MiR‐221‐3p and miR‐92a‐3p enhances smoking‐induced inflammation in COPD

BackgroundSmoking is likely to facilitate airway inflammation and finally contributes to chronic obstructive pulmonary disease (COPD). This investigation was intended to elucidate miRNAs that were involved in smoking‐induced COPD.MethodsAltogether 155 COPD patients and 77 healthy volunteers were recruited, and their serum levels of miR‐221‐3p and miR‐92a‐3p were determined. Besides, human bronchial epithelial cells (16HBECs) were purchased, and they were treated by varying concentrations of cigarette smoke extract (CSE). The 16HBECs were, additionally, transfected by miR‐221‐3p mimic, miR‐92a‐3p mimic, miR‐221‐3p inhibitor or miR‐92a‐3p inhibitor, and cytokines released by them, including TNF‐α, IL‐8, IL‐1β, and TGF‐β1, were monitored using enzyme linked immunosorbent assay (ELISA) kits.ResultsChronic obstructive pulmonary disease patients possessed higher serum levels of miR‐221‐3p and miR‐92a‐3p than healthy volunteers (p < 0.05), and both miR‐221‐3p and miR‐92a‐3p were effective biomarkers in diagnosing stable COPD from acute exacerbation COPD. Moreover, viability of 16HBECs was undermined by CSE treatment (p < 0.05), and exposure to CSE facilitated 16HBECs’ release of TNF‐α, IL‐8, IL‐1β, and TGF‐β1 (p < 0.05). Furthermore, miR‐221‐3p/miR‐92a‐3p expression in 16HBECs was significantly suppressed after transfection of miR‐221‐3p/miR‐92a‐3p inhibitor (p < 0.05), which abated CSE‐triggered increase in cytokine production and decline in viability of 16HBECs (p < 0.05).ConclusionMiR‐221‐3p and miR‐92a‐3p were involved in CSE‐induced hyperinflammation of COPD, suggesting that they were favorable alternatives in diagnosing COPD patients with smoking history.     

SARS‐CoV‐2, HIV,and Mycobacterium tuberculosis triple co‐infection

Tuberculosis (TB)‐related death has increased for the first time in a decade due to the coronavirus disease 2019 (COVID‐19), globally. People living with HIV (PLWHIV) might be at a higher risk of developing COVID‐19‐related complications. Herein, we describe the first case of a patient surviving from SARS‐CoV‐2‐TB‐HIV triple co‐infection in Cameroon. A 36‐year‐old Cameroonian woman presented at the emergency unit of the Jamot Hospital, Yaoundé with symptoms of anorexia, productive cough, weight loss, and fever. The SARS‐CoV‐2 rapid antigen test on nasopharyngeal sample was positive. Chest X‐ray showed bilateral parenchymal and tracheal calcifications most consistent with prior pulmonary histoplasmosis, varicella, or TB. She was tested HIV positive, and the sputum sample tested positive for TB on auramine staining. TB therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol) and COVID‐19 treatment were initiated, and the symptoms improved after 2 weeks of treatment. The SARS‐CoV‐2 rapid antigen and real‐time polymerase chain reaction tests were negative after 2 weeks. She was discharged home on antiretroviral therapy and TB therapy. Coinfection with both TB, HIV, and SARS‐CoV‐2 may be common in Cameroon but not reported. The similar clinical features of COVID‐19 and TB usually lead to misdiagnosis. Early diagnosis and initiation of appropriate treatment improve outcome.     

