Number Of Alveoli Research Articles

A Novel Mathematical Equation for a Noninvasive Determination of the Number of Alveoli of the Human Lung

Background: There had always been a spirited effort in understanding the transport of air or molecular oxygen plus other gases from alveolar air space into the pulmonary capillaries and from the latter back into the former using mathematical models; the determination of the number of alveoli using cadaver and invasive and partially noninvasive methods have been made. There is a need for a noninvasive method of mathematical nature, with evaluative, diagnostic, and prognostic application.
 Objectives: The objectives of this research were to derive a mathematical equation for the noninvasive determination of the number of alveoli during rest and physical activity and elucidate the usefulness and advantage of the model over known methods.
 Methods: Theoretical and computational (calculational) methods; data in the literature were substituted into the model mathematical equation for the computation of the number of alveoli in the human lungs.
 Results and Discussion: The computed number (Nalv) of alveoli differed from one country or subcontinental region to another. The Nalv for the male were expectedly larger than for the female subjects.
 Conclusion: The mathematical equation for totally noninvasive determination by computation is derivable and was derived. The total number (Nalv) of alveoli mobilised for function is a function of the width (d) of the nares (d 22/15), rate (Rv) of gas flow , and radius (ralv) of a functional alveolus . The equation has the potential to be of diagnostic, evaluative and prognostic value in medical practice. This new computational approach could be faster than other known approaches for the determination of the Nalv. A noninvasive approach by computation, relying on other noninvasively determined respiratory parameters, can eliminate the possibility of tissue damage.

Effects of gestational exposure to perfluorooctane sulfonate on the lung development of offspring rats.

Perfluorooctane sulfonate (PFOS) is a man-made fluorosurfactant widely used in industry and consumer products. Previous studies with rats suggested that gestational exposure to PFOS may affect the lung development in the offspring. The mechanism, however, is still unknown. In the present study, we have exposed 24 pregnant SD rats from gestational day 12-18 to different doses of PFOS (0, 1 or 5mg/kg BW/day). The lungs of the offspring were analyzed at postnatal days 1, 3, 7 and 14. PFOS treatment appeared to reduce the alveolar numbers, resulting in simplified alveolar structure and thickened alveolar septa. Also, PFOS treated animals had increased lung inflammation with up-regulated inflammasome associated proteins NLRP3, ASC, Caspase-1 and GSDMD and increased inflammatory cytokines IL-18 and IL-1β. At the same time, HIF-1α and VEGFA were significantly down-regulated. Since HIF-1α and VEGFA are critical factors promoting alveolar development and pulmonary angiogenesis, these results suggested that PFOS may also affect lung development by inhibiting HIF-1α and VEGFA expression. Our results here indicate that gestational exposure to PFOS may affect lung development in the offspring with pathological characteristics similar to bronchopulmonary dysplasia (BPD), a severe lung developmental defect. The results also suggest that environmental factors such as PFOS may contribute to the increasing incidence of developmental lung diseases, such as BPD, by elevating lung inflammation and inhibiting lung development.

Small airway immunoglobulin A profile in emphysema-predominant chronic obstructive pulmonary disease.

