Search Results (3,699)

Nontuberculous mycobacteria are opportunistic pathogens increasingly associated with human disease. Within this group, the Mycobacterium avium complex (MAC), which includes M. avium, M. intracellulare and M. intracellulare subsp. chimaera, is the most frequent cause of infection. The increase in MAC cases worldwide has made it crucial to understand their population structure, clinical relevance and resistance mechanisms. Recent advances in whole-genome sequencing (WGS) and molecular approaches have improved the knowledge of taxonomy, population structure and genetic diversity, while also enabling the investigation of transmission and epidemiology. Clinically, MAC most often causes chronic pulmonary disease, but extrapulmonary forms, including disseminated disease, also occur. Presentation can vary by infecting species, while host factors such as pre-existing lung disease or immunosuppression further increase the risk. Treatment outcomes remain less favourable than desired, in part due to antimicrobial resistance involving de novo-acquired mutations. Pathogenesis is also influenced by interactions between MAC and host cells, including mechanisms of immune evasion and inflammatory modulation. In addition, emerging evidence suggests that gut–lung axis dysbiosis may influence susceptibility to MAC infection. This review outlines current knowledge on the population structure, clinical significance, resistance and host–pathogen interactions of MAC. Full article

P2Y₂ receptors are a subclass of G protein-coupled receptors activated by the extracellular nucleotides ATP and UTP. These receptors are widely expressed in multiple tissues—including the brain, lungs, heart, and kidneys—and play pivotal roles in inflammation, wound healing, and cell migration. Through coupling with various G proteins, P2Y₂ receptors initiate diverse intracellular signaling pathways that mediate calcium mobilization, cytokine release, and cytoskeletal reorganization. Recent studies highlight their dual roles in health and disease. In physiological contexts, P2Y₂ receptors contribute to immune modulation and tissue repair. In pathological conditions, they are implicated in Alzheimer’s disease by promoting non-amyloidogenic processing of amyloid precursor protein and in dry eye disease by enhancing mucin secretion while modulating ocular inflammation. They also influence chloride secretion and mucosal hydration in cystic fibrosis and contribute to inflammatory regulation and epithelial repair in inflammatory bowel disease. Additionally, P2Y₂ receptors modulate breast cancer progression by regulating cell adhesion, migration, and matrix remodeling. Their involvement in blood pressure regulation via epithelial sodium channel modulation and their facilitative role in HIV-1 entry further underscore their clinical significance. These multifaceted functions position P2Y₂ receptors as promising therapeutic targets for diverse diseases, warranting further investigation for translational applications. Full article

Pulmonary neuroendocrine tumors (PULMONARY NETs) are heterogeneous tumors ranging from well-differentiated to highly aggressive neoplasms. The aim of this study is to prospectively test pre-operative circulating free DNA (cfDNA) in PULMONARY NET patients undergoing surgery and evaluate its relationship to clinicopathological features. From February to December 2024, 136 patients with suspected primary lung cancer underwent pre-operative blood sampling, of whom 21 were diagnosed with PULMONARY NETs. Total cell-free nucleic acid extraction was performed using the Genexus Purification System (Thermofisher). cfDNA was quantified using a fluorometric assay with the Qubit dsDNA HS Assay kit (Thermofisher) and a capillary electrophoresis-based assay (cell-free DNA ScreenTape kit) on the Tape Station 4200 systems (Agilent). A cfDNA quality assessment was also obtained (cfDNA sizing and % cfDNA). Most patients had Stage I (18/21.85.7%) typical carcinoids (16/21.76.2%). Nodal involvement was detected in one patient (0.5%). Six months after surgery, all patients were alive without recurrence. Larger tumors presented higher levels of cfDNA. The mean tumor size in patients with cfDNA > 40 ng was 266 mm (±16.7 mm), compared to 13.2 mm (±7.3 mm) for cfDNA < 40 ng (p-value = 0.018). Higher levels of cfDNA were observed in patients with pStages greater than IA (p-value = 0.007). Although limited by a small sample group and biases of a surgical series, we observed that larger/advanced PULMONARY NETs presented higher cfDNA levels pre-operatively. Full article

