Pentraxin 3 (PTX3), a long pentraxin and a humoral pattern recognition molecule (PRM), has been demonstrated to be protective against Aspergillus fumigatus, an airborne human fungal pathogen. We explored its mode of interaction with A. fumigatus, and the resulting implications in the host immune response. Here, we demonstrate that PTX3 interacts with A. fumigatus in a morphotype-dependent manner: (a) it recognizes germinating conidia through galactosaminogalactan, a surface exposed cell wall polysaccharide of A. fumigatus, (b) in dormant conidia, surface proteins serve as weak PTX3 ligands, and (c) surfactant protein D (SP-D) and the complement proteins C1q and C3b, the other humoral PRMs, enhance the interaction of PTX3 with dormant conidia. SP-D, C3b or C1q opsonized conidia stimulated human primary immune cells to release pro-inflammatory cytokines and chemokines. However, subsequent binding of PTX3 to SP-D, C1q or C3b opsonized conidia significantly decreased the production of pro-inflammatory cytokines/chemokines. PTX3 opsonized germinating conidia also significantly lowered the production of pro-inflammatory cytokines/chemokines while increasing IL-10 (an anti-inflammatory cytokine) released by immune cells when compared to the unopsonized counterpart. Overall, our study demonstrates that PTX3 recognizes A. fumigatus either directly or by interplaying with other humoral PRMs, thereby restraining detrimental inflammation. Moreover, PTX3 levels were significantly higher in the serum of patients with invasive pulmonary aspergillosis (IPA) and COVID-19-associated pulmonary aspergillosis (CAPA), supporting previous observations in IPA patients, and suggesting that it could be a potential panel-biomarker for these pathological conditions caused by A. fumigatus.

Given the various clinical manifestations that characterize Coronavirus Disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant proteins A (SP-A) and D (SP-D) are collectins that play a crucial role in ensuring proper alveolar function and an alteration of their serum levels was reported in several pulmonary diseases characterized by Acute Respiratory Distress Syndrome (ARDS) and pulmonary fibrosis. Considering that such clinical manifestations can also occur during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. In this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n = 51) at admission (T0) and after seven days (T1) and compared with healthy donors (n = 11). SP-D increased in COVID-19 patients compared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. In light of these results, SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia, and the early detection of SP-D serum levels could be crucial for preventive clinical management.

We previously identified surfactant protein D (SP-D) in the bottlenose dolphin Tursiops truncatus as a unique evolutionary factor of the cetacean pulmonary immune system. In this short report, recombinant SP-D of bottlenose dolphin (dSP-D) was synthesized in mammalian cells, and its properties were analyzed in vitro. The recombinant proteins were purified using Ni-carrier or Co-carrier. Sodium dodecyl sulfate poly-acrylamide gel electrophoresis and western blotting revealed a 50 kDa major band with minor secondary bands. Enzyme-linked immunosorbent assay-like methods revealed that recombinant dSP-D bonded to gram-positive and gram-negative bacterial walls. Our findings suggest the clinical usefulness of dSP-D for cetacean pneumonia.

BACKGROUND: Severe cases of COVID-19 often lead to the development of acute respiratory syndrome, a critical condition believed to be caused by the harmful effects of SARS-CoV-2 on type II alveolar cells. These cells play a crucial role in producing pulmonary surfactants, which are essential for proper lung function. Specifically focusing on surfactant proteins, including Surfactant protein A (SP-A), Surfactant protein B, Surfactant protein C, and Surfactant protein D (SP-D), changes in the levels of pulmonary surfactants may be a significant factor in the pathological changes seen in COVID-19 infection.
OBJECTIVE: This study aims to gain insights into surfactants, particularly their impacts and changes during COVID-19 infection, through a comprehensive review of current literature. The study focuses on the function of surfactants as prognostic markers, diagnostic factors, and essential components in the management and treatment of COVID-19.
RESULTS: In general, pulmonary surfactants serve to reduce the surface tension at the gas-liquid interface, thereby significantly contributing to the regulation of respiratory mechanics. Additionally, these surfactants play a crucial role in the innate immune system within the pulmonary microenvironment. Within the spectrum of COVID-19 infections, a compelling association is observed, characterized by elevated levels of SP-D and SP-A across a range of manifestations from mild to severe pneumonia. The sudden decline in respiratory function observed in COVID-19 patients may be attributed to the decreased synthesis of surfactants by type II alveolar cells.
CONCLUSIONS: Collectin proteins such as SP-A and SP-D show promise as biomarkers, offering potential avenues for predicting and monitoring pulmonary alveolar injury in the context of COVID-19. This clarification enhances our understanding of the molecular complexities contributing to respiratory complications in severe COVID-19 cases, providing a foundation for targeted therapeutic approaches using surfactants and refined clinical management strategies.

