affect various cellular functions, and play a regulatory role in different organisms including human. Until now, more than 2500 mature miRNAs in human have been discovered and registered, but still lack of information or algorithms to reveal the relations among miRNAs, environmental chemicals and human health. Chemicals in environment affect our health and daily life, and some of them can lead to diseases by inferring biological pathways. RESULTS: We develop a creditable online web server, ChemiRs, for predicting interactions and relations among miRNAs, chemicals and pathways. The database not only compares gene lists affected by chemicals and miRNAs, but also incorporates curated pathways to identify possible interactions. CONCLUSIONS: Here, we manually retrieved associations of miRNAs and chemicals from biomedical literature. We developed an online system, ChemiRs, which contains miRNAs, diseases, Medical Subject Heading (MeSH) terms, chemicals, genes, pathways and PubMed IDs. We connected each miRNA to miRBase, and every current gene symbol to HUGO Gene Nomenclature Committee (HGNC) for genome annotation. Human pathway information is also provided from KEGG and REACTOME databases. Information about Gene Ontology (GO) is queried from GO Online SQL Environment (GOOSE). With a user-friendly interface, the web application is easy to use. Multiple query results can be easily integrated and exported as report documents in PDF format. Association analysis of miRNAs and chemicals can help us understand the pathogenesis of chemical components. ChemiRs is freely available for public use at http://omics.biol.ntnu.edu.tw/ChemiRs .

Impact of Makowal type water system on crop productivity in Shivalik foothills of India.

The availability of water through community based water harvesting structure has intensified agriculture and improved livelihood of the surveyed beneficiary households in the Shivalik foothills of India. Before the introduction of Makowal Type Water Harvesting System (before MTWHS), only 83.8% farmers in kharif and 79.7% during rabi season were growing crops but after its introduction (after MTWHS) the corresponding values improved to 100% and 97.3%, respectively, thus increasing cropping intensity from 145% to 189%. Introduction of MTWHS enabled farmers to take paddy and agro-forestry during Kharif, and vegetables and fodder during Rabi season. The increase in cultivated area due to MTWHS was to the tune of 46.1% in Kharif and 36.3% during Rabi, while increase in crop productivity ranged from 55.1% to 111.3% in kharif and 8.6 to 132.0% in Rabiseason. Better availability of irrigation changed varietal spectrum in favour of hybrids and high yielding varieties and farmers started adopting improved agronomic practices targeting better input-use efficiency. The MTWHS produced positive impact on the on-farm (crops, dairy and agro-forestry) sources of income and reduced the relative dependence on off-farm activities (labour, community forest area, etc.) for earnings. This system has brought drinking water very close to hutments of rural women thus reducing their drudgery and saving time. In general, rainwater harvesting from forest watersheds has resulted in quantum jumps in crop and milk production and acted as a catalyst to tie up the economic interest of communities, along with forest protection.

Epigenetic effects of environmental chemicals bisphenol A and phthalates.

The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs) of environmental chemicals such as bisphenol A (BPA) and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1) promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues. In vitro models such as human embryonic stem cells may be extremely useful in bettering the understanding of epigenetic effects on human development, health and disease, because the formation of embryoid bodies in vitro is very similar to the early stage of embryogenesis.

SARS-CoV regulates immune function-related gene expression in human monocytic cells.

Severe acute respiratory syndrome (SARS) is characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis, and monocytes/macrophages are the key players in the pathogenesis of SARS. In this study, we compared the transcriptional profiles of SARS coronavirus (SARS-CoV)-infected monocytic cells against that infected by coronavirus 229E (CoV-229E). Total RNA was extracted from infected DC-SIGN-transfected monocytes (THP-1-DC-SIGN) at 6 and 24 h after infection, and the gene expression was profiled in oligonucleotide-based microarrays. Analysis of immune-related gene expression profiles showed that at 24 h after SARS-CoV infection: (1) IFN-α/ß-inducible and cathepsin/proteasome genes were downregulated; (2) hypoxia/hyperoxia-related genes were upregulated; and (3) TLR/TLR-signaling, cytokine/cytokine receptor-related, chemokine/chemokine receptor-related, lysosome-related, MHC/chaperon-related, and fibrosis-related genes were differentially regulated. These results elucidate that SARS-CoV infection regulates immune-related genes in monocytes/macrophages, which may be important to the pathogenesis of SARS.

