A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Tolerability After Subcutaneous Administration of Tozorakimab in Healthy Chinese Participants.

Tozorakimab is a high-affinity human immunoglobulin G1 monoclonal antibody that neutralizes interleukin (IL)-33, an IL-1 family cytokine. This phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose study (NCT05070312) evaluated tozorakimab in a healthy Chinese population. Outcomes included the characterization of the pharmacokinetic (PK) profile and immunogenicity of tozorakimab. Safety outcomes included treatment-emergent adverse events (TEAEs) and clinical laboratory, electrocardiogram, and vital sign parameters. Healthy, non-smoking, male, and female Chinese participants aged 18-45 years with a body mass index 19-24 kg/m2 were enrolled. In total, 36 participants across 2 cohorts of 18 participants were randomized 2:1 to receive a single subcutaneous dose of tozorakimab (300 mg [2 mL] or 600 mg [4 mL]) or matching placebo (2 or 4 mL). Tozorakimab showed dose-dependent serum PK concentrations with an approximate monophasic distribution in serum over time and a maximum observed peak concentration of 20.1 and 33.7 µg/mL in the 300- and 600-mg cohorts, respectively. No treatment-emergent anti-drug antibodies for tozorakimab were observed in any of the participants. There were no clinically relevant trends in the occurrence of TEAEs across the treatment groups. There were no clinically relevant trends over time in clinical laboratory (hematology, clinical chemistry, and urinalysis), electrocardiogram, or vital sign parameters in any treatment group. Overall, tozorakimab demonstrated dose-dependent systemic exposure in healthy Chinese participants and was well tolerated, with no safety concerns identified in this study.

Effects of epigallocatechin-3-gallate on oxidative stress, inflammation, and bone loss in a rat periodontitis model.

Background/purpose: Epigallocatechin-3-gallate (EGCG) is playing an increasingly important role in the treatment of oral diseases. However, its mechanisms remain to be clarified. This study aimed to investigate the effect of EGCG on oxidative and inflammatory stress and bone loss in experimental periodontitis. Materials and methods: Periodontitis was induced in rats, followed by gavage using different concentrations of EGCG for 5 weeks. The levels of interleukin-1ß (IL-1ß), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in rats were measured. The degree of alveolar bone loss and the number of inflammatory cells were detected. The integrated optical density of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), NLR pyrin domain-containing 3 (NLRP3) and nuclear factor-kappaB p65 (NF-κB p65) was measured. Results: EGCG (200 mg/kg) significantly reduced alveolar bone loss in the ligated maxillary molars and the number of inflammatory cells in the EGCG-200 group compared with the periodontitis, EGCG-100 and EGCG-400 groups. 200 mg/kg was the optimal dose of EGCG and was used in subsequent experiments. The expression levels of IL-1ß, IL-18, TNF-α and MDA were significantly lower and the expression level of SOD was significantly higher in the EGCG-200 group compared with the periodontitis group. The expression of NLRP3 and NF-κB p65 was significantly decreased, while the expression of Nrf2 and HO-1 was significantly increased in the EGCG-200 group compared with the periodontitis group. Conclusion: These results suggest that EGCG inhibits oxidative stress and inflammatory responses in the periodontitis model by modulating the Nrf2/HO-1/NLRP3/NF-κB p65 signaling pathway, thereby decreasing alveolar bone loss.

Research Trends of the Research and Development of Acupuncture and Moxibustion Therapy on Lumbar Disc Herniation: A Bibliometric Analysis.

