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1.
J Cell Mol Med ; 27(7): 962-975, 2023 04.
Article in English | MEDLINE | ID: mdl-36916028

ABSTRACT

As a novel nuclear factor E2-related factor 2 (NRF2) activator, the itaconate has shown significant therapeutic potential for oxidative stress diseases. However, its role in Vohwinkel syndrome in relation to the gap junction protein beta 2 (GJB2) mutation is still unclear. This study aimed at investigating the effect of 4-octyl itaconate (OI) on HaCaT and D66H cells and clarify its potential mechanism in vitro. The optimal concentration and treatment time of OI on HaCaT cells and D66H cells were determined by CCK-8 and LDH experiments. The effect of OI on cell proliferation was detected by EdU staining and FACS analysis of PI, while the apoptosis was evaluated by TUNEL staining and FACS analysis of Annexin V. The ROS staining was performed, and the levels of SOD, MDA, GSH and GSH/GSSG were detected to evaluate the effect of OI on oxidative damage induced by D66H-type mutation. CO-IP, Western blot, immunofluorescence and qPCR analyses were employed to detect the activation of KEAP1-NRF2-GCLC/HO-1 pathway by OI. Finally, sh-NRF2 was used to confirm the activation of this pathway by OI. Results showed that OI could improve the cell viability decreased by GJB2 gene mutation by regulating the balance between cell growth and apoptosis induced by oxidative damage. Furthermore, this alleviation process was regulated by the KEAP1-NRF2-HO-1/GCLC pathway. In conclusion, OI could improve the viability of HaCaT and D66H cells via regulating the KEAP1-NRF2-GCLC/HO-1 pathway, which provided a wide spectrum of potential targets for effective therapeutic treatments of Vohwinkel syndrome in the clinic.


Subject(s)
NF-E2-Related Factor 2 , Signal Transduction , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Oxidative Stress , Apoptosis
2.
Anal Chem ; 90(7): 4338-4347, 2018 04 03.
Article in English | MEDLINE | ID: mdl-29498509

ABSTRACT

With advances in nanotechnology, particles with various size, shape, surface chemistry, and composition can be easily produced. Nano- and microparticles have been extensively explored in many industrial and clinical applications. Ensuring that the particles themselves are not possessing toxic effects to the biological system is of paramount importance. This paper describes a proof of concept method, in which a microfluidic system is used in conjunction with a cell microarray technique aiming to streamline the analysis of particle-cell interaction in a high throughput manner. Polymeric microparticles, with different particle surface functionalities, were first used to investigate the efficiency of particle-cell adhesion under dynamic flow. Silver nanoparticles (AgNPs, 10 nm in diameter) perfused at different concentrations (0 to 20 µg/mL) in parallel streams over the cell microarray exhibited a higher toxicity compared to the static culture in the 96-well-plate format. This developed microfluidic system can be easily scaled up to accommodate a larger number of microchannels for high throughput analysis of the potential toxicity of a wide range of particles in a single experiment.


Subject(s)
High-Throughput Screening Assays , Metal Nanoparticles/chemistry , Microfluidic Analytical Techniques , Silver/chemistry , Cell Adhesion/drug effects , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Equipment Design , Humans , Molecular Structure , Particle Size , Silver/pharmacology , Surface Properties
3.
Small ; 10(15): 3153-61, 2014 Aug 13.
Article in English | MEDLINE | ID: mdl-24700510

ABSTRACT

Hierarchical TiO2 /ln2 S3 /AgInS2 trilaminar core-shell branched nanorod arrays (T-CS BNRs) have been fabricated directly on conducting glass substrates (FTO) via a facile, versatile and low-cost hydrothermal and successive ionic layer adsorption and reaction (SILAR) for photoelectrochemical (PEC) water splitting. On the basis of optimal thickness of AgInS2 shell, such TiO2 /ln2 S3 /AgInS2 T-CS BNRs exhibit a higher photocatalytic activity, the photocurrent density and efficiency for hydrogen generation are up to 22.13 mA·cm(-2) and 14.83%, which is, to the best of our knowledge, the highest value ever reported for similar nanostructures. The trilaminar architecture is able to suppress carrier recombination and increase electron collection efficiency via (i) increasing the photon absorption through the lager specific surface area of TiO2 BNRs and a sensitizer layer (AgInS2 ), (ii) a buffer layer (ln2 S3 ), (iii) a better energy level alignment.

