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1.
Anal Chem ; 96(23): 9408-9415, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38804776

ABSTRACT

Reactive oxygen species play a pivotal role in liver disease, contributing to severe liver damage and chronic inflammation. In liver injury driven by inflammation, adenosine-5'-triphosphate (ATP) and hypochlorite ion (ClO-) emerge as novel biomarkers, reflecting mitochondrial dysfunction and amplified oxidative stress, respectively. However, the dynamic fluctuations of ATP and ClO- in hepatocytes and mouse livers remain unclear, and multidetection techniques for these biomarkers are yet to be developed. This study presents RATP-NClO, a dual-channel fluorescent bioprobe capable of synchronously detecting ATP and ClO- ions. RATP-NClO exhibits excellent selectivity and sensitivity for ATP and ClO- ions, demonstrating a dual-channel fluorescence response in a murine hepatocyte cell line. Upon intravenous administration, RATP-NClO reveals synchronized ATP depletion and ClO- amplification in the livers of mice with experimental metabolic dysfunction-associated steatohepatitis (MASH). Through a comprehensive analysis of the principal mechanism of the developed bioprobe and the verification of its reliable detection ability in both in vitro and in vivo settings, we propose it as a unique tool for monitoring changes in intracellular ATP and ClO- level. These findings underscore its potential for practical image-based monitoring and functional phenotyping of MASH pathogenesis.


Subject(s)
Adenosine Triphosphate , Hypochlorous Acid , Inflammation , Animals , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/analysis , Hypochlorous Acid/analysis , Hypochlorous Acid/metabolism , Mice , Inflammation/metabolism , Fluorescent Dyes/chemistry , Liver/metabolism , Liver/pathology , Hepatocytes/metabolism , Mice, Inbred C57BL , Male , Ions/chemistry
2.
Small ; 20(13): e2307262, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37963850

ABSTRACT

Breast cancer (BC) is a major global health problem, with ≈20-25% of patients overexpressing human epidermal growth factor receptor 2 (HER2), an aggressive marker, yet access to early detection and treatment varies across countries. A low-cost, equipment-free, and easy-to-use polydiacetylene (PDA)-based colorimetric sensor is developed for HER2-overexpressing cancer detection, designed for use in low- and middle-income countries (LMICs). PDA nanoparticles are first prepared through thin-film hydration. Subsequently, hydrophilic magnetic nanoparticles and HER2 antibodies are sequentially conjugated to them. The synthesized HER2-MPDA can be concentrated and separated by a magnetic field while inheriting the optical characteristics of PDA. The specific binding of HER2 antibody in HER2-MPDA to HER2 receptor in HER2-overexpressing exosomes causes a blue-to-red color change by altering the molecular structure of the PDA backbone. This colorimetric sensor can simultaneously separate and detect HER2-overexpressing exosomes. HER2-MPDA can detect HER2-overexpressing exosomes in the culture medium of HER2-overexpressing BC cells and in mouse urine samples from a HER2-overexpressing BC mouse model. It can selectively isolate and detect only HER2-overexpressing exosomes through magnetic separation, and its detection limit is found to be 8.5 × 108 particles mL-1. This colorimetric sensor can be used for point-of-care diagnosis of HER2-overexpressing BC in LMICs.


Subject(s)
Breast Neoplasms , Diazonium Compounds , Exosomes , Nanoparticles , Polyacetylene Polymer , Pyridines , Humans , Animals , Mice , Female , Colorimetry , Exosomes/metabolism , Breast Neoplasms/metabolism , Antibodies , Magnetic Phenomena
3.
Small ; 20(4): e2305748, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37712175

