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Frontiers in Veterinary Science 2024Dromedary camel is an important livestock species with special economic value in arid and semi-arid regions of the world. Given the limited data on detailed immune cell...
Dromedary camel is an important livestock species with special economic value in arid and semi-arid regions of the world. Given the limited data on detailed immune cell composition and cell marker expression in the dromedary camel lymph node tissue, the present study was undertaken to investigate the immune cell composition of bronchial and mesenteric lymph nodes from healthy dromedary camels using flow cytometry. In this study, we applied flow cytometry and multicolor immuno-fluorescence to phenotype the main populations of immune cells in the bronchial and mesenteric camel lymph nodes and compared them with separated peripheral blood mononuclear cells and granulocytes. We used antibodies to detect several cell surface molecules associated with camel T cells (CD4, WC1), B cells (MHCII, BAQ44A), monocytes/macrophages (CD172a, CD14, CD163), in addition to the pan-leukocyte marker CD45 and the cell adhesion molecules CD44 and CD18. Compared to blood mononuclear cells, camel lymph node cells contained a higher percentage of lymphoid cells with only a minor fraction of myeloid cells. In addition, the lower expression of CD44 and CD18 on lymph node lymphocytes compared to lymphocytes from peripheral blood indicates higher frequency of naïve lymphocytes in the lymph nodes. The frequency of CD4 T cells, B cells and γδ T cells within camel lymph node lymphocytes compared to blood indicates a similar tissue distribution pattern of lymphocyte subsets in camel and bovine and supports previous reports on the similarity between the camel immune system and the immune system of other ruminants. Lymph node neutrophils were identified as CD45 CD172a, CD14, MHCII, BAQ44A, CD44, CD18 cells. In conclusion, the present study is describing the employment of flow cytometric single-cell analysis and immunostaining for the analysis of the immune cell composition in the camel lymph node.
PubMed: 38746932
DOI: 10.3389/fvets.2024.1365319 -
The Clinical Respiratory Journal May 2024This study aimed to explore the application value of human epididymis protein 4 (HE4) in diagnosing and monitoring the prognosis of lung cancer.
OBJECTIVE
This study aimed to explore the application value of human epididymis protein 4 (HE4) in diagnosing and monitoring the prognosis of lung cancer.
METHODS
First, TCGA (The Cancer Genome Atlas) databases were used to analyze whey-acidic-protein 4-disulfide bond core domain 2 (WFDC2) gene expression levels in lung cancer tissues. Then, a total of 160 individuals were enrolled, categorized into three groups: the lung cancer group (n = 80), the benign lesions group (n = 40), and the healthy controls group (n = 40). Serum HE4 levels and other biomarkers were quantified using an electro-chemiluminescent immunoassay. Additionally, the expression of HE4 in tissues was analyzed through immunohistochemistry (IHC). In vitro cultures of human airway epithelial (human bronchial epithelial [HBE]) cells and various lung cancer cell lines (SPC/PC9/A594/H520) were utilized to detect HE4 levels via western blot (WB).
RESULTS
Analysis of the TCGA and UALCAN (The University of Alabama at Birmingham Cancer Data Analysis Portal) databases showed that WFDC2 gene expression levels were upregulated in lung cancer tissues (p < 0.01). Compared with the control group and the benign group, HE4 was significantly higher in the serum of patients with lung cancer (p < 0.001). Receiver operating characteristic (ROC) analysis confirmed that HE4 had better diagnostic efficacy than classical markers in the differential diagnosis of lung cancer and benign lesions and had the highest diagnostic value in lung adenocarcinoma (area under the ROC curve [AUC] = 0.826). HE4 increased in early lung cancer and positively correlated with poor prognosis (p < 0.001). Moreover, the results of WB and IHC revealed that the expression of HE4 was increased in lung cancer cells (SPC/A549/H520) and lung cancer tissues but decreased in PC9 cells with a lack of exon EGFR19 (p < 0.05).
CONCLUSION
Serum HE4 emerges as a promising novel biomarker for the diagnosis and prognosis assessment of lung cancer.
Topics: Humans; WAP Four-Disulfide Core Domain Protein 2; Lung Neoplasms; Biomarkers, Tumor; Male; Prognosis; Female; Middle Aged; Proteins; Aged; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Immunohistochemistry
PubMed: 38742362
DOI: 10.1111/crj.13774 -
Journal of Thoracic Disease Apr 2024Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant...
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant mitochondrial signaling and mitochondrial dysfunction underlie the pathomechanisms leading to COPD. This study aims to investigate the effects of the Yiqigubiao (YQGB) pill, a traditional Chinese medicine (TCM), on Sirtuin 5 (SIRT5) and mitochondrial function in patients with COPD.