COVID‐19 vaccine‐related new‐onset lichen planus

Coronavirus disease 2019 (COVID‐19) vaccines significantly impacted world health and well‐being. However, various adverse events have been observed following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination. Cutaneous reactions have been prevalent following many vaccines, including COVID‐19 vaccines. Here, we present a case of new‐onset lichen planus in a patient who received the COVID‐19 vaccine at the same time as being infected with SARS‐CoV‐2. A 52‐year‐old woman presented to the clinic with extensive pruritic skin lesions. The eruptions had appeared a week after her second dose of the Sinopharm COVID‐19 vaccine. She mentioned a history of SARS‐CoV‐2 infection approximately 10 days following the first dose of her vaccine, causing a 1‐month delay in getting the second dose. Her past medical history was not significant. On examination, erythematous and squamous papules were demonstrated predominantly on the extremities, including inguinal and axillary folds. Moreover, desquamation of the lips was visible, and buccal lesions were also found. After consultation with a dermatologist, a skin biopsy was indicated for the patient, but she refused to undergo the procedure. Therefore, considering the typical appearance of the eruptions, lichen planus was suspected, for which she was treated with oral antihistamines and topical corticosteroids.     

Orbital inflammatory disease following mRNA SARS‐CoV‐2 vaccine

A 65‐year‐old woman reported orbital symptoms two days after her first dose and presented exacerbation of signs after the second dose of BNT162b2 mRNA vaccine. The temporal relationship between the COVID‐19 vaccination and orbital symptoms suggests a probable link between SARS‐CoV‐2 mRNA vaccine and this orbital inflammatory disease.     

Domperidone‐induced pityriasis rosea‐like drug eruption

Pityriasis rosea is a common, acute, self limiting inflammatory skin disease. Pityriasis rosea‐like eruptions (PR‐LE) have been reported after drugs. The clinical presentation of PR‐LE can be distinguished from pityriasis rosea. We reporte a 41‐year‐old woman who developed PR‐LE 5 days after administration domperidone.     

Expression and prognostic significance of m6A‐related genes in TP53‐mutant non‐small‐cell lung cancer

BackgroundTP53 is an important tumor suppressor gene on human 17th chromosome with its mutations more than 60% in tumor cells. Lung cancer is the highest incidence malignancy in men around the world. N‐6 methylase (m6A) is an enzyme that plays an important role in mRNA splicing, translation, and stabilization. However, its role in TP53‐mutant non‐small‐cell lung cancer (NSCLC) remains unknown.MethodFirst, we investigated 17 common m6A regulators'' prognostic values in NSCLC. Then, after the establishment of risk signature, we explored the diagnostic value of m6A in TP53‐mutant NSCLC. Finally, gene set enrichment analysis (GSEA), gene ontology (GO) enrichment analysis, and differential expression analysis were used to reveal the possible mechanism of m6A regulators affecting TP53‐mutant NSCLC patients.ResultsStudy showed that nine m6A regulators (YTHDC2, METTL14, FTO, METTL16, YTHDF1, HNRNPA2B1, RBM15, KIAA1429, and WTAP) were expressed differently between TP53‐mutant and wild‐type NSCLC (p < 0.05); and ALKBH5 and HNRNPA2B1 were associated with the prognostic of TP53‐mutant patients. After construction of the risk signature combined ALKBH5 and HNRNPA2B1, we divided patients with TP53 mutations into high‐ and low‐risk groups, and there was a significant survival difference between two groups. Finally, 338 differentially expression genes (DEGs) were found between high‐ and low‐risk groups. GO enrichment analysis, PPI network, and GSEA enrichment analysis showed that m6A may affect the immune environment in extracellular and change the stability of mRNA.ConclusionIn conclusion, m6A regulators can be used as prognostic predictors in TP53‐mutant patients.     

Dioscin ameliorates inflammatory bowel disease by up‐regulating miR‐125a‐5p to regulate macrophage polarization