4.
Phys Chem Chem Phys ; 16(30): 16204-13, 2014 Aug 14.
Article in English | MEDLINE | ID: mdl-24969515

ABSTRACT

Hierarchical TiO2-CuInS2 core-shell nanoarrays were fabricated directly on conducting glass substrates (FTO) via facile and low-cost hydrothermal and polyol reduction methods for photoelectrochemical (PEC) water splitting using TiO2 branched nanorod arrays (BNRs) as the reactive framework. An enhanced optical property of the core-shell structure was discovered. Firstly, TiO2 BNRs-CuS core-shell structure was synthesized through successive ionic layer adsorption and reaction (SILAR). Subsequently, TiO2 BNRs-CuInS2 core-shell structure was derived from TiO2 BNRs-CuS core-shell structure. On the basis of optimal thickness of the CuInS2 shell, such a TiO2 BNRs-CuInS2 core-shell structure exhibits higher photocatalytic activity, the photocurrent density and efficiency for hydrogen generation are up to 19.07 mA cm(-2) and 11.48%, respectively, which are probably because of the improved absorption efficiency and the appropriate gradient energy gap structure. The TiO2 BNRs-CuInS2 core-shell structure can be promising building blocks in photoelectrochemical water splitting systems.

5.
Biochim Biophys Acta Mol Cell Res ; 1871(8): 119849, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39303786

ABSTRACT

The protein synthesis within eukaryotic cells is a complex process involving various translation factors. Among these factors, eukaryotic translation initiation factor 5 A (eIF5A) emerges as a crucial translation factor with high evolutionary conservation. eIF5A is unique as it is the only protein in eukaryotic cells containing the hypusine modification. Initially presumed to be a translation initiation factor, eIF5A was subsequently discovered to act mainly during the translation elongation phase. Notably, eIF5A facilitates the translation of peptide sequences containing polyproline stretches and exerts a universal regulatory effect on the elongation and termination phases of protein synthesis. Additionally, eIF5A indirectly affects various physiological processes within the cell by modulating the translation of specific proteins. This review provides a comprehensive overview of the structure, physiological functions, various post-translational modifications of eIF5A, and its association with various human diseases. The comparison between eIF5A and its bacterial homolog, EF-P, extends the discussion to the evolutionary conservation of eIF5A. This highlights its significance across different domains of life.

6.
Biosens Bioelectron ; 267: 116825, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39369515

ABSTRACT

Circular RNA (circRNA) and microRNA (miRNA) are both non-coding RNAs (ncRNAs) that serve as biomarkers for cancer diagnosis and prognosis. Quantitative detection of these ncRNAs is of particular importance to elucidate the functional mechanisms and evaluate their potential as biomarkers. However, the inherent structures of circRNA and miRNA are different from the mRNA, conventional qRT-PCR is unsuitable for the detection of these ncRNAs. Here, we propose a sensitive method for quantitative detection of circRNA and miRNA using polydisperse droplet digital CRISPR/Cas13a (PddCas13a). It can achieve limits of detection (LOD) as low as ∼10 aM without polymerase-based amplification. To efficiently detect the circRNA and miRNA in real samples, we use a chemically modified crRNA to enhance the stability of crRNA and improve the performance of Cas13a in complex environments containing contaminants. By integrating an extraction-free procedure with PddCas13a, we experimentally demonstrate the applicability of PddCas13a by testing clinical samples. Furthermore, we develop an automated and portable instrument for PddCas13a and verify its applicability for the detection of circRNA and miRNA from exosomes in point-of-care (POC) setting. This is the first report to detect the circRNA and miRNA simultaneously in POC setting. We envision this platform could promote the research of ncRNAs.