Background: Acupuncture and moxibustion has been applied worldwide in the treatment of various pain diseases including lumbar disc herniation (LDH) and other pain, However, there has been no bibliometric analysis on this aspect in the past five years. Therefore, this study was carried out for finding research trends and fronts in this field using Citespace and VOSviewer. Methods: Publications about acupuncture therapy for LDH were extracted from the Web of Science database and PubMed with an unlimited time frame. A bibliometric analysis and visualization of results was conducted using CiteSpace 6.1.R3 and VOSviewer 1.6.18 on the information of the annual publication, countries, journals, institutions, authors, references, and keywords. Results: A total of 127 publications were included, and the number of publications had increased noticeably over the past 30 years and reached a peak in the past 3 years. The most productive country with the most publications was China, whose Medical University was the institution with the highest volume of publications. The most productive author was Chen Rixin, while the most-cited author was Kreiner DS. Chinese Acupuncture and Moxibustion was the journal with the most publications, and Spine Journal was the most frequently cited journal. In cited references, an article published in The New England Journal of Medicine by Deyo RA had the most citations and the highest centrality. Of the keywords, the five most frequently used keywords include lumbar disc herniation, acupuncture, low back pain, intervertebral disc displacement, and management. Conclusion: Acupuncture and moxibustion can help to relieve symptoms in patients. However, this field is in the early stages of development and requires more high-quality research studies and international collaborations. In addition, exploring the effectiveness and mechanism of acupuncture for LDH is the hot trend in the future.

DPA-Zinc around Polyplexes Acts Like PEG to Reduce Protein Binding While Targeting Cancer Cells.

Gene therapy holds great promise as an effective treatment for many diseases of genetic origin. Gene therapy works by employing cationic polymers, liposomes, and nanoparticles to condense DNA into polyplexes via electronic interactions. Then, a therapeutic gene is introduced into target cells, thereby restoring or changing cellular function. However, gene transfection efficiency remains low in vivo due to high protein binding, poor targeting ability, and substantial endosomal entrapment. Artificial sheaths containing PEG, anions, or zwitterions can be introduced onto the surface of gene carriers to prevent interaction with proteins; however, they reduce the cellular uptake efficacy, endosomal escape, targeting ability, thereby, lowering gene transfection. Here, it is reported that linking dipicolylamine-zinc (DPA-Zn) ions onto polyplex nanoparticles can produce a strong hydration water layer around the polyplex, mimicking the function of PEGylation to reduce protein binding while targeting cancer cells, augmenting cellular uptake and endosomal escape. The polyplexes with a strong hydration water layer on the surface can achieve a high gene transfection even in a 50% serum environment. This strategy provides a new solution for preventing protein adsorption while improving cellular uptake and endosomal escape.

Ten-m4 plays a unique role in the establishment of binocular visual circuits.

The patterning of binocular vision requires distinct molecular pathways for inputs arising from each side of the nervous system. Recent studies have demonstrated important roles for members of the Ten-m/Odz/teneurin family in the development of ipsilateral retinal projections. Here, we further highlight the significance of this gene family in visual development by identifying a role for Ten-m4 during the formation of the ipsilateral projection in the mouse. Ten-m4 was found to be expressed in the retina, dorsal lateral geniculate nucleus (dLGN), superior colliculus (SC), and primary visual cortex (V1) during development. Anterograde and retrograde tracing experiments in Ten-m4 knockout (KO) mice revealed a specific increase in ipsilateral retinal ganglion cells projecting to dLGN and SC. This increase was most prominent in regions corresponding to temporal retina. Consistent with this, EphB1 expression in the retina around the time of decussation was enhanced in this temporal region for KO mice, suggesting that the increased size of the ipsilateral population arises due to an increased number of retinal ganglion cells remaining ipsilaterally at the optic chiasm due to EphB1-mediated repulsion. The ectopic ipsilaterally targeted retinal ganglion cell projection observed in Ten-m4 KOs was associated with changes in response to ethologically relevant visual stimuli. Together, these data demonstrate a requirement for Ten-m4 in the establishment of ipsilateral projections from the retina, which likely acts in combination with other Ten-m members (Ten-m2 and Ten-m3) to promote the formation of functional binocular circuits.

Clinical feature and predictive factor analysis for spontaneous regression of retinopathy of prematurity in a Chinese population.