BackgroundDue to airway remodeling and emphysematous destruction in the lung, the two classical clinical phenotypes of chronic obstructive pulmonary disease (COPD) are emphysema and bronchiolitis. The present study was designed to investigate the levels of small airway immunoglobulin A (IgA) in COPD with “emphysema phenotype.” The study also evaluated the associations between the small airway IgA levels and the severity of disease by the extent of emphysema versus airflow limitation.MethodsThirty patients (20 with COPD and ten healthy smokers) undergoing lung resection surgery for a solitary peripheral nodule were included. The study was conducted from January 2015 to December 2018 in the Shanxi Dayi Hospital. The presence of small airway IgA expression was determined in the lung by immunohistochemistry. In vivo, Wistar rats were exposed to silica by intratracheal instillation. Rats were sacrificed at 15 and 30 days after exposure of silica (n = 10 for each group). We also evaluated airway IgA from rats.ResultsSmall airway secretory IgA (sIgA), dimeric IgA (dIgA), and dIgA/sIgA of Global Initiative for Chronic Obstructive Lung Disease grade 1–2 COPD patients showed no difference compared with smoking control subjects (5.15 ± 1.53 vs. 6.03 ± 0.85; 1.94 ± 0.66 vs. 1.67 ± 0.04; 41.69 ± 21.02 vs. 28.44 ± 9.45, all P > 0.05). dIgA/sIgA level in the lung of COPD patients with emphysema showed higher levels than that of COPD patients without emphysema (51.89 ± 24.81 vs. 31.49 ± 9.28, P = 0.03). The percentage of low-attenuation area below 950 Hounsfield units was positively correlated with dIgA/sIgA levels (r = 0.45, P = 0.047), but not associated with the severity of disease by spirometric measurements (forced expiratory volume in the first second %pred, P > 0.05). Likewise, in the rat study, significant differences in sIgA, dIgA, dIgA/sIgA, mean linear intercept, mean alveoli number, and mean airway thickness of bronchioles (VV airway, all P < 0.01) were only observed between control rats and those exposed for 30 days. However, in the group exposed for 15 days, although the VV airway was higher than that in normal rats (27.61 ± 2.26 vs. 20.39 ± 1.99, P < 0.01), there were no significant differences in IgA and emphysema parameters between the two groups (all P > 0.05).ConclusionAirway IgA concentrations in mild and moderate COPD patients are directly associated with the severity of COPD with “emphysema phenotype” preceding severe airway limitation. This finding suggests that small airway IgA might play an important role in the pathophysiology of COPD, especially emphysema phenotype.

New insight into air flow distribution in alveoli based on air- and saline-filled lungs

Understanding flow distributions in human lungs has attracted significant attention since the last few decades. However, there are still large discrepancies between different studies in the distribution of air flow into alveoli at different generations of bifurcation. In this study, a new method has been developed to calculate expansion ratio of alveoli and ratio of alveolar to ductal flow rate at different generations for air- and saline-filled lungs. The effects of alveolar number, breathing period, lung tidal volume, and surface tension are examined. It is found that the expansion ratio of alveoli varies significantly at different generations in the saline-filled lungs. For the air-filled lung, the expansion ratio of individual alveolus remains constant for different generations. The current study provides new data on the flow rate ratios which is critical for understanding flow distributions and flow behaviors in alveoli. Surface tension in alveoli and alveolar number has obvious effects on the value of flow ratio. The current study sheds new light into the flow behavior in lungs and lays the foundation for detailed study on flow and particle transport characteristics in human lungs.

Bufei Yishen Formula Restores Th17/Treg Balance and Attenuates Chronic Obstructive Pulmonary Disease via Activation of the Adenosine 2a Receptor

Bufei Yishen formula (BYF) is a Traditional Chinese Medicine (TCM) reported to ameliorate chronic obstructive pulmonary disease (COPD) by regulating the balance between T helper (Th) 17 and regulatory T (Treg) cells. However, its mechanism remains unknown. Therefore, this study aimed to explore the underlying mechanisms of BYF. Naïve CD4+ T cells were exposed to anti-CD3, anti-CD28, transforming growth factor (TGF)-β, and/or interleukin (IL)-6 to promote their differentiation into Th17 or Treg cells. A rat model of cigarette smoke- and bacterial infection-induced COPD was established and orally treated with BYF and/or an adenosine 2a receptor (A2aR) antagonist. Then, the rats were sacrificed, their lung tissues were removed for histological analysis, and their spleens were collected to evaluate Th17 and Treg cells. The results showed that BYF significantly suppressed Th17 cell differentiation and its related cytokines and enhanced Treg cell differentiation and its related cytokines. In addition, BYF activated the A2aR, increased the levels of p-signal transducer and activator of transcription (STAT)5, and decreased the level of p-STAT3 in Treg and Th17 cells. The A2aR antagonist suppressed the changes induced by BYF treatment in Th17 and Treg cells. Furthermore, the A2aR antagonist diminished the therapeutic effect of BYF on COPD, as indicated by the lung injury scores, bronchiole wall thickness, small pulmonary vessels wall thickness, bronchiole stenosis, alveolar diameters, decrease in inflammatory cytokines, increase in alveolar number, and lung functions. Similarly, the A2aR antagonist reversed the effects of BYF on the proportion of Th17 and Treg cells in the spleen. Additionally, BYF increased the protein and mRNA levels of A2aR and regulated the phosphorylation of STAT3 and STAT5 in spleen and lung tissues, which were inhibited by cotreatment with the A2aR antagonist. In conclusion, this study suggested that BYF exhibited its anti-COPD efficacy by restoring the Th17/Treg balance via activating A2aR, which may provide evidence for the clinical application of BYF in the treatment of COPD.