7.
Front Pharmacol ; 15: 1443667, 2024.
Article in English | MEDLINE | ID: mdl-39185304

ABSTRACT

Due to the pathological production of liver disease in utility particularly complexity, the morbidity and mortality of liver disease including viral hepatitis, liver fibrosis/cirrhosis and hepatocellular carcinoma (HCC) are rapidly increasing worldwide. Considering its insidious onset, rapid progression and drug resistance, finding an effective therapy is particularly worthwhile. Phyllanthus urinaria L. (P. urinaria), an ethnic medicine, can be applied at the stages of viral hepatitis, liver fibrosis/cirrhosis and HCC, which demonstrates great potential in the treatment of liver disease. Currently, there are numerous reports on the application of P. urinaria in treating liver diseases, but a detailed analysis of its metabolites and a complete summary of its pharmacological mechanism are still scarce. In this review, the phytochemical metabolites and ethnopharmacological applications of P. urinaria are summarized. Briefly, P. urinaria mainly contains flavonoids, lignans, tannins, phenolic acids, terpenoids and other metabolites. The mechanisms of P. urinaria are mainly reflected in reducing surface antigen secretion and interfering with DNA polymerase synthesis for anti-viral hepatitis activity, reducing hepatic stellate cells activity, inflammation and oxidative stress for anti-liver fibrosis/cirrhosis activity, as well as preventing tumor proliferation, invasion and angiogenesis for anti-HCC activity via relevant signaling pathways. Accordingly, this review provides insights into the future application of natural products in the trilogy of liver diseases and will provide a scientific basis for further research and rational utilization of P. urinaria.

8.
J Mol Neurosci ; 74(3): 79, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39162890

ABSTRACT

Diabetic neuropathic pain (DNP) is a diabetic complication that causes severe pain and deeply impacts the quality of the sufferer's daily life. Currently, contemporary clinical treatments for DNP generally exhibit a deficiency in effectiveness. Electroacupuncture (EA) is recognized as a highly effective and safe treatment for DNP with few side effects. Regrettably, the processes via which EA alleviates DNP are still poorly characterized. Transient receptor potential vanilloid 1 (TRPV1) and phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMKII) are overexpressed on spinal cord dorsal horn (SCDH) in DNP rats, and co-localization is observed between them. Capsazepine, a TRPV1 antagonist, effectively reduced nociceptive hypersensitivity and downregulated the overexpression of phosphorylated CaMKIIα in rats with DNP. Conversely, the CaMKII inhibitor KN-93 did not have any impact on TRPV1. EA alleviated heightened sensitivity to pain caused by nociceptive stimuli and downregulated the level of TRPV1, p-CaMKIIα, and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) in DNP rats. Intrathecal injection of capsaicin, on the other hand, reversed the above effects of EA. These findings indicated that the CaMKII/CREB pathway on SCDH is located downstream of TRPV1 and is affected by TRPV1. EA alleviates DNP through the TRPV1-mediated CaMKII/CREB pathway.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Cyclic AMP Response Element-Binding Protein , Diabetic Neuropathies , Electroacupuncture , Rats, Sprague-Dawley , TRPV Cation Channels , Animals , TRPV Cation Channels/metabolism , TRPV Cation Channels/antagonists & inhibitors , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors , Electroacupuncture/methods , Rats , Male , Cyclic AMP Response Element-Binding Protein/metabolism , Diabetic Neuropathies/therapy , Diabetic Neuropathies/metabolism , Capsaicin/pharmacology , Capsaicin/analogs & derivatives , Signal Transduction , Spinal Cord Dorsal Horn/metabolism , Benzenesulfonamides , Benzylamines
9.
Adv Sci (Weinh) ; 11(27): e2306716, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38161228