Ectopic pregnancy-derived human trophoblastic stem cells regenerate dopaminergic nigrostriatal pathway to treat parkinsonian rats.

BACKGROUND: Stem cell therapy is a potential strategy to treat patients with Parkinson's disease (PD); however, several practical limitations remain. As such, finding the appropriate stem cell remains the primary issue in regenerative medicine today. We isolated a pre-placental pluripotent stem cell from the chorionic villi of women with early tubal ectopic pregnancies. Our objectives in this study were (i) to identify the characteristics of hTS cells as a potential cell source for therapy; and (ii) to test if hTS cells can be used as a potential therapeutic strategy for PD. METHODS AND FINDINGS: hTS cells expressed gene markers of both the trophectoderm (TE) and the inner cell mass (ICM). hTS cells exhibited genetic and biological characteristics similar to that of hES cells, yet genetically distinct from placenta-derived mesenchymal stem cells. All-trans retinoic acid (RA) efficiently induced hTS cells into trophoblast neural stem cells (tNSCs) in 1-day. Overexpression of transcription factor Nanog was possibly achieved through a RA-induced non-genomic c-Src/Stat3/Nanog signaling pathway mediated by the subcellular c-Src mRNA localization for the maintenance of pluripotency in tNSCs. tNSC transplantation into the lesioned striatum of acute and chronic PD rats not only improved behavioral deficits but also regenerated dopaminergic neurons in the nigrostriatal pathway, evidenced by immunofluorescent and immunohistological analyses at 18-weeks. Furthermore, tNSCs showed immunological advantages for the application in regenerative medicine. CONCLUSIONS: We successfully isolated and characterized the unique ectopic pregnancy-derived hTS cells. hTS cells are pluripotent stem cells that can be efficiently induced to tNSCs with positive results in PD rat models. Our data suggest that the hTS cell is a dynamic stem cell platform that is potentially suitable for use in disease models, drug discovery, and cell therapy such as PD.

Bisphenol A and phthalates exhibit similar toxicogenomics and health effects.

Plastics are widely used in modern life, and their unbound chemicals bisphenol A and phthalates can leach out into the surrounding environment. BPA and PAEs have recently attracted the special attention of the scientific community, regulatory agencies and the general public because of their high production volume, widespread use of plastics, and endocrine-disrupting effects. In The Comparative Toxicogenomics Database, BPA and five most frequently curated PAEs (DEHP/MEHP and DBP/BBP/MBP) were found to have 1932 and 484 interactions with genes/proteins, respectively. Five of their top ten toxicity networks were found to be involved in inflammation, and their top ten diseases included genital, prostatic, endomentrial, ovarian and breast diseases. BPA and PAEs were found to exhibit similar toxicogenomics and adverse effects on human health owning to their 89 common interacting genes/proteins. These 89 genes/proteins may serve as biomarkers to assay the toxicities of different chemicals leached out from the widely used plastics.

Toxicokinetics/toxicodynamics with damage feedback improves risk assessment for tilapia and freshwater clam exposed to arsenic.

It has been proposed that irreversible responses of organisms exposed to contaminants are due to a systems-level feedback. Here we tested this hypothesis by reanalyzing the published data on toxicokinetics and survival probability based on a systems-level threshold damage model (TDM) incorporating with a positive damage feedback to explore the steady-state response and dynamic behavior of damage for tilapia and freshwater clam exposed to waterborne arsenic (As). We found that ultrasensitivity appeared in As-tilapia and freshwater clam systems with Hill coefficient n ≥ 4, indicating that the positive damage feedback mechanism has been triggered. We confirmed that damage can trigger a positive feedback loop that together with As stressor increases irreversibility. This study also showed that TDM with positive feedback gave a much better predictability than that of TDM at As concentrations ranging from 100 to 500 mg l(-1) for freshwater clam, whereas for tilapia, two models had nearly same performance on predictability. We suggested that mortality-time profile derived Hill coefficient could be used as a new risk indicator to assess the survival probability for species exposed to waterborne metals. We anticipated that the proposed toxicokinetics/toxicodynamics with a positive damage feedback may facilitate our understanding and manipulation of complex mechanisms of metal susceptibility among species and improve current risk assessment strategies.