Impact of litter size on survival, growth and lung alveolarization of newborn mouse pups

BackgroundLung alveolarization, the development of the alveoli, is disturbed in preterm infants with bronchopulmonary dysplasia (BPD), the most common complication of preterm birth. Animal models based on oxygen toxicity to the developing mouse lung are used to understand the mechanisms of stunted alveolarization in BPD, and to develop new medical management strategies for affected infants. The toxicity of genetic and pharmacological interventions, together with maternal cannibalism, reduce mouse litter sizes in experimental studies. The impact of litter size on normal and stunted lung alveolarization is unknown, but may influence data interpretation. The aim of the study was to assess the impact of litter size on normal and oxygen-stunted lung alveolarization in mice. MethodsBPD was experimentally modelled in newborn C57BL/6J mice by exposure to 85% O2 in the inspired air for the first 14 days of post-natal life. Perturbations to mouse lung architecture were assessed by design-based stereology, in which the alveolar density, total number of alveoli, gas-exchange surface area, and the septal thickness were estimated. ResultsLitter sizes of a single mouse were not viable to post-natal day 14. Normal lung alveolarization was comparable in mouse pups in litters of 2, 4, 6, and 8 pups per litter. Hyperoxia was equally effective at stunting lung alveolarization in mouse pups in litters of 2, 4, 6, and 8 pups per litter. ConclusionsStudies on normal lung alveolarization as well as alveolarization stunted by oxygen toxicity can be undertaken in mouse litters as small as two pups, and as large as eight pups. There is no evidence to suggest that data cannot be compared within and between litters of two to eight mouse pups.

Effect of heat stress during the early and late dry period on mammary gland development of Holstein dairy cattle

Dry period heat stress impairs subsequent milk yield. Our objective was to evaluate the effect of heat stress or cooling during the early and late dry period on mammary gland gene expression and microstructure. Cows were dried off ∼45 d before expected parturition and randomly assigned to 1 of 2 treatments: heat stress (HT, n = 39) or cooling (CL, n = 39) during the first 21 d of the dry period. On d 22, cows were switched or remained on HT and CL and this yielded 4 treatments: heat stress during the entire dry period (HTHT, n = 18); cooling during the entire dry period (CLCL, n = 20); HT for the first 21 d dry, then CL until calving (HTCL, n = 21); or CL for the first 21 d dry, then HT until calving (CLHT, n = 19). Data were analyzed in 2 periods: first 21 d dry (early dry period) and from 22 d until calving (late dry period) and analyzed using PROC MIXED or GLM in SAS (SAS Institute Inc., Cary, NC). Mammary biopsies (5-8 cows/treatment) were collected at -3, 3, 7, 14, and 25 d relative to dry-off to evaluate mammary gland gene expression and histology [i.e., cellular apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling) and proliferation (Ki67)]. Mammary alveoli number and connective tissue were visualized by hematoxylin and eosin and Mason's trichrome staining, respectively. During the early dry period, CL upregulated expression of CASP3, IGF1R, HSP90, HSF1, BECN1, ATG3, ATG5, and PRLR-LF relative to HT. However, in the late dry period, CLHT treatment upregulated expression of CASP3, CASP8, HSP70, HSP90, PRLR-LF, STAT5, CSN2, and ATG3 relative to CLCL. During the early dry period, cows exposed to HT had reduced mammary and stroma cell apoptosis and proliferation relative to CL. In addition to these findings, cows exposed to HT had lower connective tissue 3 d after dry-off relative to CL. However, in the late dry period, HTHT cows had higher connective tissue relative to CLCL. Also, in the early dry period, cows exposed to HT had greater alveoli number relative to CL, and HT decreased expression of genes related to autophagy and apoptosis in the early dry period, consistent with a delay in involution with HT. Thus, cows exposed to HT have extended involution with delayed apoptosis and autophagy signaling. Also, HT compromises mammary gland cell proliferation and leads to higher connective tissue later in the dry period. These results provide evidence that heat stress impairs overall mammary gland turnover during the dry period, which then affects secretory activity and productivity in the next lactation.

Association of Myeloid Liver Kinase B1 Depletion With a Reduction in Alveolar Macrophage Numbers and an Impaired Host Defense During Gram-Negative Pneumonia.

