Effect of Shao's five-needle therapy pretreatment on airway inflammatory response in asthmatic rats based on ROS/TXNIP/NLRP3 pathway. / 基于ROS/TXNIP/NLRP3通路探讨"邵氏五针法"é¢„å¤„ç†å¯¹å“®å–˜å¤§é¼ æ°”é“ç‚Žæ€§ååº”çš„å½±å“.

OBJECTIVES: To explore the possible mechanism of Shao's five-needle therapy pretreatment on relieving airway inflammatory response in asthmatic rats. METHODS: Forty SPF-grade SD rats were randomly divided into a blank group, a model group, an acupuncture group, and a medication group, with 10 rats in each group. Except the blank group, asthma model was established by aerosol inhalation of ovalbumin in the other 3 groups. The rats in the acupuncture group were treated with acupuncture at "Dazhui" (GV 14) and bilateral "Feishu" (BL 13) and "Fengmen" (BL 12), with each session lasting for 20 min. Acupuncture was given before each motivating, once daily for 7 consecutive days. The rats in the medication group were treated with intraperitoneal injection of dexamethasone sodium phosphate solution before each motivating, once daily for 7 days. General situation of the rats was observed in each group; ELISA method was used to detect the levels of inflammatory cytokines interleukin (IL)-1ß and IL-18 in serum; immunofluorescence staining method was performed to assess the expression of reactive oxygen species (ROS) in lung tissues; Western blot method was used to measure the protein expression of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in lung tissues. RESULTS: The rats in the blank group exhibited normal behavior, while those in the model group showed signs of respiratory distress, ear scratching, cheek rubbing, and dysphoria. Compared with the model group, the rats in the acupuncture group and the medication group showed stable respiration and relatively agile responses. Compared with those in the blank group, the serum levels of IL-18 and IL-1ß were elevated (P<0.01), the expression intensity of ROS was increased, and the protein expressions of TXNIP, NLRP3, ASC and Caspase-1 in lung tissues were increased (P<0.01) in the model group. Compared with those in the model group, the serum levels of IL-18 and IL-1ß were reduced (P<0.01), the expression intensity of ROS was lowered, and the protein expressions of TXNIP, NLRP3, ASC and Caspase-1 in lung tissues were reduced (P<0.01) in the acupuncture group and the medication group. Compared with the medication group, the protein expression of ASC in lung tissue was reduced in the acupuncture group (P<0.05). CONCLUSIONS: Pretreatment of Shao's five-needle therapy could alleviate airway inflammatory response in asthmatic rats by reducing ROS levels and decreasing the aggregation and activation of pathway-related proteins in the ROS/TXNIP/NLRP3 pathway, ultimately leading to decreased secretion of IL-1ß and IL-18. This mechanism may contribute to the effectiveness of Shao's five-needle therapy in preventing and treating asthma.

Phytochemical Analysis, Antioxidant Activities In Vitro and In Vivo, and Theoretical Calculation of Different Extracts of Euphorbia fischeriana.

Euphorbia fischeriana has a long-standing history of use in traditional medicine for the treatment of tuberculosis diseases. However, the plant's therapeutic potential extends beyond this specific ailment. The present study aimed to investigate the antioxidant properties of Euphorbia fischeriana and lay the groundwork for further research on its potential therapeutic applications. Phytochemical tests were performed on the plant, and 11 types of phytochemicals were identified. Ultraviolet-visible spectrophotometry was used to evaluate the active components and antioxidant properties of eight different solvent extracts, ultimately selecting acetone extract for further research. UHPLC-ESI-Q-TOF-MS identified 43 compounds in the acetone extract, and chemical calculations were used to isolate those with high content and antioxidant activity. Three stability experiments confirmed the extract's stability, while cell viability and oral acute toxicity studies demonstrated its relatively low toxicity. In rats, the acetone extract showed significant protective effects against D-galactosamine-induced liver damage through histopathological examination and biochemical analysis. These results suggest that Euphorbia fischeriana's acetone extract has potential in treating diseases related to oxidative imbalances. Therefore, this study highlights the plant's potential therapeutic applications while providing insight into its antioxidant properties.

