Age-related hearing loss (ARHL) is a prevalent neurodegenerative condition characterized by the progressive loss of spiral ganglion neurons (SGNs). Although oxidative stress is recognized as a central pathogenic driver of ARHL, the precise molecular triggers that initiate and amplify SGN damage remain elusive. Here, we investigated the role of the Transient Receptor Potential Vanilloid 2 (TRPV2) channel in ARHL. We found that TRPV2 expression was significantly upregulated in the SGNs of aged mice, which was associated with elevated oxidative stress. Pharmacological activation of TRPV2 in 6-month-old mice (a pre-senescent stage with preserved baseline hearing) accelerated the onset of high-frequency hearing damage, as evidenced by auditory brainstem response (ABR) measurements. Consistently, TRPV2 activation exacerbated oxidative damage (assessed by 4-HNE staining) and increased apoptotic cell death (detected via TUNEL) in the SGN population. In primary SGN cultures, TRPV2 overexpression aggravated oxidative stress, whereas TRPV2 knockdown in SH-SY5Y cells (a human neuroblastoma cell line) markedly mitigated the oxidative injury as reflected by reduced 4-HNE. Our findings establish that the age-related upregulation of TRPV2 sensitizes SGNs to oxidative stress, thereby promoting neuronal damage and exacerbating ARHL. This work highlights TRPV2 as a promising therapeutic target for intervening in the progression of ARHL.

ObjectiveThis study aims to systematically investigate the molecular mechanisms through which parabens may contribute to head and neck squamous cell carcinoma (HNSCC) carcinogenesis using integrated network toxicology and molecular docking.Materials and methodsSix commonly used parabens (ethyl-, propyl-, methyl-, heptyl-, butyl-, and benzylparaben) were selected for toxicity prediction via ProTox 3.0 and ADMETlab2.0. Their potential targets were retrieved from Swiss Target Prediction, ChEMBL, and the Similarity Ensemble Approach (SEA). HNSCC-related targets were collected from GeneCards, OMIM, and CTD, while differentially expressed genes (DEGs) were identified using TCGA-HNSC data. Functional enrichment, protein-protein interaction (PPI) network construction, hub gene identification, molecular docking, and immune infiltration analyses were performed using DAVID, STRING, Cytoscape, CB-DOCK2, and TIMER2.0.ResultsWe identified 80 common targets through which parabens may exert toxic effects in HNSCC. Among these, 12 hub genes (CCNB1, CDK1, CCNA2, CDK2, CDK4, TYMS, AURKA, CCNA1, CHEK1, CCNB2, PLK1, CDC25A) were significantly overexpressed in HNSCC tissues and were primarily enriched in cell cycle regulation, p53 signaling, and viral carcinogenesis pathways. CCNA1 was further validated as an independent prognostic factor associated with poor survival. Molecular docking revealed strong binding affinities between parabens and hub proteins. Immune infiltration analysis indicated a negative correlation between CCNA1 expression and CD8 + T cell and B cell infiltration.ConclusionsParabens may promote HNSCC progression by disrupting cell cycle regulation and immune responses via direct interactions with key hub genes. These findings provide a novel mechanistic basis for the carcinogenic potential of parabens in HNSCC and underscore the need for further experimental and epidemiological validation.

Age-related hearing loss (ARHL) represents the most common sensory disorder among the elderly population. Degeneration of spiral ganglion neurons (SGNs) is a key pathological feature of ARHL; however, the underlying mechanisms remain inadequately elucidated. Glutathione peroxidase 3 (GPX3), a vital component of the body’s antioxidant system, is integral to maintaining cellular redox homeostasis and promoting cell survival. Nevertheless, its involvement in the pathogenesis and progression of ARHL has not been sufficiently explored. Our study suggested that GPX3 expression in SGNs was significantly decreased, accompanied by increased oxidative stress and apoptosis with aging. Meanwhile, autophagy levels were downregulated in SGNs with increased age. Targeted upregulation of GPX3 in SGNs markedly reduced the hearing threshold, improved wave I amplitude, and alleviated oxidative stress and apoptosis in SGNs. Interestingly, overexpression of GPX3 also led to a significant upregulation in autophagy levels. However, the protective effect of GPX3 was reversed by the autophagy inhibitor. These findings were also confirmed in vitro experiments. Collectively, our results indicated that GPX3 could mitigate apoptosis and oxidative stress in SGNs by activating autophagy, thereby alleviating hearing loss in ARHL mice. Furthermore, we discovered that the small molecule drug ebselen could reduce degeneration and damage in SGNs and effectively enhance auditory function by activating autophagy in both in vivo and in vitro settings. These results offer novel targets and therapeutic strategies for the prevention and treatment of ARHL.

