Procyanidin C1 inhibits bleomycin-induced pulmonary fibrosis in mice by selective clearance of senescent myofibroblasts.

Pulmonary fibrosis is a formidable challenge in chronic and age-related lung diseases. Myofibroblasts secrete large amounts of extracellular matrix and induce pro-repair responses during normal wound healing. Successful tissue repair results in termination of myofibroblast activity via apoptosis; however, some myofibroblasts exhibit a senescent phenotype and escape apoptosis, causing over-repair that is characterized by pathological fibrotic scarring. Therefore, the removal of senescent myofibroblasts using senolytics is an important method for the treatment of pulmonary fibrosis. Procyanidin C1 (PCC1) has recently been discovered as a senolytic compound with very low toxicity and few side effects. This study aimed to determine whether PCC1 could improve lung fibrosis by promoting apoptosis in senescent myofibroblasts and to investigate the mechanisms involved. The results showed that PCC1 attenuates bleomycin (BLM)-induced pulmonary fibrosis in mice. In addition, we found that PCC1 inhibited extracellular matrix deposition and promoted the apoptosis of senescent myofibroblasts by increasing PUMA expression and activating the BAX signaling pathway. Our findings represent a new method of pulmonary fibrosis management and emphasize the potential of PCC1 as a senotherapeutic agent for the treatment of pulmonary fibrosis, providing hope for patients with pulmonary fibrosis worldwide. Our results advance our understanding of age-related diseases and highlight the importance of addressing cellular senescence in treatment.

Omentin-1 induces mechanically activated fibroblasts lipogenic differentiation through pkm2/yap/pparγ pathway to promote lung fibrosis resolution.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease characterized by extensive extracellular matrix (ECM) deposition by activated myofibroblasts, which are specialized hyper-contractile cells that promote ECM remodeling and matrix stiffening. New insights on therapeutic strategies aimed at reversing fibrosis by targeting myofibroblast fate are showing promise in promoting fibrosis resolution. Previously, we showed that a novel adipocytokine, omentin-1, attenuated bleomycin (BLM)-induced lung fibrosis by reducing the number of myofibroblasts. Apoptosis, deactivation, and reprogramming of myofibroblasts are important processes in the resolution of fibrosis. Here we report that omentin-1 reverses established lung fibrosis by promoting mechanically activated myofibroblasts dedifferentiation into lipofibroblasts. Omentin-1 promotes myofibroblasts lipogenic differentiation by inhibiting dimerization and nuclear translocation of glycolytic enzymes pyruvate kinase isoform M2 (PKM2) and activation of the downstream Yes-associated protein (YAP) by increasing the cofactor fructose-1,6-bisphosphate (F1, 6BP, FBP). Moreover, omentin-1 activates proliferator-activated receptor gamma (PPARγ) signaling, the master regulator of lipogenesis, and promotes the upregulation of the lipogenic differentiation-related protein perilipin 2 (PLIN2) by suppressing the PKM2-YAP pathway. Ultimately, omentin-1 facilitates myofibroblasts transformation into the lipofibroblast phenotype, with reduced collagen synthesis and enhanced degradation properties, which are crucial mechanisms to clear the ECM deposition in fibrotic tissue, leading to fibrosis resolution. Our results indicate that omentin-1 targets mechanical signal accelerates fibrosis resolution and reverses established lung fibrosis by promoting myofibroblasts lipogenic differentiation, which is closely associated with ECM clearance in fibrotic tissue. These findings suggest that targeting mechanical force to promote myofibroblast lipogenic differentiation is a promising therapeutic strategy against persistent lung fibrosis.

A partially flipped physiology classroom improves the deep learning approach of medical students.

