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1.
J Ethnopharmacol ; 283: 114532, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34416296

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qufeng Zhitong capsule (QFZTC) is a traditional Chinese medicine (TCM) clinically used for treating pain. However, the active ingredients of QFZTC and its pharmacological mechanism in the treatment of neuropathic pain (NP) remain unclear. AIM OF THE STUDY: We aimed to identify the active ingredients of QFZTC and reveal its target genes and underlying mechanism of action in NP. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used to identify the active ingredients of QFZTC. Network pharmacology analysis was conducted to determine the core targets and pathway enrichment of QFZTC. An NP mice model was established through chronic compression injury (CCI) surgery of the sciatic nerve, while von Frey instrumentation and a thermal stimulator were employed to measure the sensitivity of mice to mechanical and thermal stimuli. Immunofluorescence was used to observe the expression of TLR4 and p-P65 in microglia. Western blotting was used to detect the levels of protein expression of Iba-1, TLR4, MyD88, P65, p-P65, and c-Fos, while ELISA kits were used to detect the release of TNF-α, IL-6, and IL-1ß. RESULTS: Seven active ingredients were identified in QFZTC: gallic acid, loganylic acid, syringin, corilagin, loganin, ellagic acid, and osthole. Network analysis identified TLR4, TNF, IL6, IL1ß, and c-Fos as core targets, and Toll-like receptors and NF-κB as core signaling pathways. Treatment with QFZTC significantly relieved mechanical allodynia and thermal hyperalgesia in CCI mice models. CCI induced an increase in the expression of TLR4 and p-P65 in microglia, whereas QFZTC dose-dependently reduced the expression of Iba-1, TLR4, MyD88, and p-P65 in the spinal cord. QFZTC inhibited the expression of the c-Fos pain marker and reduced the expression of the TNF-α, IL-6, and IL-1ß inflammatory factors. CONCLUSION: We combined the active ingredients of QFZTC with network pharmacology research to clarify its biological mechanism in the treatment of NP. We demonstrated that QFZTC reduced NP in mice probably through regulating the spinal microglia via the TLR4/MyD88/NF-κB signaling pathway. Hence, QFZTC could be regarded as a potential drug for relieving NP.

2.
Environ Pollut ; 292(Pt B): 118387, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34673158

RESUMO

Ambient particulate air pollution is a risk factor for cardiovascular and respiratory disease, yet the biological mechanisms underlying this association are not well understood. The current study aimed to investigate the mediation role of microRNAs on the association between personal PM2.5 exposure and blood pressure and lung function. One hundred and twenty adults (60 truck drivers and 60 office workers) aged 18-46 years were assessed on the June 15, 2008 and at follow-up (1- to 2-weeks later). MicroRNAs were extracted from the peripheral blood samples. Compared to truck drivers, there is a significant increase in FEF25-75, FEV1, and FEV1/FVC and a decrease in PM2.5 in office workers (all p < 0.05). According to the Bonferroni corrected threshold p-value < 6.81 × 10-5 (0.05/734) used, personal PM2.5 data showed a significant positive association with miR-644 after the adjustment for age, BMI, smoking status, and habitual alcohol use. The mediation effect of miR-644 on the association between personal PM2.5 exposure and FEF25-75 [B (95%CI) = -1.342 (-2.810, -0.113)], PEF [B (95%CI) = -1.793 (-3.926, -0.195)], and FEV1/FVC [B (95%CI) = -0.119‰ (-0.224‰, -0.026‰)] was significant only for truck drivers after the adjustment for covariates. There were no similar associations with blood pressure. These results demonstrate microRNAs to potentially mediate association of PM2.5 with lung function. Subsequent studies are needed to further elucidate the potential mechanisms of action by which the mediation effect of microRNAs is achieved with this process.

