Improving aromatic higher alcohol acetates in wines by co-fermentation of Pichia kluyveri and Saccharomyces cerevisiae: growth interaction and amino acid competition.

BACKGROUND: Higher alcohol acetates (HAAs) are potent aroma-active esters that impart desirable fruity and floral aromas. However, the conversion of higher alcohol precursors into HAAs is extremely low in winemaking. To investigate the underlying yeast-yeast interaction on targeted improvement of aromatic HAAs, we evaluated fermentation activity, cell viability, amino acid consumption and HAA production when Pichia kluyveri and Saccharomyces cerevisiae were inoculated concurrently or sequentially. RESULTS: Pichia kluyveri PK-21 possessed the ability to survive and increased HAA level up to 5.2-fold in mixed fermentation. Such an increment may benefit from the efficient conversion of higher alcohol precursors into HAAs (>27-fold higher than S. cerevisiae). During mixed fermentation, the two yeasts exhibited crucial interactions regarding cell growth and amino acid competition. Saccharomyces cerevisiae dominated over the co-inoculated P. kluyveri by efficient uptake of amino acids and biomass production. However, this dominance decreased in sequential fermentation, where P. kluyveri growth increased due to the consumption of preferred amino acids prior to S. cerevisiae. Pearson correlation analysis indicated that phenylalanine and aspartic acid may act as positive amino acids in boosting P. kluyveri growth and HAA production. Laboratory-scale winemaking validated the fermentation performance of P. kluyveri in sequential inoculum, resulting in a balanced aroma profile with enhanced floral and tropical fruity characteristics in the final wines. CONCLUSION: This study proposes a microbial, non-genetically engineered approach for targeted increase of HAA production in winemaking and the findings provide new insights into yeast-yeast interactions. © 2024 Society of Chemical Industry.

Imaging features and radiologic-pathologic correlations of inflammatory pseudotumor-like follicular dendritic cell sarcoma.

BACKGROUND: Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare tumor. This study aimed to reveal the radiological characteristics of IPT-like FDCS by radiologic-pathologic correlation. RESULTS: We analyzed two cases of IPT-like FDCS in the liver, nine in the spleen, and two in both the liver and spleen concomitantly. IPT-like FDCS presented as well-defined iso- or hypodense masses on unenhanced computed tomography (CT) images in both the liver and spleen. Hyperintensities on T1-weighted images and hypointensities on T2-weighted images with hypointense rings were characteristic features in splenic cases. "Halo signs" were observed in two out of three liver tumors. Hepatic lesions showed significant enhancement, whereas splenic lesions showed only mild enhancement. Delayed annular enhancement was observed in both liver and spleen cases. On ultrasonographic examination, IPT-like FDCS presented as hypoechoic lesions with enhancement similar to that observed on CT. Hyaline fibrous pseudocapsules, which correlated with the hypointensities on T2-weighted images, were microscopically observed at the tumor edge. IPT-like FDCS was characterized by an abundance of small blood vessels and capillaries. Capillaries were also found in the fibrous capsule of some IPT-like FDCSs, which may explain the delayed annular enhancement. CONCLUSIONS: The manifestations of IPT-like FDCS in the liver and spleen showed differences that warrant them to be approached differently during diagnosis. Characteristic radiological findings of IPT-like FDCS included different enhancement patterns between liver and spleen tumors and rim-like hypointensities on T2-weighted images, as well as annular enhancement on CT and magnetic resonance images. These imaging features correlated with tumor pathology.

Corrigendum: Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity.

[This corrects the article DOI: 10.3389/fphar.2022.780148.].

Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity.

Metformin has been involved in modulating inflammatory state and inhibiting cell proliferation and angiogenesis. This study aimed to determine whether metformin alleviates airway inflammation and remodeling of experimental allergic asthma and elucidate the underlying mechanism. We sensitized and challenged mice with ovalbumin (OVA) to induce allergic asthma. During the challenge period, metformin was administered by intraperitoneal injection. By histopathological and immunohistochemical analyses, metformin-treated mice showed a significant alleviation in airway inflammation, and in the parameters of airway remodeling including goblet cell hyperplasia, collagen deposition and airway smooth muscle hypertrophy compared to those in the OVA-challenged mice. We also observed elevated levels of multiple cytokines (IL-4, IL-5, IL-13, TNF-α, TGF-ß1 and MMP-9) in the bronchoalveolar lavage fluid, OVA-specific IgE in the serum and angiogenesis-related factors (VEGF, SDF-1 and CXCR4) in the plasma from asthmatic mice, while metformin reduced all these parameters. Additionally, the activity of 5'-adenosine monophosphate-activated protein kinase a (AMPKα) in the lungs from OVA-challenged mice was remarkably lower than control ones, while after metformin treatment, the ratio of p-AMPKα to AMPKα was upregulated and new blood vessels in the sub-epithelial area as evidenced by CD31 staining were effectively suppressed. These results indicate that metformin ameliorates airway inflammation and remodeling in an OVA-induced chronic asthmatic model and its protective role could be associated with the restoration of AMPKα activity and decreased asthma-related angiogenesis.

Long non-coding RNA LINC00887 promotes progression of lung carcinoma by targeting the microRNA-206/NRP1 axis.