This study aimed to compare the impact of the partially flipped physiology classroom (PFC) and the traditional lecture-based classroom (TLC) on students' learning approaches. The study was conducted over 5 mo at Xiangya School of Medicine from February to July 2022 and comprised 71 students majoring in clinical medicine. The experimental group (n = 32) received PFC teaching, whereas the control group (n = 39) received TLC. The Revised Two-Factor Study Process Questionnaire (R-SPQ-2F) was used to assess the impact of different teaching methods on students' learning approaches. After the PFC, students got significantly higher scores on deep learning approach (Z = -3.133, P < 0.05). Conversely, after the TLC students showed significantly higher scores on surface learning approach (Z = -2.259, P < 0.05). After the course, students in the PFC group scored significantly higher in deep learning strategy than those in the TLC group (Z = -2.196, P < 0.05). The PFC model had a positive impact on deep learning motive and strategy, leading to an improvement in the deep approach, which is beneficial for the long-term development of students. In contrast, the TLC model only improved the surface learning approach. The study implies that educators should consider implementing PFC to enhance students' learning approaches.NEW & NOTEWORTHY In this article, we compare the impact of the partially flipped classroom (PFC) and the traditional lecture classroom (TLC) in a physiology course on medical students' learning approaches. We found that the PFC benefited students by significantly enhancing their deep learning motive, strategy, and approach, which was good for them. However, the TLC model only improved the surface learning motive and approach.

An online flipped classroom approach improves the physiology score and subsequent course scores of the top-performing students.

The online flipped classroom (OFC) has emerged as a new teaching method in universities worldwide, which combines asynchronous and synchronous online learning. OFC differs from the traditional flipped classroom as it does not involve face-to-face interaction between teachers and students. Instead, the class meeting is conducted online, and it is focused on active and collaborative learning (e.g., discussion rather than lecturing). To evaluate the effectiveness of the Physiology OFC, we compared it with online live teaching (OLT) offered in the same school and semester. We analyzed the exam scores of the Physiology course as well as the scores for other courses offered in the same semester and after the Physiology course. We categorized the top 27% of the exam takers as high-achieving students and the bottom 27% as low-achieving students. Our analysis found no statistically significant difference between OFC and OLT in terms of overall exam scores for all students. However, high-achieving students in OFC scored higher on the total exam score and short answer questions, but the score of case study questions (CSQs) of low-achieving students was lower. Furthermore, students in OFC scored higher in Medical Immunology and courses dominated by logical thinking such as Pharmacology and Diagnostics than students in OLT. In conclusion, our findings suggest that OFC can achieve the same teaching effectiveness as OLT, with a more positive impact on high-achieving students. The positive impact extends beyond the Physiology course to other courses where logical thinking is critical. However, the lower performance of low-achieving students in CSQs highlights the need for further research to determine the reasons for their lower performance and potential strategies to improve their learning outcomes.NEW & NOTEWORTHY An online flipped classroom approach achieved the same teaching effect as online live teaching but had a more positive impact on high-achieving students. The positive impact was not only in Physiology but also in subsequent courses where logical thinking prevailed. However, for low-achieving students, the effect of online live teaching was better.

Exploring the impact of online and offline teaching methods on the cognitive abilities of medical students: a comparative study.

BACKGROUND: Online education has become increasingly popular, but research on the effectiveness of different teaching models in developing cognitive skills is limited. This study investigated the relationship between different teaching models (online and offline) and the development of cognitive skills in clinical medicine students. METHODS: Survey data were collected from 2018 entry students who participated in online teaching and 2019 entry students in offline teaching at Xiangya School of Medicine, Central South University. National Quality Open Courses (NQROC) were provided to both groups of students. The study examined the total score of physiology final exam, score of each type of question, and NQROC learning engagement in different score segments under the two teaching models. Non-parametric statistical methods were utilized to analyze the total score of physiology final exam, score of each type of question, and the NQROC learning engagement. Spearman's rank correlation was utilized to analyze the relationship between the score of physiology final exam and the students' NQROC learning engagement. RESULTS: The study found no statistically significant difference in the total score, short-answer questions (SAQs) score, and case study questions (CSQs) score between online and offline teaching models. However, the multiple-choice questions (MCQs) score was higher in the online teaching model (Z=-4.249, P < 0.001), suggesting that online teaching may be an effective way to improve lower-order cognitive skills among students. In contrast, low-achieving students had higher total scores (Z=-3.223, P = 0.001) and scores in both MCQs (Z=-6.263, P < 0.001) and CSQs (Z=-6.877, P < 0.001) in the online teaching model. High-achieving students in the online teaching model had higher total scores (Z=-3.001, P = 0.003) and MCQs scores (Z=-5.706, P < 0.001) but lower scores in CSQs (Z=-2.775, P = 0.006). Furthermore, students' NQROC learning engagement was greater in the online teaching model. CONCLUSIONS: The results of this study suggested that online teaching was not statistically significantly different from offline in cognitive domains and was more desirable than offline in strengthening lower-order cognitive skills. However, it was important to note that offline teaching may be more effective in reinforcing higher-order cognitive skills among high-achieving students. In conclusion, this study provided important insights into the effectiveness of different teaching models in developing cognitive skills among medical students and highlighted the potential benefits of online teaching in enhancing students' lower-order cognitive skills.