Autophagy is an important factor in temozolomide (TMZ) resistance in glioblastoma (GBM). Receptor-interacting protein 2 (RIP2) is associated with autophagy, but its role and mechanism in regulating autophagy in GBM cells remain unclear. To analyze RIP2 expression in GBM in The Cancer Genome Atlas (TCGA) dataset. GBM cells were stimulated using recombinant human RIP2 protein (rRIP2) or RIP2 plasmid. Cell proliferation and apoptosis were assessed using CCK-8 assay and flow cytometry. Western blotting and immunofluorescence (IF) assays were performed to detect protein expression in cells and tumor tissues. Moreover, the relationship between RIP2-induced autophagy and TMZ resistance was verified in a GBM xenograft model. We determined that RIP2 expression was upregulated in GBM. rRIP2 and RIP2 overexpression induced TMZ resistance in the GBM cell lines. RIP2 overexpressing xenograft tumors have reduced sensitivity to TMZ. In addition, we showed that PD-L1 protein expression was upregulated in GBM tissues with RIP2 overexpression. rRIP2 and RIP2 overexpression induced autophagy in GBM cells through AMPK. Notably, RIP2 upregulated PD-L1 expression through the NF-κB signaling pathway, which induced autophagy and TMZ resistance in GBM cells. Moreover, NF-κB or autophagy inhibition reversed TMZ resistance in RIP2 overexpressing GBM cells in a xenograft model. In conclusion, RIP2 induces TMZ resistance in GBM cells by promoting autophagy through the NF-κB/PD-L1 signaling pathway, indicating that the RIP2/NF-κB/PD-L1 pathway may be therapeutic target for TMZ resistance.

BACKGROUND:Age-related hearing loss (ARHL) represents the most prevalent sensory disorder among the elderly, significantly impairing daily functioning and increasing the risk of psychiatric conditions. Although Schwann cells (SCs) are critical for maintaining auditory nerve function, the mechanisms underlying their dysfunction in ARHL remain incompletely elucidated. AIMS:To investigate BST2's role in SCs dysfunction in ARHL and assess its potential value as a serum biomarker for early ARHL diagnosis. MATERIALS AND METHODS:Adeno-associated virus (AAV) carrying a SC specific promoter-MBP, was injected into the posterior semicircular canal of mice. Immunofluorescence was employed to assess cochlear SCs function, while ELISA was used to measured BST2 levels in the serum of both humans and mice. RESULTS:Overexpression of BST2 inhibited SCs proliferation and differentiation, promoted apoptosis, and accelerated ARHL. Serum BST2 levels were elevated in both ARHL patients and mice, showing a significant positive correlation with audiometric thresholds and wave I latency of ABR. CONCLUSIONS AND SIGNIFICANCE:BST2 accelerates the progression of ARHL by exacerbating SCs dysfunction and serves as a potential serum biomarker for ARHL.

Cochlear nerve demyelination is a significant pathogenic factor of age-related hearing loss (ARHL), and Schwann cell (SC) migration function plays a key role in the maintenance and regeneration of myelin sheaths. Here, we found that bone marrow stromal antigen 2 (BST2) is significantly upregulated in cochlear SCs during aging following demyelination and hearing loss. However, specific knockdown of BST2 in SCs could obviously improve the SCs migration and the myelin sheath structure manifested in a reduction of E-cadherin expression and increased N-cadherin expression. Further mechanism analysis revealed that POU class 6 homeobox 1 (POU6F1) expression via the NF-κB pathwayleads to enhanced SCs migration ability and increased expression of the myelin protein zero (MPZ), thereby alleviating nerve demyelination and rescuing hearing loss. This study identifies BST2 as a novel therapeutic target for ARHL intervention. In conclusion, the specific downregulation of BST2 in cochlear SCs rescues age-related demyelination and hearing loss by activating the POU6F1/NF-κB pathway, thereby enhancing SC migration capacity and promoting MPZ expression.

