Pt-Cluster-Embedded Metal-Organic Frameworks-Derived Fe@C as Dual-Enzyme Mimics for NADH Detection in Serum.

Dihydro-nicotinamide adenine dinucleotide (NADH) detection is crucial since it is a vital coenzyme in organism metabolism. Compared to the traditional method based on natural NADH oxidase (NOX), nanozymes with multienzyme-like activity can catalyze multistage reactions in a singular setup, simplifying detection processes and enhancing sensitivity. In this study, an innovative NADH detection method was developed using iron-doped carbon (Fe@C) nanozyme synthesized from metal-organic frameworks with in situ reduced Pt clusters. This nanozyme composite (Pt/Fe@C) demonstrated dual NOX and peroxidase-like characteristics, significantly enhancing the catalytic efficiency and enabling NADH conversion to NAD+ and H2O2 with subsequent detection. The collaborative research involving both experimental and theoretical simulations has uncovered the catalytic process and the cooperative effect of Fe and Pt atoms, leading to enhanced oxygen adsorption and activation, as well as a decrease in the energy barrier of the key step in the H2O2 decomposition process. These findings indicate that the catalytic performance of Pt/Fe@C in NOX-like and POD-like reactions can be significantly improved. The colorimetric sensor detects NADH with a limit of detection as low as 0.4 nM, signifying a breakthrough in enzyme-mimicking nanozyme technology for precise NADH measurement.

Transcriptomics analysis reveals the signal transduction mechanism of brassinolides in tea leaves and its regulation on the growth and development of Camellia sinensis.

BACKGROUND: Brassinosteroids (BRs) are a type of sterol plant hormone that play an important role in various biochemical and physiological reactions such as promoting cell growth, increasing biomass, and improving stress resistance. RESULTS: To investigate the regulatory and molecular mechanism of BRs on the growth and development of tea plants (Camellia sinensis L.), changes in cell structure and gene expression levels of tea leaves treated with exogenous BRs were analyzed by electron microscopy and high-throughput Illumina RNA-Seq technology. The results showed that the number of starch granules in the chloroplasts and lipid globules increased and thylakoids expanded after BR treatment compared with the control. Transcriptome analysis showed that in the four BR treatments (CAA: BR treatment for 3 h, CAB: BR treatment for 9 h, CAC: BR treatment for 24 h, and CAD: BR treatment for 48 h), 3861 (1867 upregulated and 1994 downregulated), 5030 (2461 upregulated and 2569 downregulated), 1626 (815 upregulated and 811 downregulated), and 2050 (1004 upregulated and 1046 downregulated) differentially expressed genes were detected, respectively, compared with CAK (BR treatment for 0 h). Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, metabolic pathway enrichment analysis showed that the differentially expressed genes of CAA vs. CAK, CAB vs. CAK, CAC vs. CAK, and CAD vs. CAK significantly enriched the functional categories of signal transduction, cell cycle regulation, and starch, sucrose, and flavonoid biosynthesis and metabolism pathways. We also found that after spraying BR, the key genes for caffeine synthesis were downregulated. The results of qRT-PCR coincided with the findings of transcriptomic analysis. CONCLUSIONS: The present study improved our understanding of the effects of BRs on the growth and development of tea leaves and laid the foundation for the in-depth analysis of signal transduction pathways of BRs in tea leaves.

Diterpenoids with an unprecedented ring system from Euphorbia peplus and their activities in the lysosomal-autophagy pathway.

Three novel jatrophane diterpenes, cyclojatrophanes A-C (1-3), were isolated from the seeds of Euphorbia peplus. Compounds 1-3 featured an unprecedented 5/5/5/11 tetracyclic ring system incorporating ditetrahydropyran rings. Their structures including their absolute configurations were established by extensive spectroscopic analysis, X-ray crystallographic experiments and chemical transformations. In addition, these compounds could significantly activate the lysosomal-autophagy pathway.

A Simple One-Step Modification of Shrimp Shell for the Efficient Adsorption and Desorption of Copper Ions.

