Fibrosis is a progressive pathological process that severely impairs normal organ function. Current treatments for fibrosis are extremely limited, with no curative approaches available. In a recent article published in Cell, Zhang and colleagues employed drug screening using ACTA2 reporter iPSC-derived cardiac fibroblasts and identified artesunate as a potent antifibrotic drug by targeting MD2/TLR4 signaling. This study provides new insights into strategies for exploiting existing drugs to treat fibrosis.
Chronic obstructive pulmonary disease (COPD) and lung cancer are closely linked, with individuals suffering from COPD at a significantly higher risk of developing lung cancer. The mechanisms driving this increased risk are multifaceted, involving genomic instability, immune dysregulation, and alterations in the lung environment. Neutrophils, the most abundant myeloid cells in human blood, have emerged as critical regulators of inflammation in both COPD and lung cancer. Despite their short lifespan, neutrophils contribute to disease progression through various forms of programmed cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, and NETosis, a form of neutrophil death with neutrophil extracellular traps (NETs) formation. These distinct death pathways affect inflammatory responses, tissue remodeling, and disease progression in COPD and lung cancer. This review provides an in-depth exploration of the mechanisms regulating neutrophil death, the interplay between various cell death pathways, and their influence on disease progression. Additionally, we highlight emerging therapeutic approaches aimed at targeting neutrophil death pathways, presenting promising new interventions to enhance treatment outcomes in COPD and lung cancer.
Respiratory diseases pose a major public health challenge globally, necessitating collaborative efforts between basic researchers and clinicians for effective solutions. China, which is heavily impacted by a broad spectrum of respiratory disorders, has made notable strides in both research and clinical management of these diseases. The International Respiratory Medicine (IRM) meeting was organized with the primary goal of facilitating the exchange of recent research developments and promoting collaboration between Chinese and American scientists in both basic and clinical research fields. This article summarizes key insights from IRM2024, held in Shanghai, where a wide range of topics were discussed, including lung tissue development, disease mechanisms, and innovative therapeutic strategies. By integrating perspectives from basic, translational, and clinical research, IRM2024 highlighted recent advancements, addressed persistent challenges, and explored future directions in respiratory science and clinical practice. The insights gained from IRM2024 are poised to be pivotal in shaping future research and therapeutic approaches, further reinforcing the global commitment to enhancing respiratory health and improving patient outcomes.
Heart failure (HF) is a common clinical syndrome marked by reduced cardiac output, elevated intracardiac pressures, and heart dysfunction. Chronic HF (CHF) is a syndrome characterized by a lack of blood flow and impaired pumping ability to the heart over time, while acute HF (AHF) arises suddenly due to incidents like myocardial infarction or cardiac arrest. HF has a significant impact on pulmonary health and function, leading to conditions such as pulmonary edema and restrictive lung patterns. Clinical evidence highlights the bidirectional relationship between HF and lung dysfunction. Declining lung function serves as a predictor for HF progression and severity, while HF contributes to worsening lung health. Animal models that induce HF through surgical methods further demonstrate the connection between heart and lung pathology. The main mechanisms linking HF and lung dysfunction are pressure overload and chronic systemic inflammation, with changes in the extracellular matrix (ECM) also playing a role. Additionally, environmental factors like air pollution exacerbate lung inflammation, increasing the risk of both HF and chronic obstructive pulmonary disease (COPD) incidence. Combined treatment approaches involving pharmaceutical drugs such as statins, Angiotensin-converting enzyme (ACE) inhibitors, and Angiotensin receptor blockers (ARBs) may benefit by reducing inflammation. This review will explore the complex interplay between HF and lung function, emphasizing their interconnected pathophysiology and potential integrated treatment strategies.
Asthma is a common respiratory disorder characterized by chronic inflammation of the lower airways, contributing to significant morbidity, mortality, and a substantial global economic burden. It is now understood as a heterogeneous condition, with ongoing research shedding light on its complex immunological underpinnings. Ion channels, which are specialized transmembrane proteins that facilitate ion movement based on electrochemical gradients, play a crucial role in the pathophysiology of asthma. Ion channels regulate essential processes like maintaining epithelial hydroelectrolyte balance and also play a role in modulating immune responses involved in asthma. We discuss the connection between ion channel activity and immune regulation in asthma, focusing on ion channel regulation of immune cell behavior, airway hyperresponsiveness, and inflammation in asthma. Understanding ion channels in asthma could lead to the development of targeted therapies modulating their activity, thereby enhancing disease management and patient outcomes.
