Co-Expression and Localization of Angiotensin-Converting Enzyme-2 (ACE2) and the Transmembrane Serine Protease 2 (TMPRSS2) in Paranasal Ciliated Epithelium of Patients with Chronic Rhinosinusitis

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme-2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) as a primary receptor for invasion. Cell entry by the virus requires the co-expression of these molecules in the host cells. Objective We investigated ACE2 and TMPRSS2 expression and localization in paranasal epithelium of eosinophilic chronic rhinosinusitis (ECRS) patients (n = 38), non-ECRS (n = 31), and healthy controls (n = 25). CRS inflammatory patterns are characterized by the type of cytokines; we investigated whether inflammatory endotypes are associated with cell-entry molecules, as this could be linked to susceptibility to SARS-CoV-2 infection. Methods The ACE2, TMPRSS2, and other inflammatory cytokine mRNA levels were assessed by quantitative RT-PCR. The localizations of ACE2- and TMPRSS2-positive cells were examined with immunofluorescent double-staining using laser scanning confocal microscopy (LSCM). Results The non-ECRS patients showed significantly increased ACE2 and TMPRSS2 mRNA expressions compared to the ECRS patients. The CRS patients’ ACE2 and TMPRSS2 mRNA levels were positively correlated with IFN-γ ( r = 0.3227 and r = 0.3264, respectively) and TNF-α ( r = 0.4008, r = 0.3962, respectively). ACE2 and TMPRSS2 were negatively correlated with tissue eosinophils ( r = −0.3308, r = −0.3112, respectively), but not with IL-13. ACE2 mRNA levels were positively correlated with TMPRSS2 ( r = 0.7478). ACE2 and TMPRSS2 immunoreactivities were localized mainly in the epithelial ciliated cells, as confirmed by co-staining with TMPRSS2 and acetylated α-tubulin, a cilia organelle marker. Using LSCM imaging, we observed higher expressions of these molecules in the non-ECRS patients versus the ECRS patients. Conclusion ECRS patients with type 2 inflammation showed decreased ACE2 and TMPRSS2 expressions in their sinus mucosa. ACE2 and TMPRSS2 regulation seems to be positively related to IFN-γ and TNF-α production in CRS patients; ACE2 and TMPRSS2 were co-expressed in the ciliated epithelium of their paranasal mucosa, implicating the paranasal epithelium as a portal for initial infection and transmission.

Gallbladder Ciliated Foregut Cyst Suspected of Malignancy Preoperatively

Background. Gallbladder ciliated foregut cysts (CFCs) of the lower diaphragm are extremely rare. Furthermore, they are rarely suspected of malignancy preoperatively. Case Presentation. A 50-year-old woman was referred to our hospital for further examination and treatment of a gallbladder tumor that was detected using abdominal ultrasonography (US). After a close inspection, she was diagnosed with a gallbladder tumor that was possibly malignant. Accordingly, open whole layer cholecystectomy was performed because intraoperative US revealed a tumor located on the intraperitoneal side of the gallbladder, and a rapid intraoperative pathological diagnosis identified no malignancy. A postoperative pathological examination revealed a cystic lesion with thin walls covered with ciliated epithelium, which laid on a connective tissue with smooth muscle fibers. Based on the above results, the final pathological diagnosis was CFC of the gallbladder without malignancy. Conclusions. Cases of gallbladder CFC can be considered as cysts requiring treatment owing to CFCs’ potential for malignant transformation and high-frequency symptoms.

UNC-45A Is Highly Expressed in the Proliferative Cells of the Mouse Genital Tract and in the Microtubule-Rich Areas of the Mouse Nervous System

UNC-45A (Protein unc-45 homolog A) is a cytoskeletal-associated protein with a dual and non-mutually exclusive role as a regulator of the actomyosin system and a Microtubule (MT)-destabilizing protein, which is overexpressed in human cancers including in ovarian cancer patients resistant to the MT-stabilizing drug paclitaxel. Mapping of UNC-45A in the mouse upper genital tract and central nervous system reveals its enrichment not only in highly proliferating and prone to remodeling cells, but also in microtubule-rich areas, of the ovaries and the nervous system, respectively. In both apparatuses, UNC-45A is also abundantly expressed in the ciliated epithelium. As regulators of actomyosin contractility and MT stability are essential for the physiopathology of the female reproductive tract and of neuronal development, our findings suggest that UNC-45A may have a role in ovarian cancer initiation and development as well as in neurodegeneration.

