Thickness Of Smooth Muscle Layer Research Articles

Effect of Mepolizumab in airway’s remodelling in patients with late-onset severe asthma with an eosinophilic phenotype

BackgroundClinical trials and real-world experience have provided evidence for the clinical benefit of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exists regarding the impact of mepolizumab on airway remodelling. ObjectiveWe thus investigated the effect of mepolizumab on airway structural remodelling in patients treated for severe asthma in routine clinical care. MethodsMESILICO is a multicenter study involving 8 Pulmonology Departments in Greece. This study focused on patients who initiated mepolizumab for severe asthma with an eosinophilic phenotype and had late-onset disease with obstructive patterns (impaired reversibility). Forty-seven patients were recruited, of whom 41 were enrolled in the bronchoscopy sub-study. The findings were related to clinical outcome. ResultsAfter 12 months, mepolizumab treatment was associated with significant improvements in lung function and ACT score, along with a significant decrease in severe exacerbation events (p<0.001). Thirty four of the 41 participants (83%) had paired biopsies for comparative analysis. There was a significant reduction from baseline in sub-basement membrane thickness, airway smooth muscle area, airway smooth muscle layer thickness and extent of epithelial damage, as well as a decrease in tissue eosinophil numbers (all p<0.001). The extent of ASMLT reduction positively correlated with the submucosal eosinophil reduction (r= 0.599, p<0.001). ConclusionThis study identifies that 12 month of mepolizumab treatment in patients with late-onset severe asthma, who are also characterized by eosinophilic and impaired reversibility phenotypes, leads not only to clinical improvement but also reduces indices of airway tissue remodelling suggestive of a disease modifying effect.

Ciliated foregut cysts involving the hepatopancreaticobiliary system: a clinicopathological evaluation with focus on atypical features

AimsForegut cystic malformations are rare developmental abnormalities, which may involve the hepatopancreaticobiliary tract (HPBT). These cysts are composed of inner ciliated epithelium; subepithelial connective tissue layer; smooth muscle layer; and...

Thoracoscopy-Assisted Esophagectomy for Esophageal Leiomyomatosis.

Diffuse esophageal leiomyomatosis is a rare esophageal tumor characterized by circumferential thickening of smooth muscle layers of the entire esophagus. CLINICALCASE: Herein, we describe the case of a 19-year-old girl, who presented with a history of long-standing dysphagia. On evaluation she was found to have diffuse esophageal leiomyomatosis and was managed successfully by thoracoscopy-assisted esophagectomy with intra-nodal indocyanine green injection. In this report, we discuss the pre-operative workup and our surgical approach to managing this rare entity. We also discuss the available literature on the subject and the lessons learnt in managing this complex condition.

The Effects of Purple Sweet Potato (Ipomoea Batatas L.) Ethanol Extract on Bladder Urothelial Layer and Smooth Muscle Thicknesses in Menopausal Female Wistar Rats

Highlights: Purple sweet potatoes cultivated in Bali, Indonesia, were found to be rich in phytoestrogen due to the high levels of anthocyanin-type flavonoids. The phytoestrogen in purple sweet potato ethanol extract demonstrated estrogenic activity and the potential to substitute hormone replacement therapy (HRT) as the treatment of lower urinary tract symptoms. Abstract Postmenopausal women experience estrogen hormone deficiency, which can cause thinning of the smooth muscle and urothelial layer of the bladder, leading to lower urinary tract symptoms (LUTS). Hormone replacement therapy (HRT) has been the primary choice for addressing these problems. However, long-term prescription of HRT can result in several adverse effects, including a higher risk of breast cancer and cardiovascular diseases. Phytoestrogen, an estrogen-like compound derived from plants such as purple sweet potatoes (Ipomoea batatas L.), contains anthocyanin that could serve as a better alternative to estrogen replacement therapy. This study aimed to demonstrate the effects of phytoestrogens in purple sweet potatoes on the histomorphology of the bladder in menopausal female Wistar rats (Rattus norvegicus). This experimental study used a posttest-only control group design. A total of 36 Wistar rats undergoing ovariectomy were randomly assigned into two groups, with 18 samples in each group. The experimental group received the purple sweet potato ethanol extract orally, while the control group received a placebo. The structures of the smooth muscle and urothelial layer of the bladder were observed using a microscope. Data were analyzed using an independent t-test to compare bladder smooth muscle and urothelial layer thickness between groups, with a significance of p&lt;0.05. A normality test was performed to determine the normal distribution of the data. Normally distributed data were assessed to find the mean and standard deviation (SD). Significant differences were found in the mean thickness of the smooth muscle and urothelial layer between both groups (p=0.00), with both being thicker in the experimental group. In conclusion, phytoestrogens in purple sweet potatoes can influence the histomorphology of the bladder. Ovariectomized female Wistar rats that received purple sweet potato ethanol extract exhibited thicker smooth muscle and urothelial layer of the bladder.