Asthma affects millions worldwide and involves complex genetic, immunological, and environmental factors. The nasal microbiome is increasingly recognized for its role in asthma development, but inconsistent results and small sample sizes have limited a clear understanding. We aimed to clarify the nasal microbiome’s role in asthma using large datasets and meta-transcriptomic analysis. RNA-seq data was analyzed from two large public studies: GALA II (694 children of Puerto Rican heritage; 441 asthmatics, 253 controls) and CAAPA (562 individuals of African ancestry; 265 asthmatics, 297 controls). After quality control and host read removal, microbial reads were annotated using Kraken2. α and β diversity analyses compared microbial diversity between asthmatic and control groups. Differential abundance analysis was conducted separately, controlling for age and sex, with results combined via meta-analysis. We found that asthmatic patients exhibited significantly higher α diversity indices (Shannon, Berger-Parker, Inverse Simpson, Fisher’s) in nasal microbiota compared to controls in GALA II, with similar trends in CAAPA. β diversity analysis showed significant differences in microbial composition in GALA II data. Differential abundance analysis identified 20 species in GALA II and 9 species in CAAPA significantly associated with asthma. Meta-analysis revealed 11 species significantly associated with asthma, including Mycobacterium_tuberculosis. Our study demonstrates increased nasal microbiome α diversity in asthmatic patients and identifies specific microbial species associated with asthma risk. These findings enhance understanding of asthma pathogenesis from the nasal microbiome perspective and may inform future research and therapeutic strategies.
Deficiency of surfactant protein-C (SPC) increases susceptibility to lung infections and injury, and suppressed expression of SPC has been associated with the severity of acute respiratory distress syndrome (ARDS). Alveolar type 2 epithelial cells (AT2) are critical for maintenance and repair of the lung. However, the role of the SPC in the regulation of AT2 cell lineage and the underlying mechanisms are not completely understood. This study aimed to investigate the mechanisms by which SPC regulates AT2 lineages. Sftpc−/− mice were used to model the SPC deficiency in ARDS patients. We utilized three-dimensional (3D) organoids to compare AT2 lineage characteristics between wild type (WT) and Sftpc−/− mice by analyzing AT2 proliferation, alveolar type 1 cells (AT1) differentiation and CD74 expression, using colony-formation assay, immunofluorescence, flow cytometry, and immunoblots. The results showed that Sftpc−/− mice demonstrated a reduced AT2 cell population. Influenza A virus subtype H1N1 (H1N1) infected Sftpc−/− mice demonstrated reduced AT2 proliferation and AT1 differentiation. Western blot indicated elevated levels of CD74 protein in AT2 cells of Sftpc−/− mice. Colony-forming efficiency was significantly attenuated in AT2 cells isolated from Sftpc−/− mice compared to the WT controls. Podoplanin (PDPN, a marker of AT1 cells) expression and transient cell count significantly increased in Sftpc−/− organoids. Moreover, siRNA-mediated gene silencing of CD74 in AT2 cells significantly increased AT2 proliferation and AT1 differentiation in Sftpc−/− organoids. This study suggests that SPC regulates AT2 lineage in vitro and in vivo. The SPC might influence AT2 lineage during the lung epithelium repair by activating signaling mechanism involving CD74 receptor.