Removing toxic heavy metal species from aqueous solutions is a point of concern in our society. In this paper, a promising biomass adsorbent, the modified waste shrimp shell (MS), for Cu (II) removal was successfully prepared using a facile and simple one-step modification, making it possible to achieve high-efficiency recycling of the waste NaOH solution as the modification agent. The outcome shows that with the continuous increase in pH, temperature and ion concentration, the adsorption effect of MS on Cu (II) can also be continuously improved. Adsorption isotherm and adsorption kinetics were fitted with the Langmuir isotherm model and the pseudo-second-order model, respectively, and the maximum adsorption capacity of Cu (II) as obtained from the Langmuir isotherm model fitting reached 1.04 mmol/g. The systematic desorption results indicated that the desorption rate of Cu (II) in the MS could reach 100% within 6 min, where HNO3 is used as the desorption agent. Moreover, experiments have proven that after five successive recycles of NaOH as a modifier, the adsorption capacity of MS on Cu (II) was efficient and stable, maintaining tendency in 0.83-0.85 mmol/g, which shows that waste NaOH solution can be used as a modification agent in the preparation of waste shrimp shell adsorbent, such as waste NaOH solution produced in industrial production, thereby making it possible to turn waste into renewable resources and providing a new way to recycle resources.

Effects of Muscle Fatigue and Recovery on Complexity of Surface Electromyography of Biceps Brachii.

This study aimed to investigate the degree of regularity of surface electromyography (sEMG) signals during muscle fatigue during dynamic contractions and muscle recovery after cupping therapy. To the best of our knowledge, this is the first study assessing both muscle fatigue and muscle recovery using a nonlinear method. Twelve healthy participants were recruited to perform biceps curls at 75% of the 10 repetitions maximum under four conditions: immediately and 24 h after cupping therapy (-300 mmHg pressure), as well as after sham control (no negative pressure). Cupping therapy or sham control was assigned to each participant according to a pre-determined counter-balanced order and applied to the participant's biceps brachii for 5 min. The degree of regularity of the sEMG signal during the first, second, and last 10 repetitions (Reps) of biceps curls was quantified using a modified sample entropy (Ems) algorithm. When exercise was performed immediately or 24 h after sham control, Ems of the sEMG signal showed a significant decrease from the first to second 10 Reps; when exercise was performed immediately after cupping therapy, Ems also showed a significant decrease from the first to second 10 Reps but its relative change was significantly smaller compared to the condition of exercise immediately after sham control. When exercise was performed 24 h after cupping therapy, Ems did not show a significant decrease, while its relative change was significantly smaller compared to the condition of exercise 24 h after sham control. These results indicated that the degree of regularity of sEMG signals quantified by Ems is capable of assessing muscle fatigue and the effect of cupping therapy. Moreover, this measure seems to be more sensitive to muscle fatigue and could yield more consistent results compared to the traditional linear measures.

A Macromolecular Drug for Cancer Therapy via Extracellular Calcification.

Cancer chemotherapy typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways; however, severe side effects may arise. In this study, we performed a first attempt to develop macromolecular-induced extracellular chemotherapy involving biomineralization by absorbing calcium from the blood through a new type of drug, polysialic acid conjugated with folate (folate-polySia), which selectively induces biogenic mineral formation on tumor cells and results in the pathological calcification of tumors. The macromolecule-initiated extracellular calcification causes cancer cell death mainly by intervening with the glycolysis process in cancer cells. Systemic administration of folate-polySia inhibited cervical and breast tumor growth and dramatically improved survival rates in mice. This study provides an extracellular therapeutic approach for malignant tumor diseases via calcification that is ready for clinical trials and offers new insights into macromolecular anticancer drug discovery.

MiRNA155HG polymorphisms influenced the risk of liver cancer among the Han Chinese population.

BACKGROUND: Liver cancer is one of the most common cancers in the world. The primary aim of this research was to discover the correlation between single nucleotide polymorphisms (SNPs) of the MIR155HG and liver cancer risk. METHODS: The selected SNPs in MIR155HG were genotyped utilizing the Agena MassARRAY platform. We evaluated the correlation between MIR155HG polymorphisms and Liver cancer by genetic model analysis, stratification analysis and haplotype analysis. Relative risk of Liver cancer was shown based on odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Our results uncovered that rs12482371 and rs1893650 in the MIR155HG were associated with protection against Liver cancer. And the rs928883 was related to increase risk of Liver cancer. Furthermore, apart from rs77218221, other selected SNPs formed two LD blocks, and haplotype "GATAG" in block 2 elevated individual liver cancer risk. CONCLUSIONS: MIR155HG gene polymorphism may be correlated to Liver cancer susceptibility in Han Chinese population, particularly in males and aged ≤55 years.

Evaluating empowerment in genetic counseling using patient-reported outcomes.