Pengaruh Ekstrak Etanol Daun Inggu (Ruta angustifolia) terhadap Tebal Otot Polos Tuba Fallopi Tikus Strain Wistar Betina

The highest drop out of hormonal contraceptive users caused by side effects is the background for research on the use of herbal plants as antifertility substitutes for hormonal contraceptive which have minimal effects. Inggu leaves (Ruta angsutifolia) contain compounds that are interfering hormonal work such as saponins, tannins, chalepins and chalepensins, so it can be antifertitlity. To determine ethanol extract of inggu leaves effect on reducing the thickness of the smooth muscle of fallopian tube in female rats. The study used randomized post-test only controlled group was conducted using experimental animals (Wistar strain rats) divided into 4 groups with different doses (0; 0.4; 0.8; and 1.2 g/kg BW ) in February until April 2022. Measurement of the fallopian tube smooth muscle layer thickness using an Olympus CX23 microscope and ImageJ application.: Rat fallopian tube smooth muscle thickness was reduced along the dose of inggu leaf ethanol extract increased that statistically significant (p = 0.046). Ethanol extract of inggu leaves can reduce the fallopian tube smooth muscle thickness with an optimal dose of 1.2 g/kg BW.

PM2.5 Induces Airway Remodeling in Chronic Obstructive Pulmonary Diseases via the Wnt5a/β-Catenin Pathway.

BackgroundFine-particulate matter ≤2.5 μm in diameter (PM2.5)-associated airway remodeling has recently been recognized as a central feature of COPD. Activation of the Wnt/β-catenin pathway is closely related to the occurrence of airway remodeling. Accordingly, the goal of this study was to determine whether the Wnt5a/β-Catenin pathway is involved in PM2.5-induced smooth muscle proliferation in vivo and in vitro, which promotes the development of airway remodeling in subjects with COPD.MethodsThe effect of Wnt5a on β-Catenin-mediated airway remodeling was assessed using an in vivo model of PM2.5-induced COPD and PM2.5-exposed human bronchial smooth muscle cells (HBSMCs) in vitro. Small animal spirometry was used to measure lung function in mice. H&E staining and immunohistochemistry were performed to inspect emphysema and airway remodeling indices. Real-time PCR was used to detect Wnt5a, β-Catenin, TGF-β1, CyclinD1 and c-myc mRNA expression. The CCK8 assay was performed to detect cellular activity. Western blotting was performed to assess PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and TenascinC protein expression. β-Catenin expression was detected using cellular immunofluorescence.ResultsExposure to PM2.5 led to emphysema, airway wall thickening, an increased smooth muscle layer thickness, decreased lung function and increased expression of the Wnt5a, β-Catenin, PDGFRβ and Tenascin C proteins in the mouse lung tissue. BOX5 (a Wnt5a antagonist) alleviated these PM2.5-induced outcomes in mice. Moreover, PM2.5 induced the expression of the Wnt5a, β-Catenin, TGF-β1, CyclinD1 and c-myc mRNAs in HBSMCs. BOX5 also inhibited the PM2.5-induced increases in PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and Tenascin C protein expression in HBSMCs.ConclusionOur findings suggest that PM2.5 exposure induces HBSMC proliferation, contributing to airway remodeling via the Wnt5a/β-Catenin signaling pathway in vivo and in vitro, which might be a target for COPD treatment.