Survey of nitrogen use pattern in rice in the irrigated rice-wheat cropping system of Haryana, India.

Seeing the sustainability of rice-wheat cropping system (RWCS) of the Indo-Gangetic Plain, adequate crop nutrition in general and nitrogen (N) in particular holds the key to sound crop management. The excessive application or insufficient management of N means an economic loss to the farmer and may lead to yield penalties and environmental problems. Improving N management in consonance with other nutrients is much important to break yield plateaus as breeding for high yielding is not happening in recent years. Findings from farm survey are used to evaluate the on-farm N management practices in rice crop of the study area. The crop management practices (especially time of sowing/transplanting and irrigation requirement) and resource base of the farmers decided the N use pattern of the farmers. The N(Physical optimum) and N(economic optimum) exceeding the recommended levels revealed the apparent need for the revalidation of the existing recommendations. Paddy yield increased significantly within different rice types. This study generated comprehensive data on N use pattern in rice in the study area.

Trade-offs between elimination and detoxification in rainbow trout and common bivalve molluscs exposed to metal stressors.

The purpose of this paper was to examine trade-offs between elimination and detoxification in rainbow trout and three common bivalve molluscs (clam, oyster, and scallop) exposed to cadmium (Cd), copper (Cu), and zinc (Zn) based on recent reported experimental data. We incorporated metal influx threshold with subcellular partitioning to estimate rate constants of detoxification (k(d)) and elimination (k2). We found that the relationships between k2 and k(d) were negative for rainbow trout and positive for bivalve molluscs. However, the relationships between k(d) and % metal in metabolically detoxified pool were found positive for rainbow trout and negative for bivalve molluscs. Our results also indicated that rainbow trout had higher accumulation (~60-90%) in metabolically active pool when exposed to essential metals of Cu and Zn and had only 10-50% accumulation in response to non-essential metal of Cd. Based on a cluster analysis, this study indicated that similarity of physiological regulations among study species was found between Cd and Zn. Our study suggested that detoxification can be predicted by an elimination-detoxification scheme with the known elimination rate constant. We concluded that quantification of trade-offs between subcellular partitioning and detoxification provides valuable insights into the ecotoxicology of aquatic organisms and enhances our understanding of the subcellular biology of trace metals.

Proteomic comparison of human embryonic stem cells with their differentiated fibroblasts: Identification of 206 genes targeted by hES cell-specific microRNAs.

Human embryonic stem (hES)-T3 (T3ES) cells were spontaneously differentiated into autogeneic fibroblast-like T3DF cells, as feeder cells with the capacity to support the growth of undifferentiated hES cells. The proteomes of undifferentiated T3ES cells and their differentiated T3DF fibroblasts were quantitatively compared. Several heterogeneous nuclear ribonucleoproteins and glycolytic enzymes, including l-lactate dehydrogenase A (M), were found to be abundantly and differentially expressed in T3ES cells and T3DF fibroblasts, respectively. Both miRNA and mRNA profiles from the undifferentiated T3ES cells and their differentiated T3DF fibroblasts had been previously determined. In this investigation, 206 genes were found to be targets of the four hES cell-specific miRNAs of miR-302d, miR-372, miR-200c, and/or miR-367 by using two-fold differential expression and inverse expression levels (highly negative correlations) of miRNAs to their target mRNAs. That YWHAZ (14-3-3 zeta) is a target of miR-302d and miR-372 was further confirmed by proteomic comparison between T3ES cells and their differentiated T3DF fibroblasts. According to GeneOntology analyses, almost 50% of these 206 target proteins are nuclear and are involved in gene transcription. Identifying the target mRNAs of hES cell-specific miRNAs will provide a better understanding of the complex regulatory networks in hES cells. Furthermore, these miRNA-targeted proteins play important roles in differentiation of hES cells and during embryo development.