PurposeDioscin has been proven to have anti‐cancer, anti‐inflammatory, and anti‐infection roles. However, the role of Dioscin in inflammatory bowel disease (IBD) and its related mechanisms is unclear and needs further study.MethodsThe colitis model in mice was established. After Dioscin (20, 40, or 80 mg/kg) treatment, the colon length was measured by a ruler. Histopathology, inflammatory cytokines, gut permeability, tight junction proteins, macrophage infiltration, macrophage polarization, and miR‐125a‐5p level were detected by hematoxylin–eosin staining, enzyme‐linked immunosorbent assay, quantitative real‐time polymerase chain reaction (qRT‐PCR), FITC‐dextran, Western blot, and flow cytometry. In vitro experiments, after RAW264.7 cells induced by lipopolysaccharide (LPS)/interleukin‐4 (IL‐4), were treated with Dioscin and miR‐125a‐5p inhibitor, miR‐125a‐5p level, cell vitality, inflammatory cytokines, and M1/M2 marker genes were measured by qRT‐PCR and MTT assay.ResultsDioscin (20, 40, or 80 mg/kg) relieved DSS‐triggered colitis and restrained the serum and colon of pro‐inflammatory cytokines expression. Meanwhile, different concentrations'' Dioscin weakened M1 macrophage polarization but facilitated tight junction protein expressions, M2 macrophage polarization, and miR‐125a‐5p level in colitic mice. Moreover, miR‐125a‐5p inhibitor reversed the modulation of Dioscin on miR‐125a‐5p expression, cell vitality, and inflammatory cytokines in lipopolysaccharide (LPS)‐induced RAW264.7 cells. We further discovered that Dioscin restrained M1 marker gene (CD16) expression while intensifying M2 marker genes (CD206 and Arginase‐1) expressions in vitro, which was reversed by miR‐125a‐5p inhibitor.ConclusionDioscin modulated macrophage polarization by increasing miR‐125a‐5p, thereby improving the intestinal epithelial barrier function and reducing IBD.     

Prognostic value of albumin‐related ratios in HBV‐associated decompensated cirrhosis

BackgroundIdentification of effective and accurate prognostic biomarkers for hepatitis B virus‐associated decompensated cirrhosis (HBV‐DeCi) is challenging. This study was designed to determine and compare the prognostic value of albumin‐related ratios (blood urea nitrogen‐to‐albumin ratio [BAR], C‐reactive protein‐to‐albumin ratio [CAR], prothrombin time‐international normalized ratio‐to‐albumin ratio [PTAR], neutrophil count‐to‐albumin ratio [NAR], and D‐dimer‐to‐albumin ratio [DAR]) in HBV‐DeCi patients.MethodsWe retrospectively recruited 161 HBV‐DeCi patients. Receiver operating characteristic curve, DeLong test, and Cox regression analyses were used to estimate and compare the predictive value of these five albumin‐related ratios and Model for End‐Stage Liver Disease (MELD) score.ResultsA total of 29 (18.0%) patients had died 30 days after admission. The prognostic roles of CAR, DAR, PTAR, NAR, and BAR in HBV‐DeCi were different. CAR, PTAR, NAR, and BAR were significantly higher in non‐survivors compared with survivors. However, DAR did not differ between the two groups. The predictive power of BAR was superior to that of the other four albumin‐related biomarkers and similar to that of MELD score. On multivariate analysis, BAR and MELD score were identified as independent prognostic factors, and the combination of BAR and MELD score may improve the prognostic accuracy in HBV‐DeCi.ConclusionThe present findings suggest that BAR may be a simple and useful prognostic tool to predict mortality in HBV‐DeCi patients.     

Possible HSP reactivation post‐COVID‐19 vaccination and booster

A 45‐year‐old woman with a history of Henoch‐Schönlein (HSP) purpura received COVID‐19 vaccination. The patient showed HSP reactivation after COVID‐19 vaccination and booster. In HSP, autoimmune memory of vasculitis persists and might be reactivated with COVID‐19 vaccination.     

New‐onset pemphigus foliaceus following SARS‐CoV‐2 infection and unmasking multiple sclerosis: A case report

Development of pemphigus foliaceus (PF) following SARS‐CoV‐2 infection has only been reported in one patient who had received Bamlanivimab and thus might be considered as a drug‐induced case of PF. Here, we reported the first case of PF arising solely after COVID infection without taking any culprit drug.     