BackgroundLiver kinase B1 (LKB1) has been studied extensively as a tumor suppressor gene (Stk11) in the context of cancer. We hypothesized that myeloid LKB1 plays a role in innate immunity during pneumonia.MethodsMice deficient for LKB1 in myeloid cells (LysM-cre × Stk11fl/fl) or neutrophils (Mrp8-cre × Stk11fl/fl) were infected with Klebsiella pneumoniae via the airways. LysM-cre × Stk11fl/fl mice were also intranasally challenged with lipopolysaccharide (LPS).ResultsMice with myeloid LKB1 deficiency, but not those with neutrophil LKB1 deficiency, had increased bacterial loads in lungs 6–40 hours after infection, compared with control mice, pointing to a role for LKB1 in macrophages. Myeloid LKB1 deficiency was associated with reduced cytokine release into the airways on local LPS instillation. The number of classic (SiglecFhighCD11bneg) alveolar macrophages (AMs) was reduced by approximately 50% in the lungs of myeloid LKB1–deficient mice, which was not caused by increased cell death or reduced proliferation. Instead, these mice had AMs with a “nonclassic” (SiglecFlowCD11bpos) phenotype. AMs did not up-regulate glycolysis in response to LPS, irrespective of LKB1 presence.ConclusionMyeloid LKB1 is important for local host defense during Klebsiella pneumonia by maintaining adequate AM numbers in the lung.

Evaluation of Clinical and Radiographic Parameters as Dental Indicators for Postmenopausal Osteoporosis.

In the early stages, osteoporosis is relatively a silent disease characterised by low bone density with microarchitectural deterioration of the bone tissue leading to enhanced bone fragility. The objective of this study was to evaluate the relationship between age, body mass index, oral signs, and osteoporosis among postmenopausal women. The study included postmenopausal women who were divided into two groups of subjects. The osteoporotic group comprised 30 patients with osteoporosis who were diagnosed using dual-energy X-ray absorptiometry, and the non-osteoporotic group (control group) comprised 30 subjects with no evidence of osteoporosis. Panoramic radiography was performed, followed by the acquisition of two direct digital intraoral periapical radiographs from the mandibular premolar-molar region. Chi-square test revealed a statistically significant difference (p = 0.001) in the mandibular cortical shape index between the two groups. However, a statistically non-significant difference in cortical width, the panoramic mandibular index, mandibular alveolar bone resorption degree, fractal dimension, and mean number of teeth was found between the two groups. A statistically significant difference was observed in the mean age between the osteoporotic and non-osteoporotic groups. The mandibular cortical index findings (MCI) on panoramic radiograph are effective indicators of osseous changes in postmenopausal osteoporosis, thereby determining early prediction of osteoporotic fracture risk and reducing its related morbidity.

Wnt/β-catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema

Wnt/β-catenin signaling regulates progenitor cell fate decisions during lung development and in various adult tissues. Ectopic activation of Wnt/β-catenin signaling promotes tissue repair in emphysema, a devastating lung disease with progressive loss of parenchymal lung tissue. The identity of Wnt/β-catenin responsive progenitor cells and the potential impact of Wnt/β-catenin signaling on adult distal lung epithelial progenitor cell function in emphysema are poorly understood. Here, we used TCF/ Lef:H2B/GFP reporter mice to investigate the role of Wnt/β-catenin signaling in lung organoid formation. We identified an organoid-forming adult distal lung epithelial progenitor cell population characterized by a low Wnt/β-catenin activity, which was enriched in club and alveolar epithelial type (AT)II cells. Endogenous Wnt/β-catenin activity was required for the initiation of multiple subtypes of distal lung organoids derived from the Wntlow epithelial progenitors. Further ectopic Wnt/β-catenin activation specifically led to an increase in alveolar organoid number; however, the subsequent proliferation of alveolar epithelial cells in the organoids did not require constitutive Wnt/β-catenin signaling. Distal lung epithelial progenitor cells derived from the mouse model of elastase-induced emphysema exhibited reduced organoid forming capacity. This was rescued by Wnt/β-catenin signal activation, which largely increased the number of alveolar organoids. Together, our study reveals a novel mechanism of lung epithelial progenitor cell activation in homeostasis and emphysema.

Spermidine supplementation and voluntary activity differentially affect obesity-related structural changes in the mouse lung.