METHODS
Thirty-four patients with COPD were randomized into oral YQGB or placebo groups concurrent with a 24-week routine treatment. The pulmonary function was assessed by examining the levels of forced expiratory volume in one second (FEV)/forced vital capacity (FVC), FEV, and FVC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect SIRT5 expression in mitochondria isolated from peripheral blood. Flow cytometry was used to detect changes in mitochondrial membrane potential and reactive oxygen species (ROS) in peripheral blood lymphocytes. Human bronchial epithelial (HBE) cells stimulated by cigarette smoke extract (CSE) were treated with YQGB. After SIRT5 was knocked down in cells, the changes in mitochondrial membrane potential, levels of adenosine triphosphate (ATP), and ROS were detected.
RESULTS
YQGB treatment significantly improved lung function in patients with COPD. The expression of SIRT5 and the mitochondrial membrane potential significantly increased and ROS decreased in patients with COPD after YQGB treatment. The CSE decreased cell proliferation and SIRT5 expression, which was alleviated after YQGB treatment. Furthermore, SIRT5 was knocked down in CSE-stimulated HBE cells, and its expression was elevated upon YQGB treatment. The knockdown of SIRT5 significantly altered the CSE-stimulation-induced dysregulation of mitochondrial membrane potential, ATP levels, and ROS. This was also restored after YQGB treatment.
CONCLUSIONS
YQGB treatment can elevate SIRT5 expression, restore mitochondrial function in COPD, and exert protective effects.
PubMed: 38738261
DOI: 10.21037/jtd-23-1115 -
Translational Cancer Research Apr 2024Tracheobronchopathia osteochondroplastica (TPO) is a rare, benign, chronic disorder of unknown etiology. It is characterized by submucosal nodules, often calcified,...
BACKGROUND
Tracheobronchopathia osteochondroplastica (TPO) is a rare, benign, chronic disorder of unknown etiology. It is characterized by submucosal nodules, often calcified, which predominantly affect the anterolateral aspects of the trachea and main bronchi, while sparing the posterior bronchial wall. The co-occurrence of TPO and lung cancer is exceedingly rare. This report presents a case of TPO association with early-stage lung cancer, which was managed through surgical intervention. No active treatment was undertaken for the TPO.
CASE DESCRIPTION
A patient presented with a nodule in the right upper lobe, which was identified during a computed tomography (CT) scan of the chest, suggestive of early-stage lung cancer. Concurrently, multiple calcifications in the cartilaginous rings of the trachea were noted. Bronchoscopy revealed distinctive "pebblestone" nodules along the anterior and lateral tracheal walls, indicative of extensive TPO. The patient underwent bronchofiberscopy, which showed patency in the bronchial lumen of the right lung's upper lobe. A biopsy was not undertaken during this procedure. Comprehensive preoperative tests, including a blood biochemical examination, tumor-marker tests, lung-function tests, head-enhanced magnetic resonance imaging, abdominal ultrasound, and whole-body bone emission CT revealed no significant abnormalities. Despite this, the patient declined a whole-body positron emission tomography (PET)-CT scan. Given the potential malignancy of nodules in the right lung's upper lobe, the lobectomy for lung cancer was carried out, a procedure that would have proceeded irrespective of the presence or absence of TPO. Preoperative planning for potential tracheal intubation difficulties involved consultation with the anesthesiologist, resulting in a smooth intraoperative process. The pathology confirmed invasive adenocarcinoma. Post-surgery, the patient developed an infection in the right lung's lower lobe, identified as pseudomonas aeruginosa and through sputum culture and bronchoscopic lavage. Treatment with meropenem for 2 weeks, as guided by drug sensitivity results and respiratory advice, led to an improvement, allowing for discharge. A follow-up lung CT four months post-operation showed inflammation absorption in the right lower lobe.
CONCLUSIONS
Surgical resection in cases of TPO association with lung cancer may have an increased risk of postoperative pulmonary infection. Proactive intraoperative sputum aspiration by anesthesiologists and the postoperative reinforcement of anti-infection measures, guided by drug sensitivity results, are recommended.
PubMed: 38737686
DOI: 10.21037/tcr-24-410 -
Journal of Respiratory Biology and... Mar 2024Released mitochondrial DNA (mtDNA) in cells activates cGAS-STING pathway, which induces expression of interferon-stimulated genes (ISGs) and thereby promotes...