Regeneration-Associated Transitional State Cells in Pulmonary Fibrosis.

Pulmonary fibrosis is a chronic, progressive fibrosing interstitial disease. It is characterized by fibroblast proliferation, myofibroblast activation, and massive extracellular matrix deposition. These processes result in loss of lung parenchyma function. The transdifferentiation of alveolar epithelial type II (AEC2) to alveolar epithelial type I cells (AEC1) plays an important role in the epithelial repair after lung injury. Pulmonary fibrosis begins when this transdifferentiation process is blocked. Several recent studies have found that novel transitional state cells (intermediate states in the transdifferentiation of AEC2 to AEC1) can potentially regenerate the alveolar epithelium surface and promote a repair process. During the AEC2 to AEC1 trans-differentiation process after injury, AEC2 lose their specific markers and become transitional state cells. Furthermore, transdifferentiation of transitional state cells into AEC1 is the critical step for lung repair. However, transitional cells stagnate in the intermediate states in which failure of transdifferentiation to AEC1 may induce an inadequate repair process and pulmonary fibrosis. In this review, we focus on the traits, origins, functions, and activation of signaling pathways of the transitional state cell and its communication with other cells. We also provide a new opinion on pulmonary fibrosis pathogenesis mechanisms and novel therapeutic targets.

Assembly and comparative analysis of the complete mitochondrial genome of Suaeda glauca.

BACKGROUND: Suaeda glauca (S. glauca) is a halophyte widely distributed in saline and sandy beaches, with strong saline-alkali tolerance. It is also admired as a landscape plant with high development prospects and scientific research value. The S. glauca chloroplast (cp) genome has recently been reported; however, the mitochondria (mt) genome is still unexplored. RESULTS: The mt genome of S. glauca were assembled based on the reads from Pacbio and Illumina sequencing platforms. The circular mt genome of S. glauca has a length of 474,330 bp. The base composition of the S. glauca mt genome showed A (28.00%), T (27.93%), C (21.62%), and G (22.45%). S. glauca mt genome contains 61 genes, including 27 protein-coding genes, 29 tRNA genes, and 5 rRNA genes. The sequence repeats, RNA editing, and gene migration from cp to mt were observed in S. glauca mt genome. Phylogenetic analysis based on the mt genomes of S. glauca and other 28 taxa reflects an exact evolutionary and taxonomic status of S. glauca. Furthermore, the investigation on mt genome characteristics, including genome size, GC contents, genome organization, and gene repeats of S. gulaca genome, was investigated compared to other land plants, indicating the variation of the mt genome in plants. However, the subsequently Ka/Ks analysis revealed that most of the protein-coding genes in mt genome had undergone negative selections, reflecting the importance of those genes in the mt genomes. CONCLUSIONS: In this study, we reported the mt genome assembly and annotation of a halophytic model plant S. glauca. The subsequent analysis provided us a comprehensive understanding of the S. glauca mt genome, which might facilitate the research on the salt-tolerant plant species.

Ozone therapy promotes the differentiation of basal keratinocytes via increasing Tp63-mediated transcription of KRT10 to improve psoriasis.