Data about patient reported outcomes from cancer genetics services (CGS) are lacking but are essential to guide service evaluation and improvements. We measured improvement in empowerment, following genetic counseling in Singapore using a culturally-adapted version of the Genetic Counseling Outcome Scale (GCOS-24); and sought to identify factors associated with change in empowerment. The GCOS-24 was administered to 155 patients of the CGS, at pre- and post-counseling or testing timepoints. Of which, 110 patients underwent genetic testing. Individual pre- and post-counseling responses were subjected to Rasch analysis; the scale was subsequently split into cognitive control (CC) and emotional control (EC) domains. Associations of baseline characteristics with changes in pre- and post-CC and EC scores were assessed using multiple regression analysis. Both CC and EC scores showed significant improvement following genetic counseling and testing. While all items in the CC domain of being showed increases at follow-up, aspects of EC related to alleviating negative emotions (P = .88) and hopelessness (P = .2) did not show significant improvement. Our study revealed significant improvement in empowerment in patients who have received cancer genetic counseling, while revealing a need to cultivate hope and facilitate the alleviation of negative emotions in patients during genetic counseling.

Study on the virulome and resistome of a vancomycin intermediate-resistance Staphylococcus aureus.

Methicillin-resistant S. aureus (MRSA) has been considered a potential "Super Bugs", responsible for various infectious diseases. Vancomycin has been the most effective antibitic to treat MRSA originated infections. In this study, we aimed at investigating the genomic features of a vancomycin intermediate-resistance S. aureus strain Guangzhou-SauVS2 isolated from a female patient suffering from chronic renal function failure, emphasizing on its antimicrobial resistance and virulence determinants. The genome has a total length of 2,605,384 bp and the G+C content of 33.21%, with 2,239 predicted genes annotated with GO terms, COG categories, and KEGG pathways. Besides the carriage of vancomycin b-type resistance protein responsible for the vancomycin intermediate-resistance, S. aureus strain Guangzhou-SauVS2 showed resistance to ß-lactams, quinolones, macrolide, and tetracycline, due to the acquisition of corresponding antimicrobial resistance genes. In addition, virulence factors including adherence, antiphagocytosis, iron uptake, and toxin were determined, indicating the pathogenesis of the strain.

Ruthenium(II)-Catalyzed Regioselective Ortho C-H Allenylation of Electron-Rich Aniline and Phenol Derivatives.

Ortho C-H allenylation of electron-rich benzene derivatives with propargylic alcohol derivatives has been a challenge, due to their great innate tendency toward a para C-H allenylation via an SN2'-type substitution process. Here, we described a Ru(II)-catalyzed regioselective ortho C-H allenylation of electron-rich aniline and phenol derivatives, which allows the previously challenging synthesis of a broad range of ortho allenylated aniline and phenol derivatives. More significantly, highly optically active fully substituted allenes can also be prepared with high enantiomeric excess via a highly efficient chirality transfer. No para C-H allenylation product was observed in the current catalytic system, thus showing a complete reversibility of the regioselectivity.

Macrocyclic diterpenoids from the seeds of Euphorbia peplus with potential activity in inducing lysosomal biogenesis.

The first phytochemical investigation of the seeds of Euphorbia peplus led to the isolation and characterization of five new (1-5), named euphopepluanones A-E, and five known diterpenoids (6-10). Their structures were established by extensive spectroscopic analysis and X-ray crystallographic experiments. Euphopepluanones A-E (1-3) feature a very rare 5/11/5-tricyclic skeleton, and euphopepluanones D-E (4-5) represent the first report of lathyrane type diterpenoids found in E. peplus. The new compounds 1-5 were assessed for their activities to induce lysosomal biogenesis through LysoTracker Red staining, in which compounds 1 and 3 could significantly induce lysosomal biogenesis. In addition, compounds 1 and 3 could promote the nuclear translocation of TFEB, a master transcriptional factor of lysosomal genes, indicating that compounds 1 and 3 induced lysosomal biogenesis through activation of TFEB.

Use of telephone intake for family history taking at a cancer genetics service in Asia.