Overexpressed miR‐335‐5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome

BackgroundAcute coronary syndrome (ACS) may induce cardiovascular death. The correlation of mast cells related microRNAs (miRs) with risk of ACS has been investigated. We explored regulatory mechanism of miR‐335‐5p on macrophage innate immune response, atherosclerotic vulnerable plaque formation, and revascularization in ACS in relation to Notch signaling.MethodsACS‐related gene microarray was collected from Gene Expression Omnibus database. After different agomir or antagomir, or inhibitor of Notch signaling treatment, IL‐6, IL‐1β, TNF‐α, MCP‐1, ICAM‐1, and VCAM‐1 levels were tested in ACS mice. Additionally, Notch signaling‐related genes and matrix metalloproteinases (MMPs) were measured after miR‐335‐5p interference. Finally, mouse atherosclerosis, lipid accumulation, and the collagen/vessel area ratio of plaque were determined.ResultsmiR‐335‐5p targeted JAG1 and mediated Notch signaling in ACS. miR‐335‐5p up‐regulation and Notch signaling inhibition reduced expression of JAG1, Notch pathway‐related genes, IL‐6, IL‐1β, TNF‐α, MCP‐1, ICAM‐1, VCAM‐1, and MMPs, but promote TIMP1 and TIMP2 expression. Additionally, vulnerable plaques were decreased and collagen fiber contents were observed to increase after miR‐335‐5p overexpression and Notch signaling inhibition.ConclusionsOverexpression of miR‐335‐5p inhibited innate immune response of macrophage, reduced atherosclerotic vulnerable plaque formation, and promoted revascularization in ACS mice targeting JAG1 through Notch signaling.     

IL‐19 induced by IL‐13/IL‐17A in the nasal epithelium of patients with chronic rhinosinusitis upregulates MMP‐9 expression via ERK/NF‐κB signaling pathway

BackgroundTissue remodeling is a crucial characteristic of chronic rhinosinusitis (CRS). Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is crucial for the pathologic tissue remodeling in CRS. Elevation of interleukin (IL)‐19 or MMP‐9 levels in patients with CRS had been proven in previous studies. Here, we aimed to investigate the role of IL‐19 in mediating MMP‐9 expression in CRS.MethodsNasal tissue samples were collected from 45 individuals having chronic rhinosinusitis with nasal polyps (CRSwNP), 24 CRS without nasal polyps (CRSsNP), and 17 controls. Expression of IL‐19, its receptors (IL‐20R1/IL‐20R2), and MMP‐9 were investigated using RT‐qPCR and Immunofluorescence (IF). Human nasal epithelial cells (HNECs) were stimulated by IL‐19; ERK phosphorylation, nuclear factor‐κB (NF‐κB) pathway activation, and MMP‐9 level were detected by RT‐qPCR, enzyme‐linked immunosorbent assay, western blot, and IF. We also explored the effect of type1/2/3 cytokines on IL‐19 production by RT‐qPCR, and western blot.ResultsExpression levels of IL‐19, its receptors (IL‐20R1/IL‐20R2), and MMP‐9 were increased in nasal tissues from individuals with CRSwNP compared to those with CRSsNP as well as the controls. IL‐19 significantly elevated the production of MMP‐9 in HNECs. Furthermore, IL‐19 could activate the ERK and NF‐κB pathways, accompanied by increased MMP‐9 production in HNECs. Conversely, both ERK and NF‐κB inhibitors significantly attenuated the role of IL‐19 in MMP‐9 production. siRNA knockdown of IL‐20R1 suppressed ERK and NF‐κB pathway activation, thereby decreasing MMP‐9 expression. IL‐13 and IL‐17A were found to stimulate IL‐19 production in HNECs.ConclusionIL‐19, promoted by IL‐13 and IL‐17A, contributes to the upregulation of secretion of the tissue remodeling factor MMP‐9 in patients with CRS.     

