A case of response to combination treatment with TSA-DC-CTL immunotherapy and osimertinib in EGFR mutated advanced lung adenocarcinoma.

BACKGROUND: This study details a case of a patient with advanced lung adenocarcinoma harboring an exon 19 deletion in the EGFR gene. METHOD: A 46-year-old female patient was diagnosed with stage IVb left lung adenocarcinoma, with multiple bone and lymph node metastases. Following the identification of tumor-specific antigen peptides, the patient received a combination treatment of immunotherapy (TSA-DC-CTL) and oral osimertinib. Peripheral blood circulating immune cells and circulating tumor cells (CTCs) were monitored before and after treatment. PET-CT and CT scans were used to assess the tumor response to treatment. RESULTS: A significant increase in total lymphocyte percentage and decrease in the number of CTCs in the patient was observed. Imaging studies showed a notable reduction in tumor metastases. CONCLUSION: This report demonstrates the safety and efficacy of TSA-DC-CTL cell immunotherapy combined with osimertinib in the treatment of a patient with advanced lung adenocarcinoma with an EGFR exon 19 deletions. This study describes a promising new treatment option for patients with advanced lung cancer with EGFR mutations.

ncRNA-mediated SOX4 overexpression correlates with unfavorable outcomes and immune infiltration in hepatocellular carcinoma.

BACKGROUND: The activity and number of immune cells in the tumor microenvironment are closely related to the overall survival of patients with hepatocellular carcinoma (HCC). The sex-determining region Y-box 4 (SOX4) gene is abnormally expressed in various tumor tissues and is critical for tumor development. However, the correlation between SOX4 expression in HCC and tumor immunity is unclear. METHODS: SOX4 expression was explored using data from The Cancer Genome Atlas, and UALCAN databases. Real-time reverse transcription quantitative and western blotting were used to analyze SOX4 expression in several liver cancer cell lines. Additionally, correlations among SOX4 expression, cancer immune characteristics, and infiltrated immune cell gene marker sets in patients with HCC were analyzed using data from the Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, and Tumor-Immune System Interactions databases. Moreover, we evaluated SOX4 expression in HCC tissues and the correlation of SOX4 expression with survival rate. Subsequently, noncoding RNAs (ncRNAs) responsible for SOX4 overexpression were identified using expression, correlation, and survival analyses. RESULTS: SOX4 expression was significantly upregulated in HCC and correlated with a poor prognosis. Additionally, SOX4 upregulation in HCC positively correlated with immune cell infiltration, several biomarkers of immune cells, and immune checkpoint expression. Finally, the MCM3AP-AS1/hsa-miR-204-5p axis was identified as the most likely upstream ncRNA-related pathway for SOX4 in HCC. These results indicated that ncRNA-mediated upregulation of SOX4 correlated with the immune infiltration level and poor prognosis in HCC. Our findings provide new directions for the development of novel immunotherapeutic targets for HCC.

One-pot synthesis and hydrogen peroxide electrochemical sensing of 3D TiO2/MnO2 nanorods assembled microspheres.

Nanorods assembled 3D microspheres of TiO2/MnO2 were prepared via a simple one-pot hydrothermal approach. The resultant composite material exhibited remarkable electrocatalytic activity for hydrogen peroxide (H2O2) in comparison to each single component. The electrochemical sensor constructed with TiO2/MnO2 exhibited a linear relationship within the range 0.0001-5.6 mmol·L-1 for H2O2. The limit of detection (LOD) and sensitivity for H2O2 were 0.03 µmol·L-1 (S/N = 3) and 316.6 µA (mmol·L-1)-1 cm-2. Moreover, this sensor can be employed to detect trace amount of H2O2 in serum and urine samples successfully, supporting an insight and strategy for a more sensitive electrochemical sensor.

From gut to liver: unveiling the differences of intestinal microbiota in NAFL and NASH patients.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized for its global prevalence and potential progression to more severe liver diseases such as non-alcoholic steatohepatitis (NASH). The gut microbiota plays a pivotal role in the pathogenesis of NAFLD, yet the detailed characteristics and ecological alterations of gut microbial communities during the progression from non-alcoholic fatty liver (NAFL) to NASH remain poorly understood. Methods: In this study, we conducted a comparative analysis of gut microbiota composition in individuals with NAFL and NASH to elucidate differences and characteristics. We utilized 16S rRNA sequencing to compare the intestinal gut microbiota among a healthy control group (65 cases), NAFL group (64 cases), and NASH group (53 cases). Random forest machine learning and database validation methods were employed to analyze the data. Results: Our findings indicate a significant decrease in the diversity of intestinal flora during the progression of NAFLD (p < 0.05). At the phylum level, high abundances of Bacteroidetes and Fusobacteria were observed in both NAFL and NASH patients, whereas Firmicutes were less abundant. At the genus level, a significant decrease in Prevotella expression was seen in the NAFL group (AUC 0.738), whereas an increase in the combination of Megamonas and Fusobacterium was noted in the NASH group (AUC 0.769). Furthermore, KEGG pathway analysis highlighted significant disturbances in various types of glucose metabolism pathways in the NASH group compared to the NAFL group, as well as notably compromised flavonoid and flavonol biosynthesis functions. The study uncovers distinct microbiota characteristics and microecological changes within the gut during the transition from NAFL to NASH, providing insights that could facilitate the discovery of novel biomarkers and therapeutic targets for NAFLD.

Mechanistic insights into rumen function promotion through yeast culture (Saccharomyces cerevisiae) metabolites using in vitro and in vivo models.

Introduction: Yeast culture (YC) enhances ruminant performance, but its functional mechanism remains unclear because of the complex composition of YC and the uncertain substances affecting rumen fermentation. The objective of this study was to determine the composition of effective metabolites in YC by exploring its effects on rumen fermentation in vitro, growth and slaughter performance, serum index, rumen fermentation parameters, rumen microorganisms, and metabolites in lambs. Methods: In Trial 1, various YCs were successfully produced, providing raw materials for identifying effective metabolites. The experiment was divided into 5 treatment groups with 5 replicates in each group: the control group (basal diet without additives) and YC groups were supplemented with 0.625‰ of four different yeast cultures, respectively (groups A, B, C, and D). Rumen fermentation parameters were determined at 3, 6, 12, and 24 h in vitro. A univariate regression model multiple factor associative effects index (MFAEI; y) was established to correlate the most influential factors on in vitro rumen fermentation with YC metabolites (x). This identified the metabolites promoting rumen fermentation and optimal YC substance levels. In Trial 2, metabolites in YC not positively correlated with MFAEI were excluded, and effective substances were combined with pure chemicals (M group). This experiment validated the effectiveness of YC metabolites in lamb production based on their impact on growth, slaughter performance, serum indices, rumen parameters, microorganisms, and metabolites. Thirty cross-generation rams (Small tail Han-yang ♀ × Australian white sheep ♂) with good body condition and similar body weight were divided into three treatment groups with 10 replicates in each group: control group, YC group, pure chemicals combination group (M group). Results: Growth performance and serum index were measured on days 30 and 60, and slaughter performance, rumen fermentation parameters, microorganisms, and metabolites were measured on day 60. The M group significantly increased the dressing percentage, and significantly decreased the GR values of lambs (p < 0.05). The concentration of growth hormone (GH), Cortisol, insulin (INS), and rumen VFA in the M group significantly increased (p < 0.05). Discussion: These experiments confirmed that YC or its screened effective metabolites positively impact lamb slaughter performance, rumen fermentation, and microbial metabolism.