Deoxynivalenol interferes with intestinal motility via injuring the contractility of enteric smooth muscle cells: A novel hazard to the gastrointestinal tract by environmental toxins

Deoxynivalenol (DON) is a prevalent Fusarium mycotoxin, occurs predominantly in the global environment, especially in cereals, animal feed and food commodities. The widespread contamination causes a serious risk to human and animal health. DON usually impairs weight gain, which is presumably from its capacity to reduce feed intake by interfering with intestinal motility. To clarify the role of smooth muscle cells (SMCs) contractility in intestinal motility and growth inhibition caused by DON, twelve weaned piglets were firstly divided into two groups to feed control or Fusarium mycotoxin-contaminated (MC) diet. Results showed that the final body weight, average daily gain and average daily feed intake were significantly reduced in piglets fed the MC diet. Exposure to the MC diet also significantly decreased the thickness of smooth muscle layer and SMCs contractile markers expression (myosin heavy chain 11, smooth muscle actin gamma 2, transgelin, calponin 1) in jejunum and ileum of piglets. Furthermore, oral DON supplementation (3 mg/kg body weight) to mice in six consecutive days could significantly inhibit the upper intestinal transit, impede normal defecation and downregulate SMCs contractile markers expression in small intestine. Finally, we generated a porcine enteric smooth muscle cell line (PISMC), and found that DON could depress its contractility by decreasing PISMC proliferation, migration and contractile markers expression. In conclusion, these findings in vivo and in vitro suggest that DON, as a common environmental toxin, can not only reduce proliferative and motile phenotype, but also decrease contractile apparatus components (contractile markers expression) in SMCs, which in turn influences SMCs contractility and then interferes with intestinal motility and growth performance.

Transcriptomic Analysis Exploring the Molecular Mechanisms of Hanchuan Zupa Granules in Alleviating Asthma in Rat.

Objective To investigate the molecular mechanisms of HCZP treatment of asthma. Materials and Methods Thirty Sprague Dawley (SD) rats were divided into normal, asthma, and HCZP groups (n = 10). The asthma model was sensitized by 1 mg ovalbumin (OVA)/aluminum hydroxide Al(OH)3mixture and then challenged with 1% aerosolized OVA for four weeks. Rats in the HCZP group received 10.08 g/kg/d HCZP for four weeks during OVA challenge. Then, lung tissues of rats in each group were collected for RNA sequencing. Moreover, the expression level of some core genes was detected by using western blotting and immunohistochemistry. Results Inflammatory cell infiltration and pathological damage of the lungs improved in the HCZP group. Compared with the asthma group (0.049 ± 0.002 mm2/mm; 0.036 ± 0.006 mm2/mm; and 0.014 ± 0.001 mm2/mm), total wall thickness (0.042 ± 0.001 mm2/mm), inner wall thickness (0.013 ± 0.001 mm2/mm), and smooth muscle layer thickness (0.012 ± 0.001 mm2/mm) significantly decreased in the HCZP group. Bioinformatics analysis showed that hub genes such as bradykinin receptor B2 (Bdkrb2) and CD4 molecule (Cd4) had different expression patterns between model and HCZP groups. Two transcription factors, forkhead box Q1 (Foxq1) and nuclear factor of activated T cells 2 (Nfatc2), served important regulatory roles in asthma. Compared with the model group, Bdkrb2 protein expression increased and Nfatc2 protein expression decreased in the HCZP group. Discussion and Conclusion. HCZP could alleviate asthma via regulating the expression of several hub genes, which might serve as therapeutic targets for asthma. However, the mechanism of these genes will be studied in the future.