Background:Olfactory dysfunction (OD) significantly impacts health and quality of life. However, the specific mechanisms underlying olfactory disorders and effective therapeutic interventions remain unclear. Conducting a bibliometric analysis of the extensive OD literature could provide valuable insights for addressing these issues. Objective:To characterize the research landscape of olfactory disorders over the past decade and identify emerging research foci through bibliometric analysis. Materials and methods:We retrieved OD-related publications from the Web of Science Core Collection (2014-2024) and performed bibliometric analysis and visualization using the Biblioshiny online tool. Results:The analysis included 1560 articles on OD, authored by 7424 researchers across 312 journals. Annual publication output and total citations per article showed stable, slight increases. European Archives of Oto-Rhino-Laryngology, International Forum of Allergy & Rhinology, and Laryngoscope were identified as prominent journals due to high article output and H-index. Hummel T was the most prolific and influential author. Institutional collaboration analysis identified potential ideal collaborators. The United States, China, and Germany produced the most publications and collaborations. Co-occurrence and keyword evolution analyses suggested epithelial repair, neurogenesis, and quality of life as potential future research hotspots. Conclusions:This study delineates the current status and evolution of OD research, suggesting that epithelial repair, nerve regeneration, and the impact of OD on quality of life represent promising innovative research directions.

Interferon stimulated exonuclease gene 20 (ISG20) has been reported to be correlated with macrophage infiltration in glioblastoma (GBM) in previous bioinformatics-based studies. This study explores the exact effect of ISG20 on macrophage polarization in GBM. ISG20 expression in GBM tissues and cells was determined by RT-qPCR and/or immunohistochemistry. GBM cells were co-cultured with M0 macrophages (PMA-stimulated THP-1 cells) in vitro, followed by flow cytometry and ELISA to analyze the M2 polarization of macrophages. Fluorescence-contained GBM cells were intracranially injected into nude mice along with M0 macrophages to generate orthotopic xenograft tumor models. Upstream regulator of ISG20 was predicted using bioinformatics. Loss- or gain-of-function assays of Fos like 2 (FOSL2) and ISG20 were performed in GBM cells. DNA methylation level of FOSL2 was analyzed by bisulfite sequencing analysis. ISG20 was found highly expressed in GBM tissues and cells. ISG20 silencing in GBM cells decreased CD206 and CD163 levels in the co-cultured macrophages and reduced secretion of IL-10 and TGF-β. It also enhanced survival of nude mice bearing xenograft tumors, blocked tumor growth, and suppressed M2 polarization of macrophages in vivo. FOSL2, highly expressed in GBM, bound to the ISG20 promoter to activate its transcription. FOSL2 silencing similarly blocked M2 polarization of macrophages, which was negated by ISG20 overexpression. The high FOSL2 expression in GBM was attributed to DNA hypomethylation. This study demonstrates that FOSL2 is highly expressed in GBM due to DNA hypomethylation. It activates transcription of ISG20, thus promoting M2 polarization of macrophages and GBM development.

PurposeTo analyze and compare clinical research trends and hot topics in allergic rhinitis (AR) and asthma and provide valuable theoretical data and references for future research.MethodsClinical studies focusing on AR or asthma published from 2013 to 2023 were retrieved from the Web of Science Core Collection. Eligible articles were screened and analyzed using bibliometrics from multiple indicators.ResultsA total of 261 eligible articles on AR and 991 qualified articles on asthma were screened. The following bibliometric analyses identified the Journal of Allergy and Clinical Immunology as the most influential publication on AR and asthma and proved the significant contributions of Harvard University in clinical studies on AR and asthma. The analyses also revealed that the top ten prolific authors for AR were from China, the United Kingdom, Japan, and Germany, whereas the top ten productive authors for asthma were mainly from the USA. Collaborations among countries for AR were relatively concentrated in the Occident, whereas international cooperation on asthma was mainly achieved by the Occident and certain Eastern countries.ConclusionsThis study compared and analyzed the current status and evolution of AR and asthma-related clinical research using bibliometric analysis. Additionally, the study comprehensively summarized the impactful authors, institutions, and countries, and revealed the replacement and evolution of hotspots.