Psoriasis is a chronic immune-mediated inflammatory dermatosis. Recently, ozone therapy has been applicated to psoriasis treatment; however, the mechanism by which ozone therapy improves psoriasis remains unclear. The excessive proliferation and the differentiation of basal keratinocytes have been considered critical issues during pathological psoriasis process, in which keratin 6 (KRT6) and KRT10 might be involved. In the present study, KRT6, IL-17 and IL-22 protein within psoriasis lesions was decreased, while KRT10 and Tp63 protein in psoriasis lesions was increased by ozone treatment in both patient and IMQ mice psoriatic tissues. In the meantime, ozone treatment down-regulated KRT6 mRNA and protein expression while up-regulated KRT10 mRNA and protein expression within IL-22 treated primary KCs; the cell viability of KCs was suppressed by ozone treatment. Moreover, Tp63 bound to KRT10 promoter region to activate its transcription in basal keratinocytes; the promotive effects of ozone on Tp63 and KRT10 were significantly reversed by Tp63 silence. Both TP63 and KRT10 mRNA expression were significantly increased by ozone treatment in psoriasis lesions; there was a positive correlation between Tp63 and KRT10 expression within tissue samples, suggesting that ozone induces the expression of Tp63 to enhance the expression of KRT10 and the differentiation of keratinocytes, therefore improving the psoriasis. In conclusion, the application of ozonated oil could be an efficient and safe treatment for psoriasis; ozone promotes the differentiation of keratinocytes via increasing Tp63-mediated transcription of KRT10, therefore improving psoriasis.

[Research progress of endogenous bone marrow-derived mesenchymal stem cells in pulmonary fibrosis].

Pulmonary fibrosis is a chronic, diffuse, interstitial lung disease involving the pulmonary interstitium, alveoli, and bronchioles caused by various causes. There is no effective treatment. Currently, exogenous bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation has attracted much attention as a new stem cell therapy in the treatment of pulmonary fibrosis. Less attention has been paid to the functional status of endogenous BM-MSCs during pulmonary fibrosis. Based on summary on the anti-pulmonary fibrosis effect of BM-MSCs and its mechanism, this review further discusses the abnormal changes of bone marrow function in animals with pulmonary fibrosis and the role of glutamate NMDA receptor overactivation in mediating the functional inhibition of endogenous BM-MSCs induced by pulmonary fibrosis. This will provide potential ideas for finding effective treatments for pulmonary fibrosis.

[The construction and application of online open courses in Chinese colleges and universities--Taking the physiology course at Central South University of China as an example].

Massive open online course (MOOC) is a new learning model, which integrates the progress of novel educational concepts and the breakthrough of information technology. MOOC uses new web-based tools and online-environments to deliver knowledge education and lecture classes in a new paradigm. In this paper, we firstly reviewed the achievements through four stages of the construction and development of online courses of physiology in China in the past 20 years. Then, taking the physiology MOOC at Central South University of China as an example, we introduced the specific practices and experiences to construct the online physiological open course, including the online open course-based offline and online flipped classroom teaching practice. Finally, we discussed several important issues during the construction and application of online open courses, aiming to provide practical information for other universities.

[The metabolic networks of ferroptosis and links to lung diseases].

Ferroptosis is a newly discovered non-apoptotic form of regulated cell death driven by iron-dependent lipid peroxidation. The present studies have shown that many metabolic processes and homeostasis are affected by ferroptosis. It is related to many lung diseases, including acute lung injury, chronic obstructive pulmonary disease and pulmonary fibrosis, etc. Currently, the research on ferroptosis is still in its infancy. Previous studies have confirmed that ferroptosis is regulated by a variety of genes, and the mechanism is complex, mainly involving iron homeostasis and lipid peroxidation metabolism. This review summarizes some regulation networks of metabolic processes associated with ferroptosis and discusses the roles of ferroptosis in the pathophysiological progression of many lung diseases. We expected to provide new ideas and references for the treatment of these diseases.

Excessive activation of NMDA receptor inhibits the protective effect of endogenous bone marrow mesenchymal stem cells on promoting alveolarization in bronchopulmonary dysplasia.