MANAGEMENT OF AIRWAY REMODELING IN A MURINE MODEL OF ALLERGIC AIRWAY INFLAMMATION USING EXTRACELLULAR VESICLES FROM HUMAN BONE MARROW-DERIVED MESENCHYMAL STEM CELLS

The aim of this study was to evaluate the therapeutic potential of extracellular vesicles (EV) derived from human bone marrow mesenchymal stem cells (MSCs), administered by intratracheal (IT) or systemic injection(S), to treat ovalbumin (OVA)-induced asthmatic Balb/C mice. This study was approved by Ethics Committee (number: 34309914.0.0000.0020) and Ethics Committee on Animal Use (number: 904). Forty-three male Balb/C mice were divided in four groups: control (C, n=11); asthmatic (AS, n=11); intratracheal treatment (EV-IT, n=10) and systemic treatment (EV-S, n=11). AS, EV-IT and EV-S groups were submitted to asthma induction by intraperitoneal injections of OVA (10µg in 100µL) at days 0,2,4,7,9 and 10. Then these animals received by IT injections OVA (20µg in 20µL) as allergenic challenge at days 15,18 and 21. C group received sterile saline at these days. At day 22, animals were treated with EVs either locally (EV-IT) or intravenously (EV-S), while C and AS groups received sterile saline. Seven days after treatment, we performed bronchoalveolar lavage (BAL) to count total nuclear cells. The animals were euthanized using anesthetic overdose, and lungs were collected for histopathological analysis (HE, MT and PAS staining). It was performed a semi-quantitative analysis in 30 bronchioles/animal scoring for different parameters (presence and intensity of inflammatory infiltrate, epithelial and smooth muscle layer thickening, mucus production, collagen deposition). Data were analyzed using Kruskal-Wallis test followed by Dunn's test for multiple comparisons, considering significant P<0.05. EV-IT group showed significant improvement in the evaluated criteria of presence and intensity of inflammatory infiltrate, epithelial and smooth muscle cell layer thickening, mucus production and collagen deposition, as well as a reduction in total BAL cells, in comparison with AS group. EV-S group showed reduction only in total cell count in BAL fluid. In conclusion, the local application of EVs derived from hBM-MSCs is effective in controlling asthma.

Unique histological features of the tail skin of cotton rat (Sigmodon hispidus) related to caudal autotomy.

ABSTRACTCaudal autotomy in rodents is an evolutionarily acquired phenomenon enabling escape from predators, by discarding the tail skin after traumatic injuries. The histological mechanisms underlying caudal autotomy seem to differ among species. Cotton rats (Sigmodon hispidus), which are important laboratory rodents for human infectious diseases, possess a fragile tail. In this study, we compared the tail histology of cotton rats with that of laboratory rats (Rattus norvegicus), which have no fragility on their tail, to elucidate the process of rodent caudal autotomy. First, the cotton rats developed a false autotomy characterized by loss of the tail sheath with the caudal vertebrae remaining without tail regeneration. Second, we found the fracture plane was continuous from the interscale of the tail epidermis to the dermis, which was lined with an alignment of E-cadherin+ cells. Third, we found an obvious cleavage plane between the dermis and subjacent tissues of the cotton-rat tail, where the subcutis was composed of looser, finer, and fragmented collagen fibers compared with those of the rat. Additionally, the cotton-rat tail was easily torn, with minimum bleeding. The median coccygeal artery of the cotton rat had a thick smooth muscle layer, and its lumen was filled with the peeled intima with fibrin coagulation, which might be associated with reduced bleeding following caudal autotomy. Taken together, we reveal the unique histological features of the tail relating to the caudal autotomy process in the cotton rat, and provide novel insights to help clarify the rodent caudal autotomy mechanism.

Melatonin ameliorates degenerative alterations caused by age in the rat prostate and mitigates high-fat diet damages.