Family history taking is a fundamental part of genetic counseling, and however, it is also a time-consuming process. To cope with the increasing demands at the Cancer Genetics Service in Singapore, alternative methods to collect patients' family history were implemented to reduce the duration of the initial consultation and increase the clinic's capacity. Two interventions were performed in this study, where a family history questionnaire and telephone intakes (telephone calls to collect patient family history) were implemented prior to a cancer genetics consultation. The primary outcome of this study is the duration of the initial consultation in relation to both interventions while the secondary outcome is the clinic attendance rate before and after implementing the telephone intake. The impact of interventions was evaluated with a Plan-Do-Study-Act (PDSA) methodology. The use of a family history questionnaire could not be evaluated due to poor patient response while the telephone intake was found to be feasible among the local population. Two improvements were observed after the implementation of telephone intake: (a) a significant reduction in the duration of the initial consultation from 60 to 45 min (p = .001) and (b) a significant increase of 29.7% in clinic attendance (p = .01). This study demonstrates that collecting family history information ahead of genetic counseling via telephone intake is a useful measure in improving clinic capacity, which potentially resulting in optimization of clinical resources.

Effect of Different Local Vibration Frequencies on the Multiscale Regularity of Plantar Skin Blood Flow.

Local vibration has shown promise in improving skin blood flow (SBF). However, there is no consensus on the selection of the best vibration frequency. An important reason may be that previous studies utilized time- and frequency-domain parameters to characterize vibration-induced SBF responses. These parameters are unable to characterize the structural features of the SBF response to local vibrations, thus contributing to the inconsistent findings seen in vibration research. The objective of this study was to provide evidence that nonlinear dynamics of SBF responses would be an important aspect for assessing the effect of local vibration on SBF. Local vibrations at 100 Hz, 35 Hz, and 0 Hz (sham vibration) with an amplitude of 1 mm were randomly applied to the right first metatarsal head of 12 healthy participants for 10 min. SBF at the same site was measured for 10 min before and after local vibration. The degree of regularity of SBF was quantified using a multiscale sample entropy algorithm. The results showed that 100 Hz vibration significantly increased multiscale regularity of SBF but 35 Hz and 0 Hz (sham vibration) did not. The significant increase of regularity of SBF after 100 Hz vibration was mainly attributed to increased regularity of SBF oscillations within the frequency interval at 0.0095-0.15 Hz. These findings support the use of multiscale regularity to assess effectiveness of local vibration on improving skin blood flow.

Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting BRCA1/2 mutations in a Southeast Asian country.

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes have significant clinical implications for both risk-reducing and early surveillance management. The third and most recent revision of the Manchester scoring system (MSS3) used to distinguish patients indicated for germline BRCA1/2 testing included further adjustments for triple negative breast cancer, high-grade serous ovarian cancer and human epidermal growth factor 2 (HER2) receptor status. This study aims to evaluate the relative effectiveness of MSS3 in a Southeast Asian population. METHODS: All patients in our centre were tested using next-generation sequencing (NGS) panels that included full gene sequencing as well as coverage for large deletions/duplications in BRCA1/2. We calculated MSS1-3 scores for index patients between 2014 and 2017 who had undergone BRCA1/2 genetic testing and recorded their genetic test results. MSS1-3 outcomes were compared using receiver operating characteristic analysis, while associations with predictors were investigated using Fisher's exact test and logistics regression. Calculations were performed using Medcalc17. RESULTS: Of the 330 included patients, 47 (14.2%) were found to have a germline mutation in BRCA1 or BRCA2. A positive HER2 receptor was associated with a lower likelihood of a BRCA1/2mutation (OR=0.125, 95% CI 0.016 to 0.955; P=0.007), while high-grade serous ovarian cancer was conversely associated with an increased likelihood of a BRCA1/2 mutation (OR=5.128, 95% CI 1.431 to 18.370; P=0.012). At the 10% threshold, 43.0% (142/330) of patients were indicated for testing under MSS3, compared with 35.8% (118/330) for MSS1% and 36.4% (120/330) for MSS2. At the 10% threshold, MSS3 sensitivity was 91.5% and specificity 65.0%, significantly better than the previous MSS1 (P=0.037) and MSS2 (P=0.032) models. CONCLUSION: Our results indicate that the updated MSS3 outperforms previous iterations and relative to the Manchester population, is just as effective in identifying patients with BRCA1/2 mutations in a Southeast Asian population.

ABCA1 inhibits PDGF-induced proliferation and migration of rat airway smooth muscle cell through blocking TLR2/NF-κB/NFATc1 signaling.

