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Tuberculosis (TB) is a major global health threat despite its virtual elimination in developed countries. Issues such as drug accessibility, emergence of multidrug-resistant strains, and limitations of the current BCG vaccine highlight the urgent need for more effective TB control measures. This study constructed BCG strains overexpressing Rv1002c and found that the rBCG-Rv1002c strain secreted more glycosylated proteins, significantly enhancing macrophage activation and immune protection against Mycobacterium tuberculosis (M. tb). These results indicate that Rv1002c overexpression promotes elevated levels of O-glycosylation in BCG bacteriophages, enhancing their phagocytic and antigenic presentation functions. Moreover, rBCG-Rv1002c significantly upregulated immune regulatory molecules on the macrophage surface, activated the NF-κB pathway, and facilitated the release of large amounts of NO and H2O2, thereby enhancing bacterial control. In mice, rBCG-Rv1002c immunization induced greater innate and adaptive immune responses, including increased production of multifunctional and long-term memory T cells. Furthermore, rBCG-Rv1002c-immunized mice exhibited reduced lung bacterial load and histological damage upon M. tb infection. This result shows that it has the potential to be an excellent candidate for a preventive vaccine against TB.
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BACKGROUND: There is no consensus regarding age-related facial anatomical changes. In this study, aging-related changes in soft and hard cheek tissues were quantitatively analyzed using computed tomography. METHODS: We performed a retrospective study of 90 Asian females who underwent facial computed tomography. Three-dimensional model of soft tissue in apple zone was reconstructed, and age-related changes in fat volume and pyriform aperture area were quantified using Mimics software. RESULTS: The apple zone is an aesthetic unit of the infraorbital cheek, with soft tissue located between the lateral wall of the pyriform aperture and the zygomatic major muscle. The superficial fat volume significantly decreased with age (P < 0.05). In contrast, a significant decrease in total fat volume was only observed between the young and old groups (P < 0.05). In linear regression modeling, age was a significant predictor of pyriform aperture area (R2 = 0.194, P < 0.001). CONCLUSIONS: These results suggest that superficial fat atrophy and bone remodeling in the cheek with age, and both of which combine to contribute to an aging facial appearance. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Subject(s)
Cheek , Tomography, X-Ray Computed , Humans , Cheek/anatomy & histology , Cheek/diagnostic imaging , Female , Retrospective Studies , Middle Aged , Tomography, X-Ray Computed/methods , Adult , Young Adult , Aging/physiology , Age Factors , Aged , Imaging, Three-Dimensional , Asian People , Cohort StudiesABSTRACT
The tanning hormone, Bursicon, is a neuropeptide secreted by the insect nervous system that functions as a heterodimer composed of Burs-α and Burs-ß subunits. It plays a critical role in the processes of cuticle tanning and wing expansion in insects. In this study, we successfully identified the AcBurs-α and AcBurs-ß genes in Aphis citricidus. The open reading frames of AcBurs-α and AcBurs-ß were 480 and 417 bp in length, respectively. Both AcBurs-α and AcBurs-ß exhibited 11 conserved cysteine residues. AcBurs-α and AcBurs-ß were expressed during all developmental stages of A. citricidus and showed high expression levels in the winged aphids. To investigate the potential role of AcBurs-α and AcBurs-ß in wing development, we employed RNA interference (RNAi) techniques. With the efficient silencing of AcBurs-α (44.90%) and AcBurs-ß (52.31%), malformed wings were induced in aphids. The proportions of malformed wings were 22.50%, 25.84%, and 38.34% in dsAcBurs-α-, dsAcBur-ß-, and dsAcBurs-α + dsAcBur-ß-treated groups, respectively. Moreover, feeding protein kinase A inhibitors (H-89) also increased the proportion of malformed wings to 30.00%. Feeding both double-stranded RNA and inhibitors (H-89) significantly downregulated the wing development-related genes nubbin, vestigial, notch and spalt major. Silence of vestigial through RNAi also led to malformed wings. Meanwhile, the exogenous application of 3 hormones that influence wing development did not affect the expression level of AcBursicon genes. These findings indicate that AcBursicon genes plays a crucial role in wing development in A. citricidus; therefore, it represents a potential molecular target for the control of this pest through RNAi-based approaches.