Imbalance of sexual steroids milieu and oxidative stress are often observed during aging and correlated to prostate disorders. Likewise, high-fat intake has been related to prostate damage and tumor development. Melatonin (MLT) is an antioxidant whose secretion decreases in elderly and is also suggested to protect the gland. This study evaluated the impact of a long-term high-fat diet during aging on prostate morphology and antioxidant system of rats and tested the effects of MLT supplementation under these conditions. Male rats were assigned into four groups: control, treated with MLT, high-fat diet and high-fat diet treated with MLT. The high-fat diet was provided from the 24th week of age, MLT from the 48th (100 μg/kg/day) and rats were euthanized at the 62nd week. The high-fat diet increased body weight, retroperitoneal fatness, glycaemia, and circulating estrogen levels. It aggravated the aging effects, leading to epithelial atrophy (∼32% reduction of epithelial height) and collagen fibers increase (83%). MLT alone did not alter biometric and physiological parameters, except for the prostate weight decrease, whereas it alleviated biometric as well as ameliorated acinar atrophy induced by high-lipid intake. Systemic oxidative stress increased, and prostatic glutathione peroxidase activity decreased fivefold with the high-fat diet despite the indole. Regardless of the diet, MLT triggered epithelial desquamation, reduced androgen receptor-positive cells, increased smooth muscle layer thickness (12%), decreased at least 50% corpora amylacea formation, and stimulated prostatic gluthatione-S-transferase activity. In conclusion, MLT partially recovered prostate damage induced by aging and the long-term high-fat diet and ameliorated degenerative prostate alterations.

Unique blood vasculature and innervation in the cavernous tissue of murine vomeronasal organs.

The vomeronasal organ (VNO) is an accessory olfactory device related to reproductive behavior. The soft tissue of the tubular organ is composed of sensory/non-sensory epithelia and a highly developed vasculature, which in the latter the dilation and contraction of blood vessels are thought to contribute to pumping in and out luminal fluid or air, like penile erectile tissue. The present histological observation of the murine VNO revealed a more complicated vasculature than previously evaluated ones with large differences along the rostro-caudal axis. An immunohistochemical study for vasoactive substances displayed extremely dense innervation by cholinergic nerves containing nitric oxide synthase and VIP/PHI in the thick smooth muscle layer surrounding venous sinuses at light and electron microscopic levels. Furthermore, the differential distribution of cholinergic nerves and adrenergic nerves may provide a novel insight into the pumping mechanism of VNO.

Lowest observed adverse effect level of pulmonary pathological alterations due to nitrous acid exposure in guinea pigs

BackgroundWe previously demonstrated that continuous exposure to nitrous acid gas (HONO) for 4 weeks, at a concentration of 3.6 parts per million (ppm), induced pulmonary emphysema-like alterations in guinea pigs. In addition, we found that HONO affected asthma symptoms, based on the measurement of respiratory function in rats exposed to 5.8 ppm HONO. This study aimed to investigate the dose-response effects of HONO exposure on the histopathological alterations in the respiratory tract of guinea pigs to determine the lowest observed adverse effect level (LOAEL) of HONO.MethodsWe continuously exposed male Hartley guinea pigs (n = 5) to four different concentrations of HONO (0.0, 0.1, 0.4, and 1.7 ppm) for 4 weeks (24 h/day). We performed histopathological analysis by observing lung tissue samples. We examined samples from three guinea pigs in each group under a light microscope and measured the alveolar mean linear intercept (Lm) and the thickness of the bronchial smooth muscle layer. We further examined samples from two guinea pigs in each group under a scanning electron microscope (SEM) and a transmission electron microscope (TEM).ResultsWe observed the following dose-dependent changes: pulmonary emphysema-like alterations in the centriacinar regions of alveolar ducts, significant increase in Lm in the 1.7 ppm HONO-exposure group, tendency for hyperplasia and pseudostratification of bronchial epithelial cells, and extension of the bronchial epithelial cells and smooth muscle cells in the alveolar duct regions.ConclusionsThese histopathological findings suggest that the LOAEL of HONO is < 0.1 ppm.

Anatomy and histology of the foramen of ovarian bursa opening to the peritoneal cavity and its changes in autoimmune disease-prone mice.