Cellular senescence, a state of stable cell cycle arrest accompanied by a complex senescence-associated secretory phenotype (SASP), is a fundamental biological process implicated as a key driver of lung aging and lung age-related diseases (LARDs). This review provides a comprehensive overview of the rapidly evolving field of senotyping based on cellular heterogeneity in lung development and aging in health and disease. It also delves into the molecular mechanisms driving senescence and SASP production, highlighting pathways such as p53/p21, p16^INK4a/RB, mTOR, and p38 MAPK as therapeutic targets. The involvement of various novel SASP proteins, such as GDP15, cytokines/chemokines, growth factors, and DNA damage response proteins. We further highlight the effectiveness of senotherapeutics in mitigating the detrimental effects of senescent cell (SnC) accumulation within the lungs. It also outlines two main therapeutic approaches: senolytics, which selectively trigger apoptosis in SnCs, and senomorphics (also known as senostatics), which mitigate the detrimental effects of the SASP without necessarily removing the senescent cells. Various classes of senolytic and senomorphic drugs are currently in clinical trials including natural products (e.g., quercetin, fisetin, resveratrol) and repurposed drugs (e.g., dasatinib, navitoclax, metformin, rapamycin) that has demonstrated therapeutic promise in improving tissue function, alleviating LARDs, and extending health span. We discuss the future of these strategies in lung research and further elaborate upon the usability of novel approaches including HSP90 inhibitors, senolytic CAR-T cells, Antibody drug conjugate and galactose-modified prodrugs in influencing the field of personalized medicine in future. Overall, this comprehensive review highlights the progress made so far and the challenges faced in the field of cellular senescence including SnC heterogeneity, states of senescence, senotyping, immunosenescence, drug delivery, target specificity, long-term safety, and the need for robust cell-based biomarkers. Future perspectives, such as advanced delivery systems, and combination therapies, are considered critical for translating the potential of senotherapeutics into effective clinical applications for age-related pulmonary diseases/conditions. Full article

Background/Objectives: This study involved an analysis of clinical data, histological types, genetic predisposition, treatment and outcomes in PPB in children. Patients and methods: We conducted a retrospective review of children treated for PPB at Polish pediatric oncology centers between 2011 and 2024. Results: A total of fifteen children (seven boys, eight girls; median age of 39 months; range: 27–64 months) were included. Type II solid/cystic PPB and type III solid PPB were diagnosed in six and eight children, respectively (one not known). Overall, 93% of patients were diagnosed at up to 4 years of age. Metastatic disease at diagnosis was confirmed in three (20%) patients, localized in bones, bone marrow and lymph nodes. Diagnosis was confirmed via central pathology review in 11 patients (73%). DICER1 pathogenic variants were identified in eight patients. All children presented with respiratory symptoms. The tumor dimensions were >10 cm (n = 7), 5–10 cm (n = 5) and <5 cm (n = 2). No bilateral lung involvement was observed. Tumor biopsy was performed in six children (40%), with subsequent resection (R0) in five patients. Primary resection (R0) was achieved in three patients (20%) with type II (n = 1) or type III (n = 2). In the other six patients, non-radical resection was performed: R1 in four (27%) children (with a tumor rupture in one patient) and R2 (subtotal resection) in two children (13%). All patients received postoperative chemotherapy. Maintenance chemotherapy was given to two patients. No patient received radiotherapy as first-line treatment. Progressive disease occurred in two patients in the CNS and lungs. Relapsed disease appeared in three patients, all with CNS involvement. Conclusions: PPB is a rare, malignant tumor of early childhood with an uncertain prognosis. Despite multimodal treatment, patients remain at risk of progression or CNS relapse. Complete surgical resection remains a key prognostic factor. Full article

Acute lung injury (ALI) is a severe pulmonary disorder characterized by the disruption of the alveolar–capillary barrier, leading to impaired oxygenation and pulmonary edema. Current pharmacological interventions primarily involve the use of steroid drugs, oxygen radical scavengers, and bronchodilators. However, the therapeutic efficacy of these interventions remains inconsistent. Canthin-6-ones, a class of tryptophan-derived alkaloids, exhibit anti-inflammatory, antioxidant, and immunomodulatory properties. In this study, we synthesized a novel Canthin-6-one derivative, namely HCX3, and evaluated its potential beneficial effects and underlying mechanisms on ALI. Prior to the experimental study, network pharmacology analysis revealed that HCX3 may exert anti-inflammatory effects in the context of ALI through the regulation of multiple signaling pathways, including the NF-κB pathways. To validate these findings, Lipopolysaccharide (LPS) was employed to stimulate RAW 264.7 macrophages and bone marrow-derived macrophages (BMDMs) to construct cellular models of inflammatory response associated with ALI. Our data demonstrated that exposure to HCX3 significantly inhibited the transcription and the secretion of multiple pro-inflammatory mediators, including IL-1β, IL-6, and TNF-α, in a dose-dependent manner. Additionally, HCX3 reduced LPS-induced phosphorylation levels of p65 and IκB-α in macrophages, indicating an inhibitory effect of the compound on the activation of NF-κB signaling pathway. Collectively, our data suggest that HCX3 exhibits significant anti-inflammatory effects by inhibiting NF-κB-related signaling pathways, providing new insights for ALI treatment. Full article