ABSTRACT

Electronic immunosensors are indispensable tools for diagnostics, particularly in scenarios demanding immediate results. Conventionally, these sensors rely on the chemical immobilization of antibodies onto electrodes. However, globular proteins tend to adsorb and unfold on these surfaces. Therefore, self-assembled monolayers (SAMs) of thiolated alkyl molecules are commonly used for indirect gold-antibody coupling. Here, a limitation associated with SAMs is revealed, wherein they curtail the longevity of protein sensors, particularly when integrated into the state-of-the-art transducer of organic bioelectronics-the organic electrochemical transistor. The SpyDirect method is introduced, generating an ultrahigh-density array of oriented nanobody receptors stably linked to the gold electrode without any SAMs. It is accomplished by directly coupling cysteine-terminated and orientation-optimized spyTag peptides, onto which nanobody-spyCatcher fusion proteins are autocatalytically attached, yielding a dense and uniform biorecognition layer. The structure-guided design optimizes the conformation and packing of flexibly tethered nanobodies. This biolayer enhances shelf-life and reduces background noise in various complex media. SpyDirect functionalization is faster and easier than SAM-based methods and does not necessitate organic solvents, rendering the sensors eco-friendly, accessible, and amenable to scalability. SpyDirect represents a broadly applicable biofunctionalization method for enhancing the cost-effectiveness, sustainability, and longevity of electronic biosensors, all without compromising sensitivity.


Subject(s)
Biosensing Techniques , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Gold/chemistry , Electrodes , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Single-Domain Antibodies/chemistry
10.
Article in English | MEDLINE | ID: mdl-36749895

ABSTRACT

The tight regulation of the glucose concentration in the body is crucial for balanced physiological function. We developed an electrochemical transistor comprising an n-type conjugated polymer film in contact with a catalytic enzyme for sensitive and selective glucose detection in bodily fluids. Despite the promise of these sensors, the property of the polymer that led to such high performance has remained unknown, with charge transport being the only characteristic under focus. Here, we studied the impact of the polymer chemical structure on film surface properties and enzyme adsorption behavior using a combination of physiochemical characterization methods and correlated our findings with the resulting sensor performance. We developed five n-type polymers bearing the same backbone with side chains differing in polarity and charge. We found that the nature of the side chains modulated the film surface properties, dictating the extent of interactions between the enzyme and the polymer film. Quartz crystal microbalance with dissipation monitoring studies showed that hydrophobic surfaces retained more enzymes in a densely packed arrangement, while hydrophilic surfaces captured fewer enzymes in a flattened conformation. X-ray photoelectron spectroscopy analysis of the surfaces revealed strong interactions of the enzyme with the glycolated side chains of the polymers, which improved for linear side chains compared to those for branched ones. We probed the alterations in the enzyme structure upon adsorption using circular dichroism, which suggested protein denaturation on hydrophobic surfaces. Our study concludes that a negatively charged, smooth, and hydrophilic film surface provides the best environment for enzyme adsorption with desired mass and conformation, maximizing the sensor performance. This knowledge will guide synthetic work aiming to establish close interactions between proteins and electronic materials, which is crucial for developing high-performance enzymatic metabolite biosensors and biocatalytic charge-conversion devices.

11.
ACS Appl Mater Interfaces ; 14(13): 15565-15575, 2022 Apr 06.
Article in English | MEDLINE | ID: mdl-35286082

ABSTRACT

Porous silicon (pSi) is an established porous material that offers ample opportunities for biosensor design thanks to its tunable structure, versatile surface chemistry, and large surface area. Nonetheless, its potential for electrochemical sensing is relatively unexplored. This study investigates layered carbon-stabilized pSi nanostructures with site-specific functionalities as an electrochemical biosensor. A double-layer nanostructure combining a top hydrophilic layer of thermally carbonized pSi (TCpSi) and a bottom hydrophobic layer of thermally hydrocarbonized pSi (THCpSi) is prepared. The modified layers are formed in a stepwise process, involving first an electrochemical anodization step to generate a porous layer with precisely defined pore morphological features, followed by deposition of a thin thermally carbonized coating on the pore walls via temperature-controlled acetylene decomposition. The second layer is then generated beneath the first by following the same two-step process, but the acetylene decomposition conditions are adjusted to deposit a thermally hydrocarbonized coating. The double-layer platform features excellent electrochemical properties such as fast electron-transfer kinetics, which underpin the performance of a TCpSi-THCpSi voltammetric DNA sensor. The biosensor targets a 28-nucleotide single-stranded DNA sequence with a detection limit of 0.4 pM, two orders of magnitude lower than the values reported to date by any other pSi-based electrochemical DNA sensor.