3.
Plant Dis ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726475

RESUMO

Peanut scorch spot caused by Leptosphaerulina arachidicola is one of the most severe leaf diseases of peanut that causes significant yield loss. Here, we report the first high quality genome sequence of L. arachidicola JB313 isolated from an infected peanut leaf in China. The genome size is 47.66 Mb, consisting of 65 scaffolds (N50 length = 1.58 Mb) with a G+C content of 49.05%. The information in this report will provide a reference genome for future studies on peanut scorch spot pathogen in peanut.

4.
Front Pharmacol ; 12: 751667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776969

RESUMO

Angiogenesis is a crucial event in the pathogenesis of rheumatoid arthritis (RA). Arsenic trioxide (ATO, As2O3) has been reported to inhibit synovial angiogenesis via the vascular endothelial growth factor (VEGF)-centered functional module. However, the exact mechanisms of ATO on VEGF modulation remain unclear. Circular RNAs (circRNAs) are emerging as important regulators in RA, and the detailed mechanisms remain largely unknown. Here, we reported a circRNA (circHIPK3), the expression of which was significantly increased in RA fibroblast-like synoviocytes (RA-FLS) after TNF-α induction. Moreover, VEGF content in the supernatants of a RA-FLS and human dermal microvascular endothelial cell (HDMEC) co-culture as well as in RA-FLS co-cultured was significantly elevated in accordance with circHIPK3 levels. This increased VEGF expression may significantly upregulate endothelial tube formation and transwell migration, as well as microvessel sprouting in the ex vivo aortic ring assay. CircHIPK3 was further illustrated to be a sponge for the forkhead box transcription factor O1 (FOXO1)-targeting miR-149-5p, leading to the changing expression of the downstream VEGF. These networked factors mainly form a functional module regulating angiogenesis in RA-FLS, and the expression of this functional module could be significantly downregulated by ATO with a consistently reduced vascularity in vitro. In the collagen-induced arthritis (CIA) mice model, an intra-articular injection of the adeno-associated virus-si-circHIPK3 or ATO was demonstrated to alleviate the synovial VEGF expression and arthritis severity respectively. Thus, we elucidate a previously unknown mechanism between circRNAs and RA, and ATO has a significant protective effect on RA-FLS and CIA synovium via its inhibition of the angiogenic functional module of circHIPK3/miR-149-5p/FOXO1/VEGF, suggesting great potential for the combination therapy of ATO with circHIPK3 silencing.

5.
Waste Manag ; 137: 110-120, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34752944

RESUMO

To promote the use of recycled waste materials as an industrial feedstock, this study examined the preparation of carbon black (CB) by partial oxidation of a spent tyre pyrolysis oil using a drop tube furnace. The effect of reaction temperature, the residence time of gas in the reactor and inlet gas oxygen concentration on the yield and properties of the CB were evaluated. The surface chemistry, chemical composition, morphological and thermal properties of the CB samples were characterised using XPS, EA, TEM, BET, and TGA, respectively. The CB yield increased with increasing reaction temperature but decreased as the residence time or oxygen concentration increases. The CB primarily consisted of C (90.5-98.6%) and O (0.9-7.4%), with small traces of S (<1%), Si (<1%) and H (<2%). Hydroxyl, carbonyl, and carboxyl are the key functional groups found on the CB surface, with the hydroxyl groups being dominant. The CB were highly graphitic with a lattice spacing in the range of 0.338-0.350 nm and had BET surface areas of 4-22 m2g-1. The mean primary particle size ranged from 92 to 176 nm and decreased with increasing reaction temperature and oxygen concentration. The CB aggregate configuration became more complex with increasing reaction temperature, residence time and oxygen concentration. The results were not only comparable with commercial CB products from fossil fuel feedstocks but are expected to provide the needed motivation to move towards circular economy strategies, which have positive impacts from a sustainability perspective.