Released mitochondrial DNA (mtDNA) in cells activates cGAS-STING pathway, which induces expression of interferon-stimulated genes (ISGs) and thereby promotes inflammation, as frequently seen in asthmatic airways. However, whether the genetic determinant, Gasdermin B (GSDMB), the most replicated asthma risk gene, regulates this pathway remains unknown. We set out to determine whether and how GSDMB regulates mtDNA-activated cGAS-STING pathway and subsequent induction in human airway epithelial cells. Using qPCR, ELISA, native polyacrylamide gel electrophoresis, co-immunoprecipitation and immunofluorescence assays, we evaluated the regulation of GSDMB on cGAS-STING pathway in both BEAS-2B cells and primary normal human bronchial epithelial cells (nHBEs). mtDNA was extracted in plasma samples from human asthmatics and the correlation between mtDNA levels and eosinophil counts was analyzed. is significantly associated with expression in asthmatic nasal epithelial brushing samples from the Genes-environments and Admixture in Latino Americans (GALA) II study. Over-expression of promotes DNA-induced IFN and in bronchial epithelial BEAS-2B cells and nHBEs. Conversely, knockout of led to weakened induction of (IFNs) and in BEAS-2B cells. Mechanistically, GSDMB interacts with the C-terminus of STING, promoting the translocation of STING to Golgi, leading to the phosphorylation of IRF3 and induction of and . mtDNA copy number in serum from asthmatics was significantly correlated with blood eosinophil counts especially in male subjects. GSDMB promotes the activation of mtDNA and poly (dA:dT)-induced activation of cGAS-STING pathway in airway epithelial cells, leading to enhanced induction of
PubMed: 38737375
DOI: 10.35534/jrbtm.2024.10005 -
Stem Cell Research May 2024Human pluripotent stem cells (hiPSC) represent a unique opportunity to model lung development and chronic bronchial diseases. We generated a hiPSC line from a highly...
Human pluripotent stem cells (hiPSC) represent a unique opportunity to model lung development and chronic bronchial diseases. We generated a hiPSC line from a highly characterized healthy heavy smoker male donor free from emphysema or tobacco related disease. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using integration-free Sendai virus. The cell line had normal karyotype, expressed pluripotency hallmarks, and differentiated into the three primary germ layers. The reported UHOMi007-A iPSC line may be used as a control to model lung development, study human chronic bronchial diseases and drug testing.
PubMed: 38723411
DOI: 10.1016/j.scr.2024.103437 -
Frontiers in Immunology 2024Allergic asthma is a widely prevalent inflammatory condition affecting people across the globe. T cells and their secretory cytokines are central to the pathogenesis of...
Allergic asthma is a widely prevalent inflammatory condition affecting people across the globe. T cells and their secretory cytokines are central to the pathogenesis of allergic asthma. Here, we have evaluated the anti-inflammatory impact of dimethyl fumarate (DMF) in allergic asthma with more focus on determining its effect on T cell responses in allergic asthma. By utilizing the ovalbumin (OVA)-induced allergic asthma model, we observed that DMF administration reduced the allergic asthma symptoms and IgE levels in the OVA-induced mice model. Histopathological analysis showed that DMF treatment in an OVA-induced animal model eased the inflammation in the nasal and bronchial tissues, with a particular decrease in the infiltration of immune cells. Additionally, RT-qPCR analysis exhibited that treatment of DMF in an OVA-induced model reduced the expression of inflammatory cytokine (IL4, IL13, and IL17) while augmenting anti-inflammatory IL10 and Foxp3 (forkhead box protein 3). Mechanistically, we found that DMF increased the expression of Foxp3 by exacerbating the expression of nuclear factor E2-related factor 2 (Nrf2), and the in-vitro activation of Foxp3+ Tregs leads to an escalated expression of Nrf2. Notably, CD4-specific Nrf2 deletion intensified the allergic asthma symptoms and reduced the in-vitro iTreg differentiation. Meanwhile, DMF failed to exert protective effects on OVA-induced allergic asthma in CD4-specific Nrf2 knock-out mice. Overall, our study illustrates that DMF enhances Nrf2 signaling in T cells to assist the differentiation of Tregs, which could improve the anti-inflammatory immune response in allergic asthma.
Topics: Animals; Dimethyl Fumarate; NF-E2-Related Factor 2; Asthma; T-Lymphocytes, Regulatory; Mice; Signal Transduction; Disease Models, Animal; Ovalbumin; Cytokines; Mice, Inbred C57BL; Mice, Knockout; Female; Mice, Inbred BALB C
PubMed: 38711519
DOI: 10.3389/fimmu.2024.1375340 -
European Journal of Medical Research May 2024Bleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE AND OBJECTIVES
Bleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety.