We studied the role of bone marrow mesenchymal stem cells (MSCs) in our established model of bronchopulmonary dysplasia (BPD) induced by intrauterine hypoxia in the rat. First, we found that intrauterine hypoxia can reduce the number of MSCs in lungs and bone marrow of rat neonates, whereas the administration of granulocyte colony-stimulating factor or busulfan to either motivate or inhibit bone marrow MSCs to lungs altered lung development. Next, in vivo experiments, we confirmed that intrauterine hypoxia also impaired bone marrow MSC proliferation and decreased cell cycling activity. In vitro, by using the cultured bone marrow MSCs, the proliferation and the cell cycling activity of MSCs were also reduced when N-methyl-d-aspartic acid (NMDA) was used as an NMDA receptor (NMDAR) agonist. When MK-801 or memantine as NMDAR antagonists in vitro or in vivo was used, the reduction of cell cycling activity and proliferation were partially reversed. Furthermore, we found that intrauterine hypoxia could enhance the concentration of glutamate, an amino acid that can activate NMDAR, in the bone marrow of neonates. Finally, we confirmed that the increased concentration of TNF-ɑ in the bone marrow of neonatal rats after intrauterine hypoxia induced the release of glutamate and reduced the cell cycling activity of MSCs, and the latter could be partially reversed by MK-801. In summary, intrauterine hypoxia could decrease the number of bone marrow MSCs that could affect lung development and lung function through excessive activation of NMDAR that is partially caused by TNF-ɑ.

NMDA receptor activation inhibits the antifibrotic effect of BM-MSCs on bleomycin-induced pulmonary fibrosis.

Endogenous glutamate (Glu) release and N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation are associated with lung injury in different animal models. However, the underlying mechanism is unclear. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which show potential use for immunomodulation and tissue protection, play a protective role in pulmonary fibrosis (PF) process. Here, we found the increased Glu release from the BM cells of bleomycin (BLM)-induced PF mice in vivo. BLM stimulation also increased the extracellular Glu in BM-MSCs via the antiporter system xc- in vitro. The gene expression of each subunit of NMDAR was detected in BM-MSCs. NMDAR activation inhibited the proliferation, migration, and paracrine function of BM-MSCs in vitro. BM-MSCs were derived from male C57BL/6 mice, transfected with lentiviral vectors carrying the enhanced green fluorescence protein gene, pretreated with NMDA, and transplanted into the female recipient mice that were intratracheally injected with BLM to induce PF. Transplantation of NMDA-pretreated BM-MSCs significantly aggravated PF as compared with that in the normal BM-MSCs transplantation group. The sex determination gene Y chromosome and green fluorescence protein genes of BM-MSCs were detected to observe BM-MSCs homing in the fibrotic lungs. Moreover, NMDAR activation inhibited BM-MSC migration by downregulating the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 signaling axis. NMDAR activation aggravated the transforming growth factor-ß1-induced extracellular matrix production in alveolar epithelial cells and fibroblasts through the paracrine effects of BM-MSCs. In summary, these findings suggested that NMDAR activation-mediated Glu excitotoxicity induced by BLM in BM-MSCs abolished the therapeutic effects of normal BM-MSCs transplantation on BLM-induced PF.

Excessive Activation of NMDA Receptors Induced Neurodevelopmental Brain Damage and Cognitive Deficits in Rats Exposed to Intrauterine Hypoxia.

Intrauterine hypoxia is one of the most common stressors in fetuses, which can lead to abnormal brain development and permanent neurological deficits in adulthood. Neurological disorder excitotoxicity induced by hypoxia or ischemia may involve N-methyl-D-aspartate receptors (NMDARs), which are known to participate in the maturation and plasticity of developmental neurons. Inhibition of NMDARs has been reported to improve neurological outcomes in traumatic brain injuries and Alzheimer's disease. Here, we investigated if antenatal blockade of NMDARs induced by memantine could alleviate neurodevelopmental brain damage and long-term cognitive deficits in intrauterine hypoxia rats. Pregnant rats were assigned to four groups: air control, air + memantine, hypoxia, and hypoxia + memantine. The rats were exposed to hypoxic conditions (FiO2 = 0.095-0.115) for 8 h/day (hypoxia group) or given a daily memantine injection (5 mg/kg, i.p.) before hypoxia exposure from pregnant day 19 (G19) to G20 (hypoxia + memantine group).The influence of NMDARs antenatal blockade by memantine on intrauterine hypoxia-induced brain developmental damage and cognitive function was then studied. Intrauterine hypoxia resulted in decreased fetal body weight, brain weight, cognitive function, hippocampal neuron numbers, and Ki-67 proliferation index in the hippocampus. Memantine preventive treatment in pregnant rats before hypoxia exposure alleviated the aforementioned damage in vivo. Excessive activation of NMDARs contributes to fetal brain developmental damage and cognitive ability impairment induced by intrauterine hypoxia, which could be alleviated by antenatal memantine preventative treatment.