6.
Math Biosci Eng ; 18(6): 8123-8148, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34814292

RESUMO

Pork makes up the highest proportion of household expenditure on meat in China and supply and demand have been basically stable in the past decade. However, the catastrophic outbreak of African swine fever (ASF) in August 2018 disrupted the balance and reduced the national herd by half within six months. The consequence was a gross lack of supply to the market and consumer demand was unable to be met. Accordingly, live pig prices rose sharply from 2019. In order to assess the influence of ASF on the price of the live pigs, we use a price function to characterize the relationship between price of the live pigs and the nation's pig stock, and then establish a time delay ASF epidemic dynamical model with the price function. By analyzing the dynamical behaviors of the model, we calculate the basic reproductive number, discuss the stability of equilibrium, and obtain the critical conditions for Hopf bifurcation. The model reasonableness is confirmed by carrying out data fitting and parameter estimation based on price data of the live pigs, the pig stock data and the outbreak data of ASF. By performing sensitivity analysis, we intuitively show the impact of ASF on the price of live pigs and the pig stocks, and assess the key factors affecting the outbreak of ASF. The conclusion is drawn that, with the control measures adopted by related government department in China, the basic reproductive number ($ R_0 = 0.6005 $) means that the ASF epidemic has been controlled. Moreover, the price of the live pig increases linearly with $ R_0 $, while the effect of the number of infected pigs on the subsequent price is non-linear related. Our findings suggest that society and the government should pay more attention to the prevention of animal disease epidemics.

8.
Front Pharmacol ; 12: 764602, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803708

RESUMO

Alhagi pseudalhagi Desv. Extract (APE) is the major active fraction extracted from the aerial part of Alhagi pseudalhagi Desv. In view of its application in Uyghur medicine, it may be beneficial for the treatment of ulcerative colitis (UC). The aim of the present study was to investigate the possible beneficial effects of APE on UC mice and detect the possible mechanisms underlying these effects. Methods: An acute UC model was established in mice using dextran sulfate sodium. Sixty mice were randomly divided into six groups: normal, UC model, sulfasalazine (200 mg/kg), high-dose APE (APE-H, 2.82 g/kg), middle-dose APE (APE-M, 1.41 g/kg), and low-dose APE (APE-L, 0.70 g/kg) groups. Drugs were administered by gavage for 10 days after the induction of colitis. Serum and colon tissue samples were collected from the mice during the experiment, and survival signs, body weight changes, disease activity index (DAI), colon length, and colon wet weight in mice were determined after the treatment. UC-induced damage, including inflammation and ulceration of colon mucosa, were observed by the naked eye as well as using hematoxylin and eosin staining (H&E) and scanning electron microscopy and scored according to Wallace and Keean's criteria. We measured the levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-10 in the serum and colon tissues using ELISA. Additionally, the relative protein levels of toll-like receptor 4 (TLR4), nuclear factor-kappa B p65 (NF-κB p65), phosphorylated NF-κB p65 at Ser536 (p-p65 Ser536), inhibitor kappa B-kinase ß (IK-Kß), and phosphorylated IK-Kß (Ser176/180) (p-IK-Kß) in colonic mucosal epithelial tissues were detected using western blotting. The main functional components of APE were analyzed and confirmed by UPLC-MS/MS. Results: APE treatment repaired the UC-induced colon mucosa injury, reduced the weight loss, attenuated DAI, colon macroscopic damage index, and histological inflammation, and significantly downregulated the levels of inflammatory markers, including TNF-α, IL-1ß, and IL-6, in the serum and colon tissues. Additionally, APE treatment reduced the levels of TLR4 and phosphorylation of p-NF-κB and p-IK-Kß. The main components of APE are taxifolin, 3,5-dihydroxy-2-(4-hydroxyphenyl)-7-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] oxychromen-4-one, hyperoside, rutin, kaempferol, isorhamnetin, 7,8-dihydroxyflavone, and kaempferide. Conclusions: To the best of our knowledge, the present study is first to demonstrate that APE exerts a protective effect against intestinal inflammation in UC by affecting TLR4-dependent NF-κB signaling pathways.