Introduction: Prostate cancer is one of the most common neoplasia in men, and its clinical evolution is highly influenced by psycho-emotional factors, especially in elderly patients. Comorbidities, the perception of one’s identity and its impact on life quality become relevant variables in the therapeutic decision. Sexual dysfunction after treatment along with decreased libido, erectile dysfunction and ejaculatory dysfunction are significant problems in patients with prostate cancer. Case presentation: The present study presents the oncological evolution of an elderly patient with a dual diagnosis, prostate adenocarcinoma and lung squamous cell carcinoma, who faced a significant amount of medical and psychological challenges. Reluctance to hormone therapy was closely linked to the fear of sexual dysfunction, a very common reaction in elderly men concerned with maintaining autonomy and intimacy. The peculiarity of the case consists in the interaction between the evolution of the disease, the therapeutic decisions and the psychological impact on the patient. Discussion: Androgen deprivation therapy negatively influences multiple aspects of sexual function, significantly impairing the life quality of patients diagnosed with prostate cancer. In this context, therapy through acceptance and commitment is the appropriate one, its main purpose being to change the patient’s relationship with suffering—from struggle and rejection to active acceptance and value of the present. The intervention of the psychologist or the psychotherapist is essential in decision-making counseling, using coping techniques, the clarification of personal values and the involvement of the family in the decision-making process. Oncological psychology helps the patient redefine their life goals and priorities, not just to choose a treatment. Conclusions: Sexuality and psychological health are deeply affected by prostate cancer. Psychological flexibility and emotional support can mitigate this negative impact. The integration of therapy through acceptance and commitment in the rehabilitation after treatment increases effectiveness and patient satisfaction. Full article

The clinical pathway of a patient who experiences cardiac arrest and subsequently dies (with or without organ donation) is complex. It involves uncontrolled (u-) donation after circulatory death (DCD), controlled (c-) DCD, and donor after brain death (DBD). The present paper aims to summarize existing evidence on organ donation rates among out-of-hospital cardiac arrest (OHCA) patients, with a focus on these three donor categories (uDCD, DBD, and cDCD). Furthermore, the potential to expand each donor pathway in OHCA patients will be highlighted, based on available evidence. Among non-survivor OHCA patients, the prevalence of brain death (BD) is estimated to be low, though reported data are not uniform. The diagnosis of BD is made 3 to 6 days after return of spontaneous circulation. The implementation of uDCD is known to be quite challenging due to logistical, ethical, and resource issues. Its rationale is still well grounded, mainly considering two factors: (a) the high incidence of OHCA, such that uDCD donors can be considered an existing pool of potential donors; (b) the uDCD pathway shows feasibility both under organizational (i.e., only lung uDCD program) and clinical views (normothermic regional perfusion, ex vivo machine perfusion, and an appropriate donor–recipient match). Controlled DCDs are donors who died after a planned withdrawal of life-sustaining therapy (WLST). Data on the percentage of cDCD among OHCA patients is not uniform since the percentage of utilized cDCD has been estimated at around 10%. According to available evidence, each donor pathway in OHCA has the potential to be expanded, mainly by the identification of potential donors and the implementation of DCD programs. Full article

Osbana, also known as Osbane, is a cooked sausage-like product prepared from edible by-products and is one of the most popular Algerian traditional meat products. However, there is a lack of knowledge regarding its culinary preparation and consumption habits. Therefore, this study explores these aspects within the Algerian population. Using an online questionnaire, we surveyed the people who prepare (n = 581) along with those who consume Osbana (n = 928 consumers). The survey allowed us to establish a preparation diagram of Osbana following the traditional methods involving cleaning, boiling, confecting balls/sausages, cutting, seasoning, stuffing, closing balls/sausages, conserving, and cooking. Overall, the results showed that Osbana is usually prepared from lamb, using mainly white offal (intestines, stomach, and lungs) as the main component, generally stuffed in a cleaned rumen that is not scraped of its dark layer. The rough side of the rumen is frequently put on the outside of the balls/sausages. However, regional variations in its preparation have been observed. Osbana seemed to be well appreciated by 51.7% of respondents, owing to its typical sensory properties. Interestingly, it is frequently consumed at home, at most 3 times a year (79% of consumers), but mainly served during religious and social celebrations, especially for Eid El-Adha. The common dishes used for its consumption depend on the region, but overall, it is consumed with Couscous or in a sauce. Variations in the preparation of Osbana influence the way it is consumed, hence creating typical recipes in each region. Also, these differences in its preparation may lead to differences in its nutritional and sensory properties, which require further investigation. Full article