[ERα36 is involved in the proliferation promotion and anti-apoptosis effects of icaritin on MG63 cells].

The mechanism for icaritin to improve postmenopausal osteoporosis (PMOP) has not been clarified. The aim of this study was to investigate the role of estrogen receptor α36 (ERα36) in the proliferation promotion and anti-apoptosis effects of icaritin on osteoblasts and the underlying mechanism of downstream signal transduction. The ERα36 knockdown human osteosarcoma MG63 cell model was constructed by transfection of shRNA vector. Cell proliferation was detected by CCK-8, the apoptosis was detected by flow cytometry, and the activation of ERK and AKT signaling pathways was detected by Western blot. The results showed that the effects of icaritin on the proliferation and apoptosis of MG63 cells were significantly decreased after ERα36 knockdown, and icaritin could up-regulate the levels of ERK and AKT phosphorylation in MG63 cells, which could be reduced by ERα36 knockdown. The effect of icaritin on the proliferation of MG63 cells was significantly decreased by pretreating the cells with U0126 (an ERK signaling pathway blocker) and LY294002 (an AKT signaling pathway blocker), respectively. Furthermore, anti-apoptotic effect of icaritin on MG63 cells was significantly decreased after the cells were pretreated with U0126, but not with LY294002. These results suggest that icaritin exerts proliferation promotion and anti-apoptosis effects on osteoblasts through ERα36 and its downstream ERK and AKT signaling pathways.

[LIMR is involved in the inhibitory effect of antiflammin-1 on epithelial-mesenchymal transition in A549 cells].

Epithelial-mesenchymal transition (EMT) occurring in alveolar epithelial cells plays an important role in the development and progression of pulmonary fibrosis. Previous studies showed that antiflammin-1 (the active fragment of uteroglobin) effectively inhibited bleomycin-induced pulmonary fibrosis. However, its mechanism is still far from being clarified. In this study, we investigated the effects of antiflammin-1 on EMT in A549 cells induced by transforming growth factor-ß1 (TGF-ß1) and the underlying mechanism by using morphological observation and Western blot. The results showed that the expression of α-smooth muscle actin (α-SMA) increased significantly while the expression of E-cadherin decreased significantly in A549 cells following treatment with TGF-ß1 concomitant with morphological change of A549 cells from pebble-like shape epithelial cells to spindle-like mesenchymal shape. This process of EMT in A549 cells induced by TGF-ß1 was significantly inhibited when A549 cells were co-incubated with TGF-ß1 and antiflammin-1. Furthermore, the anti-lipocalin interacting membrane receptor (LIMR) antibody and PD98059 (an ERK signaling pathway blocker) attenuated the inhibitory effect of antiflammin-1 on TGF-ß1-induced EMT, respectively. Our findings indicate that antiflammin-1 can inhibit EMT in A549 cells induced by TGF-ß1, which is related to LIMR and its downstream ERK signaling pathway.

Antenatal blockade of N-methyl-D-aspartate receptors by Memantine reduces the susceptibility to diabetes induced by a high-fat diet in rats with intrauterine growth restriction.