Obesity is associated with lung function impairment and respiratory diseases; however, the underlying pathophysiological mechanisms are still elusive, and therapeutic options are limited. This study examined the effects of prolonged excess fat intake on lung mechanics and microstructure and tested spermidine supplementation and physical activity as intervention strategies. C57BL/6N mice fed control diet (10% fat) or high-fat diet (HFD; 60% fat) were left untreated or were supplemented with 3 mM spermidine, had access to running wheels for voluntary activity, or a combination of both. After 30 wk, lung mechanics was assessed, and left lungs were analyzed by design-based stereology. HFD exerted minor effects on lung mechanics and resulted in higher body weight and elevated lung, air, and septal volumes. The number of alveoli was higher in HFD-fed animals. This was accompanied by an increase in epithelial, but not endothelial, surface area. Moreover, air-blood barrier and endothelium were significantly thicker. Neither treatment affected HFD-related body weights. Spermidine lowered lung volumes as well as endothelial and air-blood barrier thicknesses toward control levels and substantially increased the endothelial surface area under HFD. Activity resulted in decreased volumes of lung, septa, and septal compartments but did not affect vascular changes in HFD-fed mice. The combination treatment showed no additive effect. In conclusion, excess fat consumption induced alveolar capillary remodeling indicative of impaired perfusion and gas diffusion. Spermidine alleviated obesity-related endothelial alterations, indicating a beneficial effect, whereas physical activity reduced lung volumes apparently by other, possibly systemic effects.

Swimming Exercise Training Attenuates the Lung Inflammatory Response and Injury Induced by Exposing to Waterpipe Tobacco Smoke.

BackgroundThe use of waterpipe tobacco smoking (WTS) is on the rise throughout the world, especially among young people and even athletes. There is a belief among consumers that exercise prevents the harmful effects of hookah smoke on the body. We examined this belief by evaluation of lung injury following to concurrent WTS and swimming endurance training in male Wistar rats.MethodsAnimals were randomly divided to sedentary control (CTL) group, exercise training group (Ex group), sedentary WTS (S) group, and exercise plus WTS (S + Ex) group.Findings8 weeks of WTS was associated with significant increase in serum level of cotinine, lung damage, reduction in alveolar number AN/SA (mm2) and increase in malondialdehyde (MDA) level of lung tissue. Combination of exercise with WTS significantly decreased these negative effects; however, it could not fully protect the lung from smoking damage. Waterpipe smoking (WPS) also significantly increased the pro-inflammatory cytokines of lung tissue such as tumor necrosis factor alpha (TNF-α) (P < 0.001), interleukin 1 beta (IL-1β) (P < 0.010), and IL-6 (P < 0.050) in comparison with CTL group. Exercise training to some degree reduced the levels of pro-inflammatory cytokines and increased the level of IL-10 as an anti-inflammatory IL and glutathione peroxidase (GPX) activity in animals exposed to WTS.ConclusionIt is suggested that combination of mild to moderate exercise with WTS may attenuate the hookah smoking-induced lung damage. This effect partly is mediated through balancing of pro/anti-inflammatory and redox systems.

Histomorphometrical and Stereological Study of the Lungs in Neonatal Rats Born to Paraquat-poisoned Pregnant Rats: Protective Effect of Coenzyme Q10

Background: Paraquat (PQ), an herbicide, is a very poisonous compound for both humans and animals. This study was conducted to examine the protective effect of the Coenzyme Q10 (CoQ10) in newborn rats from pregnant rats pre-treated with PQ. Methods: The experiments were conducted on 25 rats, divided in five groups randomly and equally: 1. Control Group received normal saline (0.1 ml/day); 2. PQ Group received PQ only (5 mg/kg/day); 3. PQ+CoQ10 Group received PQ (5 mg/kg) and CoQ10 (10 mg/kg) daily; 4. PQ+olive oil Group received PQ (5 mg/kg) and olive oil (10 mg/kg) daily; 5. Olive oil Group received olive oil (10 mg/kg/day). All of the injections were made intraperitoneally and started on the 16th day of pregnancy through to parturition. Sixteen days after parturition, the lungs were removed from the newborn rats, paraffin sections were made and stained with hematoxylin and eosin, and analyzed histomorphometrically and stereologically. Results: The results revealed that interstitial tissue and lung alveoli had normal structures in the control and olive oil groups. In PQ and PQ-olive oil groups alveolar hemorrhage, inflammation, extensive fibrosis, decreased alveolar numbers, increased mast cells, and changes in the epithelia were observed. In PQ-CoQ10 Group there was a significant recovery in all of the histological alterations. Conclusion: Generally, Coenzyme Q10 had a protective effect against lung damages caused by PQ, but a complete recovery of the damaged lung tissue would probably take longer than 16 days after birth.