AIM: To investigate the ratio of spontaneous regression of retinopathy of prematurity (ROP) and to explore the possible relevant predictive factors. METHODS: A retrospective review of 405 infants who were diagnosed with ROP and mother during pregnancy were collected. Stage, zone, and duration of ROP were recorded. Statistical analysis was performed on 51 possible predictive factors. RESULTS: Totally 356 infants showed spontaneous regression. The incidence was 100%, 95.3%, and 22.7% in stage 1, 2, and 3, respectively. The 13.4% of the ROP with plus disease eventually resolved spontaneously. All affected eyes of aggressive posterior retinopathy of prematurity (AP-ROP) failed to spontaneously regress. The mean duration of ROP was 7.2wk in patients with spontaneous resolution of ROP. Days of mechanical ventilation (OR=0.981, 95%CI, 0.965-0.997, P=0.021), retinal hemorrhage (OR=0.173, 95%CI, 0.064-0.470, P=0.001), delivery pattern (OR=2.750, 95%CI, 1.132-6.681, P=0.025), maternal anemia in pregnancy (OR=0.142, 95%CI, 0.036-0.563, P=0.005), the stages (at initial diagnosis OR=0.183, 95%CI, 0.041-0.816, P=0.026; at final diagnosis OR=0.031, 95%CI, 0.006-0.167, P<0.001), and with plus disease or not (OR=0.005, 95%CI, 0.001-0.031, P<0.001) were independent predictive factors of the spontaneous regression of ROP. CONCLUSION: Most mild ROP can spontaneously resolve. Active treatment is still recommended for stage 3 ROP, zone I ROP, AP-ROP, and ROP with plus disease. Prolonged mechanical ventilation and concurrent retinal hemorrhage reduce the likelihood of spontaneous ROP resolution. The pattern of delivery and the mother's anemia during pregnancy can also affect the prognosis of ROP.

Schisandrin B mitigates hepatic steatosis and promotes fatty acid oxidation by inducing autophagy through AMPK/mTOR signaling pathway.

BACKGROUND: Schisandrin B (Sch B), which inhibits hepatic steatosis caused by non-alcoholic fatty liver disease (NAFLD), is one of the most active dibenzocyclooctadienes isolated from Schisandra chinensis (Turcz.) Baill with various pharmacological activities. In this study, the role of Sch B-induced autophagy in lipid-lowering activities of Sch B was examined and the underlying mechanisms were elucidated. METHODS: Free fatty acid (FFA)-stimulated HepG2 cells and mouse primary hepatocytes (MPHs) and high-fat diet (HFD)-fed mice were used as NAFLD models. The role of Sch B-induced autophagy in lipid-lowering effects of Sch B was assessed using ATG5/TFEB-deficient cells and 3-methyladenine (3-MA)-treated hepatocytes and mice. RESULTS: Sch B simultaneously active autophagy through AMPK/mTOR pathway and decreased the number of lipid droplets in FFA-treated HepG2 cells and MPHs. Additionally, siATG5/siTFEB transfection or 3-MA treatment mitigated Sch B-induced autophagy and activation of fatty acid oxidation (FAO) and ketogenesis in FFA-treated HepG2 cells and MPHs. Sch B markedly decreased hepatic lipid content and activated the autophagy through AMPK/mTOR pathway in HFD-fed mice. However, the activities of Sch B were suppressed upon 3-MA treatment. Sch B upregulated the expression of key enzymes involved in FAO and ketogenesis, which was mitigated upon 3-MA treatment. Moreover, changes in hepatic lipid components and amino acids may be related to the Sch B-induced autophagy pathway. CONCLUSION: These results suggested that Sch B inhibited hepatic steatosis and promoted FAO by activation of autophagy through AMPK/mTOR pathway. Our study provides novel insights into the hepatic lipophagic activity of Sch B and its potential application in the management of NAFLD.

Frequency cumulative effect of subthreshold energy laser-activated remote phosphors irradiation on visual function in guinea pigs.

AIM: To explore the effects of laser-activated remote phosphors (LARP) on visual function in guinea pigs. METHODS: Electroretinogram (ERG) of guinea pigs were observed after LARP irradiation at different frequencies and irradiation times. We evaluated the expression of rhodopsin, ß-catenin, connexin36, calretinin, and calbindin in the retina of guinea pigs and measured the density of photoreceptor cells after high-frequency LARP irradiation. RESULTS: After LARP irradiation, the ERG results showed that the amplitude of the dark-adapted 3.0 b-wave of the model eye was lower than that of the control eye after high-frequency irradiation (P<0.05). The expression of rhodopsin, ß-catenin, connexin36, calretinin, and calbindin in the retina of guinea pig declined. CONCLUSION: There is frequency cumulative damage effect on the retina that relates to LARP illumination frequency. This has significance for staff visual protection policies under LARP lighting conditions.