The objective of this study was to determine the relationship between renal injury and inflammatory response induced by high-fat diet in rabbits and the interventional effect of allisartan. Fifteen 6-week-old healthy male rabbits were randomly divided into three groups: normal control (NC) group, high-lipid diet (HLD) group, high-lipid diet and allisartan (HLD+ALST) group. After allisartan treatment for 12 weeks, changes in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum creatinine (Scr) and blood urea nitrogen (BUN) were measured enzymatically in the three groups. The left side of the kidney tissue was kept for paraffin section, and HE staining, periodic acid-Schiff (PAS) staining and Masson staining were used to observe the renal pathologic changes. TC, TG, LDL-C, Scr and BUN levels were all higher and HDL-C levels were lower in the HLD group compared with the NC group. Compared with the HLD group, Scr and BUN levels were significantly decreased in the HLD+ALST group. The results of HE staining showed that allisartan improved the changes of renal tissue morphology in rabbits on high-fat diet, reduced glomerular mesangial cell proliferation and improved glomerulosclerosis; PAS staining showed that glomerular glycogen deposition was reduced and glomerular red staining was significantly lighter; Masson staining showed that renal tubular blue-stained collagen fibers were reduced. In conclusion, hyperlipidemia can lead to aberrant expression of multiple cellular proteins and kidney tissue morphological damage in rabbits. On the other hand, allisartan attenuated renal injury and the mechanism may be related to the downregulation of the inflammatory response.

Abstract Background Evidence shows that genetic factors play important roles in the severity of coronavirus disease 2019 (COVID-19). Sulfatase modifying factor 1 (SUMF1) gene is involved in alveolar damage and systemic inflammatory response. Therefore, we speculate that it may play a key role in COVID-19. Results We found that rs794185 was significantly associated with COVID-19 severity in Chinese population, under the additive model after adjusting for gender and age (for C allele = 0.62, 95% CI = 0.44–0.88, P = 0.0073, logistic regression). And this association was consistent with this in European population Genetics Of Mortality In Critical Care (GenOMICC: OR for C allele = 0.94, 95% CI = 0.90–0.98, P = 0.0037). Additionally, we also revealed a remarkable association between rs794185 and the prothrombin activity (PTA) in subjects (P = 0.015, Generalized Linear Model). Conclusions In conclusion, our study for the first time identified that rs794185 in SUMF1 gene was associated with the severity of COVID-19.

PURPOSE:The hyperinflammatory response is one of the main complications associated with novel coronavirus disease 2019 (COVID-19), and there is no effective treatment for cytokine storm. Therefore, it is important to investigate the key genes associated with severity of the disease.METHODS:In this study, we used a microarray data set to analyze the key genes associated with severe illness in patients with COVID-19. The proportion of immune cells was determined using the CIBERSORT algorithm. The key genes were further verified by detecting the levels of cytokines and chemokines in the serum of patients. Additionally, macrophages were stimulated with SARS-CoV-2 spike protein and chemokine ligand (CCL) 2. The expression of cytokines, ERK1/2, and NF-κB in macrophages was detected.RESULTS:Four hub genes were identified. Among them, C-C motif chemokine receptor 2 (CCR2) was an upregulated hub gene, while killer cell lectin-like receptor subfamily K member 1 (KLRK1), macrophage colony-stimulating factor receptor (CSF1R), and CD3D human recombinant protein (CD3D) were downregulated genes. Immune cell type identification found that the proportion of monocytes was higher in patients with severe COVID-19 than that in controls. Moreover, levels of CCL2 were significantly higher in patients with COVID-19. When stimulated with SARS-CoV-2 S protein and CCL2, macrophages secreted more inflammatory cytokines. The expression level of ERK1/2 was elevated.CONCLUSIONS:These results suggested that S protein and CCL2 may mediate macrophage inflammatory responses through the ERK1/2 signaling pathway. This study provides a basis for clinical treatment and improves the prognosis of critically ill patients with COVID-19.

