Evidence construction of Jinshuibao capsules against stable chronic obstructive pulmonary disease: A systematic review and network pharmacology.

Background: Jinshuibao capsules has been utilized in treating stable chronic obstructive pulmonary disease (COPD) for a long time. While the evidence-based evidence and network pharmacology to clarify the therapeutic efficacy and pharmacological mechanisms of Jinshuibao capsules have remained elusive. Objectives: Integrating evidence-based medicine and network pharmacology to explain the therapeutic efficacy and pharmacological mechanisms of Jinshuibao capsules for stable COPD. Methods: Cochrane Library, Web of Science, EMBASE, PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, VIP Information Resource Integration Service Platform (CQVIP), and China Biomedicine (SinoMed) databases were searched. Studies were selected according to the inclusion and exclusion criteria. Statistical analysis was performed using the RevMan 5.3 software (Cochrane, London, UK). In network pharmacology, components of Jinshuibao capsules were screened, stable COPD-related genes were then identified and the 'component-target-pathway' network constructed. Results: Meta-analysis revealed that Jinshuibao capsules exerts therapeutic effects on stable COPD by increasing the levels of FEV1% pred, FEV1/FVC ratio, FEV1, FVC, and PaO2 while decreasing the level of PaCO2. In addition, Jinshuibao capsules could effectively increase the levels of CD3+, CD4+/CD8+ ratio, Th17/Treg ratio, and SOD while reduce the levels of IL-8 and TNF-α. Network pharmacology identified 22 active compounds and 419 intersection gene targets. AKT1, SRC, MAPK1, STAT3, and MAPK3 were top 5 key target proteins. Besides, 20 potential pathways of Jinshuibao capsules on stable COPD were identified, like endocrine resistance, AGE-RAGE signaling pathway in diabetic complications, and chemical carcinogenesis-receptor activation. Conclusion: Jinshuibao capsules could positively influence patients with stable COPD, while the efficacy and safety of Jinshuibao capsules in the treatment of COPD could not be reliably confirmed. These findings suggest that Jinshuibao capsules exerts effect on stable COPD through multi-target, multi-component and multi-pathway mechanism. Future studies may explore the active components of Jinshuibao capsules.

Notoginsenoside R1 treatment facilitated Nrf2 nuclear translocation to suppress ferroptosis via Keap1/Nrf2 signaling pathway to alleviated high-altitude myocardial injury.

High-altitude myocardial injury (HAMI) represents a critical form of altitude illness for which effective drug therapies are generally lacking. Notoginsenoside R1, a prominent constituent derived from Panax notoginseng, has demonstrated various cardioprotective properties in models of myocardial ischemia/reperfusion injury, sepsis-induced cardiomyopathy, cardiac fibrosis, and myocardial injury. The potential utility of notoginsenoside R1 in the management of HAMI warrants prompt investigation. Following the successful construction of a HAMI model, a series of experimental analyses were conducted to assess the effects of notoginsenoside R1 at dosages of 50 mg/Kg and 100 mg/Kg. The results indicated that notoginsenoside R1 exhibited protective effects against hypoxic injury by reducing levels of CK, CK-MB, LDH, and BNP, leading to improved cardiac function and decreased incidence of arrhythmias. Furthermore, notoginsenoside R1 was found to enhance Nrf2 nuclear translocation, subsequently regulating the SLC7A11/GPX4/HO-1 pathway and iron metabolism to mitigate ferroptosis, thereby mitigating cardiac inflammation and oxidative stress induced by high-altitude conditions. In addition, the application of ML385 has confirmed the involvement of Nrf2 nuclear translocation in the therapeutic approach to HAMI. Collectively, the advantageous impacts of notoginsenoside R1 on HAMI have been linked to the suppression of ferroptosis via Nrf2 nuclear translocation signaling.

Identification of a myofibroblast differentiation program during neonatal lung development.

Alveologenesis is the final stage of lung development in which the internal surface area of the lung is increased to facilitate efficient gas exchange in the mature organism. The first phase of alveologenesis involves the formation of septal ridges (secondary septae) and the second phase involves thinning of the alveolar septa. Within secondary septa, mesenchymal cells include a transient population of alveolar myofibroblasts (MyoFBs) and a stable but poorly described population of lipid-rich cells that have been referred to as lipofibroblasts or matrix fibroblasts (MatFBs). Using a unique Fgf18CreER lineage trace mouse line, cell sorting, single-cell RNA sequencing and primary cell culture, we have identified multiple subtypes of mesenchymal cells in the neonatal lung, including an immature progenitor cell that gives rise to mature MyoFB. We also show that the endogenous and targeted ROSA26 locus serves as a sensitive reporter for MyoFB maturation. These studies identify a MyoFB differentiation program that is distinct from other mesenchymal cell types and increases the known repertoire of mesenchymal cell types in the neonatal lung.

Identification of a myofibroblast differentiation program during neonatal lung development.

Alveologenesis is the final stage of lung development in which the internal surface area of the lung is increased to facilitate efficient gas exchange in the mature organism. The first phase of alveologenesis involves the formation of septal ridges (secondary septae) and the second phase involves thinning of the alveolar septa. Within secondary septa, mesenchymal cells include a transient population of alveolar myofibroblasts (MyoFB) and a stable but poorly described population of lipid rich cells that have been referred to as lipofibroblasts or matrix fibroblasts (MatFB). Using a unique Fgf18CreER lineage trace mouse line, cell sorting, single cell RNA sequencing, and primary cell culture, we have identified multiple subtypes of mesenchymal cells in the neonatal lung, including an immature progenitor cell that gives rise to mature MyoFB. We also show that the endogenous and targeted ROSA26 locus serves as a sensitive reporter for MyoFB maturation. These studies identify a myofibroblast differentiation program that is distinct form other mesenchymal cells types and increases the known repertoire of mesenchymal cell types in the neonatal lung.