Background: The strains of COVID-19 are constantly mutating, and the effectiveness of Chinese inactivated vaccines against the COVID-19 Delta variant has not been described clearly. Methods: The clinical data of patients with the COVID-19 Delta variant in the 2021 Nanjing outbreak were retrospectively reviewed. Results: There were 212 patients with the COVID-19 Delta variant (unvaccinated, n = 56, 26.42%; vaccinated, n = 156, 73.58%) included in our cohort study. The median age was 45.5 (38, 53) years old. Eighty-seven subjects (41.04%) were airport staff, and 94 patients (44.34%) in 32 families were infected. There were 53 (25.00%) and 103 (48.58%) cases with one-dose and two-dose vaccination, respectively, and 55 (25.94%), 147 (69.34%) and 10 (4.72%) had mild, moderate and severe symptoms, respectively. The duration of viral shedding, or viral shedding time (VST), was significantly longer in unvaccinated individuals compared to vaccinated individuals (p = 0.0008). Moreover, the duration was significantly longer in patients who received one vaccine dose than those who received two doses (p < 0.0001). The mild patients had significantly shorter VSTs than the moderate subjects (p < 0.0001). Disease severity and vaccination dose were independent predictors for VST by Cox regression models. Conclusions: These results suggest that two-dose vaccination could reduce VST in patients with the COVID-19 Delta variant. Chinese inactivated vaccines may decrease the disease severity of cases with the COVID-19 Delta variant.
The nucleus of the solitary tract (NTS) is the primary hub for sensing and integrating respiratory information. It integrates input from the vagus and glossopharyngeal nerve. It interacts with other brainstem nuclei, such as the nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DMV), to transmit information and initiate a neuroreflex response to respiratory stimuli. In a recent issue of the journal Nature, Su et al. demonstrated that Dbh+ neurons in the NTS can receive signals from vagal Trpv1+ sensory neurons that sense allergen−induced IL−4 production in mast cells and pass the signal to Chat+ neurons in the NA by releasing norepinephrine. Subsequently, NA Chat+ neurons drive allergen−induced airway hyperresponsiveness by projecting onto cholinergic pulmonary ganglia in the lungs. This study not only provides new insights into the regulation of allergen−induced airway hyperresponsiveness by lung−vagus–brainstem interoceptive circuit but also provides us with new strategies to combat asthma.
The aim of the study was to compare Hypoxic Ventilatory Response (HVR) of sleep apnea in Uygur patients stemming from higher altitude and Chinese Han patients from sea level. 276 subjects with or without snoring from the Karamay community were recruited. 226 subjects (n = 71 Han OSA patients, n = 75 Uygur OSA patients, n = 52 for Uygur control subjects without OSA, n = 28 Han control subjects without OSA) were matched for age and gender. All patients were assessed via polysomnography (PSG). Lung function was assessed. Apnea-hypopnea index (AHI), mean SaO2 (MSaO2%), lowest SaO2 (LSaO2%), the number of desaturations ≥4% per hour (ODI4), FEV1/FVC ratio, HVR, △VE/△SaO2 and the pulse responses to hypoxia changes (ΔPulse/ΔSaO2) were calculated. A multiple logistic regression using a binary outcome for HVR was applied. (1) In control subjects without OSA, those living at high altitude (Uygur) had a lower HVR than control subjects living at sea level (Han) [−0.35L·min−1 per %SpO2(−0.49 to−0.20 L·min−1 per %SpO2) vs.−0.44 L·min−1 per %SpO2(−0.55 to −0.21 L·min−1 per %SpO2)]. (2) Compared to patients with OSA living at sea level (Han), those OSA patients living at high altitude (Uygur) had a higher neck circumference [43 cm (range 39–45 cm) vs. 42 cm (41–46) cm], higher abdominal circumference [110 cm (102–120 cm) vs. 101 cm (98–111 cm], higher LSaO2 [81% (72–85%) vs. 76% (68–81%)], lower AHI [26 events/h (16–43 events/h) vs. 36 events/h (24–62 events/h)] and lower ODI4 [15/h (7–29/h) vs. 37/h (20–54/h)]. (3) Considering patients with mild OSA, those who lived at high altitude (Uygur) had a weaker HVR compared to Han patients [−0.31 L·min−1 per %SpO2(−0.42 to −0.20 L·min−1 per %SpO2) vs.−0.47 L·min−1 per %SpO2(−0.59 to −0.21 L·min−1 per %SpO2)]. However, in moderate and severe OSA the difference in HVR between people living at high and low altitudes was not significant. In people living at high altitude (Uygur) compared to sea level (Han), HVR is weaker both in control subjects and those with mild OSA, but this difference between populations living at different altitudes in those with moderate and severe OSA is not obvious.