First reported case of delayed‐type hypersensitivity reaction to non‐hyaluronic acid Polycaprolactone dermal filler following COVID‐19 vaccination: A case report and a review of the literature

Cases of filler reactions after COVID‐19 vaccination have been reported. Here, we present the first case of delayed‐type reaction (DTR) to non‐hyaluronic acid Polycaprolactone dermal filler after the second dose of Sinopharm COVID‐19 vaccine which was improved with administration of topical and intralesional steroids.     

Prognostic value of inflammation‐immunity‐nutrition score in patients with hepatocellular carcinoma treated with anti‐PD‐1 therapy

BackgroundThere are no validated biomarkers that can predict the clinical benefit of immune checkpoint blockers against the programmed cell death protein 1 (PD‐1) treatments in hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic value of inflammation‐immunity‐nutrition score (IINS) in patients with HCC treated with anti‐PD‐1 therapy.MethodsA consecutive series of 101 HCC patients treated with PD‐1 inhibitors in Sichuan Provincial People''s Hospital between January 2018 and August 2020 were enrolled in the retrospective study. IINS (0–6) was constructed based on pretreatment high‐sensitivity C‐reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The patients were divided into high and low IINS groups according to IINS values. Prognostic values of each variable were evaluated with univariate and multivariate time‐dependent Cox regression analyses. Survival curves were calculated and compared using the Kaplan–Meier method and log‐rank test. The prognostic performance of IINS was further compared with that of other traditional prognostic indicators by receiver operating characteristic (ROC) curve and the areas under the ROC curve.ResultsPatients with low IINS had longer overall survival (OS) (HR: 4.711, 95% CI: 1.80–12.37, p = .001) and progression‐free survival (HR: 3.411, 95% CI: 1.79–6.51, p < .0001) than those with high IINS. The multivariate analysis identified IINS (HR: 3.746, 95% CI: 1.05–13.38, p = .042) and tumor number (HR: 5.111, 95% CI: 1.075–24.299, p = .04) as independent prognostic factors. According to ROC analysis, IINS (AUC =0.729, 95% CI: 0.597–0.861, p = .002) presented better prognostic performance than other traditional prognostic indicators. The area of the IINS‐CA19‐9 under the ROC curve (AUC) was higher than that of the IINS or CA19‐9 levels for the prediction of OS.ConclusionThe results suggest that IINS may be an independent prognostic indicator for HCC patients treated with anti‐PD‐1 therapy. IINS‐CA19‐9 classification may be more effective in predicting clinical benefit of anti‐PD‐1 therapy in HCC patients.     

Heterogeneity assessment of vaccine‐induced effects using point‐of‐care surrogate neutralization test for severe acute respiratory syndrome coronavirus 2

IntroductionCoronavirus disease (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global pandemic even after vaccination. We aimed to identify immunological heterogeneity over time in vaccinated healthcare workers using neutralization antibodies and neutralizing activity tests.MethodsSerum samples were collected from 214 healthcare workers before vaccination (pre) and on days 22, 90, and 180 after receiving the first dose of BNT162b2 vaccine (day 0). Neutralization antibody (NAb, SARS‐CoV‐2 S‐RBD IgM/IgG) titers and two kinds of surrogate virus neutralization tests (sVNTs) were analyzed (UMIN000043851).ResultsThe NAb (SARS‐CoV‐2 S‐RBD IgG) titer peaked on day 90 after vaccination (30,808.0 μg/ml ± 35,211; p < 0.0001) and declined on day 180 (11,678.0 μg/ml ± 33,770.0; p < 0.0001). The neutralizing activity also peaked on day 90 and declined with larger individual differences than those of IgG titer on day 180 (88.9% ± 15.0%, 64.8% ± 23.7%, p < 0.0001). We also found that the results of POCT‐sVNT (immunochromatography) were highly correlated with those of conventional sVNT (ELISA).ConclusionsNeutralizing activity is the gold standard for vaccine efficacy evaluation. Our results using conventional sVNT showed large individual differences in neutralizing activity reduction on day 180 (64.8% ± 23.7%), suggesting an association with the difference in vaccine efficacy. POCT‐sVNT is rapid and user‐friendly; it might be used for triage in homes, isolation facilities, and event venues without restrictions on the medical testing environment.     