BACKGROUND: Radiation-induced lung disease is a potentially fatal, dose-limiting toxicity commonly seen after radiotherapy of thoracic malignancies, including breast cancer.
OBJECTIVE: To evaluate and compare the early lung toxicity induced by 3D-CRT and IMRT radiotherapy treatment modalities in breast cancer female patients using biochemical, dosimetry and clinical data.
METHODS: this study included 15 normal healthy controls, 15 breast cancer patients treated with IMRT, and 15 breast cancer patients treated with 3D-CRT. One blood sample was obtained from the control group and 3 blood samples were withdrawn from cases before RT, after RT and after 3 months of RT.
RESULTS: IMRT delivered higher radiation dose to the breast tumor and lower doses to the lung as an organ at risk. There was a non-significant increase in the serum levels of IL-6 before IMRT and 3D-CRT compared with its levels in the control group. There were significant increases in serum levels of IL-6 after RT (IMRT and 3DCRT) compared with its levels before RT. There was a non-significant decrease in the serum levels of IL-6 after 3 months of RT (IMRT and 3D-CRT) compared with its serum levels immediately after RT. There was a non-significant increase in the serum levels of SP-D before RT (IMRT and 3D-CRT) compared with its levels in the control group. There were significant-increases in serum levels of SP-D after RT (IMRT and 3D-CRT) compared with its levels before RT. There was a non-significant decrease in the serum levels of SP-D after 3 months of radiotherapy (IMRT and 3D-CRT) compared with its serum levels immediately after RT.
CONCLUSIONS: serum of levels IL-6 and SP-D can be used to diagnose the occurrence of early lung toxicity due to radiotherapy and the rate of recovery from radiation pneumonitis is apparent in case of IMRT than 3D-CRT.

BACKGROUND: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry.
METHODS: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3).
RESULTS: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low.
CONCLUSIONS: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.

Surfactant protein A (SP-A) and Surfactant protein D (SP-D) glycoproteins play a crucial role in maintaining lung homeostasis and lung host defense. Interestingly, these proteins are also expressed in extra-pulmonary tissues, including the female genital tract. The ovarian tissue, where SP-A and SP-D expression increases with follicular development, may serve as the primary site of defense for this tissue. However, their functions in these tissues are not well understood and are currently an active area of research. Therefore, the objective of this study is to investigate the expression of SP-A and SP-D in the ovine ovary throughout the ovarian cycle using immunohistochemistry by semiquantitative intensity classification and Western blotting techniques. These findings revealed the presence of SP-A and SP-D in various compartments of the ovary, such as the follicular epithelium, granulosa cells, cumulus cells, theca cells, oocyte I, follicular fluid, and luteal cells of Graafian follicles, excluding the corpus albicans. SP-A and SP-D likely act as a first line of defense against potential pathogens that infiltrate the ovaries. Further investigation of the differential expression of SP-A and SP-D proteins in ovarian follicles will provide a basis for understanding their interactions with key proteins involved in oogenesis.