Background and Objective: The complexity and specificity of Chinese herbal medicine (CHM) has limited its wide application, despite presenting outstanding contributions to allergic rhinitis (AR). This study aimed to identify the core CHM and its active components, hoping to promote the accurate treatment of AR and the wide application of CHM. Materials and Methods: A rigorous scientific and logical research thought was designed by authors. Then, a series of public databases and bioinformatic tools were employed to conduct the present analysis according to the user guidelines. The data statistics involved in the relevant public databases and tools were automatically completed by their system background. Notably, p<0.05 indicated significant differences. Results: This study retrieved 76 eligible studies and excavated 74 effective prescriptions, which focused on discussing the efficacy of CHM on AR. Based on the 74 effective prescriptions, this study mined 153 herbs and constructed the formula-herb-ingredient-AR target network. Eventually, this study identified 10 core herbs and the valuable active ingredients of CHM for AR, including spathulenol, caryophyllene oxide and dibutyl phthalate. Additionally, this study confirmed the molecular mechanism of the active ingredients on AR, that is, the three active ingredients could concurrently regulate the calcium signaling pathway by targeting HTR2A, CHRM2, CHRM3 and NOS3, which in turn modulated AR. Conclusion: This study identified the core herbal ingredients, including spathulenol, caryophyllene oxide and dibutyl phthalate for AR and discussed the molecular mechanism of them modulating the calcium signaling pathway. This finding marked the place of CHM in AR pharmacotherapy.

Introduction: Immune factors contribute to the onset of myelodysplastic syndrome (MDS). Arginine metabolism affects tumor-associated macrophage (TAM) polarization. This study investigated the infiltration of TAMs and effect of arginine metabolism key enzymes on MDS prognosis.Methods: We used the GEO (Gene Express Omnibus database) dataset "GSE19429" to analyze and compare metabolism-associated pathways between MDS patients with excess blasts and those without. The markers of TAMs and arginine metabolism key enzymes, including CD68, iNOS, ARG1 and ASS1 were included in this study. A cohort of 79 patients with acute myeloid leukemia or MDS extracted from GenomicScape's online data mining platform was used to analyze the prognostic significance of the mRNA levels. Fifty-eight patients with primary MDS admitted to Sichuan University's West China Hospital from 2013 to 2017 were evaluated for protein levels. The coexpression of CD68, iNOS, and ARG1 was investigated using an Opal polychromatic immunofluorescence kit.Results: The "Arginine and proline metabolism" pathways (p(adjusted) = 0.01) were associated with excess blasts in patients with MDS. In the mRNA expression cohort, patients with low NOS2 (or iNOS) and high ARG1, ASS1, and CD68 expression levels had worse prognosis. Patients with high CD68 (p = 0.01), high iNOS (p < 0.01), low ARG1 (p = 0.01), and negative ASS1 (p = 0.02) protein expression levels had better prognoses. iNOS and ARG1 were coexpressed with CD68 in MDS patients with or without excess blasts, respectively.Conclusions: Arginine metabolism may contribute to the prognosis of patients with MDS by affecting TAM polarization.