The ovarian bursa is a small peritoneal cavity enclosed by the mesovarium and mesosalpinx, which surrounds the ovaries and oviductal infundibulum in mammals. The ovarian bursa is considered as the structure facilitating the transport of ovulated oocytes into the oviduct. Our previous study revealed reduced oocyte pick-up function in the oviduct of lupus-prone MRL/MpJ-Faslpr/lpr mouse, suggesting the possibility of an escape of ovulated oocytes into the peritoneal cavity, despite the presence of an almost complete ovarian bursa in the mouse. In this study, we revealed anatomical and histological characteristics of the ovarian bursa in C57BL/6N, MRL/MpJ, and MRL/MpJ-Faslpr/lpr mice. All strains had the foramen of ovarian bursa (FOB), with a size of approximately 0.04 to 0.12cm2 , surrounded by the ligament of ovarian bursa (LOB), which is part of the mesosalpinx. The LOB was partially lined with the cuboidal mesothelial cells and consisted of a thick smooth muscle layer in all strains. In 6-month-old MRL/MpJ-Faslpr/lpr mice, in which the systemic autoimmune abnormality deteriorated and oocyte pick-up function was impaired, the size of the FOB tended to be larger than that of other strains. Additionally, in MRL/MpJ-Faslpr/lpr mice at 6months of age, there was infiltration by numerous immune cells in the mesosalpinx suspending the isthmus; however, the LOB prevented severe inflammation and showed deposition of collagen fibers. These results not only indicate that the FOB is a common structure within mice, but also imply the physiological function of the LOB and its role in maintaining the microenvironment around the ovary, as well as regulating healthy reproduction.

High-resolution imaging of the actin cytoskeleton and epithelial sodium channel, CFTR, and aquaporin-9 localization in the vas deferens.

Vas deferens is a conduit for sperm and fluid from the epididymis to the urethra. The duct is surrounded by a thick smooth muscle layer. To map the actin cytoskeleton of the duct and its epithelium, we reacted sections of the proximal and distal regions with fluorescent phalloidin. Confocal microscopic imaging showed that the cylinder-shaped epithelium of the proximal region has a thick apical border of actin filaments that form microvilli. The epithelium of the distal region is covered with tall stereocilia (13-18 µm) that extend from the apical border into the lumen. In both regions, the lateral and basal cell borders showed a thin lining of actin cytoskeleton. The vas deferens epithelium contains various channels to regulate the fluid composition in the lumen. We mapped the localization of the epithelial sodium channel (ENaC), aquaporin-9 (AQP9), and cystic fibrosis transmembrane conductance regulator (CFTR) in the rat and mouse vas deferens. ENaC and AQP9 immunofluorescence were localized on the luminal surface and stereocilia and also in the basal and smooth muscle layers. CFTR immunofluorescence appeared only on the luminal surface and in smooth muscle layers. The localization of all three channels on the apical surface of the columnar epithelial cells provides clear evidence that these channels are involved concurrently in the regulation of fluid and electrolyte balance in the lumen of the vas deferens. ENaC allows the flow of Na+ ions from the lumen into the cytoplasm, and the osmotic gradient generated provides the driving force for the passive flow of water through AQP channels.

Relationship of a thinned medial layer to the attenuated contractile response in atherosclerotic coronary arteries.