Sputnik‐V vaccine‐induced panniculitis as a local reactions

Here, a case of Sputnik‐V vaccine‐induced panniculitis was reported. The patient developed erythema, induration, and local tenderness at the injection site after 13 days of the injection. Ultra‐sonography imaging showed inflammation in subcutaneous layers including fat tissue compatible with panniculitis. She received ibuprofen and warm compress, and all symptoms resolved.     

Dynamic observation of SARS‐CoV‐2 IgM,IgG, and neutralizing antibodies in the development of population immunity through COVID‐19 vaccination

BackgroundCurrently, mass vaccine inoculation against coronavirus disease‐2019 (COVID‐19) has been being implemented globally. Rapid and the large‐scale detection of serum neutralizing antibodies (NAbs) laid a foundation for assessing the immune response against SARS‐CoV‐2 infection and vaccine. Additional assessments include the duration of antibodies and the optimal time for a heightened immune response.MethodsThe performance of five surrogate NAbs—three chemiluminescent immunoassay (CLIA) and two enzyme‐linked immunosorbent assays (ELISAs)—and specific IgM and IgG assays were compared using COVID‐19‐vaccinated serum (n = 164). Conventional virus neutralization test (cVNT) was used as a criterion and the diagnostic agreement and correlation of the five assays were evaluated. We studied the antibody responses after the two‐dose vaccine in volunteers up to 6 months.ResultsThe sensitivity and specificity of five surrogate NAb assays ranged from 84% to 100%. Our cVNT results indicated great consistency with the surrogate assays. At 28 days after primary vaccination, the seropositivities of the NAbs, IgG, and IgM were 6%, 4%, and 13%, respectively. After the booster dose, seropositivities reached 14%, 65%, and 97%, respectively. Six months after receipt of the second dose, the NAb positive rate was eventually maintained at 66%. In all COVID‐19 convalescents, patients were detected with 100% NAb sat three months after discharge.ConclusionCOVID‐19 vaccine induced a humoral immune response lasting at least six months. Rapid serological detection was used as a proxy for identifying changes in immunity levels and as a guide to whether an individual may require a booster vaccination.     

IL‐23/IL‐17 axis and soluble receptors isoforms sIL‐23R and sIL‐17RA in patients with rheumatoid arthritis‐presenting periodontitis

BackgroundRheumatoid arthritis (RA) and periodontitis (P) are chronic inflammatory diseases characterized by joint and radiographic bone loss, respectively. IL‐23 and IL‐17 have an essential role in the immunopathogenesis of RA, and P. IL‐23 stimulates Th17 cells through which produces IL‐17, IL‐21, and RANKL. IL‐17 stimulates fibroblasts to produce RANKL, which initiates bone loss in the joints in RA and the periodontal tissue in periodontitis. The aim of this study was to determine the expression pattern of IL‐23/IL‐17 axis and soluble receptors isoforms sIL‐23R and sIL‐17RA of patients with RA presenting P (RAP).Material and methodsHealthy subjects (HS) (n = 42), patients with P (n = 40), RA (n = 20), and patients with RAP (n = 40) were included. Plasma samples were obtained to evaluate the IL‐23, IL‐17A, sIL‐23R, and sIL‐17RA by ELISA technique. A nonparametric Mann‐Whitney U test was used to compare the differences between groups. A Chi‐square was used to compare gender, grade and stage of periodontitis, and DAS28‐ESR between the groups. Spearman''s rank correlation coefficient was used to study the association between the molecules and clinical parameters.ResultsIL‐23 levels were increased in the RAP group, and lower sIL‐23R levels were found in the RAP groups. However, IL‐17A was lower in the P and RAP group but not in RA patients. RAP group showed a decrease IL‐17A levels in advanced stages of the periodontal disease.ConclusionThese results suggest that IL‐23 and IL‐17A tend to downregulate their expression patterns when patients present both rheumatoid arthritis and periodontitis.