Intrauterine growth retardation (IUGR) is closely related to the later development of type 2 diabetes in adulthood. Excessive activation of N-methly-D-aspartate receptors (NMDARs) causes excitatory neurotoxicity, resulting in neuronal injury or death. Inhibition of NMDARs enhances the glucose-stimulated insulin secretion and survival of islet cells in type 2 diabetic mouse and human islets. Here, we examined whether antenatal blockade of NMDARs by Memantine could decrease the risk of diabetes induced by a high-fat (HF) diet at adulthood in IUGR rats. Pregnant SD rats were assigned to four groups: control, IUGR, Memantine, and Memantine + IUGR. The pregnant rats were exposed to hypoxic conditions (FiO2 = 0.105) for 8 h/day (IUGR group) or given a daily Memantine injection (5 mg/kg, i.p.) before hypoxia exposure from embryonic day (E) 14.5 to E 20.5 (Memantine + IUGR). The offspring were fed an HF diet with 60% of the calories from age 4 to 12 weeks. We found that NMDAR mRNAs were expressed in the fetal rat pancreas. An HF diet resulted in a high rate of diabetes at adulthood in the IUGR group. Antenatal Memantine treatment decreased the risk of diabetes at adulthood of rats with IUGR, which was associated with rescued glucose tolerance, increased insulin release, improved the insulin sensitivity, and increased expression of genes related to beta-cell function in the pancreas. Together, our results suggest that antenatal blockade of NMDARs by Memantine in pregnant rats improves fetal development and reduces the susceptibility to diabetes at adulthood in offspring.

Omentin-A Novel Adipokine in Respiratory Diseases.

Adipokines, secreted by the adipose tissue, are extensively involved in the regulation and maintenance of various physiological and pathological processes, including insulin sensitivity, energy expenditure, glucose and lipid metabolism, inflammatory activity, neuroendocrine activity, immunity, cancer, homeostasis, angiogenesis, cardiovascular function, breeding and bone metabolism, and all functions of the endocrine-reproductive system axis. Omentin is a recently identified adipokine, which has become a research hotspot due to its pleiotropic effects on various diseases. However, the specific receptor for omentin has not been identified so far. In this study, we report that omentin levels fluctuate in various diseases. In addition, we have focused on the pleiotropic roles of omentin in pulmonary diseases, as it may act as a biomarker for malignant pleural mesothelioma (MPM) and is related to disease severity. Omentin may play significant roles in other pulmonary diseases, such as asthma, obstructive sleep apnea syndrome (OSAS), pulmonary arterial hypertension (PAH), acute respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD). This review summarizes the advances in current knowledge and future trends, which may provide a concise and general view on omentin and its effects on pulmonary biology.

[The platelet-producing function of lung].

It is generally believed that platelets are cytoplasmic bodies with biological activity falling off the cytoplasm of megakaryocytes from bone marrow. However, a large number of megakaryocytes have been found in the lung tissue in many researches. Whether the lung has the function of producing platelets has been controversial. In this paper, we briefly review the proposition, early stage researches, the latest confirmations and possible meaning of the hypothesis of platelet-producing function of lung.

N-methyl-D-aspartate receptor activation mediates lung fibroblast proliferation and differentiation in hyperoxia-induced chronic lung disease in newborn rats.

BACKGROUND: Previous studies have suggested that endogenous glutamate and its N-methyl-D-aspartate receptors (NMDARs) play important roles in hyperoxia-induced acute lung injury in newborn rats. We hypothesized that NMDAR activation also participates in the development of chronic lung injury after withdrawal of hyperoxic conditions. METHODS: In order to rule out the anti-inflammatory effects of NMDAR inhibitor on acute lung injury, the efficacy of MK-801 was evaluated in vivo using newborn Sprague-Dawley rats treated starting 4 days after cessation of hyperoxia exposure (on postnatal day 8). The role of NMDAR activation in hyperoxia-induced lung fibroblast proliferation and differentiation was examined in vitro using primary cells derived from the lungs of 8-day-old Sprague-Dawley rats exposed to hyperoxic conditions. RESULTS: Hyperoxia for 3 days induced acute lung injury in newborn rats. The acute injury almost completely disappeared 4 days after cessation of hyperoxia exposure. However, pulmonary fibrosis, impaired alveolarization, and decreased pulmonary compliance were observed on postnatal days 15 and 22. MK-801 treatment during the recovery period was found to alleviate the chronic damage induced by hyperoxia. Four NMDAR 2 s were found to be upregulated in the lung fibroblasts of newborn rats exposed to hyperoxia. In addition, the proliferation and upregulation of alpha-smooth muscle actin and (pro) collagen I in lung fibroblasts were detected in hyperoxia-exposed rats. MK-801 inhibited these changes. CONCLUSIONS: NMDAR activation mediated lung fibroblast proliferation and differentiation and played a role in the development of hyperoxia-induced chronic lung damage in newborn rats.