Background and Objectives: Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition associated with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and emphysema, and with liver involvement through a distinct toxic gain-of-function mechanism. Despite its clinical relevance, AATD remains underdiagnosed and exhibits marked phenotypic heterogeneity. Artificial intelligence (AI) has shown growing potential in respiratory medicine, yet its application to AATD is still limited. This systematic review synthesizes the clinical evidence on AI in AATD, primarily in the respiratory domain and, where available, in hepatic outcomes. Materials and Methods: We conducted a PRISMA-guided search (PubMed, Web of Science, IEEE Xplore) for original, peer-reviewed articles (January 2014–September 2025) applying AI to detection, classification, stratification, or prediction tasks in AATD. Results: Six studies met eligibility criteria. Supervised models (e.g., XGBoost, penalized regression, Transformer-based architectures) and one unsupervised approach were identified. Applications included screening in COPD populations, prediction of emphysema progression from CT, proteomic modeling of lung function, identification of clinical subgroups, and prediction of clinical outcomes in AATD-associated liver disease. External validation and genotype diversity remained limited across studies. Conclusions: Although AI shows promise in improving detection, prognosis, and patient stratification in AATD across both respiratory and hepatic manifestations, the current evidence remains limited. Broader, multicenter validation in genotype-diverse cohorts is required to confirm its clinical utility and support the implementation of precision medicine in AATD. Full article

Neutrophils are among the first cells to be recruited to the lungs during Chlamydia pneumoniae infection in mouse models; however, their regulatory functions are not yet fully understood. This study examined the mechanisms and significance of IL-10-producing neutrophils throughout C. pneumoniae pulmonary infection in C57BL/6 mice. Our findings revealed that infection with C. pneumoniae induces IL-10 secretion in bone marrow-derived neutrophils, depending on Toll-like receptor 2 (TLR2) activation. This process involves TLR2-dependent mitochondrial reactive oxygen species (ROS) production, which triggers the endoplasmic reticulum (ER) stress pathway, including IRE1α and subsequent Xbp1 splicing. Inhibition of this pathway or depletion of neutrophils (using the 1A8 monoclonal antibody) significantly reduces IL-10 levels in bronchoalveolar lavage fluid (BALF) in vivo. Conversely, the absence of IL-10-producing neutrophils, whether through depletion or TLR2 deficiency, leads to increased IL-12p70 and IFN-γ-positive NK cells, along with decreased regulatory T cells and M2-like macrophages. This results in a lower bacterial burden in the lungs but causes more severe pulmonary damage and decreased survival rates. These findings highlight that IL-10 produced by neutrophils via the TLR2-mitochondrial ROS–ER stress pathway is essential for modulating pulmonary immune responses and maintaining immune homeostasis during C. pneumoniae infection, thereby preventing excessive inflammation and tissue damage. Full article

Background/Objectives: Subarachnoid cysts in children, while often linked to trauma, can also rupture spontaneously without any apparent injury. Their etiology remains complex, involving congenital, traumatic, and infectious factors. This article explores the risks, pathophysiology, and management strategies related to spontaneous rupture in pediatric cases reported in the literature through the means of a systematic review. Materials and Methods: A systematic review of Web of Science, Scopus, PubMed and the Virtual Health Library (BVS, for its acronym in Spanish) was conducted; the online software Ryyan was used to manage the references and conduct the filtering process. The National Heart, Lung, and Blood Institute (NHLBI) quality assessment tool was used to assess bias for each type of study. Results: We analyzed the data of 101 articles; in total we found that 331 pediatric patients with arachnoid cyst were diagnosed with intracranial hemorrhage and 1030 patients had an unruptured arachnoid cyst. The most common cyst diameter was between 5–7 cm in the bleeding group vs. 3–4.5 cm in the non-bleeding group. A head trauma trigger was identified in 36.25% of cases of bleeding and 10.6% were sports related. Most of the hemorrhages were subdural, followed by a mixed pattern between subdural and intracystic. In both groups the arachnoid cyst was mostly located in the middle cranial fossa in the left side. The bleeding arachnoid cysts were mostly treated with surgery, but conservative treatment was also effective; the outcome was good in the majority of cases. Conclusions: Further research is required to elucidate the pathophysiological mechanisms underlying hemorrhage associated with arachnoid cysts in the pediatric population. Nevertheless, upon identification of an arachnoid cyst, neurosurgical follow-up is warranted. Bleeding tends to occur only in the presence of high-risk features and can be precipitated by traumatic events. Full article