9.
Ann Transl Med ; 9(19): 1497, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34805359

RESUMO

Background: Long-term exposure to ultraviolet (UV) radiation can cause cutaneous squamous cell carcinoma (cSCC), which is one of the most common malignant cancers worldwide. Actinic keratosis (AK) is generally considered a precancerous lesion of cSCC. However, the pathogenesis and oncogenic processes of AK and cSCC remain elusive, especially in the context of photodamage. Methods: In this study, transcriptome sequencing was performed on AK, cSCC, normal sun-exposed skin (NES) tissues, and normal non-sun-exposed skin (NNS) from 24 individuals. Bioinformatics analysis to identify the differentially expressed genes (DEGs) of 4 groups, and potential key genes of cSCC were validated by real-time quantitative reverse transcription PCR (qRT-PCR). Results: A total of 46,930 genes were differentially expressed in the 4 groups, including 127 genes that were differentially expressed between NES and NNS, 420 DEGs in AK compared to NES, 1,658 DEGs in cSCC compared to NES, and 1,389 DEGs in cSCC compared to AK. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that the DEGs are involved in multiple pathways, including extracellular matrix (ECM)-receptor interaction, immune, inflammatory, microbial infection, and other related pathways. Finally, 5 new genes (HEPHL1, FBN2, SULF1, SULF2, and TCN1) were confirmed significantly upregulated in cSCC. Conclusions: Using transcriptome sequencing and integrated bioinformatical analysis, we have identified key DEGs and pathways in cSCC, which could improve our understanding of the cause and underlying molecular events of AK and cSCC. HEPHL1, FBN2, SULF1, SULF2, and TCN1 may be novel potential biomarkers and therapeutic targets of cSCC.

11.
Genes Environ ; 43(1): 49, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34742356

RESUMO

BACKGROUND: Increasing evidence suggested N6-methyladenosine (m6A) modification is crucial for male germline development. However, m6A modification of lncRNAs gains a little attention in amphibians in recent years. Xenopus laevis (X. laevis) was chosen to be an ideal model organism for testing environmental endocrine disrupting chemicals (EDCs) exposure and resultant effects. Atrazine (AZ) as an endocrine disrupt can effect development of testis in amphibians. Our previous study revealed that m6A is a highly conserved modification across the species. RESULTS: The results of m6A sequences showed that m6A-methylated lncRNAs enriched in intergenic region in testes of X. laevis. We further examined the differential expression of lncRNAs m6A sites in testes of AZ-exposed and compared with that in animals from control group. The results indicated that up to 198 differentially methylated m6A sites were detected within 188 lncRNAs, in which 89 significantly up-methylated sites and 109 significantly down-methylated sites. Data from KEGG pathway analysis indicated that AZ-affected lncRNAs m6A sites were mainly involved in 10 pathways in which 3 mutual pathways were found in the result of differentially m6A-methylated mRNAs. CONCLUSIONS: These findings suggested that differentially m6A-methylated lncRNAs and these 3 pathways may act on regulatory roles in abnormal testis development of AZ-exposed X. laevis. This study for the first time provides insights into the profile of lncRNAs m6A modifications in amphibian species.

12.
Int J Cardiol ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34774886

RESUMO

BACKGROUND: Selecting best candidates for prolonged poststroke cardiac monitoring in acute ischemic stroke (AIS) patients is still challenging. We aimed to develop a machine learning (ML) model to select AIS patients at high risk of poststroke atrial fibrillation (AF) for prolonged cardiac monitoring and then to compare ML model with traditional risk scores and classic statistical logistic regression (classic-LR) model. METHODS: AIS patients from July 2012 to September 2020 across Nanjing First Hospital were collected. We performed the LASSO regression for selecting the critical features and built five ML models to assess the risk of poststroke AF. The SHAP and partial dependence plot (PDP) method were introduced to interpret the optimal model. We also compared ML model with CHADS2 score, CHA2DS2-VASc score, AS5F score, HAVOC score, and classic-LR model. RESULTS: A total of 3929 AIS patients were included. Among the five ML models, deep neural network (DNN) was the model with best performance. It also exhibited superior performance compared with CHADS2 score, CHA2DS2-VASc score, AS5F score, HAVOC score and classic-LR model. The results of SHAP and PDP method revealed age, cardioembolic stroke, large-artery atherosclerosis stroke, and NIHSS score at admission were the top four important features and revealed the DNN model had good interpretability and reliability. CONCLUSION: The DNN model achieved best performance and improved prediction performance compared with traditional risk scores and classic-LR model. The DNN model can be applied to identify AIS patients at high risk of poststroke AF as best candidates for prolonged poststroke cardiac monitoring.