The Role of Parathyroid Hormone in Alveolar Bone Resorption on Postmenopausal Women

Background: Postmenopausal women exhibit reduced bone mineralization, which causes bone resorption, including that of alveolar bone. Parathyroid hormone has been shown to play a role in alveolar bone resorption. Objective: This study aims to analyze relationships between parathyroid hormone and other factors that may contribute to alveolar bone resorption in postmenopausal women. Methods: This cross-sectional study included 82 postmenopausal women aged 50–74 years, who resided in Central and East Jakarta, Indonesia. Subjects' data were obtained through questionnaires, dental examinations, and blood collection for the examination of parathyroid hormone levels by enzyme-linked immunosorbent assay and using panoramic radiography to measure bone resorption. Results: Spearman correlation analysis showed a significant correlation between parathyroid hormone level (p = 0.005) and extent of alveolar bone resorption, but age (p = 0.292), menopausal duration (p = 0.244), and number of missing teeth (p = 0.517) were not significantly correlated with the extent of alveolar bone resorption. Conclusion: Various factors play a role in the mechanism of bone resorption, so knowing the role of each factor is expected to reduce the effects of alveolar bone resorption that occurs in postmenopause. Among the factors investigated in this study, the parathyroid hormone was the sole factor correlated with postmenopausal alveolar bone resorption.

Biological sex influences susceptibility to Acinetobacter baumannii pneumonia in mice.

Acinetobacter baumannii (A. baumannii) is an extremely versatile multidrug-resistant pathogen with a very high mortality rate; therefore, it has become crucial to understand the host response during its infection. Given the importance of mice for modeling infection and their role in preclinical drug development, equal emphasis should be placed on the use of both sexes. Through our studies using a murine model of acute pneumonia with A. baumannii, we observed that female mice were more susceptible to infection. Likewise, treatment of male mice with estradiol increased their susceptibility to infection. Analysis of the airway compartment revealed enhanced inflammation and reduced neutrophil and alveolar macrophage numbers compared with male mice. Depletion of either neutrophils or alveolar macrophages was important for bacterial clearance; however, depletion of alveolar macrophages further exacerbated female susceptibility because of severe alterations in metabolic homeostasis. Our data highlight the importance of using both sexes when assessing host immune pathways.

Ablation of glutaredoxin 1 promotes pulmonary angiogenesis and alveolar formation in hyperoxia-injured lungs by modifying HIF-1α stability and inhibiting the NF-κB pathway

Glutaredoxin 1 (Grx1) is an important thiol transferase that catalyses the deglutathionylation of proteins through its active site. Deletion of Grx1 increases levels of glutathione-protein adducts and improves ischaemic revascularization. In this study, we investigated whether the absence of Grx1 ameliorates pathological changes in blood vessels and alveoli in a mouse model exposed to hyperoxic conditions. High oxygen exposure for three consecutive weeks increased the levels of Grx1 in the lungs of hyperoxic mice from control levels, while Grx1 levels in Grx1 knockout (KO) mice were significantly reduced under high oxygen conditions. Exposure to 85% oxygen for 21 days reduced alveolarization in wild-type (WT) mice but increased the numbers of alveoli and the survival rate of Grx1 KO littermates. Importantly, vascular endothelial growth factor receptor 2 (VEGFR2) and vascular endothelial growth factor A (VEGFA) expressions were increased in Grx1 KO mice after hyperoxia treatment, and these effects were probably attributable to increased hypoxia-inducible factor (HIF)-1α expression. On the other hand, in response to nuclear factor (NF)-κB inhibition by Grx1 ablation, chemokine and caspase-3 levels were reduced, although the Bcl-2:Bax ratio was increased. Here, we provide evidence that Grx1 plays an important role in regulating pathological damage under hyperoxic conditions by promoting HIF-1α stability and inhibiting the NF-κB pathway in vivo. Our study highlights the functional importance of the Grx1/protein S-glutathionylation (PSSG) redox module in the regulation of ischaemic revascularization, indicating potential clinical and therapeutic applications.