Planar polarization of cilia in the zebrafish floor-plate involves Par3-mediated posterior localization of highly motile basal bodies

Epithelial cilia, whether motile or primary, often display an off-centered planar localization within the apical cell surface. This form of planar cell polarity (PCP) involves the asymmetric positioning of the ciliary basal body (BB). Using the mono-ciliated epithelium of the embryonic zebrafish floor-plate, we investigated the dynamics and mechanisms of BB polarization by live-imaging. BBs were highly motile, making back-and-forth movements along the antero-posterior axis and contacting both the anterior and posterior membranes. Contacts exclusively occurred at junctional Par3 patches and were often preceded by membrane digitations extending towards the BB, suggesting focused cortical pulling forces. Accordingly, BBs and Par3 patches were linked by dynamic microtubules. Later, BBs became less motile and eventually settled at posterior apical junctions enriched in Par3. BB posterior positioning followed Par3 posterior enrichment and was impaired upon Par3 depletion or disorganization of Par3 patches. In the PCP mutant Vangl2, BBs were still motile but displayed poorly-oriented membrane contacts that correlated with Par3 patch fragmentation and lateral spreading. We propose an unexpected function for posterior Par3 enrichment in controlling BB positioning downstream of the PCP pathway.

Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms

Idiopathic pulmonary fibrosis is a progressive and debilitating lung disease with large unmet medical need and few treatment options. We describe an analysis connecting single cell gene expression with bulk gene expression-based subsetting of patient cohorts to identify IPF patient subsets with different underlying pathogenesis and cellular changes. We reproduced earlier findings indicating the existence of two major subsets in IPF and showed that these subsets display different alterations in cellular composition of the lung. We developed classifiers based on the cellular changes in disease to distinguish subsets. Specifically, we showed that one subset of IPF patients had significant increases in gene signature scores for myeloid cells versus a second subset that had significantly increased gene signature scores for ciliated epithelial cells, suggesting a differential pathogenesis among IPF subsets. Ligand-receptor analyses suggested there was a monocyte-macrophage chemoattractant axis (including potentially CCL2-CCR2 and CCL17-CCR4) among the myeloid-enriched IPF subset and a ciliated epithelium-derived chemokine axis (e.g. CCL15) among the ciliated epithelium-enriched IPF subset. We also found that these IPF subsets had differential expression of pirfenidone-responsive genes suggesting that our findings may provide an approach to identify patients with differential responses to pirfenidone and other drugs. We believe this work is an important step towards targeted therapies and biomarkers of response.

UNC-45A is Highly Expressed in the Proliferative Cells of the Mouse Genital Tract and in the Microtubule-Rich Areas of the Mouse Nervous System

UNC-45A is a cytoskeletal-associated protein with a dual and non-mutually exclusive role as a regulator of the acto-myosin system and as a Microtubule (MT)-destabilizing protein. UNC-45A is overexpressed in human cancers including in ovarian cancer patients resistant to the MT-stabilizing drug Paclitaxel. Mapping of UNC-45A in the mouse upper genital tract and central nervous system reveals its enrichment in highly proliferating and prone to remodeling cells and in microtubule-rich areas of in the ovaries and in neurons respectively. In both apparatuses UNC-45A is also abundantly expressed in the ciliated epithelium. Because regulators of acto-myosin contractility and MT stability are essential for the physiopathology of the female reproductive tract and of neuronal development our findings suggest that UNC-45A may have a role in ovarian cancer initiation and development and in neurodegeneration.

Nasal overshoot: Probably a new entity

Background: Congenital masses of the nasal tip are extremely rare. Differential diagnoses include nasal-tip teratoma, nasal chondromesenchymal hamartoma (NCMH), and heterotopic nasal glioma. Herein, the case of a newborn is reported that does not match with any of these differential diagnoses. Case presentation: A newborn male presented with a congenital pedunculated mass arising from the nasal columella. The mass was symmetrically bilobed which is very unusual for any hamartomatous or neoplastic lesions. Histologically, it was composed of cartilage and ciliated epithelium. Conclusion: Based on the uniqueness of the case it is hypothesized that the lesion could be an embryological error of frontonasal process overshoot defying, hitherto unknown, controlling mechanism. More research is needed to know how the morphometric proportion of the human body is determined by Nature.

The congenital sternoclavicular sinus: a single-institution retrospective study of 88 patients

Background Sinus near the sternoclavicular joint was considered as a rare congenital neck abnormality. Though it was reported as a dermoid sinus in some literatures, the embryological origin of the sinus was unclear. This study aimed at reviewing the clinical and histological characteristics and analyzing the possible embryological origin of this malformation in children. Methods The medical records of all patients with congenital sternoclavicular sinus who underwent surgical resection between March 2018 through June 2020 were reviewed retrospectively. The clinical presentations, complications, histological examination, and treatment were analyzed. Results Of the 88 patients with congenital sternoclavicular sinus included, the mean age of surgery was 2.73 ± 1.71 years old. The sinuses occurred on the left side in 73 (83.0%) cases. Sixty-three patients experienced sinus infection and 44 patients underwent incision and drainage before excision. All patients received surgical resection with one patient who recurred after surgery. Histopathological examination showed that the sinuses were lined by squamous epithelium in most patients. However, ciliated epithelium was observed in one patient and salivary glands were detected in two patients. Conclusions The congenital sternoclavicular sinus should be excised promptly to prevent recurrent infection. According to the ciliated epithelium and salivary gland were found in the wall of sinus, it should be viewed as the skin side remnant of the fourth branchial cleft rather than a dermoid cyst/sinus.