Search

In recent years, the role of ferroptosis in pulmonary fibrosis has garnered increasing interest as a potential therapeutic target. Pulmonary fibrosis is a pathological process characterized by the accumulation of extracellular matrix in affected lung tissues, and currently, there are no effective therapies for preventing or reversing the fibrotic lesions. Ferroptosis is a form of programmed cell death that is regulated by a network of enzymes and signaling pathways. Dysregulation of ferroptosis has been implicated in several diseases, including pulmonary fibrosis. The accumulation of lipid peroxides in the course of ferroptosis causes damage to cell membranes and other cellular components, leading ultimately to cell death. Relevant targets for therapeutic intervention in ferroptosis include key enzymes, such as glutathione peroxidase 4, transcription factors like nuclear factor erythroid 2-related factor 2, and iron chelation. This review provides an overview of the emerging role of ferroptosis in pulmonary fibrosis and highlights potential therapeutic targets in this pathway. Further research is needed to develop safe and effective approaches targeting ferroptosis in treatment of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

As a highly conserved, multifunctional protein with multiple domains, p62/SQSTM1 plays a crucial role in several essential cellular activities, particularly selective autophagy. Recent research has shown that p62 is crucial in eradicating intracellular bacteria by xenophagy, a selective autophagic process that identifies and eliminates such microorganisms. This review highlights the various roles of p62 in intracellular bacterial infections, including both direct and indirect, antibacterial and infection-promoting aspects, and xenophagy-dependent and independent functions, as documented in published literature. Additionally, the potential applications of synthetic drugs targeting the p62-mediated xenophagy mechanism and unresolved questions about p62's roles in bacterial infections are also discussed. [ABSTRACT FROM AUTHOR]

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), China updated a total of seven editions of the official guidelines. We analyzed the treatment of patients to understand how the several editions of diagnosis and treatment recommendation guided the local medical institutions from a regional perspective. Methods: This study included a total of 93 patients who were suspected or confirmed cases of COVID-19. We analyzed the use of antiviral treatments, antibiotics, steroid, and life support measures in these patients. Based on the time of admission and the update of the official recommendations, we compared the treatments complied with the updated versions of the diagnosis and treatment recommendation. Results: All the 93 cases received different types of antiviral drugs. There were 41 cases of the use of antiviral drugs did not comply with the recommendations. There were 82 cases who received antibiotics, and 31 cases did not comply with the recommendations. 53 patients who received steroids, but only 3 patients comply with the recommendations. One patient was treated with extracorporeal membrane oxygenation (ECMO), but the timing was delayed compared with the recommendations. 91 patients were cured and discharged, one died, and one was still treated in hospital for other diseases after being tested negative. Conclusions: The antiviral treatment initially involved too many types of drugs, and the duration of medication was too long. There was also an overuse of antibiotics. In addition, the use of steroids did not comply with the recommendations. The timing of intubation for mechanical ventilation and the timing of using ECMO were more con servative. [ABSTRACT FROM AUTHOR]

Copyright of Proceedings of the Estonian Academy of Sciences is the property of Teaduste Akadeemia Kirjastus and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Proceedings of the Estonian Academy of Sciences is the property of Teaduste Akadeemia Kirjastus and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A previous study found that an AAAG-rich Oligodeoxynucleotide (ODN), designated as MS19, could lessen the acute lung inflammatory injury (ALII) in mice infected by influenza viruses. Bioinformatics analysis found that MS19 is consensus with the binding site of interferon regulatory factor 5 (IRF5) in the regulatory elements of pro-inflammatory genes. This study established a septic peritonitis model in Institute of Cancer Research (ICR) mice infected with Escherichia coli (E. coli), and found that MS19 prolonged the survival of the mice and down-regulated the expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). In cultured RAW264.7 cells, MS19 significantly reduced the expression of iNOS, IRF5, IL-6, and TNF-α and inhibited the nuclear translocation of IRF5. This data may provide a new insight for understanding how MS19 reduces the excessive inflammatory responses in sepsis. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells contribute to tumor initiation, heterogeneity, and recurrence, and are critical targets in cancer therapy. Sprouty4 (Spry4) is a potent inhibitor of signal transduction pathways elicited by receptor tyrosine kinases, and has roles in regulating cell proliferation, migration and differentiation. Spry4 has been implicated as a tumor suppressor and in modulating embryonic stem cells. Objectives: The purpose of this research was to test the novel idea that Spry4 regulates cancer stem cell properties in breast cancer. Methods: Loss-of function of Spry4 in human MDA-MB-231 cell was used to test our hypothesis. Spry4 knockdown or control cell lines were generated using lentiviral delivery of human Spry4 or non-targeting control shRNAs, and then selected with 2 µg/ml puromycin. Cell growth and migratory abilities were determined using growth curve and cell cycle flow cytometry analyses and scratch assays, respectively. Xenograft tumor model was used to determine the tumorigenic activity and metastasis in vivo. Cancer stem cell related markers were evaluated using immunoblotting assays and fluorescence-activated cell sorting. Cancer stem cell phenotype was evaluated using in vitro mammosphere formation and drug sensitivity tests, and in vivo limiting dilution tumor formation assay. Results: Two out of three tested human Spry4 shRNAs significantly suppressed the expression of endogenous Spry4 in MDA-MB-231 cells. Suppressing Spry4 expression increased MDA-MB-231 cell proliferation and migration. Suppressing Spry4 increased β3-integrin expression, and CD133+CD44+ subpopulation. Suppressing Spry4 increased mammosphere formation, while decreasing the sensitivity of MDA-MB-231 cells to Paclitaxel treatment. Finally, suppressing Spry4 increased the potency of MDA-MB-231 cell tumor initiation, a feature attributed to cancer stem cells. Conclusions: Our findings provide novel evidence that endogenous Spry4 may have tumor suppressive activity in breast cancer by suppressing cancer stem cell properties in addition to negative effects on tumor cell proliferation and migration. [ABSTRACT FROM AUTHOR]

