Ischemia/reperfusion-induced edema (IRE), one of the most significant causes of mortality after lung transplantation, can be mimicked ex vivo in isolated perfused mouse lungs (IPL). Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel studied in endothelium; however, its role in the lung epithelium remains elusive. Here, we show enhanced IRE in TRPV4-deficient (TRPV4 –/– ) IPL compared with that of WT controls, indicating a protective role of TRPV4 in maintenance of the alveolar epithelial barrier. By immunohistochemistry, mRNA profiling, and electrophysiological characterization, we detected TRPV4 in bronchial epithelium, alveolar epithelial type I (ATI), and alveolar epithelial type II (ATII) cells. Genetic ablation of TRPV4 resulted in reduced expression of the water-conducting aquaporin-5 (AQP-5) channel in ATI cells. Migration of TRPV4 –/– ATI cells was reduced, and cell barrier function was impaired. Analysis of isolated primary TRPV4 –/– ATII cells revealed a reduced expression of surfactant protein C, and the TRPV4 activator GSK1016790A induced increases in current densities only in WT ATII cells. Moreover, TRPV4 –/– lungs of adult mice developed significantly larger mean chord lengths and altered lung function compared with WT lungs. Therefore, our data illustrate essential functions of TRPV4 channels in alveolar epithelial cells and in protection from edema formation.

Candida bloodstream infections (CBI) are one of the most common nosocomial infections globally, and they account for a high mortality rate. The increasing global prevalence of drug-resistant Candida strains has also been posing a challenge to clinicians. In this study, we comprehensively evaluated the biofilm formation and production of hemolysin and proteinase of 63 CBI isolates derived from a hospital setting in Hong Kong as well as their antifungal susceptibility both in the presence and in the absence of human serum, using standard methodology. Candida albicans was the predominant species among the 63 CBI isolates collected, and non-albicans Candida species accounted for approximately one third of the isolates (36.5%). Of them, Candida tropicalis was the most common non-albicans Candida species. A high proportion (31.7%) of the CBI isolates (40% of C. albicans isolates, 10% of C. tropicalis isolates, 11% of C. parapsilosis isolates, and 100% of C. glabrata isolates) were found to be resistant to fluconazole. One of the isolates (C. tropicalis) was resistant to amphotericin B. A rising prevalence of drug-resistance CBI isolates in Hong Kong was observed with reference to a previous study. Notably, all non-albicans Candida species, showed increased hemolytic activity relative to C. albicans, whilst C. albicans, C. tropicalis, and C. parapsilosis exhibited proteinase activities. Majority of the isolates were capable of forming mature biofilms. Interestingly, the presence of serum distorted the yeast sensitivity to fluconazole, but not amphotericin B. Taken together, our findings demonstrate that CBI isolates of Candida have the potential to express to varying extent their virulence attributes (e.g., biofilm formation, hemolysin production, and proteinase activity) and these, together with perturbations in their antifungal sensitivity in the presence of serum, may contribute to treatment complication in candidemia. The effect of serum on antifungal activity warrants further investigations, as it has direct clinical relevance to the treatment outcome in subjects with candidemia.

Members of the transient receptor potential (TRP) superfamily are broadly expressed in our body and contribute to multiple cellular functions. Most interestingly, the fourth member of the vanilloid family of TRP channels (TRPV4) serves different partially antagonistic functions in the respiratory system. This review highlights the role of TRPV4 channels in lung fibroblasts, the lung endothelium, as well as the alveolar and bronchial epithelium, during physiological and pathophysiological mechanisms. Data available from animal models and human tissues confirm the importance of this ion channel in cellular signal transduction complexes with Ca2+ ions as a second messenger. Moreover, TRPV4 is an excellent therapeutic target with numerous specific compounds regulating its activity in diseases, like asthma, lung fibrosis, edema, and infections.

Our respiratory system is exposed to toxicants and pathogens from both sides: the airways and the vasculature. While tracheal, bronchial and alveolar epithelial cells form a natural barrier in the airways, endothelial cells protect the lung from perfused toxic compounds, particulate matter and invading microorganism in the vascular system. Damages induce inflammation by our immune response and wound healing by (myo)fibroblast proliferation. Members of the transient receptor potential (TRP) superfamily of ion channel are expressed in many cells of the respiratory tract and serve multiple functions in physiology and pathophysiology. TRP expression patterns in non-neuronal cells with a focus on TRPA1, TRPC6, TRPM2, TRPM5, TRPM7, TRPV2, TRPV4 and TRPV6 channels are presented, and their roles in barrier function, immune regulation and phagocytosis are summarized. Moreover, TRP channels as future pharmacological targets in chronic obstructive pulmonary disease (COPD), asthma, cystic and pulmonary fibrosis as well as lung edema are discussed.

Extramedullary plasmactyoma is the solitary, soft tissue form of plasma cell neoplasm but lack the defining features of medullary or multiple myeloma. The diagnosis is difficult to make in routine practice setting due to the morphological and immunohistochemical overlap with plasmablastic lymphoma. We report a case of plasmablastic extramedullary plasmacytoma in a 52-year-old in the mandibular lingual gingiva and discuss its differential from plasmablastic lymphoma. The gingival mass regressed with primary radiotherapy.