ABSTRACT

The rapid transmission and numerous re-emerging human influenza virus variants that spread via the respiratory system have led to severe global damage, emphasizing the need for detection tools that can recognize active and intact virions with infectivity. Here, this work presents a plasmonic vesicle-mediated fusogenic immunoassay (PVFIA) comprising gold nanoparticle (GNP) encapsulating fusogenic polymeric vesicles (plasmonic vesicles; PVs) for the label-free and colorimetric detection of influenza A virus (IAV). The PVFIA combines two sequential assays: a biochip-based immunoassay for target-specific capture and a PV-induced fusion assay for color change upon the IAV-PV fusion complex formation. The PVFIA demonstrates excellent specificity in capturing the target IAV, while the fusion conditions and GNP induce a significant color change, enabling visual detection. The integration of two consecutive assays results in a low detection limit (100.7919 EID50 mL-1 ) and good reliability (0.9901), indicating sensitivity that is 104.208 times higher than conventional immunoassay. Leveraging the PV viral membrane fusion activity renders the PVFIA promising for point-of-care diagnostics through colorimetric detection. The innovative approach addresses the critical need for detecting active and intact virions with infectivity, providing a valuable tool with which to combat the spread of the virus.


Subject(s)
Influenza A virus , Metal Nanoparticles , Humans , Colorimetry/methods , Gold , Reproducibility of Results
4.
Small ; 19(26): e2207117, 2023 06.
Article in English | MEDLINE | ID: mdl-36960666

ABSTRACT

African swine fever virus (ASFV) is a severe and persistent threat to the global swine industry. As there are no vaccines against ASFV, there is an immense need to develop easy-to-use, cost-effective, and rapid point-of-care (POC) diagnostic platforms to detect and prevent ASFV outbreaks. Here, a novel POC diagnostic system based on affinity column chromatography for the optical detection of ASFV is presented. This system employs an on-particle hairpin chain reaction to sensitize magnetic nanoclusters with long DNA strands in a target-selective manner, which is subsequently fed into a column chromatography device to produce quantitatively readable and colorimetric signals. The detection approach does not require expensive analytical apparatus or immobile instrumentation. The system can detect five genes constituting the ASFV whole genome with a detection limit of ≈19.8 pm in swine serum within 30 min at laboratory room temperature. With an additional pre-amplification step using polymerase chain reaction (PCR), the assay is successfully applied to detect the presence of ASFV in 30 suspected swine samples with 100% sensitivity and specificity, similar to quantitative PCR. Thus, this simple, inexpensive, portable, robust, and customizable platform for the early detection of ASFV can facilitate the timely surveillance and implementation of control measures.


Subject(s)
African Swine Fever Virus , African Swine Fever , Swine , Animals , African Swine Fever Virus/genetics , African Swine Fever/diagnosis , Polymerase Chain Reaction/methods , Chromatography, Affinity , Sensitivity and Specificity , Magnetic Phenomena
5.
Analyst ; 147(22): 5028-5037, 2022 Nov 07.
Article in English | MEDLINE | ID: mdl-36190457

ABSTRACT

The continued uncertainty of emerging infectious viral diseases has led to an extraordinary urgency to develop advanced molecular diagnostic tests that are faster, more reliable, simpler to use, and readily available than traditional methods. This study presents a system that can accurately and rapidly trace viral nucleic acids by employing flap endonuclease 1 (FEN1)-assisted specific DNA cleavage reactions and surface-enhanced Raman scattering (SERS)-based analysis. The designed Raman tag-labeled 5'- and 3'-flap provider DNA yielded structurally defined DNA substrates on magnetic nanoparticle surfaces when a target was present. The FEN1 enzyme subsequently processes the substrates formed via an invasive cleavage reaction, producing 5'-flap DNA products. Magnetic separation allows efficient purification of flap products from reaction mixtures. The isolated solution was directly applied onto high aspect-ratio plasmonic silver nanopillars serving as SERS-active substrates to induce amplified SERS signals. We verified the developed SERS-based sensing system using a synthetic target complementary to an avian influenza A (H9N2) virus gene and examined the detection performance of the system using complementary DNA (cDNA) derived from H9N2 viral RNA. As a result, we could detect a synthetic target with a detection limit of 41.1 fM with a single base-pair discrimination ability and achieved multiplexed detection capability for two targets. Using cDNA samples from H9N2 viruses, we observed a high concordance of R2 = 0.917 between the data obtained from SERS and the quantitative polymerase chain reaction. We anticipate that this enzyme-assisted SERS sensor may provide insights into the development of high-performance molecular diagnostic tools that can respond rapidly to viral pathogens.