The aim of the present study was to analyze the clinical significance of the dynamic monitoring of blood lactic acid levels, the oxygenation index and C-reactive protein (CRP) levels in patients with severe pneumonia. The clinical data of 34 cases with severe pneumonia were collected. According to the clinical outcome, the patients were divided into a survival group (n=26) and a fatality group (n=8). Various factors, including the blood lactic acid level, oxygenation index, CRP level and acute physiology and chronic health evaluation II (APACHE II) score, were retrospectively analyzed in order to investigate whether these values had clinical significance for the prognosis of the patients. No statistically significant differences with regard to age, gender, initial concentrations of blood lactic acid and CRP, and APACHE II scores were observed between the two groups at admission to the Intensive Care Unit. However, the blood lactic acid levels were found to decrease to a normal level within 12-24 h after treatment in the survival group, while the levels were maintained at a higher concentration in the fatality group, even at 72 h after treatment (P<0.05). Furthermore, the oxygenation index in the survival group was significantly higher when compared with that in the fatality group. The oxygenation index was maintained at a normal level in the survival group, while the oxygenation index levels were below normal and continued to decline in the fatality group. A positive correlation was observed between the blood lactic acid level and the APACHE II scores (r=0.656, P<0.05). Therefore, the present study demonstrated that dynamic monitoring of blood lactic acid, oxygenation index and CRP levels in patients with severe pneumonia can be used to evaluate the therapeutic efficiency, in addition to serving as a prognosis indicator, for patients with severe pneumonia. [ABSTRACT FROM AUTHOR]

To develop effective anti-lung cancer vaccines, we directly mixed mycobacterial heat shock protein 65 (MHSP65) and tumor cell lysate (TCL) from Lewis lung cancer cells in vitro and tested its efficacy on stimulating anti-tumor immunity. Our results showed that MHSP65–TCL immunization significantly inhibited the growth of lung cancer in mice and prolonged the survival of lung cancer bearing mice. In vivo and in vitro data suggest that MHSP65–TCL could induce specific CTL responses and non-specific immunity, both of which could contribute to the tumor inhibition. Thus, this report provides an easy approach to prepare an efficient TCL based tumor vaccine. [ABSTRACT FROM AUTHOR]

To predict the epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma using quantitative radiomic biomarkers and semantic features. We analyzed the computed tomography (CT) images and medical record data of 104 patients with lung adenocarcinoma who underwent surgical excision and EGFR mutation detection from 2016 to 2018 at our center. CT radiomic and semantic features that reflect the tumors’ heterogeneity and phenotype were extracted from preoperative non-enhanced CT scans. The least absolute shrinkage and selection operator method was applied to select the most distinguishable features. Three logistic regression models were built to predict the EGFR mutation status by combining the CT semantic with clinicopathological characteristics, using the radiomic features alone, and by combining the radiomic and clinicopathological features. Receiver operating characteristic (ROC) curve analysis was performed using five-fold cross-validation and the mean area under the curve (AUC) values were calculated and compared between the models to obtain the optimal model for predicting EGFR mutation. Furthermore, radiomic nomograms were constructed to demonstrate the performance of the model. In total, 1025 radiomic features were extracted and reduced to 13 features as the most important predictors to build the radiomic signature. The combined radiomic and clinicopathological features model was developed based on the radiomic signature, sex, smoking, vascular infiltration, and pathohistological type. The AUC was 0.90  ±  0.02 for the training, 0.88  ±  0.11 for the verification, and 0.894 for the test dataset. This model was superior to the other prediction models that used the combined CT semantic and clinicopathological features (AUC for the test dataset: 0.768) and radiomic features alone (AUC for the test dataset: 0.837). The prediction model built by radiomic biomarkers and clinicopathological features, including the radiomic signature, sex, smoking, vascular infiltration, and pathological type, outperformed the other two models and could effectively predict the EGFR mutation status in patients with peripheral lung adenocarcinoma. The radiomic nomogram of this model is expected to become an effective biomarker for patients with lung adenocarcinoma requiring adjuvant targeted treatment. [ABSTRACT FROM AUTHOR]

An abstract of the article "Chromosomal Imbalances Detected by Array CGH From Thirty Chinese Non-Smoker Adenocarcinomas of the Lung" is presented.