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Messenger RNA (mRNA)-based therapeutic agents have demonstrated significant potential in recent times, particularly in the context of the COVID-19 pandemic outbreak. As a promising prophylactic and therapeutic strategy, polypeptide-based mRNA delivery systems attract significant interest because of their low cost, simple preparation, tuneable sizes and morphology, convenient large-scale production, biocompatibility, and biodegradability. In this review, we begin with a brief discussion of the synthesis of polypeptides, followed by a review of commonly used polypeptides in mRNA delivery, including classical polypeptides and cell-penetrating peptides. Then, the challenges against mRNA delivery, including extracellular, intracellular, and clinical barriers, are discussed in detail. Finally, we highlight a range of strategies for polypeptide-based mRNA delivery, offering valuable insights into the advancement of polypeptide-based mRNA carrier development.
Subject(s)
Cell-Penetrating Peptides , Pandemics , Humans , RNA, Messenger/geneticsABSTRACT
BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a unique, rarely metastatic tumor composed of myofibroblasts and fibrous spindle cells with inflammatory cell infiltration that can affect any organ in the human body. By reviewing the relevant literature on PubMed, we found that this is the first case report of IMT with both gastric and cardiac involvement. CASE PRESENTATION: A 57-year-old male patient was admitted to the hospital with complaints of malaise, poor appetite, and epigastric pain with black stools. We found a mass in the patient's stomach and left atrium by contrast-enhanced computed tomography, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography, and other tests. The patient underwent laparoscopic Billroth II subtotal gastrectomy and Braun's gastrointestinal reconstruction under general anesthesia. On the 46th day following stomach surgery, the cardiac tumor was removed under general anesthesia. The patient has treated with doxorubicin 70 mg of D1 chemotherapy two months after cardiac surgery. Postoperative pathological immunohistochemistry of the mass confirmed the diagnosis of an IMT. His review three months after the cardiac surgery suggested the progression of the left atrial mass, but he declined further treatment and finally died one month after the review. CONCLUSIONS: As a unique class of tumors that rarely metastasize, IMTs have an unknown etiology and pathogenesis, and distant metastasis is primarily observed in patients with negative activin receptor-like kinase (ALK) expression. The preferred treatment for IMT is complete surgical resection, and the effectiveness of adjuvant therapy for patients with distant metastases is still being determined. The clinical presentation of IMT lacks specificity and is often related to the location of tumor growth, which poses a diagnostic challenge. Pathological immunohistochemistry is the only way to confirm the diagnosis at present. Our case report reminds clinicians that a category of ALK-negative IMT with a tendency toward distant metastasis should not be ignored.
Subject(s)
Heart Neoplasms , Laparoscopy , Male , Humans , Middle Aged , Anaplastic Lymphoma Kinase , Stomach , Heart Neoplasms/diagnosis , Heart Neoplasms/surgeryABSTRACT
Recently, flexible temperature sensors have attracted significant interest due to their wide-ranging applications in areas such as biomedical monitoring, environmental monitoring, electronic skin, and intelligent robots. However, a combination of high sensitivity and high resolution remains a critical challenge. These properties depend on the synthesis techniques of the sensitive materials. In this work, we use a laser irradiation method to prepare a silver nanoparticle-modified carbon nanotube (Ag-MWCNT) which is further mixed with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS). The developed temperature sensor exhibited a high sensitivity of -0.45% °C-1 and linearity with an R2 value of 0.998 in the temperature range of 25-80 °C. Additionally, the sensor demonstrated remarkable repeatability, making it suitable for real-time temperature monitoring of the human body and environment. This temperature sensor is successfully demonstrated in practical applications such as monitoring the temperature of various parts of the human body and sensing the spatial temperature. These demonstrations highlight their significant potential in electronic skin and other related fields.