13.
Appl Intell (Dordr) ; : 1-12, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34764586

RESUMO

This paper proposes a susceptible exposed infectious recovered model (SEIR) with isolation measures to evaluate the COVID-19 epidemic based on the prevention and control policy implemented by the Chinese government on February 23, 2020. According to the Chinese government's immediate isolation and centralized diagnosis of confirmed cases, and the adoption of epidemic tracking measures on patients to prevent further spread of the epidemic, we divide the population into susceptible, exposed, infectious, quarantine, confirmed and recovered. This paper proposes an SEIR model with isolation measures that simultaneously investigates the infectivity of the incubation period, reflects prevention and control measures and calculates the basic reproduction number of the model. According to the data released by the National Health Commission of the People's Republic of China, we estimated the parameters of the model and compared the simulation results of the model with actual data. We have considered the trend of the epidemic under different incubation periods of infectious capacity. When the incubation period is not contagious, the peak number of confirmed in the model is 33,870; and when the infectious capacity is 0.1 times the infectious capacity in the infectious period, the peak number of confirmed in the model is 57,950; when the infectious capacity is doubled, the peak number of confirmed will reach 109,300. Moreover, by changing the contact rate in the model, we found that as the intensity of prevention and control measures increase, the peak of the epidemic will come earlier, and the peak number of confirmed will also be significantly reduced. Under extremely strict prevention and control measures, the peak number of confirmed cases has dropped by nearly 50%. In addition, we use the EEMD method to decompose the time series data of the epidemic, and then combine the LSTM model to predict the trend of the epidemic. Compared with the method of directly using LSTM for prediction, more detailed information can be obtained.

14.
Front Psychol ; 12: 721783, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764910

RESUMO

The present event-related potential (ERP) study explored whether masked emotion-laden words could facilitate the processing of both emotion-label words and emotion-laden words in a valence judgment task. The results revealed that emotion-laden words as primes failed to influence target emotion-label word processing, whereas emotion-laden words facilitated target emotion-laden words in the congruent condition. Specifically, decreased late positivity complex (LPC) was elicited by emotion-laden words primed by emotion-laden words of the same valence than those primed by emotion-laden words of different valence. Nevertheless, no difference was observed for emotion-label words as targets. These findings supported the mediated account that claimed emotion-laden words engendered emotion via the mediation of emotion-label words and hypothesized that emotion-laden words could not prime emotion-label words in the masked priming paradigm. Moreover, this study provided additional evidence showing the distinction between emotion-laden words and emotion-label words.