Objective: Aneurysms occurring in the ophthalmic segment (C6) of the internal carotid artery (ICA) have complex anatomy. This poses a challenge for the use of traditional open surgery, which is gradually being replaced by endovascular treatment (EVT). However, multiple aneurysm (MA) EVT, especially in MAs occurring ipsilaterally, has not been specifically described or discussed. The present study aimed to propose a more concise clinical classification standard for ipsilateral C6 ICA MAs and report on the clinical experience with EVT.Methods: The cases of 18 patients with ipsilateral C6 ICA MAs treated with EVT were retrospectively reviewed. The treatment results and procedure-related complications were recorded, and clinical and angiographic follow-ups were performed at least six months after surgery.Results: A total of 38 ipsilateral C6 ICA aneurysms were treated during the study period and classified into four main types and six total subtypes based on anatomical features. There was a failure to coil through the stent in one aneurysm, while the remaining 37 were successfully treated using various EVT methods. Of these, 36 were completely concluded. One aneurysm had a size reduction, and one had no changes during the angiographic follow-up. All Tubridge flow diverter stents were patent. All patients achieved satisfactory clinical outcomes and were independent at the final follow-up.Conclusion: EVT may be safe and feasible for the treatment of C6 ICA MAs. Traditional stent-assisted coiling methods, the Willis covered stent, and the double-layered low-profile visualized intraluminal support stent all achieved favorable results. The flow diverter stent is also considered a safe and efficient option for selected aneurysms, but the visual deficit risk should be considered. The present study introduces a new EVT classification option based on the anatomical features of an aneurysm.(c) 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Laryngeal squamous cell carcinoma (LSCC) is a common malignancy among men in the anatomical position of head and neck. Hoarseness, pharyngalgia, and dyspnea are common symptoms. LSCC is a complex polygenic carcinoma that is caused by many factors involving polygenic alteration, environmental pollution, tobacco, and human papillomavirus. Classical protein tyrosine phosphatase nonreceptor type 12 (PTPN12) has been extensively studied to decipher its mechanism as a tumor suppressor gene in various human carcinomas; however, there is no comprehensive elucidation of the PTPN12 expression and its regulatory mechanisms in LSCC. As such, we expect to provide new insights for finding new biomarkers and effective therapeutic targets in LSCC. Immunohistochemical staining, western blot (WB), and quantitative real-time RT-PCR (qRT-PCR) were used for the messenger RNA (mRNA) and protein expression analyses of PTPN12, respectively. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, clone formation, transwell migration, and transwell invasion assays were used to assess the proliferation, migration, and invasion ability of LSCC cells. Online prediction and design software tools (http://www.targetscan.org/ and http://www.microRNA.org) were used to predict associated miRNA. Studying the targeted regulatory relationship between miR-146b-3p and PTPN12 was based on dual luciferase reporter gene analysis. qRT-PCR was used to assess miR-146b-3p expression in LSCC. miR-146b-3p inhibitor and mimic were transfected, followed by qRT-PCR and WB assays to detect the expression of PTPN12. The gain and loss functional experiments were used to investigate the effects of miR-146b-3p transfection on the proliferation, migration, and invasion of tumor cells. Online bioinformatics prediction software (https://cn.string-db.org/ and https://www.genecards.org/) was used to determine potential downstream target genes of PTPN12. qRT-PCR and WB analyses were used to assess the mRNA and protein expression levels of target genes. Our study showed significantly decreased mRNA and protein expression levels of PTPN12 in LSCC compared with the adjacent normal tissues. The lower PTPN12 mRNA expression was correlated with pathological differentiation, and lower PTPN12 protein expression was correlated with the TNM stage in LSCC tissues. The subsequent in vitro functional analyses showed the inhibitory effect of PTPN12 over-expression on the proliferation, migration, and invasiveness abilities of LSCC cell line. Using online prediction and design software, miR-146b-3p was searched to target PTPN12. The miR-146b-3p was expressed at a high level in LSCC tissues and cell lines. Luciferase reporter assay exhibited that miR-146b-3p inhibited the luciferase activity of PTPN12 markedly. The functional analyses showed the tumor-promoting role of miR-146b-3p on the proliferation, migration, and invasiveness abilities of LSCC cell. Furthermore, co-transfection of cells with miR-146b-3p and PTPN12 significantly restored the inhibitory effect of PTPN12 on LSCC cell growth, migration, and invasiveness. This phenomenon unveiled that miR-146b-3p regulated the proliferation, migration, and invasion of LSCC cells by targeting PTPN12. EGFR and ERBB2 were selected as the downstream-regulation target genes. Up-regulation of PTPN12 significantly suppressed EGFR expression. Accordingly, the miR-146b-3p mimic significantly up-regulated the EGFR expression. However, up-regulation of PTPN12 and miR-146b-3p mimic suppressed ERBB2 protein expression but induced its gene expression. Down-regulation of PTPN12 is associated with up-regulation of miR-146b-3p in LSCC. Moreover, PTPN12 serves as a tumor suppressor gene through regulating the proliferation, migration, and invasion of LSCC cells. miR-146b-3p/PTPN12 axis is expected to be a novel therapeutic target in LSCC.

Background Microglia are important immune cells, which can be induced by lipopolysaccharide (LPS) into M1 phenotype that express pro-inflammatory cytokines. Some studies have shown that microRNAs play critical roles in microglial activation. Objective This study was designed to investigate the role of miR-200c-3p in regulating inflammatory responses of LPS-treated BV2 cells. Methods The expression of miR-200c-3p in BV2 cells was detected by real-time PCR. Receptor-interacting protein 2 (RIP2) was predicted as a target gene of miR-200c-3p. Their relationship was verified by dual-luciferase reporter assay. The function of miR-200c-3p and RIP2 in microglial polarization and NF-κB signaling was further evaluated. Results LPS treatment reduced miR-200c-3p expression in a dose-dependent and time-dependent manner in BV2 cells. LPS treatment increased the expression of M1 phenotype markers inducible nitric oxide synthase (iNOS) and major histocompatibility complex class (MHC)-II, promoted the release of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and enhanced the nuclear translocation and phosphorylation of nuclear factor-kappaB (NF-κB) p65. Reversely, miR-200c-3p mimics down-regulated the levels of these inflammatory factors. Furthermore, RIP2 was identified to be a direct target of miR-200c-3p. RIP2 knockdown had a similar effect to miR-200c-3p mimics. Overexpression of RIP2 eliminated the inhibitory effect of miR-200c-3p on LPS-induced M1 polarization and NF-κB activation in BV2 cells. Conclusions MiR-200c-3p mimics suppressed LPS-induced microglial M1 polarization and NF-κB activation by targeting RIP2. MiR-200c-3p/RIP2 might be a potential therapeutic target for the treatment of neuroinflammation-associated diseases.