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A grain-oriented steel containing 6.5% Si, characterized by a notable Goss texture, was effectively manufactured through the rolling technique, incorporating both intrinsic inhibitors and additional inhibitors. This investigation focuses on tracking the development of texture and magnetic properties during the manufacturing process and delineates the mechanism underlying secondary recrystallization. The empirical findings clearly demonstrated the significant influence of nitriding duration and quantity on the secondary recrystallization process. In instances where additional nitrogen is absent, the intrinsic inhibitors alone do not lead to secondary recrystallization. However, when the nitriding duration is 90 s and the nitriding amount is 185 ppm, a complete secondary recrystallization structure with a strong Goss texture enables the finished products have excellent magnetic properties. The preferential growth of Goss grains is mainly governed by the enhanced mobility of high-energy (HE) grain boundaries. With the increase in annealing temperature, the occurrence of 20°-45° HE grain boundaries with Goss grains becomes more progressively frequent. At the secondary recrystallization temperature of 1000 °C, the frequency of 20°-45° HE grain boundaries with Goss grains reaches 62.7%, providing favorable conditions for the abnormal growth of Goss grains. This results in a secondary recrystallization structure predominantly characterized by a strong Goss texture. In light of these observations, the present study provides fundamental theoretical insights and serves as a valuable procedural guideline for the industrial manufacturing of 6.5% Si grain-oriented electrical steels.
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INTRODUCTION: Meta-analysis of the results of transanal total mesorectal excision (taTME) and laparoscopic TME (laTME) regarding perioperative and oncological outcomes have been conducted. Due to the lack of high-quality randomized controlled trials (RCTs) and prospective studies in the included literature, the conclusions are unreliable. This study included RCTs and prospective studies for analysis to obtain more reliable conclusions. MATERIALS AND METHODS: Systematic searches of the PubMed, Embase, and Cochrane Library databases were conducted up to June 2023. To assess the quality, the Cochrane quality assessment tool and the Newcastle-Ottawa Scale were employed. The perioperative and oncological outcomes were then analyzed. The I2 statistic was used to evaluate statistical heterogeneity and sensitivity analyses was conducted. RESULTS: A total of 22 studies, comprising 5056 patients, were included in the analysis, of which 6 were RCTs and 16 were prospective studies. The conversion rate in the taTME group was significantly lower than that in the laTME group (OR 0.14, 95% CI 0.09 to 0.22, P < 0.01), and the circumferential resection margin (CRM) was longer (MD 0.99 mm, 95% CI 0.66 to 1.32 mm, P < 0.01), with a lower rate of positive CRM involvement (OR 0.68, 95% CI 0.47 to 0.97, P = 0.03). No statistically significant differences were found in terms of the operation time, intraoperative blood loss, complications, anastomotic leakage, uroschesis, obstruction, secondary operation, hospital stay, urethral injury, readmission, mortality rate within 30 days, mesorectal resection quality, number of harvested lymph nodes, distal resection margin (DRM), positive DRM, local recurrence, and distance recurrence (P > 0.05). CONCLUSION: According to the findings of this meta-analysis, which is based on RCTs and prospective studies, taTME appears to have an advantage over laTME in terms of conversion rate and CRM involvement.
Subject(s)
Laparoscopy , Rectal Neoplasms , Transanal Endoscopic Surgery , Humans , Prospective Studies , Margins of Excision , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Treatment Outcome , Transanal Endoscopic Surgery/methods , Randomized Controlled Trials as Topic , Rectal Neoplasms/pathology , Laparoscopy/methods , Rectum/surgeryABSTRACT
OBJECTIVE: The study was conducted to screen differentially expressed miRNAs in sows at early pregnancy by high-throughput sequencing and explore its mechanism of action on embryo implantation. METHODS: The blood serum of pregnant and non-pregnant Landrace×Yorkshire sows were collected 14 days after artificial insemination, and exosomal miRNAs were purified for high throughput miRNA sequencing. The expression patterns of 10 differentially expressed (DE) miRNAs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The qRT-PCR quantified the abundance of serum exosomal miR-192 in pregnant and control sows, and the diagnostic power was assessed by receiver operating characteristic (ROC) analysis. The target genes of DE miRNAs were predicted with bioinformatics software, and the functional and pathway enrichment analysis was performed on gene ontology and the Kyoto encyclopedia of genes and genomes terms. Furthermore, a luciferase reporter system was used to identify the target relation between miR-192 and integrin alpha 4 (ITGA4), a gene influencing embryo implantation in pigs. Finally, the expression levels of miRNAs and the target gene ITGA4 were analyzed by qRT-PCR, and western blot, with the proliferation of BeWo cells detected by cell counting kit-8 (CCK-8). RESULTS: A total of 221 known miRNAs were detected in the libraries of the pregnant and non-pregnant sows, of which 55 were up-regulated and 67 were down-regulated in the pregnant individuals compared with the non-pregnant controls. From these, the expression patterns of 10 DE miRNAs were validated. The qRT-PCR analysis further confirmed a significantly higher expression of miR-192 in the serum exosomes extracted from pregnant sows, when compared to controls. The ROC analysis revealed that miR-192 provided excellent diagnostic accuracy for pregnancy (area under the ROC curve [AUC] = 0.843; p>0.001). The dual-luciferase reporter assay indicated that miR-192 directly targeted ITGA4. The protein expression of ITGA4 was reduced in cells that overexpressed miR-192. Overexpression of miR-192 resulted in the decreased proliferation of BeWo cells and regulated the expression of cell cycle-related genes. CONCLUSION: Serum exosomal miR-192 could serve as a potential biomarker for early pregnancy in pigs. miR-192 targeted ITGA4 gene directly, and miR-192 can regulate cellular proliferation.