Combining bioaccumulation and coping mechanism to enhance long-term site-specific risk assessment for zinc susceptibility of bivalves.

The purpose of this study is to conduct a long-term site-specific risk assessment for zinc (Zn) susceptibility of bivalves, green mussel Perna viridis and hard clam Ruditapes philippinarum, based on published experimental data by linking the biologically-based damage assessment model with the subcellular partitioning concept. A comprehensive risk modeling framework was developed to predict susceptibility probability of two bivalve species exposed to waterborne Zn. The results indicated that P. viridis accumulates more Zn toxicity, whereas both toxic potency and the recovery rate of Zn are higher for R. philippinarum. We found that negative linear correlations exist in elimination-recovery and elimination-detoxification relationships, whereas a positive linear correlation was observed in recovery-detoxification relationships for bivalves exposed to waterborne Zn. Simulation results showed that the spatial differences of susceptibility primarily resulted from the variation of waterborne Zn concentration under field conditions. We found that R. philippinarum is more susceptible of Zn than P. viridis under the same exposure condition. Results also suggested that Zn posed no significant susceptibility risk to two bivalve species in Taiwan. We suggested that these two species can be used to biomonitor the water quality on Taiwan coastal areas.

Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E.

Viruses rely on the host translation machinery to complete their life cycles. Picornaviruses use an internal ribosome entry site to initiate cap-independent protein translation and in parallel host cap-dependent translation is shut off. This process is thought to occur primarily via cleavage of host translation initiation factors eIF4GI and eIF4GII by viral proteases. Here we describe another mechanism whereby miR-141 induced upon enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation, and silencing of eIF4E can completely reverse the inhibitory effect of the miR-141 antagomiR on viral propagation. Ectopic expression of miR-141 promotes the switch from cap-dependent to cap-independent translation. Moreover, we identified a transcription factor, EGR1, which is partly responsible for miR-141 induction in response to enterovirus infection. Our results suggest that upregulation of miR-141 upon enterovirus infection can facilitate viral propagation by expediting the translational switch.

Hepatitis C virus NS2 protein serves as a scaffold for virus assembly by interacting with both structural and nonstructural proteins.

Many aspects of the assembly of hepatitis C virus (HCV) remain incompletely understood. To characterize the role of NS2 in the production of infectious virus, we determined NS2 interaction partners among other HCV proteins during productive infection. Pulldown assays showed that NS2 forms complexes with both structural and nonstructural proteins, including E1, E2, p7, NS3, and NS5A. Confocal microscopy also demonstrated that NS2 colocalizes with E1, E2, and NS5A in dot-like structures near lipid droplets. However, NS5A did not coprecipitate with E2 and interacted only weakly with NS3 in pulldown assays. Also, there was no demonstrable interaction between p7 and E2 or NS3 in such assays. Therefore, NS2 is uniquely capable of interacting with both structural and nonstructural proteins. Among mutations in p7, NS2, and NS3 that prevent production of infectious virus, only p7 mutations significantly reduced NS2-mediated protein interactions. These p7 mutations altered the intracellular distribution of NS2 and E2 and appeared to modulate the membrane topology of the C-terminal domain of NS2. These results suggest that NS2 acts to coordinate virus assembly by mediating interactions between envelope proteins and NS3 and NS5A within replication complexes adjacent to lipid droplets, where virus particle assembly is thought to occur. p7 may play an accessory role by regulating NS2 membrane topology, which is important for NS2-mediated protein interactions and therefore NS2 function.

Identification of microRNAs expressed highly in pancreatic islet-like cell clusters differentiated from human embryonic stem cells.