[Correlation between active component content and color of Atractylodes Lancea and A. chinensis based on color difference principle].

We explored the correlations between the color difference values [ΔL~*(lightness), Δa~*(red-green), Δb~*(yellow-blue)] and the content of four active components(including sesquiterpenoids and polyacetylenes) in the powder of Atractylodes lancea and A. chinensis, aiming to provide reference for the quality evaluation of Atractylodis Rhizoma and establish a qualitative model that can distinguish between A. lancea and A. chinensis based on the chromatic values. The tristimulus values(L~*, a~*, and b~*) of 23 batches of A. lancea and A. chinensis were measured by a color difference meter. The content of atractylenolide Ⅱ, ß-eudesmol, atractylodin, and atractylone in the 23 batches of samples were measured by high performance liquid chromatography(HPLC). Principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were performed to establish the qualitative models for distinguishing between A. lancea and A. chinensis. SPSS was employed to analyze the correlations between the tristimulus values and the content of the four index components. The results showed that the established PCA and PLS-DA models can divide the A. lancea and A. chinensis samples into two regions, and the tristimulus values of A. lancea and A. chinensis were positively correlated with the content of ß-eudesmol and atractylodin. Therefore, the PCA and PLS-DA models can successfully identify A. lancea and A. chinensis, and the appearance color can be used to quickly predict the internal quality of Atractylodis Rhizoma. This study provides a reference for the quality evaluation of Atractylodis Rhizoma and the modern research on the color of Chinese medicinal materials.

Assessment of integrated patterns of human-animal-environment health: a holistic and stratified analysis.

BACKGROUND: Data-driven research is a very important component of One Health. As the core part of the global One Health index (GOHI), the global One Health Intrinsic Drivers index (IDI) is a framework for evaluating the baseline conditions of human-animal-environment health. This study aims to assess the global performance in terms of GOH-IDI, compare it across different World Bank regions, and analyze the relationships between GOH-IDI and national economic levels. METHODS: The raw data among 146 countries were collected from authoritative databases and official reports in November 2021. Descriptive statistical analysis, data visualization and manipulation, Shapiro normality test and ridge maps were used to evaluate and identify the spatial and classificatory distribution of GOH-IDI. This paper uses the World Bank regional classification and the World Bank income groups to analyse the relationship between GOH-IDI and regional economic levels, and completes the case studies of representative countries. RESULTS: The performance of One Health Intrinsic Driver in 146 countries was evaluated. The mean (standard deviation, SD) score of GOH-IDI is 54.05 (4.95). The values (mean SD) of different regions are North America (60.44, 2.36), Europe and Central Asia (57.73, 3.29), Middle East and North Africa (57.02, 2.56), East Asia and Pacific (53.87, 5.22), Latin America and the Caribbean (53.75, 2.20), South Asia (52.45, 2.61) and sub-Saharan Africa (48.27, 2.48). Gross national income per capita was moderately correlated with GOH-IDI (R2 = 0.651, Deviance explained = 66.6%, P < 0.005). Low income countries have the best performance in some secondary indicators, including Non-communicable Diseases and Mental Health and Health risks. Five indicators are not statistically different at each economic level, including Animal Epidemic Disease, Animal Biodiversity, Air Quality and Climate Change, Land Resources and Environmental Biodiversity. CONCLUSIONS: The GOH-IDI is a crucial tool to evaluate the situation of One Health. There are inter-regional differences in GOH-IDI significantly at the worldwide level. The best performing region for GOH-IDI was North America and the worst was sub-Saharan Africa. There is a positive correlation between the GOH-IDI and country economic status, with high-income countries performing well in most indicators. GOH-IDI facilitates researchers' understanding of the multidimensional situation in each country and invests more attention in scientific questions that need to be addressed urgently.

Comprehensive assessment of osteoporosis in lumbar spine using compositional MR imaging of trabecular bone.