Subject(s)
Influenza A Virus, H9N2 Subtype , Metal Nanoparticles , Nucleic Acids , Animals , Spectrum Analysis, Raman/methods , Gold/chemistry , Flap Endonucleases , DNA, Complementary , DNA/analysis , Metal Nanoparticles/chemistry
6.
J Nanobiotechnology ; 18(1): 54, 2020 Mar 24.
Article in English | MEDLINE | ID: mdl-32209114

ABSTRACT

BACKGROUND: Influenza viruses (IVs) have become increasingly resistant to antiviral drugs that target neuraminidase and matrix protein 2 due to gene mutations that alter their drug-binding target protein regions. Consequently, almost all recent IV pandemics have exhibited resistance to commercial antiviral vaccines. To overcome this challenge, an antiviral target is needed that is effective regardless of genetic mutations. MAIN BODY: In particular, hemagglutinin (HA), a highly conserved surface protein across many IV strains, could be an effective antiviral target as it mediates binding of IVs with host cell receptors, which is crucial for membrane fusion. HA has 6 disulfide bonds that can easily bind with the surfaces of gold nanoparticles. Herein, we fabricated porous gold nanoparticles (PoGNPs) via a surfactant-free emulsion method that exhibited strong affinity for disulfide bonds due to gold-thiol interactions, and provided extensive surface area for these interactions. A remarkable decrease in viral infectivity was demonstrated by increased cell viability results after exposing MDCK cells to various IV strains (H1N1, H3N2, and H9N2) treated with PoGNP. Most of all, the viability of MDCK cells infected with all IV strains increased to 96.8% after PoGNP treatment of the viruses compared to 33.9% cell viability with non-treated viruses. Intracellular viral RNA quantification by real-time RT-PCR also confirmed that PoGNP successfully inhibited viral membrane fusion by blocking the viral entry process through conformational deformation of HA. CONCLUSION: We believe that the technique described herein can be further developed for PoGNP-utilized antiviral protection as well as metal nanoparticle-based therapy to treat viral infection. Additionally, facile detection of IAV can be achieved by developing PoGNP as a multiplatform for detection of the virus.


Subject(s)
Antiviral Agents/pharmacology , Gold/pharmacology , Influenza A virus/drug effects , Metal Nanoparticles/chemistry , Animals , Dogs , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H3N2 Subtype/drug effects , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H9N2 Subtype/drug effects , Influenza A Virus, H9N2 Subtype/genetics , Influenza A virus/genetics , Madin Darby Canine Kidney Cells , Membrane Fusion , Porosity , RNA, Viral/analysis , RNA, Viral/genetics , Virus Internalization
7.
Adv Funct Mater ; 28(34): 1800960, 2018 Aug 22.
Article in English | MEDLINE | ID: mdl-32313543

ABSTRACT

Highly pathogenic avian influenza virus (HPAIV) infections have occurred continuously and crossed the species barrier to humans, leading to fatalities. A polymerase chain reaction based molecular test is currently the most sensitive diagnostic tool for HPAIV; however, the results must be analyzed in centralized diagnosis systems by a trained individual. This requirement leads to delays in quarantine and isolation. To control the spread of HPAIV, rapid and accurate diagnostics suitable for field testing are needed, and the tests must facilitate a differential diagnosis between HPAIV and low pathogenic avian influenza virus (LPAIV), which undergo cleavage specifically by trypsin- or furin-like proteases, respectively. In this study, a differential avian influenza virus rapid test kit is developed and evaluated in vitro and using clinical specimens from HPAIV H5N1-infected animals. It is demonstrated that this rapid test kit provides highly sensitive and specific detection of HPAIV and LPAIV and is thus a useful field diagnostic tool for H5N1 HPAIV outbreaks and for rapid quarantine control of the disease.