Subject(s)
Biosensing Techniques , Nanostructures , Carbon/chemistry , Nanostructures/chemistry , Porosity , Silicon/chemistry
12.
Adv Mater ; 34(35): e2202972, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35772173

ABSTRACT

Conventional biosensors rely on the diffusion-dominated transport of the target analyte to the sensor surface. Consequently, they require an incubation step that may take several hours to allow for the capture of analyte molecules by sensor biorecognition sites. This incubation step is a primary cause of long sample-to-result times. Here, alternating current electrothermal flow (ACET) is integrated in an organic electrochemical transistor (OECT)-based sensor to accelerate the device operation. ACET is applied to the gate electrode functionalized with nanobody-SpyCatcher fusion proteins. Using the SARS-CoV-2 spike protein in human saliva as an example target, it is shown that ACET enables protein recognition within only 2 min of sample exposure, supporting its use in clinical practice. The ACET integrated sensor exhibits better selectivity, higher sensitivity, and lower limit of detection than the equivalent sensor with diffusion-dominated operation. The performance of ACET integrated sensors is compared with two types of organic semiconductors in the channel and grounds for device-to-device variations are investigated. The results provide guidelines for the channel material choice in OECT-based biochemical sensors, and demonstrate that ACET integration substantially decreases the detection speed while increasing the sensitivity and selectivity of transistor-based sensors.


Subject(s)
Biosensing Techniques , COVID-19 , Biosensing Techniques/methods , Convection , Electrochemical Techniques/methods , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Transistors, Electronic
13.
Front Physiol ; 13: 858274, 2022.
Article in English | MEDLINE | ID: mdl-35669574

ABSTRACT

Feather performs important physiological functions in birds, and it is also one of the economic productions in goose farming. Understanding and modulating feather follicle development during embryogenesis are essential for bird biology and the poultry industry. CHIR-99021 is a potent Wnt/ß-catenin signaling pathway activator associated with feather follicle development. In this study, goose embryos (Anser cygnoides) received an in ovo injection of CHIR-9902, which was conducted at the beginning of feather follicle development (E9). The results showed that feather growth and feather follicle development were promoted. The Wnt signaling pathway was activated by the inhibition of GSK-3ß. Transcriptomic analyses showed that the transcription changes were related to translation, metabolism, energy transport, and stress in dorsal tissue of embryos that received CHIR-99021, which might be to adapt and coordinate the promoting effects of CHIR-99021 on feather follicle development. This study suggests that in ovo injection of CHIR-99021 is a potential strategy to improve feather follicle development and feather-related traits for goose farming and provides profiling of the Wnt signaling pathway and transcriptome in dorsal tissue of goose embryos for further understanding of feather follicle development.

14.
Epigenomics ; 13(6): 411-422, 2021 03.
Article in English | MEDLINE | ID: mdl-33641342

ABSTRACT

Aim: To explore the roles of lncRNA NONHSAT177112.1 in the inflammatory injury of human cardiomyocytes (HCMs) induced by lipopolysaccharide (LPS). Materials & methods: The sublocalization of NONHSAT177112.1 was detected by FISH. HCMs were stimulated with LPS to induce inflammatory injury. NONHSAT177112.1 expression was detected by quantitative real-time PCR. Cell apoptosis and viability were detected by flow cytometry and CCK-8 assays. The expression of inflammatory cytokines and myocardial enzymes were detected by PCR and ELISA. Results: NONHSAT177112.1 is expressed in the nucleus and cytoplasm. NONHSAT177112.1 showed dynamic expression that first increased and then decreased during LPS stimulation. NONHSAT177112.1 knockdown reversed the promotion effect of LPS on inflammatory injury. Conversely, NONHSAT177112.1 overexpression exerted the opposite effects. Conclusion: NONHSAT177112.1 aggravates inflammatory injury in LPS-treated HCMs.