15.
Biol Trace Elem Res ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34775542

RESUMO

Previous studies evaluating the role of magnesium supplementation as a preventative strategy for preeclampsia showed inconsistent results. We performed a meta-analysis or randomized controlled trials (RCTs) to evaluate the influence of oral magnesium supplementation on the incidence of preeclampsia in pregnant women. Relevant studies were obtained by search of Medline, Embase, and Cochrane's Library databases. A random effects model was used to pool the results. Influences of study characteristics of the outcome were evaluated by predefined subgroup analyses. Seven RCTs with 2653 pregnant women were included. Pooled results showed that oral magnesium supplementation during pregnancy significantly reduced the risk of preeclampsia (risk ratio [RR]: 0.76, 95% confidence interval [CI]: 0.59 to 0.98, P = 0.04) with no significant heterogeneity (P for Cochrane's Q test = 0.42, I2 = 1%). The result was not significant for the outcome of severe preeclampsia (RR: 0.54, 95% CI: 0.18 to 1.69, P = 0.29; I2 = 0%), although only two studies were available. Subgroup analysis showed that oral magnesium supplementation did not significantly reduce the risk of preeclampsia in normal pregnant women (RR: 0.91, 95% CI: 0.67 to 1.25, P = 0.57), but the preventative effect was significant in studies with normal and high-risk pregnant women (RR: 0.54, 95% CI: 0.35 to 0.83, P = 0.005; P for subgroup difference = 0.04). In conclusion, oral supplementation of magnesium may reduce the risk of preeclampsia, which may be more remarkable in high-risk pregnant women.

16.
Cell Cycle ; : 1-15, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779712

RESUMO

Previously our results showed miR-222-3p was significantly downregulated in retinoic acid-induced neural tube defect (NTD) mouse model through transcriptome. Down-regulation of miR-222-3p may be a causative biomarker in NTDs. In this study, RNA was extracted from mouse embryos at E8.5, E9.5 and E10.5, and the expression level of miR-222-3p was measured by quantitative real-time PCR analysis. The preliminary mechanism of miR-222-3p in NTDs involved in cell proliferation, apoptosis and migration was investigated in mouse HT-22 cell line. The expression of miR-222-3p was significantly decreased at E8.5, E9.5 and E10.5 developed in mouse embryos which were consistent with our transcriptome sequencing. Suppression of miR-222-3p in HT-22 cells resulted in the inhibition of cell proliferation and migration, cell cycle and apoptosis. Moreover, DNA damage transcript 4 (Ddit4) was identified as a direct and functional target of miR-222-3p. miR-222-3p is negatively regulated by Ddit4. The mutation of binding site of Ddit4 3'UTR abrogated the responsiveness of luciferase reporters to miR-222-3p and showed that Ddit4 expression partially attenuated the function of miR-222-3p. We preliminatively confirmed that low expression of miR-222-3p has reduced the expression of ß-catenin, TCF4 and other related genes in the Wnt/ß-catenin signaling pathway.Collectively, these results demonstrated that miR-222-3p regulates the Wnt/ß-catenin signaling pathway through Ddit4 inhibition in HT-22 cells, resulted in cell proliferation and apoptosis imbalance, and thus led to neural tube defects.

17.
Front Endocrinol (Lausanne) ; 12: 741764, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745009

RESUMO

PCOS has a wide range of negative impacts on women's health and is one of the most frequent reproductive systemic endocrine disorders. PCOS has complex characteristics and symptom heterogeneity due to the several pathways that are involved in the infection and the absence of a comm14on cause. A recent study has shown that the main etiology and endocrine aspects of PCOS are the increased level of androgen, which is also known as "hyperandrogenemia (HA)" and secondly the "insulin resistance (IR)". The major underlying cause of the polycystic ovary is these two IR and HA, by initiating the disease and its severity or duration. As a consequence, study on Pathogenesis is crucial to understand the effect of "HA" and "IR" on the pathophysiology of numerous symptoms linked to PCOS. A deep understanding of the pattern of the growth in PCOS for HA and IR can help ameliorate the condition, along with adjustments in nutrition and life, as well as the discovery of new medicinal products. However, further research is required to clarify the mutual role of IR and HA on PCOS development.

18.
Cell Rep ; 37(6): 109977, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34758308

RESUMO

Tumor necrosis factor (TNF) is a key driver of several inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, in which affected tissues show an interferon-stimulated gene signature. Here, we demonstrate that TNF triggers a type-I interferon response that is dependent on the cyclic guanosine monophosphate-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. We show that TNF inhibits PINK1-mediated mitophagy and leads to altered mitochondrial function and to an increase in cytosolic mtDNA levels. Using cGAS-chromatin immunoprecipitation (ChIP), we demonstrate that cytosolic mtDNA binds to cGAS after TNF treatment. Furthermore, TNF induces a cGAS-STING-dependent transcriptional response that mimics that of macrophages from rheumatoid arthritis patients. Finally, in an inflammatory arthritis mouse model, cGAS deficiency blocked interferon responses and reduced inflammatory cell infiltration and joint swelling. These findings elucidate a molecular mechanism linking TNF to type-I interferon signaling and suggest a potential benefit for therapeutic targeting of cGAS/STING in TNF-driven diseases.