8.
BMC Biotechnol ; 17(1): 34, 2017 03 27.
Article in English | MEDLINE | ID: mdl-28347305

ABSTRACT

BACKGROUND: Placental defects in somatic cell nuclear transfer (SCNT) are a major cause of complications during pregnancy. One of the most critical factors for the success of SCNT is the successful epigenetic reprogramming of donor cells. Recently, it was reported that the placental weight in mice cloned with the aggregated SCNT method was significantly reduced. Here, we examine the profile of abnormal gene expression using microarray technology in both regular SCNT and aggregated SCNT placentas as well as in vivo fertilization placentas. One SCNT embryo was aggregated with two 2 to 4 -cell stage tetraploid embryos from B6D2F1 mice (C57BL/6 × DBA/2). RESULTS: In SCNT placentas, 206 (1.6%) of the 12,816 genes probed were either up-regulated or down-regulated by more than two-fold. However, 52 genes (0.4%) showed differential expression in aggregated SCNT placentas compared to that in controls. In comparison of both types of SCNT placentas with the controls, 33 (92%) out of 36 genes were found to be up-regulated (>2-fold) in SCNT placentas. Among 36 genes, 13 (36%) genes were up-regulated in the aggregated SCNT placentas. Eighty-five genes were down-regulated in SCNT placentas compared with the controls. However, only 9 (about 10.5%) genes were down-regulated in the aggregated SCNT placentas. Of the 34 genes known as imprinted genes, expression was lower in SCNT placentas than that in the controls. Thus, these genes may be the cause of placentomegaly in mice produced post SCNT. CONCLUSIONS: These results suggest that placentomegaly in the SCNT placentas was probably caused by abnormal expression of multiple genes. Taken together, these results suggest that abnormal gene expression in cloned placentas was reduced in a genome-wide manner using the aggregation method with tetraploid embryos.


Subject(s)
Gene Expression Regulation/physiology , Nuclear Transfer Techniques , Oocytes/cytology , Oocytes/metabolism , Placenta/cytology , Placenta/metabolism , Proteome/metabolism , Animals , Cells, Cultured , Female , Gene Expression Profiling , Hybrid Cells/cytology , Hybrid Cells/metabolism , Mice , Pregnancy
9.
Gen Comp Endocrinol ; 233: 8-15, 2016 07 01.
Article in English | MEDLINE | ID: mdl-27174750

ABSTRACT

We prepared monoclonal antibodies (mAbs) against a recombinant tethered follicle-stimulating hormone (rec-FSH) from Japanese eel Anguilla japonica that was produced in Escherichia coli. Positive hybridomas (clones eFA-C5, eFA-C10, eFA-C11, eFA-C12, eFA-C13, and eFB-C14) were selected by using the eel FSH antigen in ELISA, and anti-eel FSH mAbs were purified from culture supernatants by performing affinity chromatography. Three of the 6mAbs were characterized and their isotypes were identified as IgG2b (eFA-C5 and eFA-C11) and IgG1 (eFB-C14). In western blotting assays, the mAbs recognized the antigen as a 24.3-kDa band, and further detected bands of 34 and 32kDa in the supernatants of CHO cells transfected with cDNA encoding tethered eel FSHß/α and LHß/α, respectively. PNase F-mediated deglycosylation of the recombinant proteins resulted in a drastic reduction in their molecular weight, to 7-9kDa. The mAbs eFA-C5 and eFA-C11 recognized the eel FSHα-subunit that is commonly encoded among glycoprotein hormones, whereas eFB-C14 recognized the eel FSHß-subunit, and immunohistochemical analysis revealed that the staining by these mAbs was specifically localized in the eel pituitary. We also established an ELISA system for detecting rec-tethered FSHß/α and LHß/α produced from CHO cell lines. Measurement of biological activities in vitro revealed that only weak activity of rec-FSHß/α was detected. The activity of rec-LHß/α was found to be increased in a dose-dependent manner for eel oocyte maturation.