Coronary arteries with advanced atherosclerosis do not necessarily have greater contractile responses than those with early atherosclerosis. This study aimed to clarify the relationship between thickness of the medial layer and the contractile response to acetylcholine (ACh) in coronary artery using optical coherence tomography (OCT). The OCT and the vasomotor response to ACh in the left anterior descending coronary artery were assessed in 32 patients with previous myocardial infarction. The intimal and medial layer areas were measured by planimetric analysis of the OCT images. The coronary contractile response to ACh had a positive linear relationship with medial area (r = 0.61, P < 0.001). In contrast, the relationship between the coronary contractile response to ACh and intimal area was described by an inverted U-shaped curve that was fitted to a quadratic regression model (R2 = 0.35, P = 0.002, y-axis, contraction; x-axis, intimal area). The contractile response increased as the intimal layer thickened up to the inflection point; thereafter, the contractile response declined. The relationship between medial area and intimal area was also described by an inverted U-shaped curve that was fitted to a quadratic regression model (R2 = 0.41, P < 0.01, y-axis, medial area; x-axis, intimal area). The medial area increased as the intimal area thickened up to the inflection point; thereafter, the medial area thinned. In conclusion, the thinned medial layer was associated with the attenuated contractile response in a coronary artery with greater atherosclerosis.NEW & NOTEWORTHY This is the first clinical study to show the relationship between the contractile response and the thickness of medial smooth muscle layer in coronary artery of patients with previous myocardial infarction using OCT. The contractile response to acetylcholine was attenuated, and medial layer area was thinned in coronary artery with greater atherosclerosis compared with those in coronary artery with mild or moderate atherosclerosis. The coronary contractile response was positively correlated with thickness of the medial layer in coronary arteries with either mild or greater atherosclerosis. Thus, coronary arteries with advanced atherosclerosis do not necessarily have greater contractile responses than those with early atherosclerosis, which could be related to the thinned medial layer.

Preliminary Report: The Relevance of Tumor Necrosis Factor-α in Acquired Primary Lymphedema-A Histopathological Investigation.

Background: Lymphedema includes primary lymphedema (P-LE) and secondary lymphedema (S-LE), which is a chronic progressive disease. The former group is further classified as congenital and acquired P-LE (AP-LE); its etiology is unclear, and only a few studies on its pathophysiology exist. We hypothesized that an autoimmune disease or self-inflammatory mechanism occurs in lymphatic vessels, leading to obstruction. Methods and Results: We enrolled 46 patients with lymphedema who underwent lymphaticovenous anastomosis (LVA) from January to October 2015. Collecting lymph ducts were obtained during LVA. We performed hematoxylin/eosin staining and immunostaining for LYVE-1, IL-1β, IL-6, and TNF-α. There were no substantial histological differences between the two types of lymphedema, whereas some differences in expression of inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α, were observed. Only a few inflammatory cells could be seen around the vessels. Although no significant differences in expression of IL-1β were found between AP-LE and S-LE, TNF-α was more highly expressed in the smooth muscle layer in AP-LE patients than in S-LE patients. There were no significant morphological differences in the collecting ducts of lymphatic vessels between S-LE and P-LE. Nevertheless, higher levels of TNF-α accumulation were found in the thick smooth muscle layer of P-LE patients than in that of S-LE patients. Conclusion: TNF-α-related inflammation in collecting ducts of lymphatic vessels is an important characteristic of the pathology of P-LE. TNF-α inhibitors might improve symptoms of AP-LE.

Maternal 1-nitropyrene exposure during pregnancy increases susceptibility of allergic asthma in adolescent offspring.

1-nitropyrene (1-NP) is widespread in the environment, as a typical nitrated polycyclic aromatic hydrocarbon. The purpose of this research was to explore the effects of gestational 1-NP exposure on susceptibility of allergic asthma in offspring. Maternal mice were exposed to 1-NP (100 μg kg-1) by gavage throughout the whole pregnancy. Pups were sensitized by injecting with ovalbumin (OVA) on postnatal day (PND)23, 29, and 36, respectively. At 7 days following the last injection, sensitized mice were exposed to aerosol OVA. As expected, there were quite a few inflammatory cells in the lungs of OVA-sensitized pups, accompanied by bronchial wall thickening and hyperemia. Elevated goblet cells and overproduced mucus were observed in the airways of OVA-sensitized pups. Interestingly, gestational 1-NP exposure aggravated infiltration of inflammatory cells, mainly eosinophils, in OVA-sensitized offspring. Although it had little effect on airway smooth muscle layer thickening and basement membrane fibrosis, gestational 1-NP exposure aggravated goblet cell hyperplasia, Muc5ac mRNA upregulation, and mucus secretion in the airways of OVA-sensitized and challenged offspring. Mechanistically, gestational 1-NP exposure aggravated elevation of pulmonary IL-5 in OVA-sensitized pups. These findings suggest that gestational 1-NP exposure increases susceptibility of allergic asthma in offspring.