19.
Cancer Biol Med ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34606182

RESUMO

OBJECTIVE: There are many hereditary breast cancer patients in China, and multigene panel testing has been a new paradigm of genetic testing for these patients and their relatives. However, the magnitude of breast cancer risks related to multiple breast cancer susceptibility genes are largely unknown in Chinese women. METHODS: We screened pathogenic variants in 15 established or potential breast cancer susceptibility genes from 8,067 consecutive Chinese female breast cancer patients and 13,129 Chinese cancer-free female controls. These breast cancer patients were unselected for age at diagnosis or family history. RESULTS: We found that pathogenic variants in TP53 [odds ratio (OR): 16.9, 95% confidence interval (CI): 5.2-55.2]; BRCA2 (OR: 10.4, 95% CI: 7.6-14.2); BRCA1 (OR: 9.7, 95% CI: 6.3-14.8); and PALB2 (OR: 5.2, 95% CI: 3.0-8.8) were associated with a high risk of breast cancer. ATM, BARD1, CHEK2, and RAD51D were associated with a moderate risk of breast cancer with ORs ranging from 2-fold to 4-fold. In contrast, pathogenic variants of NBN, RAD50, BRIP1, and RAD51C were not associated with increased risk of breast cancer in Chinese women. The pathogenic variants of PTEN, CDH1, and STK11 were very rare, so they had a limited contribution to Chinese breast cancer. Patients with pathogenic variants of TP53, BRCA1, BRCA2, and PALB2 more often had early-onset breast cancer, bilateral breast cancer, and a family history of breast cancer and/or any cancer. CONCLUSIONS: This study provided breast cancer risk assessment data for multiple genes in Chinese women, which is useful for genetic testing and clinical management of Chinese hereditary breast cancer.

20.
Front Bioeng Biotechnol ; 9: 730925, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604188

RESUMO

Chemotherapy for the treatment of nasopharyngeal carcinoma (NPC) is usually associated with many side effects; therefore, its treatment options have not yet been completely resolved. Improving distribution to the targeted tumor region and enhancing the cellular uptake of drugs can efficiently alleviate the above adverse medical effects. Near-infrared (NIR) laser light-mediated photothermal therapy (PTT) and photodynamic therapy (PDT) are promising strategies for cancer treatment. In the present study, we developed an efficient multifunctional nanocluster with enhanced targeting and aggregation efficiency for PTT and PDT that is composed of a biocompatible folic acid (FA), indocyanine green (ICG) and 2-cyanobenzothiazole (CBT)-functionalized peptide labeled with an aldehyde sodium alginate-modified magnetic iron oxide nanoparticle (ASA-MNP)-based nanocarrier. FA can bind to folate receptors on cancer cell membranes to enhance nanocluster uptake. CBT-modified peptide can react with glutathione (GSH), which is typically present at higher levels in cancer cells, to form intracellular aggregates and increase the local concentration of the nanodrug. In in vitro studies, these nanodrugs displayed the desired uptake capacity by NPC cells and the ability to suppress the growth of cancer cells under laser irradiation. Animal studies validated that these nanodrugs are safe and nontoxic, efficiently accumulate in NPC tumor sites following injection via the caudal vein, and shows superior inhibition of tumor growth in a tumor-bearing mouse model upon near-infrared laser irradiation. The results indicate the potential application of the multifunctional nanoparticles (NPs), which can be used as a new method for the treatment of folate receptor-positive NPC.

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