Subject(s)
Apoptosis , Inflammation/pathology , Lipopolysaccharides/adverse effects , Myocytes, Cardiac/pathology , RNA, Long Noncoding/genetics , Cell Survival , Cells, Cultured , Humans , Inflammation/etiology , Inflammation/metabolism , MicroRNAs/genetics , Myocytes, Cardiac/immunology , Myocytes, Cardiac/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Signal Transduction
15.
Nat Biomed Eng ; 5(7): 666-677, 2021 07.
Article in English | MEDLINE | ID: mdl-34031558

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid and sensitive protein detection and quantification in simple and robust formats for widespread point-of-care applications. Here, we report on nanobody-functionalized organic electrochemical transistors with a modular architecture for the rapid quantification of single-molecule-to-nanomolar levels of specific antigens in complex bodily fluids. The sensors combine a solution-processable conjugated polymer in the transistor channel and high-density and orientation-controlled bioconjugation of nanobody-SpyCatcher fusion proteins on disposable gate electrodes. The devices provide results after 10 min of exposure to 5 µl of unprocessed samples, maintain high specificity and single-molecule sensitivity in human saliva and serum, and can be reprogrammed to detect any protein antigen if a corresponding specific nanobody is available. We used the sensors to detect green fluorescent protein, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV) spike proteins, and for the COVID-19 screening of unprocessed clinical nasopharyngeal swab and saliva samples with a wide range of viral loads.


Subject(s)
Biosensing Techniques/methods , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Nanotechnology/methods , Severe acute respiratory syndrome-related coronavirus/pathogenicity , COVID-19/virology , Humans , Single-Domain Antibodies/immunology
16.
Medicine (Baltimore) ; 98(37): e17155, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31517860

ABSTRACT

RATIONALE: Sporotrichosis is a subacute or chronic infection caused by sporothrix schenckii complex. The misdiagnosis rate of sporotrichosis is very high. Fungal microscopic examination and timely culture help us make an accurate diagnosis and treatment. We observed that combined treatments are more effective than monotherapy in treatment of sporotrichosis. PATIENT CONCERNS: A 47-year-old female complained of pustules and scabs on her nose tip that lasted for 1 month at our hospital. She was diagnosed with skin infection and treated with antibiotics for 20 days. Nonetheless, the treatment did not result in any improvement with the lesion. DIAGNOSES: The results on bacterial culture, sensitive test, special stains, and multiple acid-fast cultures were negative. Finally, fungi were observed by KOH. Finally, fungal hyphae were observed by KOH and by fluorescent staining. Taupe filamentous colonies of sporothrix-like species appeared by fungal culture. The diagnosis of sporotrichosis was finally confirmed based on the lesion characteristics and the results of laboratory examination. INTERVENTIONS: The lesions did not alleviate with Itraconazole oral administration for 1 month. Then we treated the patient with the combination therapy of itraconazole (ITR) and terbinafine. At the same time, the compound glycyrrhizin tablet was used for liver protection. OUTCOMES: The patient was free of clinical symptoms of sporotrichosis following the treatment and did not have complications during an 8-month follow-up. LESSONS: We should always be alert to sporotrichosis although it is not a very common disease. It is important to adapt fungi microscopic analysis and culture for an accurate diagnosis. ITR is the first choice for sporotrichosis. However, combination treatment is more effective for stubborn cases.


Subject(s)
Antifungal Agents/therapeutic use , Itraconazole/therapeutic use , Sporotrichosis/drug therapy , Terbinafine/therapeutic use , Diagnosis, Differential , Drug Therapy, Combination , Female , Humans , Middle Aged , Nose , Sporotrichosis/diagnosis , Sporotrichosis/pathology
17.
Biomed Pharmacother ; 120: 109381, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31542616

