Milk-derived small extracellular vesicles: a new perspective on dairy nutrition.

Milk contains bioactive compounds that have multiple essential benefits. Milk-derived small extracellular vesicles (M-sEVs) have emerged as novel bioactive milk components with various beneficial biological functions and broad applications. The M-sEVs from different mammalian sources have similar composition and bioactive functions. The digestive stability and biocompatibility of the M-sEVs provide a good foundation for their physiological functions. Evidence suggests that M-sEVs promote intestinal, immune, bone, neural, liver, and heart health and show therapeutic effects against cancer, indicating their potential for use in functional foods. In addition, M-sEVs can be developed as natural delivery carriers owing to their superior structural characteristics. Further studies are needed to elucidate the relationship between the specific components and functions of M-sEVs, standardize their extraction processes, and refine relevant clinical trials to advance the future applications of M-sEVs. This review summarizes the structure and composition of M-sEVs isolated from different milk sources and discusses several common extraction methods. Since the introduction of M-sEVs for digestion and absorption, studies have been conducted on their biological functions. Furthermore, we outline the theoretical industrial production route, potential application scenarios of M-sEVs, and the future perspectives of M-sEV research.

A case report of right upper lung adenosquamous carcinoma resection following neoadjuvant targeted therapy.

The patient was a middle-aged male smoker who had space-occupying lesions in the right upper lung, Positron emission tomography-computed tomography (PET-CT) suggested right upper lung cancer with multiple mediastinal lymph node metastases. Endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-GS-TBLB) performed in the bronchus of the right apical segment confirmed the lesion as squamous cell carcinoma. Neoadjuvant therapy was planned. Because genetic testing revealed the epidermal growth factor receptor (EGFR) L858R mutation, the possibility of adenosquamous carcinoma was considered. The patient was clinically diagnosed with right upper lung squamous cell carcinoma c-T3N2M0, stage IIIB, and PS 1 point. Dacomitinib was selected for the targeted therapy. Eight weeks after the initiation of treatment, efficacy was assessed as a partial response (PR), suggesting a possibility of R0 resection. After sufficient communication with the patient and his family members, on July 1, 2020, thoracoscopic radical resection of the right upper lung cancer was performed under general anesthesia. Postoperative pathology confirmed adenosquamous carcinoma, of which 80% were adenocarcinoma and 20% were squamous cell carcinoma; no tumor thrombus was seen in the interstitial vessels; and the tumor did not invade the visceral pleura. There was no cancerous infiltration in the bronchial stump of the right upper lung. The following were the results for lymph nodes submitted for examination: L2 (0/1), L4 (0/4), L7 (0/3), L8 (0/7), L10 (0/1), L11 (0/2) and L11 (frozen 0/1) showed no cancer metastasis. The postoperative diagnosis was as follows: adenosquamous carcinoma of the right upper lung p-T2N0M0, stage Ib. After surgery, 4 cycles of the GC (gemcitabine + carboplatin) chemotherapy regimen were given, with continued targeted therapy recommended for 2 years. The patient has been followed-up and is in good condition.

Concomitant lung adenocarcinoma and pulmonary cryptococcosis confirmed by pathologic examinations.

To describe the characteristics of concomitant lung cancer and pulmonary cryptococcosis (PC) cases.A total of 8 patients with lung cancer and coexisting PC, who were admitted to Fuzhou Pulmonary Hospital of Fujian from 1st January 2009 to 31st December 2015 and whose diagnoses were confirmed by pathological examinations, were studied.One patient had a history of diabetes mellitus and 1 had a history of treated with surgery. The lesions in 7 cases manifested as nodular shadows; only 1 case showed the lesion of the 2 diseases mergedmixed together, and it manifested as a large flake-like infiltrated shadow in the same lobe. The histological type in all of the patients was lung adenocarcinoma. Lung cancer stage was advanced (III-IV) in 25.0% of the cases. The 5 patients who received surgery and drug treatment are presently healthy following resection. Recurrence and metastasis of lung cancer following surgery occurred in 2 patients in whom the tumor was controlled again after anti-tumor treatment. One patient with advanced lung cancer and PC was treated with antifungal therapy in combination with antineoplastic chemotherapy, but she failed to improve and died 10 months after symptom onset during the follow-up period.PC coexisting with pulmonary carcinoma is rare. PC can manifest as pulmonary nodules and mimic malignant lesions, so it must be considered during a differential diagnosis of pulmonary nodules, especially in immunosuppressed patients.

First successful combination of extracorporeal membrane oxygenation (ECMO) with video-assisted thoracic surgery (VATS) of pulmonary bullae resection in the management of refractory pneumothorax in a critically ill patient with H7N9 pneumonia and acute respiratory distress syndrome: A case report.