MATERIALS AND METHODS
In this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications.
RESULTS
Exactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182).
CONCLUSION
A pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding.
REGISTRATION NUMBER
NCT04047667 ( www.
CLINICALTRIALS
gov identifier).
Topics: Humans; Male; Female; Lung Diseases, Interstitial; Middle Aged; Aged; Prospective Studies; Bronchoscopy; Cryosurgery; Biopsy; Hemorrhage; Lung; Bronchi
PubMed: 38702744
DOI: 10.1186/s40001-024-01871-y -
The New Microbiologica May 2024Acute respiratory tract infection (ARTI) is common in all age groups, especially in children and the elderly. About 85% of children who present with bronchiolitis are...
Acute respiratory tract infection (ARTI) is common in all age groups, especially in children and the elderly. About 85% of children who present with bronchiolitis are infected with respiratory syncytial virus (RSV); however, nearly one-third are coinfected with another respiratory virus, such as human rhinovirus (HRV). Therefore, it is necessary to explore the immune response to coinfection to better understand the molecular and cellular pathways involving virus-virus interactions that might be modulated by innate immunity and additional host cell response mechanisms. This study aims to investigate the host innate immune response against RSV-HRV coinfection compared with monoinfection. Human primary bronchial/tracheal epithelial cells (HPECs) were infected with RSV, HRV, or coinfected with both viruses, and the infected cells were collected at 48 and 72 hours. Gene expression profiles of IL-6, CCL5, TNF-α, IFN-β, IFN-λ1, CXCL10, IL-10, IL-13, IRF3, and IRF7 were investigated using real-time quantitative PCR, which revealed that RSV-infected cells exhibited increased expression of IL-10, whereas HRV infection increased the expression of CXCL10, IL-10, and CCL5. IFN-λ1 and CXCL10 expression was significantly different between the coinfection and monoinfection groups. In conclusion, our study revealed that two important cytokines, IFN-λ1 and CXCL10, exhibited increased expression during coinfection.
Topics: Humans; Rhinovirus; Coinfection; Chemokine CXCL10; Epithelial Cells; Respiratory Syncytial Virus Infections; Bronchi; Picornaviridae Infections; Interferons; Respiratory Syncytial Virus, Human; Cells, Cultured; Respiratory Syncytial Viruses; Interferon Lambda; Interleukins
PubMed: 38700885
DOI: No ID Found -
Evaluation of biological markers for the risk assessment of carbon black in epidemiological studies.Frontiers in Public Health 2024Engineered nanomaterials (ENMs) have been suggested as being capable of promoting inflammation, a key component in the pathways associated with carcinogenesis,... (Review)
Review
BACKGROUND/OBJECTIVES
Engineered nanomaterials (ENMs) have been suggested as being capable of promoting inflammation, a key component in the pathways associated with carcinogenesis, cardiovascular disease, and other conditions. As a result, the risk assessment of biological markers as early-stage indicators has the potential to improve translation from experimental toxicologic findings to identifying evidence in human studies. The study aims to review the possible early biological changes in workers exposed to carbon black (CB), followed by an evidentiary quality evaluation to determine the predictive value of the biological markers.
METHODS
We conducted a literature search to identify epidemiological studies that assessed biological markers that were involved in the inflammatory process at early stages among workers with exposure to CB. We reviewed the studies with specific reference to the study design, statistical analyses, findings, and limitations.
RESULTS
We identified five Chinese studies that investigated the potential impact of exposure to CB on inflammatory markers, bronchial wall thickening, genomic instability, and lung function impairment in CB production workers. Of the five Chinese studies, four were cross-sectional; another study reported results at two-time points over six years of follow-up. The authors of all five studies concluded positive relationships between exposure and the inflammatory cytokine profiles. The weak to very weak correlations between biomarkers and early-stage endpoints were reported.
CONCLUSION
Most inflammatory markers failed to satisfy the proposed evidentiary quality criteria. The significance of the results of the reviewed studies is limited by the cross-sectional study design, inconsistency in results, uncertain clinical relevance, and high occupational exposures. Based on this review, the risk assessment relying on inflammatory markers does not seem appropriate at this time. Nevertheless, the novel research warrants further exploration in assessing exposure to ENMs and corresponding potential health risks in occupational settings.
Topics: Humans; Biomarkers; Soot; Risk Assessment; Occupational Exposure; Epidemiologic Studies; Inflammation
PubMed: 38689765
DOI: 10.3389/fpubh.2024.1367797