Therapeutic effect of a traditional Chinese medicine formulation on experimental choroidal neovascularization in mouse.

AIM: To investigate therapeutic effects of traditional Chinese medicine formulations, Hexuemingmu (HXMM) on laser-induced choroidal neovascularization (CNV) and follow-up effect in mice. METHODS: C57BL/6 mice of 8-week-old were used and CNV was induced with 577 nm laser photocoagulation. Animals were randomly divided into groups and different doses of HXMM were administered daily. One, four, and eight weeks after the intervention, the electroretinogram (ERG), fundus fluorescence angiography, choroidal flat mount and immunofluorescence staining were preformed to evaluate the function and CNV formation. The expression levels of angiogenic proteins were determined by Western blotting and immunofluorescence staining. An analysis of variance and Kruskal-Wallis test were used to test the differences among the groups. RESULTS: The results showed that HXMM effectively increased amplitude of ERG of mice (P<0.05), alleviated fundus CNV leakage (P<0.05), and reduced the area of neovascularization and the expression of angiogenic proteins (P<0.05) after laser-induced CNV. CONCLUSION: HXMM can protect the retinal function of mice after laser-induced CNV, and inhibit the CNV development.

MXene/Carbon Nanotube Hybrids: Synthesis, Structures, Properties, and Applications.

Since the successful preparation of few-layer transition metal carbides from three-dimensional MAX phases in 2011, MXenes (known as a family of layered transition metal carbides, nitrides, and carbonitrides) have been intensively studied. Though MXenes have been adopted as active materials in many applications, issues including aggregation and restacking are likely to hamper their potential applications. In order to address these prevailing challenges, the concept of MXene/carbon nanotube (CNT) hybrids was proposed initially in 2015, where CNTs were incorporated as the spacers and conductive additives. Ever since, MXene/CNT hybrids with different architectures have been synthesized by a number of methods and applied in numerous fields. Herein, after the discussion about general synthesis approaches, architectures, and properties of the hybrids, this Review summarized the recent advances in the application of MXene/CNT hybrids in energy storage devices, sensors, electrocatalysis, electromagnetic interference shielding, and water treatment, in which the function of individual components was clarified. In the end, the current research trend in this field were discussed and several technical issues were highlighted along with some suggestions on future research directions.

Effects on newborns of applying bupivacaine combined with different doses of fentanyl for cesarean section.

BACKGROUND: The choice of anesthesia for cesarean section is very important. AIM: To compare the effects of applying bupivacaine combined with different doses of fentanyl on newborns after cesarean section. METHODS: We randomly divided one hundred and twenty patients undergoing cesarean section into the following 4 groups: group B (bupivacaine group), group BF10 (bupivacaine combined with 10 µg fentanyl), group BF30 (bupivacaine combined with 30 µg fentanyl) and group BF50 (bupivacaine combined with 50 µg fentanyl). The heart rate, mean arterial pressure, block plane fixation time and sensory block time were recorded. Umbilical artery blood was then collected immediately after fetal delivery for blood gas analysis and qualitative detection of fentanyl. Additionally, data on the neonatal 1-min and 5-min Apgar scores, results of umbilical artery blood gas analysis and qualitative detection of fentanyl in umbilical artery blood were recorded. RESULTS: Although the mean arterial pressure decreased in all four groups at 3 min after anesthesia, the percentage of the decrease was less than 20% of the baseline. In addition, there were no significant differences in the 1-min or 5-min Apgar scores or the umbilical artery blood gas analysis among the four groups (P > 0.05). Moreover, the concentration of fentanyl in umbilical artery blood was qualitatively detected using an ELISA kit, and the results in the four groups were negative. CONCLUSION: Bupivacaine combined with fentanyl spinal anesthesia is effective in cesarean section.

[Distribution Characteristics and Pollution Evaluation of Nitrogen and Organic Matter in Overlying Water and Sediment of Guyun River and Jinshan Lake in Zhenjiang City].