OBJECTIVE: To evaluate the effect of esketamine combined with distal limb ischemic preconditioning (LIP) for lung protection in elderly patients undergoing thoracoscopic radical surgery for lung cancer.
METHODS: This randomized trial was conducted in 160 patients undergoing elective thoracoscopic surgery for lung cancer, who were randomized into control group (with saline injection and sham LIP), esketamine group, LIP group, and esketamine + LIP group (n=40). Before anesthesia induction, according to the grouping, the patients received an intravenous injection with 0.5 mg/kg esketamine or 10 ml saline (in control group). LIP was induced by applying a tourniquet 1-2 cm above the popliteal fossa in the left lower limb to block the blood flow for 5 min for 3 times at the interval of 5 min, and sham LIP was performed by applying the tourniquet without pressurization for 30 min. Oxygenation index (OI) and alveolar-arterial PO2 difference (A-aDO2) were calculated before induction (T0), at 30 min (T0.5) and 1 h (T1) of one-lung ventilation (OLV), and at 1 h after two-lung ventilation (T3). Serum levels of SP-D, CC-16 and TNF-α were measured by ELISA at T0, T1, T2 (2 h of OLV), T3, and 24 h after the operation (T4). The length of hospital stay and postoperative pulmonary complications of the patients were recorded.
RESULTS: Compared with those in the control group, the patients in the other 3 groups had significantly lower CC-16, SP-D and TNF-α levels, shorter hospital stay, and lower incidences of lung infection and lung atelectasis (all P < 0.05). Serum CC-16, SP-D and TNF-α levels, hospital stay, incidences of complications were significantly lower or shorter in the combined treatment group than in esketamine group and LIP group (all P < 0.05).
CONCLUSIONS: In elderly patients undergoing thoracoscopic radical surgery for lung cancer, treatment with esketamine combined with LIP can alleviate acute lung injury by enhancing anti-inflammatory response to shorten postoperative hospital stay, reduce lung complications and promote the patients\' recovery.

UNASSIGNED: To review the association of surfactant protein-D with type 2 diabetes mellitus, infections, oxidative stress and inflammation, and the changes in oxidative stress markers in type 2 diabetes mellitus.
METHODS: The systematic review was conducted from April to September 2022, and comprised search on PubMed, Web of Sciences, Scopus, Science Direct and Google Scholar databases for relevant studies published in English language between January 1, 2000, and June 30, 2022. The search was updated in September 2022. After transferring literature to Mendeley, relevant data was extracted from the included studies. Quality assessment for eligible studies was done using Joanna Briggs Institute Critical Appraisal Checklist. Quality of evidences was assessed by using Grading of Recommendations Assessment, Development and Evaluation tool.
RESULTS: Of the 203 studies identified, 18(8.9%) were analysed; 16(89%) with humans and 2(11%) with animals as subjects There were 5 (31.25%) studies for SP-D, of which 4 (80%) studies reported lower surfactant protein-D in type 2 diabetes mellitus cases than controls. Its significant negative association with glycated haemoglobin was reported by 1(20%) study and 2(40%) studies with fasting blood glucose levels. Higher surfactant protein-D in type 2 diabetes mellitus cases and its positive association with glycated haemoglobin was reported by 1(20%) study. Recurrent infections were frequent in type 2 diabetes mellitus patients. Malondialdehyde level was higher and superoxide dismutase activity was lower in type 2 diabetes mellitus cases, reflecting oxidative stress. Animal studies also showed that reactive oxygen species generating from hypochlorous acid during oxidative stress promoted the formation of non-disulfide linkages in surfactant protein-D structure, resulting in its decreased functionality.
UNASSIGNED: Surfactant protein-D, oxidative stress, inflammation and infections were found to be linked to each other for pathogenesis of infections in type 2 diabetes mellitus.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant global morbidity and mortality. This study aimed to investigate the clinical significance of serum vascular endothelial growth factor A (VEGF-A) in COVID-19 patients and its association with disease severity and pulmonary injury.
We prospectively collected data from 71 hospitalized COVID-19 patients between June 2020 and January 2021. Patients were classified as either mild or severe based on their oxygen requirements during hospitalization. Serum VEGF-A levels were measured using an ELISA kit.
In comparison to mild cases, significantly elevated serum VEGF-A levels were observed in severe COVID-19 patients. Furthermore, VEGF-A levels exhibited a positive correlation with white blood cell count, neutrophil count, and lymphocyte count. Notably, serum surfactant protein-D (SP-D), an indicator of alveolar epithelial cell damage, was significantly higher in patients with elevated VEGF-A levels.
These results suggest that elevated serum VEGF-A levels could serve as a prognostic biomarker for COVID-19 as it is indicative of alveolar epithelial cell injury caused by SARS-CoV-2 infection. Additionally, we observed a correlation between VEGF-A and neutrophil activation, which plays a role in the immune response during endothelial cell injury, indicating a potential involvement of angiogenesis in disease progression. Further research is needed to elucidate the underlying mechanisms of VEGF-A elevation in COVID-19.