BACKGROUND:Circular RNA (circRNA) plays an important role in regulating cell biological function and has been shown to be involved in cancer progression, including oral squamous cell carcinoma (OSCC). Circ-KIAA0907 has been found to play an anti-cancer role in OSCC, so it is worth exploring more functions and new mechanisms of circ-KIAA0907 in OSCC progression.METHODS:Quantitative real-time PCR (qRT-PCR) was used to detect the expression of circ-KIAA0907, microRNA (miR)-96-5p, and unc-13 homolog C (UNC13C). Transwell assay, flow cytometry, and colony formation assay were employed to measure the migration, invasion, apoptosis, and radiosensitivity of cells. Besides, glucose uptake, lactate production, and extracellular acidification rate (ECAR) were determined to evaluate the glycolysis ability of cells. Dual-luciferase reporter assay and RIP assay were performed to confirm the interactions among circ-KIAA0907, miR-96-5p, and UNC13C. And RNA pull-down assay was used to verify the binding degree of miR-96-5p to its targets. Moreover, UNC13C protein level was examined using western blot (WB) analysis. OSCC xenograft models were constructed to perform in vivo experiments.RESULTS:Circ-KIAA0907 was a stability circRNA with lowly expression in OSCC. Overexpressed circ-KIAA0907 could inhibit migration, invasion, and glycolysis, while promoting apoptosis and radiosensitivity in OSCC cells. In the terms of mechanism, circ-KIAA0907 could sponge miR-96-5p to regulate UNC13C expression. MiR-96-5p overexpression could reverse the inhibitory effect of circ-KIAA0907 on OSCC progression, and UNC13C knockdown also could overturn the suppressive effect of miR-96-5p inhibitor on OSCC progression. Animal experiments revealed that circ-KIAA0907 could reduce the tumor growth of OSCC by regulating the miR-96-5p/UNC13C axis.CONCLUSION:Our study suggests that circ-KIAA0907 restrains OSCC progression via the miR-96-5p/UNC13C axis, indicating that it may be a potential target for OSCC treatment.

Objective:To investigate the clinical data of asymptomatic patients with 2019 novel Coronavirus (2019-nCoV) infection in Shijiazhuang and provide scientific evidence for prevention and treatment of Coronavirus Disease 2019(COVID-19).Methods:Retrospective study was conducted to analyze the clinical features and laboratory data of 9 asymptomatic 2019-nCoV infected patients, admitted to the Fifth Hospital of Shijiazhuang from January 21, 2020 to February 21, 2020.Results:Asymptomatic infection was found in all age groups, including 5 males and 4 females. On the first day of admission, the detection result of leukocytes, lymphocytes and neutrophils in asymptomatic patients were at normal levels. On the third day after admission, the results increased and continued to stabilize on the twelfth day. The levels of alanine aminotransferase and lactate dehydrogenase were at normal levels during hospitalization, without transient increase or decrease. The level of C-reactive protein reached the highest level on the third day after admission, but it was always in the normal range. D-dimer level was relatively stable during hospitalization. The absolute value of T cell subsets showed that the levels of CD 3+ , CD 4+ , CD 8+ T cells in asymptomatic infection patients were higher than those determined before admission. The average duration of pharyngeal nucleic acid positive detection in asymptomatic patients was 11.88 days. The average cycle threshold of ORF1ab gene and N gene was 36.94 and 35.43 respectively. Conclusions:The inflammatory reaction in patients with asymptomatic 2019-nCoV infection was mild, and the immune function was relatively good.