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INTRODUCTION: MicroRNAs (miRNAs)-a class of small endogenous non-coding RNAs-are widely involved in post-transcriptional gene regulation of numerous physiological processes. High-throughput sequencing revealed that the miR-192 expression level appeared to be significantly higher in the blood exosomes of sows at early gestation than that in non-pregnant sows. Furthermore, miR-192 was hypothesized to have a regulatory role in embryo implantation; however, the target genes involved in exerting the regulatory function of miR-192 required further elucidation. METHODS: In the present study, potential target genes of miR-192 in porcine endometrial epithelial cells (PEECs) were identified through biotin-labeled miRNA pull-down; functional and pathway enrichment analysis was performed via gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Bioinformatic analyses were concurrently used to predict the potential target genes associated with sow embryo implantation. In addition, double luciferase reporter vectors, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and Western blot were performed to verify the targeting and regulatory roles of the abovementioned target genes. RESULTS: A total of 1688 differentially expressed mRNAs were identified via miRNA pull-down. Through RT-qPCR, the accuracy of the sequencing data was verified. In the bioinformatics analysis, potential target genes of miR-192 appeared to form a dense inter-regulatory network and regulated multiple signaling pathways, such as metabolic pathways and the PI3K-Akt, MAPKs, and mTOR signaling pathways, that are relevant to the mammalian embryo implantation process. In addition, CSK (C-terminal Src kinase) and YY1 (Yin-Yang-1) were predicted to be potential candidates, and we validated that miR-192 directly targets and suppresses the expression of the CSK and YY1 genes. CONCLUSION: We screened 1688 potential target genes of miR-192 were screened, and CSK and YY1 were identified as miR-192 target genes. The outcomes of the present study provide novel insights into the regulatory mechanism of porcine embryo implantation and the identification of miRNA target genes.
Subject(s)
Endometrium , MicroRNAs , Animals , Female , Epithelial Cells/metabolism , Gene Expression Profiling , Gene Regulatory Networks , Mammals/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/metabolism , RNA, Messenger/genetics , Signal Transduction/genetics , Swine/genetics , Endometrium/metabolismABSTRACT
The relationship between plasma EBV-DNA load (PEDL) and Epstein-Barr virus (EBV)-encoded small RNA (EBER) during the early treatment of lymphoma remains unclear. We explored discrepancies in PEDL and variables associated with EBER and evaluated the consistency between EBER and qualitative analysis of PEDL (qPEDL). Serial measurements of PEDL were performed to determine the dynamic changes of PEDL in early treatment of lymphoma. As a result, the median PEDL of non-Hodgkin's lymphoma NKT cell subtype (NHL-NKT) was higher than that of non-Hodgkin's lymphoma B cell subtype (NHL-B), the median PEDL of extranodal NK/T cell lymphoma (ENKTCL) was higher than that of diffuse large B cell lymphoma (DLBCL), and the median PEDL of EBER positive was higher than that of EBER negative. Age, Ki-67 ⧠80%, Bcl-2 ⧠80%, p53, and qPEDL were related to EBER. The PEDL could distinguish NHL-B, DLBCL, NHL-NKT, and ENKTCL from other lymphoma subtypes. EBER-positive patients spent more time with viral "turn negative (TN)" and "continuous positive (CP)" and less time with viral "continuous negative (CN)." The median PEDL of CP was higher than that of TN. In conclusion, although EBER affects the levels of PEDL in general, it has poor concordance with qPEDL. Our results show, for the first time, that high PEDL and positive EBER present a strong association with viral recurrence and persistent infection in the early treatment of lymphoma.