Subject(s)
Anguilla , Antibodies, Monoclonal/analysis , Antibodies, Monoclonal/immunology , Follicle Stimulating Hormone/immunology , Anguilla/immunology , Anguilla/metabolism , Animals , Antibodies, Monoclonal/metabolism , CHO Cells , Cricetinae , Cricetulus , Female , Follicle Stimulating Hormone/metabolism , Follicle Stimulating Hormone, beta Subunit/metabolism , Luteinizing Hormone, beta Subunit/metabolism , Oogenesis , Pituitary Gland/metabolism , Protein Binding , Recombinant Proteins/immunology , Recombinant Proteins/metabolism
10.
Anim Biotechnol ; 27(4): 223-30, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27565865

ABSTRACT

Transcription activator-like effector nucleases (TALENs) are a new type of engineered nuclease that is very effective for directed gene disruption in any genome sequence. We investigated the generation of mice with genetic knockout (KO) of the G protein-coupled receptor kinase (GRK) 5 gene by microinjection of TALEN mRNA. TALEN vectors were designed to target exons 1, 3, and 5 of the mouse GRK5 gene. Flow cytometry showed that the activity of the TALEN mRNAs targeted to exons 1, 3, and 5 was 8.7%, 9.7%, and 12.7%, respectively. The TALEN mRNA for exon 5 was injected into the cytoplasm of 180 one-cell embryos. Of the 53 newborns, three (5.6%) were mutant founders (F0) with mutations. Two clones from F028 showed a 45-bp deletion and F039 showed the same biallelic non-frame-shifting 3-bp deletions. Three clones from F041 were shown to possess a combination of frame-shifting 2-bp deletions. All of the mutations were transmitted through the germline but not to all progenies (37.5%, 37.5%, and 57.1% for the F028, F039, and F041 lines, respectively). The homozygote GRK5-KO mice for 28 and 41 lines created on F3 progenies and the homozygous genotype was confirmed by PCR, T7E1 assay and sequencing.


Subject(s)
G-Protein-Coupled Receptor Kinase 5/genetics , Gene Targeting/methods , Mice, Knockout/genetics , Transcription Activator-Like Effector Nucleases/genetics , Animals , Female , Male , Mice , Mice, Inbred C57BL , Mutation
11.
Int J Mol Sci ; 16(3): 4904-17, 2015 Mar 04.
Article in English | MEDLINE | ID: mdl-25749471

ABSTRACT

To determine the production of recombinant human protein C (rec-hPC) in milk, we created two homozygous mice lines for the goat ß-casein/hPC transgene. Females and males of both lines (#10 and #11) displayed normal growth, fertility, and lactated normally. The copy number of the transgene was about fivefold higher in #10 line as compared to #11 line. mRNA expression of the transgene was only detected in the mammary glands of both lines. Furthermore, mRNA expression was fourfold higher on day 7 than on day 1 during lactation. Northern blot analysis of mRNA expression in the #10 line of transgenic (Tg) mice indicated a strong expression of the transgene in the mammary glands after seven days of lactation. Comparison of rec-hPC protein level with that of mRNA in the mammary glands showed a very similar pattern. A 52-kDa band corresponding to the hPC protein was strongly detected in mammary glands of the #10 line during lactation. We also detected two bands of heavy chain and one weak band of light chain in the milk of the #10 and #11 lines. One single band at 52 kDa was detected from CHO cells transfected with hPC cDNA. hPC was mainly localized in the alveolar epithelial cell of the mammary glands. The protein is strongly expressed in the cytoplasm of the cultured mammary gland tissue. hPC protein produced in milk ranged from 2 to 28 ng/mL. These experiments indicated that rec-hPC can be produced at high levels in mice mammary glands.


