Inhalation exposure of adult D. melanogaster to cigarette smoke induced changes in physiological parameters and the expression of COPD-associated orthologous genes. Transcriptomic responses were more profound in females, indicating sex-specific responses to inhaled toxicants. Furthermore, enrichment analyses of the differentially expressed genes in females pointed to biomolecules associated with response to nicotine and detoxification. D. melanogaster thus provides a powerful model system to test the efficacy of new potential drugs for COPD treatment.

Introduction: Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas aeruginosa are three of the most common gram-negative bacteria responsible for respiratory disease. The modes by which these bacteria interact with their host remain under study. Objectives: We aimed at the identification and functional enrichment analysis (FEA) relative to cellular components and disease of the human gene interaction network with the aforementioned bacteria. Methods: The Human Pathogen Interaction Database 3.0 (HPIDB: http://hpidb.igbb.msstate.edu/) was used to identify the human proteins interacting with the three pathogens. Gene symbols corresponding to the retrieved proteins were entered as a list in the tool ToppFun of the ToppGene database (https://toppgene.cchmc.org/enrichment.jsp). Results: Eleven human proteins were found to interact with the bacterial pathogens: CFAH, VTN, CEAM1, SFN, YWHAB, YWHAQ, YWHAH, YWHAZ, YWHAG, YWHAE, and RAC1. FEA relative to cellular components showed that these proteins are associated with adherens and anchoring junctions, as well as with membrane vesicles. In terms of diseases, the most significantly enriched annotation even after multiple comparison correction was lung adenocarcinoma. Conclusion: Current literature supports that infection with gram negative bacteria facilitates tumor progression in patients with non-small-cell lung cancer. Our findings suggest a potential link of gram-negative bacterial infection to lung adenocarcinoma. Further experimental data are required to establish such an association.

Cardiovascular toxicity is an important complication of treatment for hematologic malignancies, but it is often discussed mainly in terms of direct myocardial injury. Endothelial injury may provide a common link between several cardiovascular complications seen in these patients. Endothelial dysfunction may already be present because of the malignancy itself and can be further increased by anticancer treatment, immune activation and haematopoietic stem cell transplantation. Oxidative stress, reduced nitric oxide availability, inflammation, increased vascular permeability and activation of coagulation can shift the endothelium from a protective to a pro-inflammatory and prothrombotic state. These changes could contribute to hypertension, thrombosis, atherosclerotic disease, coronary microvascular dysfunction, arterial stiffness and myocardial dysfunction. The role of endothelial injury is particularly relevant with BCR-ABL inhibitors, proteasome inhibitors, CAR-T-cell therapy, bispecific antibodies and transplantation, although the mechanisms and strength of evidence differ between treatments. Several circulating biomarkers and tools, including angiopoietin-2, von Willebrand factor, soluble thrombomodulin, adhesion molecules and the Endothelial Activation and Stress Index, may help identify endothelial injury, but their clinical roles still remain unclear. This review examines endothelial injury across hematologic malignancies and their treatments and discusses its role in cardiovascular toxicity, current approaches to vascular protection and the main gaps that need to be addressed before endothelial assessment can become part of routine cardio-oncology care.

Pleural mesothelial cells have a primary cilium (PC), a solitary sensory organelle facing the extracellular environment. The BBSome is critical for the PC function and comprises several BBS proteins. Extracellular stimuli, like the ones encountered during a pleural effusion (osmotic, inflammatory, and oxidative stress‐related signals) could influence the PC and BBSome. Using 2D and 3D culture models of benign mesothelial and primary malignant pleural mesothelioma cells we explored the BBSome components gene expression under hyperosmotic, inflammatory, and oxidative stress. We also assessed their effects in combination with PC perturbing drugs in the context of cell adhesion and cell migration, which are critical for tissue healing. These extracellular stimuli changed the expression patterns of BBS genes, while changes in cell adhesion were dependent on the cell and stimulus type. Cell migration was also sensitive to stress stimuli and the native PC length was critical in this context. Our results provide considerable insight into the molecular and phenotypical changes underlying PC responses of benign and malignant mesothelial cells to extracellular stimuli. Further research will be needed to assess the potential therapeutic implications of PC extracellular stimulation in malignant pleural disease.

Background/Objectives: Congestion drives most heart-failure (HF) hospitalizations, and several strategies now titrate therapy to a directly measured congestion signal rather than to symptoms; whether they differ by the signal measured has not been examined comparatively. Methods: We performed a systematic review and contrast-based network meta-analysis of randomized trials comparing imaging- or device-based congestion-triggered management with usual care. Thirteen chronic-phase trials formed a star network (no closed loops; rankings exploratory) of four strategies, pressure-guided (N1), lung ultrasound (N2), transthoracic lung impedance (N3), and cardiac-implantable-electronic-device (CIED) intrathoracic impedance (N5), with HF hospitalization as the primary outcome and six prespecified sensitivity analyses; four acute trials formed a gap map. Results: Only pressure-guided monitoring reduced HF hospitalization (0.72, 95% confidence interval 0.57–0.90), stable across sensitivities and matching external data. Lung ultrasound did not reduce hospitalization (0.72, 0.48–1.08) or mortality but reduced urgent visits (0.26, 0.13–0.50). The apparent CIED-impedance harm (1.12, 0.77–1.63) reflected an audible-alert trial and dissolved when early-terminated trials were excluded (0.87). Lung impedance gave the largest estimate (0.51, 0.31–0.83) but rested on one trial. No strategy tested in more than one trial reduced mortality. Conclusions: The congestion signal acted upon, and who receives the alert, track with the effect, although signal and workflow cannot be separated within trials; clinicians should match modality to the intended outcome, as these tools defer hospitalization, not death.