Subject(s)
Epstein-Barr Virus Infections , Lymphoma, Extranodal NK-T-Cell , Lymphoma, Large B-Cell, Diffuse , Humans , Herpesvirus 4, Human/genetics , Epstein-Barr Virus Infections/complications , Persistent Infection , Lymphoma, Large B-Cell, Diffuse/pathology , DNA, Viral , RNA, ViralABSTRACT
Ovarian dysfunction, including premature ovarian insufficiency and decreased ovarian reserve, affects the ovarian reserve and is one of the leading causes of female infertility. More and more cases of ovarian dysfunction are associated with genetic factors. Here, we identified eight potential variants in five genes (MSH4, HFM1, SYCE1, FSHR, and C14orf39) from six independent families by exome sequencing. The splice-site variants in SYCE1 and MSH4 affected canonical splicing isoforms, leading to missing protein domains or premature termination. Our findings expand the mutational spectrum of ovarian dysfunction and provide potential biomarkers for future genetic counseling and for more personalized treatments. Exome sequencing was shown to be a useful tool to better dissect the genetic basis for ovarian dysfunction and yielded a genetic diagnosis in about 5.0% (6/124) of cases in a cohort of 124 patients with ovarian dysfunction.
Subject(s)
Menopause, Premature , Primary Ovarian Insufficiency , Humans , Female , Primary Ovarian Insufficiency/diagnosis , Primary Ovarian Insufficiency/genetics , Menopause, Premature/genetics , Mutation , Genetic TestingABSTRACT
@#In September 2020, three pulmonary tuberculosis cases were identified during school physical examinations at a senior high school in a district (School B) of Hangzhou City. Immediate epidemiological surveys were performed by local district and Hangzhou Center for Disease Control and Prevention, and a pulmonary tuberculosis outbreak involving 9 cases in 6 schools were identified. All cases were once Grade 9 students in Class of 2019 at a junior high school (School A), and the source of infection might be a laboratory-confirmed cases (index case) in this class reported in April, 2019. Following exposure to index case, other cases developed disease onset or were screened after entering senior high schools. In November, 2020, tuberculin skin test and chest X-ray scan were performed to screen pulmonary tuberculosis among 43 students and teachers in a class of Grade 9 in Class of 2019 at School A, and 17 students strongly positive for tuberculin skin test were given prophylactic therapy. No pulmonary tuberculosis case were identified until June 2021. It is suggested that early epidemiological surveys facilitates the identification of the epidemiological correlation between cases. Active search for individuals with common exposure history and prophylactic therapy are required if a possible outbreak is found, which is helpful to avoid the spread of the outbreak.
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OBJECTIVE: To investigate the involvement of HOX transcript antisense RNA (HOTAIR) in the injury of renal tubular epithelial cells induced by high glucose. Results: In high glucose-induced HK-2 cells, the expression of HOTAIR was upregulated, resulting in suppressed cell proliferation. Meanwhile, HOTAIR upregulates the expression of pro-apoptotic proteins Bax and cleaved caspase-3, while downregulating the expression of the anti-apoptotic protein Bcl-2. Luciferase reporter assays revealed that HOTAIR could target miR-126-5p. Additionally, it was found that the PI3K/Akt signaling pathway serves as a downstream target of miR-126-5p. Knockdown of HOTAIR relieved apoptosis, whereas further inhibition of miR-126-5p led to apoptosis in HK-2 cells. Conclusions: HOTAIR plays a regulatory role in mediating high glucose-induced injuries in HK-2 cells, specifically affecting apoptosis and cell viability, via the miR-126-5p/PI3K/Akt signaling pathway.