Subject(s)
Milk/metabolism , Protein C/metabolism , Recombinant Proteins/metabolism , Animals , CHO Cells , Caseins/genetics , Cricetinae , Cricetulus , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunohistochemistry , Male , Mammary Glands, Animal/metabolism , Mammary Glands, Animal/pathology , Mice , Mice, Transgenic , Protein C/genetics , RNA, Messenger/metabolism , Recombinant Proteins/analysis , Transfection
12.
ACS Nano ; 18(6): 4847-4861, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38189789

ABSTRACT

Infectious diseases pose persistent threats to public health, demanding advanced vaccine technologies. Nanomaterial-based delivery systems offer promising solutions to enhance immunogenicity while minimizing reactogenicity. We introduce a self-assembled vaccine (SAV) platform employing antigen-polymer conjugates designed to facilitate robust immune responses. The SAVs exhibit efficient cellular uptake by dendritic cells (DCs) and macrophages, which are crucial players in the innate immune system. The high-density antigen presentation of this SAV platform enhances the affinity for DCs through multivalent recognition, significantly augmenting humoral immunity. SAV induced high levels of immunoglobulin G (IgG), IgG1, and IgG2a, suggesting that mature DCs efficiently induced B cell activation through multivalent antigen recognition. Universality was confirmed by applying it to respiratory viruses, showcasing its potential as a versatile vaccine platform. Furthermore, we have also demonstrated strong protection against influenza A virus infection with SAV containing hemagglutinin, which is used in influenza A virus subunit vaccines. The efficacy and adaptability of this nanostructured vaccine present potential utility in combating infectious diseases.


Subject(s)
Communicable Diseases , Influenza A virus , Influenza Vaccines , Nanostructures , Humans , Antigens , Immunity, Humoral , Immunoglobulin G , Antibodies, Viral , Adjuvants, Immunologic
13.
Biosens Bioelectron ; 258: 116347, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38723332

ABSTRACT

Monitoring drug efficacy is significant in the current concept of companion diagnostics in metastatic breast cancer. Trastuzumab, a drug targeting human epidermal growth factor receptor 2 (HER2), is an effective treatment for metastatic breast cancer. However, some patients develop resistance to this therapy; therefore, monitoring its efficacy is essential. Here, we describe a deep learning-assisted monitoring of trastuzumab efficacy based on a surface-enhanced Raman spectroscopy (SERS) immunoassay against HER2-overexpressing mouse urinary exosomes. Individual Raman reporters bearing the desired SERS tag and exosome capture substrate were prepared for the SERS immunoassay; SERS tag signals were collected to prepare deep learning training data. Using this deep learning algorithm, various complicated mixtures of SERS tags were successfully quantified and classified. Exosomal antigen levels of five types of cell-derived exosomes were determined using SERS-deep learning analysis and compared with those obtained via quantitative reverse transcription polymerase chain reaction and western blot analysis. Finally, drug efficacy was monitored via SERS-deep learning analysis using urinary exosomes from trastuzumab-treated mice. Use of this monitoring system should allow proactive responses to any treatment-resistant issues.


Subject(s)
Biomarkers, Tumor , Biosensing Techniques , Breast Neoplasms , Deep Learning , Exosomes , Receptor, ErbB-2 , Spectrum Analysis, Raman , Trastuzumab , Trastuzumab/therapeutic use , Animals , Exosomes/chemistry , Female , Mice , Breast Neoplasms/drug therapy , Breast Neoplasms/urine , Spectrum Analysis, Raman/methods , Humans , Biomarkers, Tumor/urine , Immunoassay/methods , Antineoplastic Agents, Immunological/therapeutic use
14.
Cells ; 12(9)2023 05 01.
Article in English | MEDLINE | ID: mdl-37174692

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) refers to a range of conditions in which excess lipids accumulate in the liver, possibly leading to serious hepatic manifestations such as steatohepatitis, fibrosis/cirrhosis and cancer. Despite its increasing prevalence and significant impact on liver disease-associated mortality worldwide, no medication has been approved for the treatment of NAFLD yet. Liver X receptors α/ß (LXRα and LXRß) are lipid-activated nuclear receptors that serve as master regulators of lipid homeostasis and play pivotal roles in controlling various metabolic processes, including lipid metabolism, inflammation and immune response. Of note, NAFLD progression is characterized by increased accumulation of triglycerides and cholesterol, hepatic de novo lipogenesis, mitochondrial dysfunction and augmented inflammation, all of which are highly attributed to dysregulated LXR signaling. Thus, targeting LXRs may provide promising strategies for the treatment of NAFLD. However, emerging evidence has revealed that modulating the activity of LXRs has various metabolic consequences, as the main functions of LXRs can distinctively vary in a cell type-dependent manner. Therefore, understanding how LXRs in the liver integrate various signaling pathways and regulate metabolic homeostasis from a cellular perspective using recent advances in research may provide new insights into therapeutic strategies for NAFLD and associated metabolic diseases.


Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Liver X Receptors/metabolism , Inflammation , Receptors, Cytoplasmic and Nuclear/therapeutic use , Cholesterol/metabolism
15.
Sci Rep ; 13(1): 15174, 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37704744

ABSTRACT

Clastic successions found in the carbonate platform of continental margin during the Ordovician-Silurian Transition (OST) period are archives for interpreting paleo-depositional systems. Here, we report in-situ δ18Oquartz and 87Sr/86Srcarbonate isotope chemo-stratigraphy for an unconformable clastic unit from the Cathaysia terrane that rifted off the Gondwana Supercontinent in the Early Paleozoic Era. Our results suggest a depositional proxy and model for geological events attributed to rapid changes in the sedimentary environment during the OST period. Importantly, these results present crucial clues that infer the influence of Paleo-Tethys Sea opening, global eustatic regression, and rapid sedimentary provenance change. Our study provides insight into paleo-tracer that could be a key method for interpreting depositional system of carbonate platform based on in-situ mineral isotope chemo-stratigraphy that preserves the original value of provenance and geochemical condition.

16.
Int J Nanomedicine ; 18: 7865-7888, 2023.
Article in English | MEDLINE | ID: mdl-38146467

ABSTRACT

Lung cancer is one of the most common malignant tumors worldwide and is characterized by high morbidity and mortality rates and a poor prognosis. It is the leading cause of cancer-related death in the United States and worldwide. Most patients with lung cancer are treated with chemotherapy, radiotherapy, or surgery; however, effective treatment options remain limited. In this review, we aim to provide an overview of clinical trials, ranging from Phase I to III, conducted on drug delivery systems for lung cancer treatment. The trials included oral, inhaled, and intravenous administration of therapeutics. Furthermore, the study also talks about the evolving paradigm of targeted therapy and immunotherapy providing promising directions for personalized treatment. In addition, we summarize the best results and limitations of these drug delivery systems and discuss the potential capacity of nanomedicine.


Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Nanomedicine , Drug Delivery Systems , Lung , Infusion Pumps
17.
BMC Med Genomics ; 16(1): 332, 2023 12 19.
Article in English | MEDLINE | ID: mdl-38114957

ABSTRACT

BACKGROUND: Several genome-wide association studies (GWAS) have been performed to identify variants related to chronic diseases. Somatic variants in cancer tissues are associated with cancer development and prognosis. Expression quantitative trait loci (eQTL) and methylation QTL (mQTL) analyses were performed on chronic disease-related variants in TCGA dataset. METHODS: MuTect2 calling variants for 33 cancers from TCGA and 296 GWAS variants provided by LocusZoom were used. At least one mutation was found in TCGA 22 cancers and LocusZoom 23 studies. Differentially expressed genes (DEGs) and differentially methylated regions (DMRs) from the three cancers (TCGA-COAD, TCGA-STAD, and TCGA-UCEC). Variants were mapped to the world map using population locations of the 1000 Genomes Project (1GP) populations. Decision tree analysis was performed on the discovered features and survival analysis was performed according to the cluster. RESULTS: Based on the DEGs and DMRs with clinical data, the decision tree model classified seven and three nodes in TCGA-COAD and TCGA-STAD, respectively. A total of 11 variants were commonly detected from TCGA and LocusZoom, and eight variants were selected from the 1GP variants, and the distribution patterns were visualized on the world map. CONCLUSIONS: Variants related to tumors and chronic diseases were selected, and their geological regional 1GP-based proportions are presented. The variant distribution patterns could provide clues for regional clinical trial designs and personalized medicine.