Effects of IFN-γ on immune cell kinetics during the resolution of acute lung injury.

The immunologic responses that occur early in the acute respiratory distress syndrome (ARDS) elicit immune‐mediated damage. The mechanisms underlying the resolution of ARDS, particularly the role of signaling molecules in regulating immune cell kinetics, remain important questions. Th1‐mediated responses can contribute to the pathogenesis of acute lung injury (ALI). Interferon‐gamma (IFN‐γ) orchestrates early inflammatory events, enhancing immune‐mediated damage. The current study investigated IFN‐γ during resolution in several experimental models of ALI. The absence of IFN‐γ resulted in altered kinetics of lymphocyte and macrophage responses, suggesting that IFN‐γ present in this microenvironment is influential in ALI resolution. Genetic deficiency of IFN‐γ or administering neutralizing IFN‐γ antibodies accelerated the pace of resolution. Neutralizing IFN‐γ decreased the numbers of interstitial and inflammatory macrophages and increased alveolar macrophage numbers during resolution. Our results underline the complexity of lung injury resolution and provide insight into the effects through which altered IFN‐γ concentrations affect immune cell kinetics and the rate of resolution. These findings suggest that therapies that spatially or temporally control IFN‐γ signaling may promote ALI resolution. Identifying and elucidating the mechanisms critical to ALI resolution will allow the development of therapeutic approaches to minimize collateral tissue damage without adversely altering the response to injury.

Pulmonary Hypoplasia Associated with Ascites and Hydrothorax in a Newborn Pig

Background: Pulmonary hypoplasia is characterized by incomplete development of the lungs, owing to congenital defectsor the action of toxic substances. Moreover, it has rarely been described in pigs. Ascites or hydroperitoneum is characterized by the presence of fluid inside the abdominal cavity and does not generally cause changes in the abdominal organs. However, hydrothorax, characterized by the presence of fluid within the thoracic cavity, is responsible for the compression of thoracic organs and consequent heart and respiratory failure. This study aims to describe a case of congenital pulmonary hypoplasia associated with ascites and hydrothorax in a newborn pig.Case: A male neonate Landrace pig that died shortly after delivery was presented for necropsy with increased abdominal volume and bilateral extension of the pelvic limbs. The pig belonged to a litter of 13 piglets, four of which died shortly after birth. The rest of the piglets were poorly developed, but only one was presented for necropsy. Significant external changes, along with permanent distension, interpreted as arthrogriposis, were observed in the pelvic limbs. The skin of the ventral abdominal region was thin, with evidence of all blood vessels, interpreted as telangectasis. An internal examination revealed the presence of a slightly yellowish liquid in the thoracic and abdominal cavities, interpreted as hydrothorax and ascites, respectively. The lungs were reduced in size, indicating pulmonary hypoplasia. The liver had rounded edges, which were dark red and firm, with an irregular surface. Significant microscopic findings were observed in the lungs, which were divided by fibrous connective tissue and showed evidence of small and atrophied alveoli. Furthermore, connective tissue was observed around the peribronchiolar regions and underdeveloped cartilage around the airways. The liver showed dilation of the centrilobular veins. Moreover, the sinusoids were filled with erythrocytes, indicating congestion.Discussion: Pulmonary hypoplasia is a rare birth defect in pigs and can be accompanied by malformations of other organs, including anasarca. Pulmonary hypoplasia is caused by conditions that compress the lungs, such as congenital diaphragmatic hernia, intrathoracic masses, and pleural effusion or malformations in the chest cavity. However, none of these conditions were observed in the current case. Instead, the histopathological changes observed in the lungs were characteristic of pulmonary hypoplasia. A microscopic examination revealed that the hypoplastic lungs showed a reduced number of alveoli, replacement of the peribronchiolar smooth muscle by the connective tissue, and underdeveloped cartilage around the airways, all of which are characteristic of pulmonary hypoplasia. Vascular telangiectasia is characterized by abdominal distention due to a marked ascitic condition. Invariably, ascitic fluid accumulation results from changes in hydrodynamic parameters. The hydrothorax observed in this animal was suggestive of changes in the hydrodynamic parameters, which consequently led to fluid accumulation in the chest cavity. This has been previously described in a newborn pig infected with Clostridium difficile. The permanently and bilaterally extended pelvic joints observed at birth in this animal were interpreted as arthrogriposis. This change is attributed to various factors, such as fetal paralysis in pigs that ingest toxic substances like alkaloids present in Conium maculatum and in the stalks of Nicotiana tabacum and Datura stramunium. The literature describes pelvic limb paralysis in Landrace pigs as a genetically inherited disorder. However, it was not possible for us to establish the cause of arthrogriposis for certain in this pig.