RATIONALE: At present, data regarding refractory pneumothorax treated with video-assisted thoracic surgery (VATS) in combination with extracorporeal membrane oxygenation (ECMO) in critically ill patients with H7N9 pneumonia have never been reported. PATIENT CONCERNS: A laboratory-confirmed case of human infection with avian influenza A (H7N9) virus was treated in our hospital. Acute respiratory distress syndrome (ARDS) developed and the patient was oxygenated via veno-venous ECMO due to the failure of mechanical ventilation. Unfortunately, a right refractory pneumothorax occurred. Despite treatment with pleural drainage and select bronchial occlusion, the patient still failed to improve. DIAGNOSIS: Fatal H7N9 pneumonia complicated with severe ARDS, pulmonary bullae, and refractory pneumothorax. INTERVENTIONS: Successful combination of ECMO with VATS of pulmonary bullae resection was performed and pneumothorax was cured. OUTCOMES: One week after the operation, ECMO was removed. However, the patient finally developed multiorgan failure (MOF) complicated by refractory hypoxemia due to progressive lung fibrosis and died 36 days after admission. LESSONS: Although the patient died of MOF triggered by severe lung fibrosis at last, the successful treatment of refractory pneumothorax by combination of ECMO with VATS is encouraging. Thus, when refractory pneumothorax in a patient with severe pulmonary dysfunction fails to improve through routine therapy, the treatment of pneumothorax by VATS based on ECMO support can be considered as a feasible selection.

The stress response HPA-axis hormone, glucocorticoid, reduces cellular SKA complex gene expression.

The Spindle- and Kinetochore-Associated (SKA) complex has been proven to be involved in many human mental behavioral disorders. Glucocorticoid, a hypothalamic-pituitary-adrenal (HPA) axis hormone, is a critical mediator of stress response in neurons. However, the underlying mechanisms of glucocorticoid's effects on human neuronal cells remain unclear. This study demonstrates that increased extracellular glucocorticoid levels significantly reduce neuronal cell SKA complex genes' expression levels, followed by altered neuronal cell viability and neurite development. The results suggest that the abnormality of this HPA-axis hormone could impact the neuronal cell functions through the alternation of SKA complex functions, which might induce cell death.

Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3ß/ß-catenin signaling pathways.

Sulforaphane is a common antioxidant selectively abundant in cruciferous plants, which exhibits effective anti-cancer actions in control of tumorigenesis or progression of various cancers. A recent study has shown that sulforaphane attenuates the EGFR signaling pathway in non-small cell lung cancer (NSCLC), suggesting its potential anti-metastatic effects. In this study we assessed the involvement of sulforaphane and miR-616-5p in epithelial-mesenchymal transition (EMT) and NSCLC metastasis. Sulforaphane suppressed the cell proliferation in human NSCLC cell lines H1299, 95C and 95D with IC50 values of 9.52±1.23, 9.04±1.90 and 17.35±2.03 µmol/L, respectively. At low concentrations (1-5 µmol/L), sulforaphane dose-dependently inhibited the migration and invasion of 95D and H1299 cells with relatively high metastatic potential. The anti-metastatic action of sulforaphane was confirmed in 95D and H1299 cell xenografts in vivo. In fresh NSCLC tissue samples from 179 patients, miR-616-5p levels were upregulated in late-stage NSCLCs, and strongly correlated with risk of NSCLC recurrence and metastasis. Consistent with the clinic observation, miR-616-5p levels in the 3 NSCLC cell lines were correlated with their metastatic ability, and were decreased by sulforaphane treatment. Silencing miR-616-5p markedly suppressed the migration and invasion of 95D cells in vitro and NSCLC metastasis in vivo. Further studies revealed that miR-616-5p directly targeted GSK3ß and decreased its expression, whereas sulforaphane decreased miR-616-5p levels by histone modification, and followed by inactivation of the GSK3ß/ß-catenin signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in NSCLC cells. Our findings suggest that sulforaphane is a potential adjuvant chemotherapeutic agent for the prevention of NSCLC recurrence and metastasis, and miR-616-5p can be clinically utilized as a biomarker or therapeutic target to inhibit metastasis.

Histopathological findings in a critically ill patient with avian influenza A (H7N9).

To date, data regarding the pulmonary histopathology of human H7N9 disease are scarce. We herein describe a patient with a severe case of avian influenza A (H7N9). A chest computerized tomography (CT) scan showed diffuse ground-glass opacities and consolidation throughout the lungs. A resection of pulmonary bullae in the right middle lobe was performed by video-assisted thoracic surgery (VATS) based on the extracorporeal membrane oxygenation (ECMO) supportive technique on the 23(rd) day after the onset of symptoms because of a right pneumothorax persistent air leak. The histopathological findings of the resected lung tissue revealed pneumocyte hyperplasia and fibroproliferative changes along with diffuse alveolar damage. Bronchoalveolar lavage fluid (BALF) specimens for influenza A (H7N9) virus were continuously positive for more than three weeks, despite oseltamivir treatment, and continuous viral replication significantly prolonged the course of the disease. The patient's clinical status continuously deteriorated, with the development of refractory hypoxemia due to progressive and rapid lung fibrosis, which was confirmed by the final histological changes observed from a limited post-mortem biopsy of lung tissue. Pre-terminally, he developed multi-organ failure and died on the 39(th) day after symptom onset, despite corticosteroid treatment.