Subject(s)
Genome-Wide Association Study , Neoplasms , Humans , Neoplasms/genetics , Mutation , Quantitative Trait Loci , Chronic Disease
18.
Nat Commun ; 14(1): 8153, 2023 Dec 09.
Article in English | MEDLINE | ID: mdl-38071202

ABSTRACT

Accurate diagnosis of Alzheimer's disease (AD) in its earliest stage can prevent the disease and delay the symptoms. Therefore, more sensitive, non-invasive, and simple screening tools are required for the early diagnosis and monitoring of AD. Here, we design a self-assembled nanoparticle-mediated amplified fluorogenic immunoassay (SNAFIA) consisting of magnetic and fluorophore-loaded polymeric nanoparticles. Using a discovery cohort of 21 subjects, proteomic analysis identifies adenylyl cyclase-associated protein 1 (CAP1) as a potential tear biomarker. The SNAFIA demonstrates a low detection limit (236 aM), good reliability (R2 = 0.991), and a wide analytical range (0.320-1000 fM) for CAP1 in tear fluid. Crucially, in the verification phase with 39 subjects, SNAFIA discriminates AD patients from healthy controls with 90% sensitivity and 100% specificity in under an hour. Utilizing tear fluid as a liquid biopsy, SNAFIA could potentially aid in long-term care planning, improve clinical trial efficiency, and accelerate therapeutic development for AD.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/metabolism , Proteomics , Reproducibility of Results , Immunoassay , Early Diagnosis , Biomarkers/metabolism , Amyloid beta-Peptides
19.
Cyberpsychol Behav Soc Netw ; 25(6): 369-376, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35639371

ABSTRACT

The long-term uncertainty and persistence of isolation caused by the COVID-19 pandemic created prolonged emotional distress individually and collectively. As the pandemic progressed, the dynamic ride of emotional experience was expressed live and shared online, particularly on social media. In this study, we collected posted messages on Twitter for a longitudinal investigation to determine how emotional experiences changed over time during the pandemic. In total, we analyzed 41,868,013 COVID-19-related tweets in English posted from January 21 to July 31, 2020. Using a stage model, the results demonstrated that there were three stages during the pandemic characterized by distinct emotional changes. The first stage features high anxiety and negative emotions compared with the other stages, possibly due to the lack of information about the disease. The second stage shows the dynamic ride of all emotions and an increase in negative emotions (particularly anger) as the COVID-19 pandemic proceeds. In the third stage, most emotions are stabilized, except for depression, despite the protracted pandemic.


Subject(s)
COVID-19 , Social Media , Emotions , Humans , Pandemics
20.
Nano Res ; 15(3): 2254-2262, 2022.
Article in English | MEDLINE | ID: mdl-34567436

ABSTRACT

A recurrent pandemic with unpredictable viral nature has implied the need for a rapid diagnostic technology to facilitate timely and appropriate countermeasures against viral infections. In this study, conductive polymer-based nanoparticles have been developed as a tool for rapid diagnosis of influenza A (H1N1) virus. The distinctive property of a conductive polymer that transduces stimulus to respond, enabled immediate optical signal processing for the specific recognition of H1N1 virus. Conductive poly(aniline-co-pyrrole)-encapsulated polymeric vesicles, functionalized with peptides, were fabricated for the specific recognition of H1N1 virus. The low solubility of conductive polymers was successfully improved by employing vesicles consisting of amphiphilic copolymers, facilitating the viral titer-dependent production of the optical response. The optical response of the detection system to the binding event with H1N1, a mechanical stimulation, was extensively analyzed and provided concordant information on viral titers of H1N1 virus in 15 min. The specificity toward the H1N1 virus was experimentally demonstrated via a negative optical response against the control group, H3N2. Therefore, the designed system that transduces the optical response to the target-specific binding can be a rapid tool for the diagnosis of H1N1. Electronic Supplementary Material: Supplementary material (Table S1 and Figs. S1-S8) is available in the online version of this article at 10.1007/s12274-021-3772-6.

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