OBJECTIVES: To comprehensively assess osteoporosis in the lumbar spine, a compositional MR imaging technique is proposed to quantify proton fractions for all the water components as well as fat in lumbar vertebrae measured by a combination of a 3D short repetition time adiabatic inversion recovery prepared ultrashort echo time (STAIR-UTE) MRI and IDEAL-IQ. METHODS: A total of 182 participants underwent MRI, quantitative CT, and DXA. Lumbar collagen-bound water proton fraction (CBWPF), free water proton fraction (FWPF), total water proton fraction (TWPF), bone mineral density (BMD), and T-score were calculated in three vertebrae (L2-L4) for each subject. The correlations of the CBWPF, FWPF, and TWPF with BMD and T-score were investigated respectively. A comprehensive diagnostic model combining all the water components and clinical characteristics was established. The performances of all the water components and the comprehensive diagnostic model to discriminate between normal, osteopenia, and osteoporosis cohorts were also evaluated using receiver operator characteristic (ROC). RESULTS: The CBWPF showed strong correlations with BMD (r = 0.85, p < 0.001) and T-score (r = 0.72, p < 0.001), while the FWPF and TWPF showed moderate correlations with BMD (r = 0.65 and 0.68, p < 0.001) and T-score (r = 0.47 and 0.49, p < 0.001). The high area under the curve values obtained from ROC analysis demonstrated that CBWPF, FWPF, and TWPF have the potential to differentiate the normal, osteopenia, and osteoporosis cohorts. At the same time, the comprehensive diagnostic model shows the best performance. CONCLUSIONS: The compositional MRI technique, which quantifies CBWPF, FWPF, and TWPF in trabecular bone, is promising in the assessment of bone quality. KEY POINTS: • Compositional MR imaging technique is able to quantify proton fractions for all the water components (i.e., collagen-bound water proton fraction (CBWPF), free water proton fraction (FWPF), and total water proton fraction (TWPF)) in the human lumbar spine. • The biomarkers derived from the compositional MR imaging technique showed moderate to high correlations with bone mineral density (BMD) and T-score and showed good performance in distinguishing people with different bone mass. • The comprehensive diagnostic model incorporating CBWPF, FWPF, TWPF, and clinical characteristics showed the highest clinical diagnostic capability for the assessment of osteoporosis.

Cytoskeletal protein SPTA1 mediating the decrease in erectile function induced by high-fat diet via Hippo signaling pathway.

BACKGROUND: The mechanism of high-fat diet (HFD)-induced decrease in erectile function has not been elucidated, and in previous studies, spectrin alpha, erythrocytic 1 (SPTA1) is a cytoskeletal protein that regulates cellular function, which belongs to a family of proteins that can affect cell and tissue growth and development by regulating YAP, an effector on the Hippo signaling pathway, but its particular role has not been elucidated. OBJECTIVE: To explore the role of SPTA1 in the abnormality of erectile function induced by HFD. METHODS: We analyzed the penile tissues of mice on normal diet and HFD by transcriptomics and screened for differentially expressed genes, further identified closely related target genes in rat penile tissues, and verified target gene expression in in vitro construction of high-glucose (HG)-treated corpus cavernosum endothelial cells (CCECs) and corpus cavernosum smooth muscle cells (CCSMCs) models. The distribution of target genes in various cell populations in penile tissues was retrieved by single-cell sequencing Male Health Atlas database. Moreover, interfering with target genes was further applied to explore the mechanisms involved in erectile function decline. RESULTS: Transcriptomic analysis screened out down-regulated differential gene SPTA1; Western blot and immunohistochemistry results showed that SPTA1 expression significantly decreased in the penile tissues of Sprague-Dawley (SD) rats in the HFD group. Immunofluorescence staining showed a positive expression of CD31 and VWF in CCECs and a positive expression of α-SMA in CCSMCs. The expression level of SPTA1 protein significantly decreased in the HG group of CCECs and CCSMCs. The expression of SPTA1 mRNA significantly decreased in CCSMCs while significantly increased in CCECs. SPTA1 may have various expression patterns and biological functions in different cell populations. Real-time quantitative PCR results showed that the siSPTA1 transfected in CCSMCs had a significant interference effect compared with the control siNC. Transfection of siSPTA1 into CCSMCs resulted in the significant down-regulation of mRNA and protein expression of eNOS, and significant up-regulation of YAP, Caspase-1, GSDMD, GSDMD-N IL-18, and IL-1ß protein expression levels. The expression level of CCSMCs contractile-type protein α-SMA was significantly down-regulated. CONCLUSIONS: The down-regulation of SPTA1 in SD rats fed with HFD may induce cell pyroptosis and lead to the decrease of erectile function by activating the Hippo pathway; these findings may provide new therapeutic targets for improving erectile function.