ABSTRACT

BACKGROUND: Qinghuo Rougan Formula (QHRGF) is a traditional Chinese medicine (TCM) that has been widely apllied to treat uveitis for several decades. However, the inhibitory mechanism of QHRGF in uveitis has remained to be an enigma. METHODS: The Chinese herbal medicine pharmacology data and analysis platform wereused to search and screen for the effective components of the QHRGF compound injection and to analyse possible therapeutic targets based on network topology. In addition, various known disease target databases were enraolled, the therapeutic target proteins in uveitis were screened, and a protein-protein interaction (PPI) network was constructed. Enrichment analysis was performed on key nodes. Finally, the inhibitory effect of QHRGF on uveitis was verified by experiments. RESULTS: We identified 259 major candidate targets of QHRGF and successfully constructed a 'QHRGF-compound-target-uveitis' network. Above-mentioned targets revealed by Gene enrichment analysis have played an significant role in the cell cycle, autoimmune disease, apoptosis and related signal pathways. We demonstrated that QHRGF attenuates local inflammation in experimental autoimmune uveoretinitis (EAU) rats by regulating natural killer T (NKT) cells and inhibiting MAPK signal pathways. CONCLUSION: QHRGF may regulate the local immune response and inflammatory factors mainly through the MAPK signal pathway. For autoimmune uveitis, QHRGF may be a promising, long-lasting treatment strategy.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Databases, Protein , Drugs, Chinese Herbal/pharmacology , Protein Interaction Maps , Systems Biology , Uvea/drug effects , Uveitis/drug therapy , Animals , Disease Models, Animal , Female , Humans , Mitogen-Activated Protein Kinases/metabolism , Natural Killer T-Cells/drug effects , Natural Killer T-Cells/immunology , Natural Killer T-Cells/metabolism , Rats, Inbred Lew , Signal Transduction , Uvea/immunology , Uvea/metabolism , Uvea/pathology , Uveitis/immunology , Uveitis/metabolism , Uveitis/pathology
18.
Lab Chip ; 17(3): 501-510, 2017 01 31.
Article in English | MEDLINE | ID: mdl-28074962

ABSTRACT

This paper describes the use of crossed laminar flow microfluidics for the selective capture of multiple cell types on-chip aiming for high throughput screening of various cell treatment compounds. Parallel laminar streams containing different cell types were perfused and captured on a cell adhesion protein-functionalized reaction area. Thereafter, parallel streams containing cell treatment solutions were delivered orthogonally over the captured cells. Multiple cell types and a range of cell treatment conditions could therefore be assessed in a single experiment. We were also able to sort mixed cell populations via antibody array clusters, and to further deliver treatments to subpopulations of cells. Moreover, using solutions with different tonicities, we successfully demonstrated the incorporation of a live/dead cell viability assessment on-chip for a direct read out assay following the treatments. This crossed laminar flow microfluidics for generation of a cell-based assay could therefore offer an interesting platform for high throughput screening of potential drug candidates, nanoparticle toxicity testing, or other cellular and molecular interventions.


Subject(s)
Cell Separation/instrumentation , High-Throughput Screening Assays/instrumentation , Microfluidic Analytical Techniques/instrumentation , Cell Line , Cell Separation/methods , Equipment Design , High-Throughput Screening Assays/methods , Humans , Microfluidic Analytical Techniques/methods
19.
Chem Commun (Camb) ; 51(13): 2597-600, 2015 Feb 14.
Article in English | MEDLINE | ID: mdl-25572525

ABSTRACT

We report a novel promising semiconductor of Ag3CuS2 serving as absorber material in inorganic-organic solid-state solar cells for the first time, and the device (ITO/ZnO/Ag3CuS2/P3HT/Pt) exhibits a power conversion efficiency of 2.01%. This study opens up an available method to develop various ternary absorber materials for tertiary generation solar cells.

20.
ACS Appl Mater Interfaces ; 6(19): 17119-25, 2014 Oct 08.
Article in English | MEDLINE | ID: mdl-25208689

ABSTRACT

Highly ordered AgInS2-modified ZnO nanoarrays were fabricated via a low-cost hydrothermal chemical method, and their application as all-solid-state solar cells was also tested. A sensitizer and a buffer layer were developed around the surface of ZnO nanotubes in the preparation process, and this method is easily be manipulated to produce uniform structure. In this structure, the ZnO served as direct electron transport path, the ZnS as the buffer layer, and the ternary sensitizer AgInS2 as absorber and outer shell. The novel all-solid-state hybrid solar cells (ITO/ZnO/ZnS/AgInS2/P3HT/Pt) showed improved short-circuit current density (Jsc) of 7.5 mA/cm(2), open-circuit voltage (Voc) of 512 mV, giving rise to a power conversion efficiency of 2.11%, which is the relatively highest value ever reported for ZnO-based all-solid-state hybrid solar cells. This better result is attributed to the improved absorption spectrum, high speed of photoinduced charge transmission velocity, and appropriate gradient energy gap structure, which implies a promising application in all-solid-state solar cells.

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