Type 1 diabetes is an autoimmune destruction of pancreatic islet beta cell disease, making it important to find a new alternative source of the islet beta cells to replace the damaged cells. hES (human embryonic stem) cells possess unlimited self-renewal and pluripotency and thus have the potential to provide an unlimited supply of different cell types for tissue replacement. The hES-T3 cells with normal female karyotype were first differentiated into EBs (embryoid bodies) and then induced to generate the T3pi (pancreatic islet-like cell clusters derived from T3 cells), which expressed pancreatic islet cell-specific markers of insulin, glucagon and somatostatin. The expression profiles of microRNAs and mRNAs from the T3pi were analysed and compared with those of undifferentiated hES-T3 cells and differentiated EBs. MicroRNAs negatively regulate the expression of protein-coding mRNAs. The T3pi showed very high expression of microRNAs, miR-186, miR-199a and miR-339, which down-regulated the expression of LIN28, PRDM1, CALB1, GCNT2, RBM47, PLEKHH1, RBPMS2 and PAK6. Therefore, these microRNAs and their target genes are very likely to play important regulatory roles in the development of pancreas and/or differentiation of islet cells, and they may be manipulated to increase the proportion of beta cells and insulin synthesis in the differentiated T3pi for cell therapy of type I diabetics.

Phthalates: toxicogenomics and inferred human diseases.

Phthalates are widely used as plasticizers to soften and increase the flexibility in polyvinyl chloride plastics, but they can leach into the surrounding environment. There is sufficient evidence in rodents that phthalate exposure causes developmental and reproductive toxicity. The curated interactions between 16 phthalates and genes/proteins were obtained from Comparative Toxicogenomics Database (CTD), and a total of 445 interactions between the five most frequently curated phthalates (DEHP/MEHP and DBP/BBP/MBP) and 249 unique genes/proteins were found. The GeneOntology, pathways and networks of these 249 unique genes/proteins were fully analyzed. The pathways and networks of top 34 genes/proteins were found to be very similar to those of the 249 unique genes/proteins. Thus, the top 34 genes/proteins may serve as molecular biomarkers of phthalate toxicity. The top three phthalate toxicity categories were found to be cardiotoxicity, hepatotoxicity and nephrotoxicity, and the top 20 diseases included cardiovascular, liver, urologic, endocrine and genital diseases.

A feeder-free culture using autogeneic conditioned medium for undifferentiated growth of human embryonic stem cells: comparative expression profiles of mRNAs, microRNAs and proteins among different feeders and conditioned media.

BACKGROUND: Human embryonic stem (hES) cell lines were derived from the inner cell mass of human blastocysts, and were cultured on mouse embryonic fibroblast (MEF) feeder to maintain undifferentiated growth, extensive renewal capacity, and pluripotency. The hES-T3 cell line with normal female karyotype was previously used to differentiate into autogeneic fibroblast-like cells (T3HDF) as feeder to support the undifferentiated growth of hES-T3 cells (T3/HDF) for 14 passages. RESULTS: A feeder-free culture on Matrigel in hES medium conditioned by the autogeneic feeder cells (T3HDF) was established to maintain the undifferentiated growth of hES-T3 cells (T3/CMHDF) for 8 passages in this investigation. The gene expression profiles of mRNAs, microRNAs and proteins between the undifferentiated T3/HDF and T3/CMHDF cells were shown to be very similar, and their expression profiles were also found to be similar to those of T3/MEF and T3/CMMEF cells grown on MEF feeder and feeder-free Matrigel in MEF-conditioned medium, respectively. The undifferentiated state of T3/HDF and T3/CMHDF as well as T3/MEF and T3/CMMEF cells was evidenced by the very high expression levels of "stemness" genes and low expression levels of differentiation markers of ectoderm, mesoderm and endoderm in addition to the strong staining of OCT4 and NANOG. CONCLUSION: The T3HDF feeder and T3HDF-conditioned medium were able to support the undifferentiated growth of hES cells, and they would be useful for drug development and toxicity testing in addition to the reduced risks of xenogeneic pathogens when used for medical applications such as cell therapies.