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Aim: This study aimed to assess the risk factors for depression among parents who have lost their only child (PLOCs). Methods: We used a cross-sectional survey to reveal the risk factors of depression among PLOCs. Multi-stage, stratified, cluster sampling was used to recruit the participants. The cluster sampling method was used to select PLOCs in Hangzhou, Zhejiang Province, and Wuhu, Anhui Province, while the stratified cluster sampling method was used in Anshun, Guizhou Province. A total of 651 PLOCs were recruited in this study. Participants completed the Social Support Rating Scale (SSRS) and the Geriatric Depression Scale-15 (GDS-15). Socio-demographics were also collected, including age, sex, monthly income, education level, marital status, self-reported health, and a number of diseases were collected as well. Chi-square tests and binary logistic regression were conducted to analyze the influence of these factors on PLOCs' mental status. Results: Two hundred and fifty-eight PLOCs (39.56%) reported depression. Compared to PLOCs living in Wuhu, those living in Hangzhou (OR = 3.374, CI = 2.337-4.870) had a higher risk of depression. Being single (OR = 1.449, CI = 1.019-2.061) and the presence/absence of grandchildren (OR = 0.430, CI = 0.274-0.676)were significantly associated with the depression status of PLOCs. Conclusion: The sampled Chinese PLOCs reported a high prevalence of depression that was influenced by their place of residence, marital status, and presence/absence of grandchildren. This may highlight the need for routine assessment and help of this group by the relevant stakeholders (including government, non-profit social organizations, and professional psychologists) with more attention paid to single and low-income PLOCs that have no grandchildren. It is imperative to build a comprehensive care system of "extended family-community-society-government" for this vulnerable group.
Subject(s)
Depression , Only Child , Aged , Child , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Humans , ParentsABSTRACT
This study aimed to promote the coordinated development of regional social economy and ecological environment, build a better living environment, accurately prevent and control pollution, and carry out in-depth surveys and general surveys of air pollution in Beijing, Tianjin, and Hebei. Based on 6 years (June 2014 to December 2019) of ground environmental observation data and satellite data from 2000 to 2019, the distribution characteristics and evolution trend of air pollution in different time and spatial scales were analyzed. The results showed that:â according to the daily average concentration of PM2.5 at the sites, the pollution in the Beijing-Tianjin-Hebei region showed the characteristics of more days, heavy levels, and overall improvement. Pollution mainly occurred from October to April of the following year, accounting for nearly half a year. The pollution level of PM2.5 was the best at Zhangjiakou, followed by Qinhuangdao. â¡ Based on the 20-year average PM2.5 annual average concentration data retrieved from satellites, the PM2.5 concentration presented a spatial distribution characteristic in which that in the plains was higher than that in mountain area, and PM2.5 concentration in the city was higher than that in the suburbs. PM2.5 concentration changed with time, showing a four-stage bimodal structure of "M"-type evolution characteristics, which gradually increased starting in 2000; the first peak appeared in 2006 and gradually decreased from 2007 to 2012. It rose sharply to the second peak in 2013 and then decreased yearly until 2017. ⢠The monthly average AOT data based on satellites every 10 years indicated that the value of AOT in the first time period (2000-2009) was larger than that in the same month of the second time period (2010-2019). The maximum value was in July, and the minimum value was in December. The monthly average AOT in Zhangjiakou and Chengde changed slightly over the past 20 years, and the seasonal and spatial differences were significant in the plain area. ⣠Judging from the daily average value of O3-8h observed at the stations, good levels of O3-8h concentrations in the Beijing-Tianjin-Hebei area occurred frequently and widely from March to October. There were at least seven instances of light pollution levels, and the moderate pollution levels and above were not observed. ⤠The daily average value of SO2 observed on the ground showed that there was no light pollution or above; the good pollution level occurred in winter, and most appeared in the form of pollution for several consecutive days. ⥠The analysis of AQI data revealed that from 2015 to 2019, the proportion of AQI excellent grades in Beijing increased from 27% to 38%, and the proportion of Tianjin AQI good grades increased from 44% to 64%. The highest proportion of Handan AQI superior grades appeared in 2016, accounting for only 9%. ⦠The 20-year monthly average concentration of SO2 data based on satellites showed that high-value areas were in Handan, Xingtai, and Shijiazhuang, and low-value areas were in Zhangjiakou and Chengde. The 20-year average NO2 data showed that the high-value centers were in Beijing, Tianjin, Tangshan, Handan, Xingtai, and Shijiazhuang.