Zhenjiang City is located in the intersection of the Yangtze River and the Beijing-Hangzhou Grand Canal, which is the most important water transportation hub in China, with abundant water resources and a dense river network. In recent years, the water quality in this region has declined with the rapid development of the economy and enhanced anthropogenic activity. Therefore, it is crucial to understand the state of water and sediment pollution in rivers and lakes of Zhenjiang City, which can provide important basic data for improving the water environment quality for this region. In total, 21 sampling sites (including 10 sites from Jinshan Lake and 11 sites from the ancient canal) in Zhenjiang City were selected, and overlying water and sediment samples were sampled in winter and summer, respectively. In addition, the physical and chemical parameters of overlying water and sediment samples were determined, respectively, and the organic index as well as organic nitrogen index were analyzed in order to evaluate the degree of sediment contamination in this region. Results showed that ① The TN concentration of overlying water changed from 1.95 mg·L-1 to 15.71 mg·L-1 in the winter and from 0.64 mg·L-1 to 12.09 mg·L-1 in the summer, with mean values of 4.01 mg·L-1 and 4.07 mg·L-1, respectively, which are higher than those of the surface water Ⅴ class standard. In addition, the ranked order of NH4+-N was as follows:winter < summer and river > lake; ② the TN content in the sediment samples ranged from 394.61 mg·kg-1 to 3288.09 mg·kg-1 and from 869.21 mg·kg-1 to 3598.04 mg·kg-1, respectively, with the mean values of 1928.58 mg·kg-1 and 2068.40 mg·kg-1. The ranked order of TN, NH4+-N, NO3--N, and Org-N was as follows:winter > summer for lake sediment samples. For river sediment samples, the ranked order of TN was winter < summer, whereas those of NH4+-N and NO3--N were winter > summer, indicating more complicated seasonal distribution for river sediment. In addition, the NO3--N content was higher in lake sediment than in river sediment, whereas that of NH4+-N was higher in river sediment than in lake sediment. The C/N ratio results indicated that the organic matter in sediments primarily resulted from endogenous pollution in this region; ③ Results of organic nitrogen index confirmed that 60% sediment samples from the lake in winter and the river in summer belong to the Ⅳ pollution level, indicating that organic nitrogen pollution existed in these samples. The results of organic index confirmed that 70% and 54.55% sediments samples belong to the Ⅱ pollution level, indicating that the sediments were not severely polluted in rivers and lakes of Zhenjiang City. The results demonstrate that sediments in rivers and lakes of Zhenjiang City are mainly polluted by nitrogen. Our findings provide important basic data for nitrogen control schemes in river water and sediment in Zhenjiang City.

Association of Aldehyde Dehydrogenase 2 Gene Polymorphism with Myocardial Infarction.

OBJECTIVE: This study explored the correlation between myocardial infarction (MI) and the Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene in the Qingyuan area. METHODS: The Glu504Lys polymorphism of the ALDH2 gene was analyzed using the polymerase chain reaction and deoxyribonucleic acid microarray analysis for 468 patients diagnosed with MI for the first time and 132 healthy subjects. RESULTS: There was a significant difference in the distribution of the ALDH2 genotype between the MI group and the control group (P = 0.0492), but there was no significant difference in allele frequency between the two groups (P = 0.1363). The clinical data showed that there were statistically significant differences (P < 0.05) in the two groups' gender and age distributions, rates of diabetes and hypertension, levels of alcohol and tobacco use, serological levels of heart markers, blood lipids and glucose. The subgroup analysis of ALDH2 genotypes found that alcohol consumption, high levels of myoglobin, and low levels of high-density lipoprotein cholesterol were significantly associated with a higher incidence of MI (P < 0.05). After adjusting for gender, hypertension, diabetes, and other related influencing factors, logistic regression analysis showed that the ALDH2 genotype GA/AA was an independent risk factor for MI (P < 0.05, OR = 1.479, 95% CI = 1.003-2.179). CONCLUSION: The presence of risk alleles with the genetic effect (ALDH2 genotype GA/AA) is an independent risk factor for MI.