Reprogramming is a hallmark of cancer, enabling tumour cells to sustain rapid proliferation, resist cell death, and adapt to hostile microenvironments. This review explores the expression profiles of key metabolic enzymes and transporters involved in glucose, amino acid, and lipid metabolism across the five most deadly cancers worldwide: lung, breast, colorectal, liver, and gastric cancers. Through a comparative analysis, we identify consistent upregulation of glycolytic enzymes such as LDHA, PKM2, and HK2, as well as nutrient transporters like GLUT1, ASCT2, and LAT1, which contribute to cancer progression, metastasis, and therapy resistance. The role of enzymes involved in glutaminolysis (e.g., GLS1, GDH), one-carbon metabolism (e.g., SHMT2, PHGDH), and fatty acid synthesis (e.g., FASN, ACLY) is also examined, with emphasis on their emerging relevance as diagnostic, prognostic, and predictive biomarkers. While several metabolic proteins show strong potential for clinical translation, only a few, such as tumour M2-pyruvate kinase (TuM2-PK) and serum LDH measurement, have progressed into clinical use or trials. This review addresses some of the challenges in biomarker development. Ultimately, our findings underscore the importance of metabolic proteins not only as functional drivers of malignancy but also as promising candidates for biomarker discovery. Advancing their clinical implementation could significantly enhance early detection, treatment stratification, and personalized oncology. Full article

Cellular plasticity enables cells to dynamically adapt their phenotype in response to environmental cues, a process central to development, tissue repair, and disease. Among the most studied plasticity programs is epithelial–mesenchymal transition (EMT), a transcriptionally controlled process by which epithelial cells acquire mesenchymal traits. Originally described in embryogenesis, EMT is now recognized as a key driver in both tumor progression and fibrotic remodeling. In cancer, EMT and hybrid epithelial/mesenchymal (E/M) states promote invasion, metastasis, stemness, therapy resistance, and immune evasion. In fibrotic diseases, partial EMT (pEMT) contributes to fibroblast activation and excessive extracellular matrix deposition, sustaining organ dysfunction mainly in the kidney, liver, lung, and heart. This review integrates recent findings on the molecular regulation of EMT, including signaling pathways (TGF-β, WNT, NOTCH, HIPPO), transcription factors (SNAIL, ZEB, TWIST), and regulatory layers involving microRNAs and epigenetic modifications. Moreover, we discuss the emergence of pEMT states as drivers of phenotypic plasticity, functional heterogeneity, and poor prognosis. By comparing EMT in cancer and fibrosis, we reveal shared mechanisms and disease-specific features, emphasizing the translational relevance of targeting EMT plasticity. Finally, we explore how cutting-edge technologies, such as single-cell transcriptomics and lineage tracing, are reshaping our understanding of EMT across pathological contexts. Full article

Background/Objectives: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established, minimally invasive method for sampling mediastinal and hilar lymph nodes. It has high sensitivity and specificity for diagnosing lymph node involvement. However, achieving a definitive cytopathological diagnosis can be challenging owing to the limited presence of atypical tumor cells. The scanning single-molecule counting (SSMC) method enables rapid measurement of target molecule expression. This study assessed the correlation between miR-200c expression measured by SSMC and lymph node metastasis confirmed by cytopathology. Methods: Following EBUS-TBNA in patients with lung cancer or suspected lung cancer, we flushed 22-gauge biopsy needles with 1 mL saline and extracted microRNA (miRNA) from the lavage fluid. The quality of SSMC results for miR-200c was evaluated and compared with that of quantitative real-time polymerase chain reaction (RT-qPCR). Results: Linear regression analysis of miR-200c between SSMC and RT-qPCR showed a statistically significant positive correlation (R² = 0.81, p < 0.0001), demonstrating the feasibility of SSMC for evaluating miRNA in lymph nodes. Based on these findings, we enrolled and analyzed 100 lymph nodes from 86 patients. High miR-200c expression detected lymph node metastasis with high sensitivity (85.7%) and specificity (83.3%) and an AUC of 0.88. No discordance was observed between the standard SSMC and rapid methods. Conclusions: The expression of miR-200c, as measured by SSMC, may serve as a biomarker for molecular nodal staging. The rapid SSMC method provides results within 30 min, significantly faster than conventional RT-qPCR, and may complement rapid on-site cytological evaluation. Full article