Analysis of Differential Gel Electrophoresis of Paclitaxol Resistant and Sensitive Lung Adenocarcinoma Cells' Secretome

Background and objective Paclitaxol (PTX) resistance is one of main factors which affect the outcome of chemotherapy of lung adenocarcinoma. The aim of this study is to compare the secreted protein expression profiles between Paclitaxol (PTX) resistant and sensitive lung adenocarcinoma cells by proteomic research method, so as to provide evidence of choosing individual chemotherapy drugs in clinical treatment. Methods Total secreted proteins extracted from a PTX sensitive cell line A549 and a PTX resistant cell line A549-Taxol were separated by fluorscent differential gel electrophoresis (DIGE). High quality 2-DE profiles were obtained and analyzed by Decyder 6.5 analysis software to screen differentially expressed protein spots. Those spots were identified by mass spectrometry. Results 2-DE patterns of lung adenocarcinoma cells with high-resolution and reproducibility were obtained. 76 significantly differentially expressed protein spots were screened, 19 proteins were identified by mass spectrometry. The identified proteins could be classified into different catogories: metabolic enzyme, extracellular matrix (ECM) degradation enzyme, cytokine, signal transducer, cell adhesion, and so on. Conclusion Multiple secreted proteins related to chemoresistance of A549-Taxol cells were identified in this study for the first time. The results presented here would provide clues to identify new serologic chemoresistant biomarkers of NSCLC

Clinical characteristics and prognostic factors for short-term outcomes of autoimmune glial fibrillary acidic protein astrocytopathy: a retrospective analysis of 33 patients

BackgroundAutoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a recently discovered inflammatory central nervous system (CNS) disease, whose clinical characteristics and prognostic factors for short-term outcomes have not been defined yet. We aimed to assess the symptoms, laboratory tests, imaging findings, treatment, and short-term prognosis of GFAP-A.MethodsA double-center retrospective cohort study was performed between May 2018 and July 2022. The clinical characteristics and prognostic factors for short-term outcomes were determined.ResultsWe enrolled 33 patients with a median age of 28 years (range: 2–68 years), 15 of whom were children (<18 years). The clinical spectrum is dominated by meningoencephalomyelitis. Besides, we also found nausea, vomiting, poor appetite, and neuropathic pain in some GFAP-A patients, which were not mentioned in previous reports. And adults were more prone to limb numbness than children. Magnetic resonance imaging revealed lesions involving the brain parenchyma, meninges, and spinal cord, exhibiting patchy, linear, punctate, and strip T2 hyperintensities. First-line immunotherapy, including corticosteroid and gamma globulin, was effective in most patients in the acute phase (P = 0.02). However, patients with overlapping AQP4 antibodies did not respond well to first-line immunotherapy and coexisting neural autoantibodies were more common in women. Additionally, the short-term prognosis was significantly better in children than in adults (P = 0.04). Positive non-neural autoantibodies and proven viral infection were independent factors associated with poor outcomes (P = 0.03, 0.02, respectively).ConclusionWe expanded the spectrum of clinical symptoms of autoimmune GFAP-A. The clinical symptoms and short-term prognosis differed between children and adults. Positive non-neural autoantibodies and proven viral infection at admission suggest a poor short-term prognosis

Unraveling the transcriptome-based network of tfh cells in primary sjogren syndrome: insights from a systems biology approach

BackgroundPrimary Sjogren Syndrome (pSS) is an autoimmune disease characterized by immune cell infiltration. While the presence of follicular T helper (Tfh) cells in the glandular microenvironment has been observed, their biological functions and clinical significance remain poorly understood.MethodsWe enrolled a total of 106 patients with pSS and 46 patients without pSS for this study. Clinical data and labial salivary gland (LSG) biopsies were collected from all participants. Histological staining was performed to assess the distribution of Tfh cells and B cells. Transcriptome analysis using RNA-sequencing (RNA-seq) was conducted on 56 patients with pSS and 26 patients without pSS to uncover the underlying molecular mechanisms of Tfh cells. To categorize patients, we employed the single-sample gene set enrichment analysis (ssGSEA) algorithm, dividing them into low- and high-Tfh groups. We then utilized gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and deconvolution tools to explore functional and immune infiltration differences between the low- and high-Tfh groups.ResultsPatients with pSS had a higher positive rate of the antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB and hypergammaglobulinaemia and higher levels of serum IgG compared to the non-pSS. Histopathologic analyses revealed the presence of Tfh cells (CD4+CXCR5+ICOS+) in germinal centers (GC) within the labial glands of pSS patients. GSEA, WGCNA, and correlation analysis indicated that the high-Tfh group was associated with an immune response related to virus-mediated IFN response and metabolic processes, primarily characterized by hypoxia, elevated glycolysis, and oxidative phosphorylation levels. In pSS, most immune cell types exhibited significantly higher infiltration levels in the high-Tfh group compared to the low-Tfh group. Additionally, patients in the Tfh-high group demonstrated a higher positive rate of the ANA, rheumatoid factor (RF), and hypergammaglobulinaemia, as well as higher serum IgG levels.ConclusionOur study suggests that Tfh cells may play a crucial role in the pathogenesis of pSS and could serve as potential therapeutic targets in pSS patients

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

BackgroundCheckpoint inhibitor–related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined.MethodsWe conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase’s characteristics.ResultsThere were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005).ConclusionsThe general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised

Single internal carotid cavernous sinus aneurysm presented as bilateral painful ophthalmoplegia: a case report

Abstract Background Intracranial aneurysms are the most common vascular cause of painful ophthalmoplegia. Symptoms include retro-orbital pain, diplopia, ophthalmoplegia, trigeminal neuropathy, or a combination of these. Most single aneurysms cause ipsilateral, painful ophthalmoplegia. Here, we report the first, to our knowledge, case of bilateral painful ophthalmoplegia possibly caused by an aneurysm of the cavernous segment of the left internal carotid artery. Case presentation A 62-year-old male patient presented with headache and bilateral ptosis. Laboratory tests revealed hypopituitary function. Computerized tomography angiography showed a large aneurysm in the cavernous sinus segment of the left internal carotid artery. Aneurysm embolization was performed in the Nerve Interventional Department. Four months after surgery, the patient's symptoms returned to normal. Conclusions This case suggests that patients with bilateral painful ophthalmoplegia should be screened for aneurysms using computed tomography angiography or magnetic resonance angiography immediately

Impacts of Maternal Diet and Alcohol Consumption during Pregnancy on Maternal and Infant Gut Microbiota

(1) Background: Maternal diet and alcohol consumption can influence both maternal and infant’s gut microbiota. These relationships are still not examined in the Chinese population. The purpose of this study was to explore the effect of alcohol consumption and maternal diet during pregnancy on maternal and infant’s gut microbiota. (2) Methods: Twenty-nine mother-child dyads were enrolled in central China. Fecal samples of mothers during late pregnancy and of newborns within 48 h were collected. The V3–V4 regions of 16S rRNA sequences were analyzed. A self-administrated questionnaire about simple diet frequency in the past week was completed by mothers before childbirth. The demographic information was finished by mothers at 24 h after childbirth. (3) Results: Among these 29 mothers, 10 mothers reported alcohol consumption during pregnancy. The PCoA (β-diversity) showed significant difference in maternal gut microbiota between the alcohol consumption group vs. the non-alcohol consumption group (abund-Jaccard, r = 0.2, p = 0.006). The same phenomenon was observed in newborns (unweighted-UniFrac full tree, r = 0.174, p = 0.031). Maternal alcohol consumption frequency showed positive associations with maternal Phascolarctobacterium (p = 0.032) and Blautia (p = 0.019); maternal Faecalibacterium (p = 0.013) was negatively correlated with frequency of alcohol consumption. As for newborns, a positive relationship showed between Megamonas (p = 0.035) and newborns with maternal alcohol consumption. The diet was not associated with both maternal and infant’s gut microbiota. (4) Conclusions: Maternal alcohol consumption during pregnancy influenced the gut microbiota on both mothers and the newborns. Future research is needed to explore these relationships in a lager birth cohort. Understanding the long-term effect of alcohol consumption on maternal and newborns’ gut microbiota is needed

H3K36 Histone Methyltransferase Setd2 Is Required for Murine Embryonic Stem Cell Differentiation toward Endoderm

Setd2 is known as a histone-H3K36-specific methyltransferase. However, its role in physiological function remains unclear. In this study, we show that Setd2 mainly regulates differentiation of murine embryonic stem cells (mESCs) toward primitive endoderm. Furthermore, we show that downregulated endoderm-related genes in Setd2−/− mESCs are associated with an aberrantly low level of Erk activity and that enforced expression of Fgfr3 can rescue the defective Erk pathway in Setd2−/− mESCs. Interestingly, the transcriptional initiation of Fgfr3 is directly regulated through histone H3K36me3 modification in its distal promoter region by Setd2. These results indicate that Setd2 controls the primitive endoderm differentiation of mESCs by regulating the Fgfr3-Erk signaling

Nuclear mitochondria-related genes-based molecular classification and prognostic signature reveal immune landscape, somatic mutation, and prognosis for glioma

Background: Glioma is the most frequent malignant primary brain tumor, and mitochondria may influence the progression of glioma. The aim of this study was to analyze the role of nuclear mitochondria related genes (MTRGs) in glioma, identify subtypes and construct a prognostic model based on nuclear MTRGs and machine learning algorithms. Methods: Samples containing both gene expression profiles and clinical information were retrieved from the TCGA database, CGGA database, and GEO database. We selected 16 nuclear MTRGs and identified two clusters of glioma. Prognostic features, microenvironment, mutation landscape, and drug sensitivity were compared between the clusters. A prognostic model based on multiple machine learning algorithms was then constructed and validated by multiple datasets. Results: We observed significant discrepancies between the two clusters. Cluster One had higher nuclear MTRG expression, a lower survival rate, and higher immune infiltration than Cluster Two. For the two clusters, we found distinct predictive drug sensitivities and responses to immune therapy, and the infiltration of immune cells was significantly different. Among the 22 combinations of machine learning algorithms we tested, LASSO was the most effective in constructing the prognostic model. The model's accuracy was further verified in three independent glioma datasets. We identified MGME1 as a vital gene associated with infiltrating immune cells in multiple types of tumors. Conclusion: In short, our research identified two clusters of glioma and developed a dependable prognostic model based on machine learning methods. MGME1 was identified as a potential biomarker for multiple tumors. Our results will contribute to precise medicine and glioma management