Airway remodeling is a key feature of asthma, characterized by abnormal proliferation and migration of airway smooth muscle cells (ASMCs). ABCA1, a member of the ATP-binding cassette family of active transporters, plays an essential role in the progression of lung diseases. However, the contributions of ABCA1 in ASMCs remain to be explored. The purpose of the present study was to investigate the functional role and potential molecular mechanism of ABCA1 in platelet derived growth factor (PDGF)-induced primary rat ASMC proliferation and migration. We observed that PDGF- led to a significant decrease in the expression of ABCA1. Overexpression of ABCA1 strikingly suppressed PDGF-induced ASMC proliferation accompanied by a decrease in the expression of PCAN stimulated by PDGF. Additionally, augmentation of ABCA1 dramatically restrained PDGF-induced migration concomitant with attenuate the accumulation of MMP-2 and MMP-9 in response to PDGF. Furthermore, forced expression of ABCA1 enhanced contractile phenotype markers proteins including α-SMA along with sm-MHC, sm-α-actin, and calponin reduced by PDGF. Meanwhile, introduction of ABCA1 depressed ECM over-deposition induced by PDGF as reflected by a decrease in the expression of ECM protein collagen I and fibronectin. More importantly, addition of ABCA1 effectively suppressed the activity of TLR2/NF-κB signaling as well as diminished the expression of NFATc1 in rat ASMCs after PDGF stimulation. Interestingly, blockage of TLR2/NF-κB signaling effectively inhibited PDGF-induced proliferation and migration, these effects were similar to ABCA1. Taken together, these data implicated that ABCA1 suppressed PDGF-induced proliferation, migration, and contraction in rat ASMCs at least partly through TLR2/NF-κB/NFATc1 signaling, which might offer hope for the future treatment of airway remodeling in asthma.

Matrix Metalloproteinase 9 Facilitates Hepatitis B Virus Replication through Binding with Type I Interferon (IFN) Receptor 1 To Repress IFN/JAK/STAT Signaling.

Hepatitis B virus (HBV) infection may cause acute hepatitis B, chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC). However, the mechanisms by which HBV evades host immunity and maintains chronic infection are largely unknown. Here, we revealed that matrix metalloproteinase 9 (MMP-9) is activated in peripheral blood mononuclear cells (PBMCs) of HBV-infected patients, and HBV stimulates MMP-9 expression in macrophages and PBMCs isolated from healthy individuals. MMP-9 plays important roles in the breakdown of the extracellular matrix and in the facilitation of tumor progression, invasion, metastasis, and angiogenesis. MMP-9 also regulates respiratory syncytial virus (RSV) replication, but the mechanism underlying such regulation is unknown. We further demonstrated that MMP-9 facilitates HBV replication by repressing the interferon (IFN)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, IFN action, STAT1/2 phosphorylation, and IFN-stimulated gene (ISG) expression. Moreover, MMP-9 binds to type I IFN receptor 1 (IFNAR1) and facilitates IFNAR1 phosphorylation, ubiquitination, subcellular distribution, and degradation to interfere with the binding of IFANR1 to IFN-α. Thus, we identified a novel positive-feedback regulation loop between HBV replication and MMP-9 production. On one hand, HBV activates MMP-9 in infected patients and leukocytes. On the other hand, MMP-9 facilitates HBV replication through repressing IFN/JAK/STAT signaling, IFNAR1 function, and IFN-α action. Therefore, HBV may take the advantage of MMP-9 function to establish or maintain chronic infection.IMPORTANCE Hepatitis B virus (HBV) infection may cause chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). However, the mechanisms by which HBV maintains chronic infection are largely unknown. Matrix metalloproteinase 9 (MMP-9) plays important roles in the facilitation of tumor progression, invasion, metastasis, and angiogenesis. However, the effects of MMP-9 on HBV replication and pathogenesis are not known. This study reveals that MMP-9 expression is activated in patients with CHB, and HBV stimulates MMP-9 production in PBMCs and macrophages. More interestingly, MMP-9 in turn promotes HBV replication through suppressing IFN-α action. Moreover, MMP-9 interacts with type I interferon receptor 1 (IFNAR1) to disturb the binding of IFN-α to IFNAR1 and facilitate the phosphorylation, ubiquitination, subcellular distribution, and degradation of IFNAR1. Therefore, these results discover a novel role of MMP-9 in viral replication and reveal a new mechanism by which HBV evades host immunity to maintain persistent infection.

Impact of subsidies on cancer genetic testing uptake in Singapore.