Ligilactobacillus Salivarius LCK11 Prevents Obesity by Promoting PYY Secretion to Inhibit Appetite and Regulating Gut Microbiota in C57BL/6J Mice.

SCOPE: Obesity is a common disease worldwide and there is an urgent need for strategies to preventing obesity. METHODS AND RESULTS: The anti-obesity effect and mechanism of Ligilactobacillus salivarius LCK11 (LCK11) is studied using a C57BL/6J male mouse model in which obesity is induced by a high-fat diet (HFD). Results show that LCK11 can prevent HFD-induced obesity, reflected as inhibited body weight gain, abdominal and liver fat accumulation and dyslipidemia. Analysis of its mechanism shows that on the one hand, LCK11 can inhibit food intake through significantly improving the transcriptional and translational levels of peptide YY (PYY) in the rectum, in addition to the eventual serum PYY level; this is attributed to the activation of the toll-like receptor 2/nuclear factor-κB signaling pathway in enteroendocrine L cells by the peptidoglycan of LCK11. On the other hand, LCK11 supplementation effectively reduces the Firmicutes/Bacteroidetes ratio and shifts the overall structure of the HFD-disrupted gut microbiota toward that of mice fed on a low-fat diet; this also contributes to preventing obesity. CONCLUSION: LCK11 shows the potential to be used as a novel probiotic for preventing obesity by both promoting PYY secretion to inhibit food intake and regulating gut microbiota.

Precision cut lung slices: an ex vivo model for assessing the impact of immunomodulatory therapeutics on lung immune responses.

Chronic inflammatory diseases of the respiratory tract, such as chronic obstructive pulmonary disease (COPD) and asthma, are severe lung diseases that require effective treatments. In search for new medicines for these diseases, there is an unmet need for predictive and translatable disease-relevant in vitro/ex vivo models to determine the safety and efficacy of novel drug candidates. Here, we report the use of precision cut lung slices (PCLS) as a potential ex vivo platform to study compound effects in a physiologically relevant environment. PCLS derived from an elastase-challenged mouse model display key characteristics of increased inflammation ex vivo, which is exacerbated further upon challenge with LPS, mimicking the immune insult of a pathogen triggering disease exacerbation. Such LPS-induced inflammatory conditions are significantly abrogated by immunomodulatory agents targeting specific inflammatory signaling pathways in the absence of cytotoxic effects in lung slices. Thus, an ex vivo model of PCLS with a simulated pathogenic insult can replicate proposed in vivo pharmacological effects and thus could potentially act as a valuable tool to investigate the underlying mechanisms associated with lung safety, therapeutic efficacy and exacerbations with infection.

Lactiplantibacillus plantarum H-87 prevents high-fat diet-induced obesity by regulating bile acid metabolism in C57BL/6J mice.

Bile salt hydrolase (BSH)-producing bacteria are negatively related to the body weight gain and energy storage of the host. We aimed to obtain a novel BSH-producing strain with excellent anti-obesity effect and explained its mechanism. Here, we selected a strain named Lactiplantibacillus plantarum H-87 (H-87) with excellent ability to hydrolyze glycochenodeoxycholic acid (GCDCA) and tauroursodeoxycholic acid (TUDCA) in vitro from 12 lactobacilli, and evaluated its anti-obesity effect in high-fat diet (HFD)-fed C57BL/6J mice. The results suggested that H-87 could inhibit HFD-induced body weight gain, fat accumulation, liver lipogenesis and injury, insulin resistance and dyslipidemia. In addition, H-87 could colonize in the ileum and hydrolyze GCDCA and TUDCA, reflected as changes in the concentrations of GCDCA, TUDCA, CDCA and UDCA in the ileum or liver. Furthermore, the study identified that H-87 reduced TUDCA and GCDCA levels in the ileum, which decreased the GLP-1 secretion by L cells to alleviate insulin resistance in HFD-fed mice. Furthermore, H-87 increased the CDCA level in the ileum and liver to activate FXR signaling pathways to inhibit liver lipogenesis in HFD-fed mice. In addition, the decrease of intestinal conjugated bile acids (TUDCA and GCDCA) also increased fecal lipid content and decreased intestinal lipid digestibility. In conclusion, H-87 could inhibit liver fat deposition, insulin resistance and lipid digestion by changing bile acid enterohepatic circulation, and eventually alleviate HFD-induced obesity.