Long non-coding RNAs (lncRNAs) have been reported to participate in multiple biological processes, including tumorigenesis. In the current study, the function of a novel lncRNA LINC00887 was investigated in lung carcinoma. For this purpose, LINC00887 expression was assessed by reverse-transcription quantitative PCR. Cell viability was determined by the CCK-8 and EdU assays. Cell invasion, migration were assessed by the transwell and wound healing assays, respectively. A dual luciferase assay was used for analysis of the interaction between LINC00887 and miR-206, as well as the relationship of miR-206 with NRP1. A tumor xenograft study was performed to investigate the LINC00887-miR-206-NRP1 axis in vivo. The expression levels of LINC00887 were upregulated in lung carcinoma tissues and cells compared with adjacent tissues or normal cells (BEAS-2B). Knockdown LINC00887 significantly inhibited the proliferation, migration and invasion of lung carcinoma A549 and NCI-H460 cells. Furthermore, LINC00887 was identified as a competing endogenous RNA and to directly interact with miR-206. Mechanistically, miR-206 was demonstrated to regulate neuropilin-1 (NRP1) expression by targeting the NRP1 3'-untranslated region. The results of the present study suggested that the LINC00887-miR-206-NRP1 axis served a critical role in regulating lung carcinoma cell proliferation, migration and invasion. In addition, xenograft tumor model experiments revealed that silencing LINC00887 suppressed lung carcinoma tumor growth of in vivo. In summary, our results suggest that LINC00887 may serve an oncogenic role in lung carcinoma by targeting the miR-206/NRP1 axis, providing a potential therapeutic target for patients with lung carcinoma.

miR­205­3p promotes lung cancer progression by targeting APBB2.

Non­small cell lung cancer (NSCLC), a leading cause of cancer­associated mortality, has resulted in low survival rates and a high mortality worldwide. Accumulating evidence has suggested that microRNAs (miRs) play critical roles in the regulation of cancer progression and the present study aimed to explore the underlying mechanism of miR­205 in NSCLC. Reverse transcription­quantitative PCR was performed, which determined that miR­205 expression was upregulated in NSCLC, and the present study detected the upregulation of miR­205­3p in a number of NSCLC cell lines and NSCLC tissues. In addition, the mediation of amyloid ß precursor protein­binding family B member 2 (APBB2) by miR­205­3p was demonstrated. Moreover, miR­205­3p was predicted to directly target the 3'untranslated region of APBB2, which was confirmed using a dual­luciferase reporter assay. It was found that lentivirus mediated­APBB2 knockdown could promote cellular viability and suppress apoptosis in NSCLC cells, as determined via MTT, TUNEL and flow cytometry assays. Thus, the current findings highlighted the potential promotive impact of miR­205­3p on NSCLC processes and may provide theoretical evidence for miR­205­3p as a potential clinical gene therapy target.

Evaluation of three-dimensional arterial spin labeling perfusion imaging for the pathological investigation of musculoskeletal tumors.

The present study aimed to assess the clinical utility of three-dimensional arterial spin labeling (3D-ASL) perfusion imaging in discriminating between benign, intermediate and malignant musculoskeletal tumors, as well as to analyze the correlation between tumor blood flow (TBF) and microvessel density (MVD). 3D-ASL was performed on 44 patients with musculoskeletal tumor using a 3.0-T magnetic resonance system to obtain TBF values prior to surgery. TBF was independently measured by two radiologists. The TBF values of different groups were compared by one-way analysis of variance. A receiver operating characteristic (ROC) curve was applied to assess the threshold and diagnostic reliability of TBF. Immunohistochemical staining of tumor specimens was performed using a cluster of differentiation 34 monoclonal antibody to calculate MVD counts. The correlation between TBF and MVD counts was analyzed using correlative analysis. Pathology results for a total of 44 cases were obtained by surgery. Good interobserver agreement was found for the TBF values independently determined by the two radiologists (intra-class correlation coefficient test, 0.891; P<0.05). TBF and MVD values in the malignant group were significantly higher compared with that of the benign, and intermediate groups. No significant difference was found between the TBF and MVD values of the benign, and intermediate groups. According to the ROC analysis, the area under the curve was largest (0.951) when 45.5 ml/min/100 g was considered as the TBF cut-off value in the diagnosis. The diagnostic sensitivity and specificity were 90.5 and 100%, respectively. Additionally, a significant positive correlation was found between TBF and MVD (r, 0.784; P<0.05). The results of the present study suggest that 3D-ASL is valuable in discriminating between benign, intermediate and malignant musculoskeletal tumors. 3D-ASL may be utilized to evaluate angiogenesis in musculoskeletal tumors in vivo.

Ulinastatin- and thymosin α1-based immunomodulatory strategy for sepsis: A meta-analysis.

OBJECTIVE: This meta-analysis was performed to evaluate the efficacy of ulinastatin (UTI) and thymosin α1 (Tα1) based immunomodulatory strategy in sepsis patients. METHODS: A systematic search was made of MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases. Randomized clinical trials on treatment of sepsis with the combination of ulinastatin and Tα1, compared with placebo, were reviewed. Studies were pooled to relative risk (RR) and weighted mean differences (WMD), with 95% confidence interval (CI). RESULTS: Six trials (enrolling 915 participants) met the inclusion criteria. Compared with placebo, the combination of ulinastatin and Tα1 presented significant effects on 28-day all-cause mortality (RR 0.67; 95% CI 0.57 to 0.80), 90-day all-cause mortality (RR 0.75; 95% CI 0.61 to 0.93), TNF-α (WMD -73.86ng/L; 95% CI -91.00 to -56.73ng/L), IL-6 (WMD -55.04ng/L; 95% CI -61.22 to -48.85ng/L), and duration of mechanical ventilation (WMD -2.26days; 95% CI -2.79 to -1.73days). CONCLUSIONS: Immunomodulatory therapy that combines ulinastatin and Tα1 significantly improves all-cause mortality, inflammatory mediators and duration of mechanical ventilation in subjects with sepsis.