Subject(s)
Air Pollution , Particulate Matter , Air Pollution/analysis , Beijing , Cities , Environmental Pollution/analysis , Particulate Matter/analysisABSTRACT
AIMS: We aimed to explore the evidence of brain microglia activation in diabetic neuropathic pain (DNP) and the effect and mechanism of glucagon-like peptide-1 receptor agonist (GLP-RA) on DNP via brain microglia. METHODS: Brain microglia activation was observed in DNP rats by positron emission tomography/computed tomography. The behavior of neuropathic pain was assessed in DNP rats after intracerebroventricular administration of GLP-1RA or microglial inhibitor minocycline. RNA sequencing was performed to explore the target of GLP-1RA on brain microglia. NOD-like receptor protein 3 (NLRP3) expression in brain microglia was evaluated in mentioned-above DNP rats, and the activation of NLRP3 inflammasome was analyzed in microglia treated with GLP-1RA. RESULTS: Microglia were activated in the cortex and thalamus of DNP rats. The thermal and mechanical allodynia were alleviated in DNP rats via intracerebroventricular administration of GLP-1RA or minocycline. And the activation of brain microglia was attenuated in DNP rats by intracerebroventricular administration of GLP-1RA. The expression of NLRP3 in brain microglia, which was found by RNA sequencing, was reduced in DNP rats by administration of GLP-1RA. Furthermore, GLP-1RA attenuated NLRP3 inflammasome activation in microglia triggered by LPS. CONCLUSION: GLP-1RA could alleviate DNP, possibly mediated by the suppression of brain microglia NLRP3 inflammasome activation.
Subject(s)
Diabetes Mellitus , Diabetic Neuropathies , Neuralgia , Animals , Brain/metabolism , Diabetes Mellitus/metabolism , Diabetic Neuropathies/drug therapy , Diabetic Neuropathies/metabolism , Glucagon-Like Peptide-1 Receptor/agonists , Humans , Inflammasomes/metabolism , Inflammasomes/pharmacology , Microglia/metabolism , Minocycline/metabolism , Minocycline/pharmacology , Minocycline/therapeutic use , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Proteins/metabolism , Neuralgia/drug therapy , Neuralgia/metabolism , RatsABSTRACT
Exosomes are nanosized extracellular vesicles that can be released from cancer cells. It has been shown that cancer cellderived exosomes may be associated with carcinogenesis by transferring signaling proteins from malignant to neighboring nonmalignant cells. In addition, annexin A1 (ANXA1) is a wellknown oncogene, that can be released from extracellular vesicles by cancer cells. However, the role of exosomal ANXA1 in the celltocell communication of thyroid cancer and thyroid follicular epithelial cells remains unclear. In the present study, the protein expression levels of ANXA1 in thyroid cancer cells and thyroid cancer cellderived exosomes were analyzed using western blot analysis. In addition, Cell Counting Kit8 and Transwell assays were used to determine cell viability and invasion, respectively. The protein expression levels of ANXA1 were increased in thyroid cancer tissues and thyroid cancer cell lines. In addition, overexpression of ANXA1 significantly increased the proliferation and invasion of the SW579 cells, while knockdown of ANXA1 expression exerted the opposite results. Furthermore, ANXA1 was transferred from the SW579 cells to the Nthyori31 cells via exosomes. Exosomal ANXA1 markedly promoted the proliferation, invasion and epithelialtomesenchymal transition of the Nthyori31 cells. In addition, SW579 cellderived exosomal ANXA1 promoted tumor growth in a xenograft mouse model. Collectively, these findings indicated that SW579 cellderived exosomal ANXA1 promoted thyroid cancer development and Nthyori31 cell malignant transformation. Therefore, these findings may aid in the development of effective treatment methods for thyroid cancer.