Crosstalk between Mast Cells and Lung Fibroblasts Is Modified by Alveolar Extracellular Matrix and Influences Epithelial Migration.

Mast cells play an important role in asthma, however, the interactions between mast cells, fibroblasts and epithelial cells in idiopathic pulmonary fibrosis (IPF) are less known. The objectives were to investigate the effect of mast cells on fibroblast activity and migration of epithelial cells. Lung fibroblasts from IPF patients and healthy individuals were co-cultured with LAD2 mast cells or stimulated with the proteases tryptase and chymase. Human lung fibroblasts and mast cells were cultured on cell culture plastic plates or decellularized human lung tissue (scaffolds) to create a more physiological milieu by providing an alveolar extracellular matrix. Released mediators were analyzed and evaluated for effects on epithelial cell migration. Tryptase increased vascular endothelial growth factor (VEGF) release from fibroblasts, whereas co-culture with mast cells increased IL-6 and hepatocyte growth factor (HGF). Culture in scaffolds increased the release of VEGF compared to culture on plastic. Migration of epithelial cells was reduced by IL-6, while HGF and conditioned media from scaffold cultures promoted migration. In conclusion, mast cells and tryptase increased fibroblast release of mediators that influenced epithelial migration. These data indicate a role of mast cells and tryptase in the interplay between fibroblasts, epithelial cells and the alveolar extracellular matrix in health and lung disease.

Astragaloside IV attenuates cerebral ischemia­reperfusion injury in rats through the inhibition of calcium­sensing receptor­mediated apoptosis.

Cerebral ischemia­reperfusion injury (CIRI), caused by the reperfusion of blocked vessels following ischemic stroke, can lead to secondary brain injury. Throughout CIRI, apoptosis serves an important role. Astragaloside IV is a potential neuroprotectant that alleviates CIRI by inhibiting apoptosis. The calcium­sensing receptor (CaSR) is a G­protein­coupled receptor, the activation of which aggravates ischemia­reperfusion injury. The aim of the present study was to investigate whether the protective effect of Astragaloside IV on CIRI may be associated with the regulation of CaSR. A rat middle cerebral artery occlusion/reperfusion (MCAO/R) model and an oxygen and glucose deprivation/reoxygenation (OGD/R) model of pheochromocytoma (PC12) cells were used to study the neuronal injury induced by CIRI. Neurological function scores (NFS), 2,3,5­triphe­nylterazolium chloride and hematoxylin and eosin staining were used to determine brain damage in rats. Cell viability was measured to evaluate the injury of OGD/R PC12 cells. Western blotting was used to examine the expression of proteins associated with apoptosis and CaSR. The CaSR antagonist NPS­2143 and agonist GdCl3 were used to further confirm the effects of CaSR during the process of apoptosis. The results demonstrated that Astragaloside IV alleviated CIRI by decreasing the NFS of rats, reducing the infarction volume of the brain and promoting the viability of PC12 cells, as well as inhibiting the expression of cleaved caspase­3 and CaSR, which was induced by CIRI. The results of the present study suggested that the activation of CaSR may be involved in CIRI­induced brain damage in rats, and that Astragaloside IV may alleviate CIRI by inhibiting CaSR activation­induced apoptosis.

Complete mitochondrial genome of the black-winged fly, Felderimyia fuscipennis (Diptera: Tephritidae) and its phylogenetic relationship within family Tephritidae.

The black-winged fly, Felderimyia fuscipennis (Diptera: Tephritidae), is an insect pest of bamboo shoot, mainly distributed in Thailand, Malaysia and Yunnan Province and Guangxi Autonomous Region, China. The complete sequence of the mitogenome of F. fuscipennis has been determined in this study. The whole mitogenome sequence is 16,536 bp in length, which totally contains 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and a non-coding region (putative control region, CR). The phylogeny indicates that F. fuscipennis of subfamily Trypetinae was monophyletic and clearly separated from both Dacinae and Tephritinae with high bootstrap value supported.