Chronic exposure to non-eruptive volcanic activity as cause of bronchiolar histomorphological alteration and inflammation in mice

It is estimated that 10% of the worldwide population lives in the vicinity of an active volcano. However, volcanogenic air pollution studies are still outnumbered when compared with anthropogenic air pollution studies, representing an unknown risk to human populations inhabiting volcanic areas worldwide. This study was carried out in the Azorean archipelago of Portugal, in areas with active non-eruptive volcanism. The hydrothermal emissions within the volcanic complex of Furnas (São Miguel Island) are responsible for the emission of nearly 1000 tons of CO2 per day, along with H2S, the radioactive gas – radon, among others. Besides the gaseous emissions, metals (e.g., Hg, Cd, Al, Ni) and particulate matter are also released into the environment. We test the hypothesis that chronic exposure to volcanogenic air pollution alters the histomorphology of the bronchioles and terminal bronchioles, using the house mouse, Mus musculus, as bioindicator species. Mus musculus were live-captured at three different locations: two villages with active volcanism and a village without any type of volcanic activity (reference site). The histomorphology of the bronchioles (diameter, epithelium thickness, smooth muscle layer thickness, submucosa thickness and the histological evaluation of the peribronchiolar inflammation) and of the terminal bronchioles (epithelium thickness and classification) were evaluated. Mice chronically exposed to volcanogenic air pollution presented bronchioles with increased epithelial thickness, increased smooth muscle layer, increased submucosa thickness and increased peribronchiolar inflammation. Similarly, terminal bronchioles presented structural alterations consistent with bronchodysplasia. For the first time we demonstrate that chronic exposure to non-eruptive volcanically active environments causes inflammation and histomorphological alterations in mice lower airways consistent with asthma and chronic bronchitis. These results reveal that chronic exposure to non-eruptive volcanic activity represents a risk factor that can affect the health of the respiratory system of humans inhabiting hydrothermal areas.

Bakuchiol suppresses oestrogen/testosterone-induced Benign Prostatic Hyperplasia development through up-regulation of epithelial estrogen receptor β and down-regulation of stromal aromatase

Estrogens and androgens play critical roles during benign prostatic hyperplasia (BPH) development. Estrogen receptors (ERs), androgen receptor (AR) and aromatase, the key conversion enzyme of androgen to estrogen, are thought to be the effective targets for BPH treatment. Bakuchiol (Ba)-containing herb Psoralea corylifolia has been long-termed used for BPH patients in traditional Chinese medicine while the role and regulatory mechanism of Ba involved remain unclear. Human prostatic cell lines WPMY-1 and BPH-1 and oestrodial/testosterone-induced BPH rats were used as the in vitro and in vivo models. Ba significantly inhibited the proliferation of WPMY-1 and BPH-1 cells. In E2/T-induced BPH model, Ba treatment also significantly inhibited the enlargement of prostate, decreased PI values, reduced the thickness of periglanular smooth muscle layer, and down-regulated the expressions of PCNA and smooth muscle cell marker α-SMA, all of which were highly induced in BPH rats. Moreover, the basal and PGE2-induced expressions of aromatase were reduced in Ba-stimulated WPMY-1 cells, while the expression of ERβ was highly increased in Ba-stimulated BPH-1 cells, both of which are consistent with the findings in Ba group in vivo. Ba induced ERE activity in BPH-1 cells as E2 did; however, silence of ERβ not ERα, blocked Ba-induced ERE activity while E2 still exhibited the significant ERE activity, indicating the regulation of estrogen signaling by Ba is particularly via ERβ. In conclusion, by down-regulation of stromal aromatase and up-regulation of epithelial ERβ, Ba contributes to the balance of estrogen and androgen signaling and further inhibits BPH development.