Effect of asiaticoside on hyperoxia-induced bronchopulmonary dysplasia in neonatal rats and related mechanism

To study the protective effect of asiaticoside against hyperoxia-induced bronchopulmonary dysplasia in neonatal rats based on the microRNA-155 (miR-155)/suppressor of cytokine signaling-1 (SOCS1) axis. Neonatal rats were randomly divided into a control group, a model group, a low-dose asiaticoside group (10 mg/kg), a middle-dose asiaticoside group (25 mg/kg), a high-dose asiaticoside group (50 mg/kg), and a budesonide group (1.5 mg/kg), with 12 rats in each group. All rats except those in the control group were exposed to a high concentration of oxygen for 14 days to establish a neonatal rat model of bronchopulmonary dysplasia. The low-, middle-, and high-dose asiaticoside groups were given asiaticoside at different doses by gavage, and those in the budesonide group were given budesonide aerosol treatment. Hematoxylin and eosin staining was used to observe lung tissue development and measure radial alveolar count (RAC) and mean linear intercept (MLI). Superoxide dismutase (SOD) and malondialdehyde (MDA) detection kits were used to measure the levels of SOD and MDA in lung tissue. ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SOCS1 in lung tissue. Western blotting was used to measure the protein expression of SOCS1 in lung tissue. Compared with the control group, the model group had the symptoms of bronchopulmonary dysplasia such as a disordered structure of lung tissue, enlargement of alveolar fusion, uneven alveolar septa, enlargement of average alveolar space, and a reduction in alveolar number. The model group also had significant increases in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05) and significant reductions in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Compared with the model group, the low-, middle-, and high-dose asiaticoside groups and the budesonide group had significant improvement in the above symptoms of bronchopulmonary dysplasia, significant reductions in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05), and significant increases in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Asiaticoside improved the above symptoms and indices in a dose-dependent manner. There were no significant differences in the above indices between the high-dose asiaticoside and budesonide groups (P>0.05). Asiaticoside can alleviate inflammation injury induced by hyperoxia in neonatal rats and improve the symptoms of bronchopulmonary dysplasia in a dose-dependent manner, possibly by down-regulating the expression of miR-155 and up-regulating the expression of SOCS1.

The effects of intro-oral parathyroid hormone on the healing of tooth extraction socket: an experimental study on hyperglycemic rats.

Objective To investigate the effects of intro-oral injection of parathyroid hormone (PTH) on tooth extraction wound healing in hyperglycemic rats.Methodology 60 male Sprague-Dawley rats were randomly divided into the normal group (n=30) and DM group (n=30). Type 1 diabetes mellitus (DM) was induced by streptozotocin. After extracting the left first molar of all rats, each group was further divided into 3 subgroups (n=10 per subgroup), receiving the administration of intermittent PTH, continuous PTH and saline (control), respectively. The intermittent-PTH group received intra-oral injection of PTH three times per week for two weeks. A thermosensitive controlled-release hydrogel was synthesized for continuous-PTH administration. The serum chemistry was determined to evaluate the systemic condition. All animals were sacrificed after 14 days. Micro-computed tomography (Micro-CT) and histological analyses were used to evaluate the healing of extraction sockets.Results The level of serum glucose in the DM groups was significantly higher than that in the non-DM groups (p<0.05); the level of serum calcium was similar in all groups (p>0.05). Micro-CT analysis showed that the DM group had a significantly lower alveolar bone trabecular number (Tb.N) and higher trabecular separation (Tb.Sp) than the normal group (p<0.05). The histological analyses showed that no significant difference in the amount of new bone (hard tissue) formation was found between the PTH and non-PTH groups (p>0.05).Conclusions Bone formation in the extraction socket of the type 1 diabetic rats was reduced. PTH did not improve the healing of hard and soft tissues. The different PTH administration regimes (continuous vs. intermittent) had similar effect on tissue healing. These results demonstrated that the metabolic characteristics of the hyperglycemic rats produced a condition that was unable to respond to PTH treatment.