PURPOSE: Previous reports cite high costs of clinical cancer genetic testing as main barriers to patient's willingness to test. We report findings of a pilot study that evaluates how different subsidy schemes impact genetic testing uptake and total cost of cancer management. METHODS: We included all patients who attended the Cancer Genetics Service at the National Cancer Centre Singapore (January 2014-May 2016). Two subsidy schemes, the blanket scheme (100% subsidy to all eligible patients), and the varied scheme (patients received 50%-100% subsidy dependent on financial status) were compared. We estimated total spending on cancer management from government's perspective using a decision model. RESULTS: 445 patients were included. Contrasting against the blanket scheme, the varied scheme observed a higher attendance of patients (34 vs 8 patients per month), of which a higher proportion underwent genetic testing (5% vs 38%), while lowering subsidy spending per person (S$1098 vs S$1161). The varied scheme may potentially save cost by reducing unnecessary cancer surveillance when first-degree relatives uptake rate is above 36%. FINDINGS: Provision of subsidy leads to a considerable increase in genetic testing uptake rate. From the government's perspective, subsidising genetic testing may potentially reduce total costs on cancer management.

Characterization of atrazine binding to dissolved organic matter of soil under different types of land use.

Atrazine is widely used in agriculture. In this study, dissolved organic matter (DOM) from soils under four types of land use (forest (F), meadow (M), cropland (C) and wetland (W)) was used to investigate the binding characteristics of atrazine. Fluorescence excitation-emission matrix-parallel factor (EEM-PARAFAC) analysis, two-dimensional correlation spectroscopy (2D-COS) and Stern-Volmer model were combined to explore the complexation between DOM and atrazine. The EEM-PARAFAC indicated that DOM from different sources had different structures, and humic-like components had more obvious quenching effects than protein-like components. The Stern-Volmer model combined with correlation analysis showed that log K values of PARAFAC components had a significant correlation with the humification of DOM, especially for C3 component, and they were all in the same order as follows: meadow soil (5.68)>wetland soil (5.44)>cropland soil (5.35)>forest soil (5.04). The 2D-COS further confirmed that humic-like components firstly combined with atrazine followed by protein-like components. These findings suggest that DOM components can significantly influence the bioavailability, mobility and migration of atrazine in different land uses.

Let-7i-Induced Atg4B Suppression Is Essential for Autophagy of Placental Trophoblast in Preeclampsia.

Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated. In vitro, let-7i mimics suppressed the autophagic activities in human HTR-8/SVneo trophoblast cell line (HTR-8) and human placental choriocarcinoma cell line JEG-3, whereas let-7i inhibitor enhanced the activities. As a potential target of let-7i, autophagy-related 4B cysteine peptidase (Atg4B) had an increased expression level in SPE. As expected, the increased expression of Atg4B was negatively regulated by let-7i using dual luciferase reporter assay. Furthermore, these trophoblast-like cells transfected with the let-7i mimic or inhibitors resulted in a significant change of Atg4B in both mRNA and protein level. More importantly, Atg4B overexpression could partly reverse let-7i mimic-reduced LC3II/I levels; whereas Atg4B silencing partly attenuated let-7i inhibitor-induced the level of LC3II/I expression. Taken together, these findings suggest that let-7i is able to regulate autophagic activity via regulating Atg4B expression, which might contribute to the pathogenesis of PE. J. Cell. Physiol. 232: 2581-2589, 2017. © 2016 Wiley Periodicals, Inc.

HCV-induced miR-21 contributes to evasion of host immune system by targeting MyD88 and IRAK1.

Upon recognition of viral components by pattern recognition receptors, such as the toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like helicases, cells are activated to produce type I interferon (IFN) and proinflammatory cytokines. These pathways are tightly regulated by the host to prevent an inappropriate cellular response, but viruses can modulate these pathways to proliferate and spread. In this study, we revealed a novel mechanism in which hepatitis C virus (HCV) evades the immune surveillance system to proliferate by activating microRNA-21 (miR-21). We demonstrated that HCV infection upregulates miR-21, which in turn suppresses HCV-triggered type I IFN production, thus promoting HCV replication. Furthermore, we demonstrated that miR-21 targets two important factors in the TLR signaling pathway, myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase 1 (IRAK1), which are involved in HCV-induced type I IFN production. HCV-mediated activation of miR-21 expression requires viral proteins and several signaling components. Moreover, we identified a transcription factor, activating protein-1 (AP-1), which is partly responsible for miR-21 induction in response to HCV infection through PKCε/JNK/c-Jun and PKCα/ERK/c-Fos cascades. Taken together, our results indicate that miR-21 is upregulated during HCV infection and negatively regulates IFN-α signaling through MyD88 and IRAK1 and may be a potential therapeutic target for antiviral intervention.