Hierarchical clock-scale hand-drawn mapping as a simple method for bronchoscopic navigation in peripheral pulmonary nodule.

BACKGROUND: A feasible and economical bronchoscopic navigation method in guiding peripheral pulmonary nodule biopsy is lacking. OBJECTIVE: To investigate the utility of hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. METHODS: We developed a hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. Patients with peripheral pulmonary nodules were recruited and assigned to two groups in this retrospective study, subjects in VBN group received conventional bronchoscopy in conjunction with virtual bronchoscopic navigation (VBN) and radial probe endobronchial ultrasound (RP-EBUS) for biopsy (VBN group), while HBN group underwent ultrathin bronchoscopy and RP-EBUS under the guidance of hand-drawn bronchoscopic navigation (HBN). The demographic characteristics, procedural time, operating cost and diagnostic yield were compared between these two groups. RESULTS: Forty-eight patients with peripheral pulmonary nodule were enrolled in HBN group, while 42 in VBN group. There were no significant differences between VBN and HBN groups in terms of age, gender, lesion size, location and radiographic type. The time of planning pathway (1.32 vs. 9.79 min, P < 0.001) and total operation (23.63 vs. 28.02 min, P = 0.002), as well as operating cost (758.31 ± 125.21 vs.1327.70 ± 116.25 USD, P < 0.001) were markedly less in HBN group, compared with those in VBN group. The pathological diagnostic efficiency of benign and malignant disease in HBN group appeared similar with those in VBN group, irrespective of the size of pulmonary lesion (larger or smaller than 20 mm). The total diagnostic yield of HBN had no marked difference from that of VBN (75.00% vs. 61.90%, P = 0.25). CONCLUSIONS: Hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation could serve as a feasible and economical method for guiding peripheral pulmonary nodule biopsy, providing a comparable diagnostic yield in comparison with virtual bronchoscopic navigation.

Towards a global One Health index: a potential assessment tool for One Health performance.

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

Assessment of Osteoporosis in Lumbar Spine: In Vivo Quantitative MR Imaging of Collagen Bound Water in Trabecular Bone.

AIM: Bone collagen matrix makes a crucial contribution to the mechanical properties of bone by imparting tensile strength and elasticity. The collagen content of bone is accessible via quantification of collagen bound water (CBW) indirectly. We prospectively study the performance of the CBW proton density (CBWPD) measured by a 3D short repetition time adiabatic inversion recovery prepared ultrashort echo time (STAIR-UTE) magnetic resonance imaging (MRI) sequence in the diagnosis of osteoporosis in human lumbar spine. METHODS: A total of 189 participants with a mean age of 56 (ranged from 50 to 86) years old were underwent MRI, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DXA) in lumbar spine. Major fracture risk was also evaluated for all participants using Fracture Risk Assessment Tool (FRAX). Lumbar CBWPD, bone marrow fat fraction (BMFF), bone mineral density (BMD) and T score values were calculated in three vertebrae (L2-L4) for each subject. Both the CBWPD and BMFF were correlated with BMD, T score, and FRAX score for comparison. The abilities of the CBWPD and BMFF to discriminate between three different cohorts, which included normal subjects, patients with osteopenia, and patients with osteoporosis, were also evaluated and compared using receiver operator characteristic (ROC) analysis. RESULTS: The CBWPD showed strong correlation with standard BMD (R2 = 0.75, P < 0.001) and T score (R2 = 0.59, P < 0.001), as well as a moderate correlation with FRAX score (R2 = 0.48, P < 0.001). High area under the curve (AUC) values (≥ 0.84 using QCT as reference; ≥ 0.76 using DXA as reference) obtained from ROC analysis demonstrated that the CBWPD was capable of well differentiating between the three different subject cohorts. Moreover, the CBWPD had better correlations with BMD, T score, and FRAX score than BMFF, and also performed better in cohort discrimination. CONCLUSION: The STAIR-UTE-measured CBWPD is a promising biomarker in the assessment of bone quality and fracture risk.

Diverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis.

MicroRNA-199a-5p (miR-199a-5p) and -3p are enriched in the myocardium, but it is unknown whether miR-199a-5p and -3p are co-expressed in cardiac remodeling and what roles they have in cardiac hypertrophy and fibrosis. We show that miR-199a-5p and -3p are co-upregulated in the mouse and human myocardium with cardiac remodeling and in Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs) and cardiac fibroblasts (CFs). miR-199a-5p and -3p could aggravate cardiac hypertrophy and fibrosis in vivo and in vitro. PPAR gamma coactivator 1 alpha (Ppargc1a) and sirtuin 1 (Sirt1) were identified as target genes to mediate miR-199a-5p in promoting both cardiac hypertrophy and fibrosis. However, miR-199a-3p aggravated cardiac hypertrophy and fibrosis through targeting RB transcriptional corepressor 1 (Rb1) and Smad1, respectively. Serum response factor and nuclear factor κB p65 participated in the upregulation of miR-199a-5p and -3p in Ang-II-treated NMVCs and mouse CFs, and could be conversely elevated by miR-199a-5p and -3p. Together, Ppargc1a and Sirt1, Rb1 and Smad1 mediated the pathological effect of miR-199a-5p and -3p by promoting cardiac hypertrophy and fibrosis, respectively. This study suggests a possible new strategy for cardiac remodeling therapy by inhibiting miR-199a-5p and -3p.

Culture and purification of SD rat corpus cavernosum endothelial cells by enzymatic digestion combined with mechanical extrusion and fixed-point digestion.

To explore a new method of in vitro culture and purification of rat corpus cavernosum endothelial cells (CCECs). Male Sprague-Dawley rats' penile tissue were digested with elastase or collagenase combined with mechanical extrusion to isolate and culture the CCECs. The fixed-point digestion method was used to purify the primary cells. High-purity CCECs were successfully isolated. Following the digestion of the primary CCECs by elastase or collagenase coupled with mechanical extrusion, the cells were paving stone- and cobblestone-shaped over 10 days. The cell purity yielded in the second generation (P2) CCECs after using the fixed-point digestion method was significantly high. Compared with primary CCECs extracted by elastase digestion combined with the mechanical extrusion method, CCECs cultured by collagenase digestion yielded higher purity and a more stable morphology after fixed-point digestion and purification. Immunofluorescence staining of the third generation CCECs and the expression results of endothelial cell-associated marker antibodies CD31 and VWF were positive, and flow cytometry showed the purity of CCECs was 96.9%. Enzymatic digestion combined with mechanical extrusion and fixed-point digestion is a simple, economical method for in vitro culture and purification of CCECs, which is conducive to studying the pathophysiological mechanisms of endothelial dysfunction and erectile dysfunction.

Hybrid stenting with silicone Y stents and metallic stents in the management of severe malignant airway stenosis and fistulas.

BACKGROUND: Airway stenting is frequently used in the palliative treatment of patients with advanced tumor-induced airway stenosis and fistulas. However, there is paucity of studies regarding the use of airway stents in restoring patency. The aim of the study was to assess the efficacy and safety of hybrid silicon Y stents and covered self-expanding metal stents (SEMS) and in reestablishing patency in airway stenoses and fistulas. METHODS: This retrospective study included 31 patients between January 2016 to December 2019 with inoperable complex malignant airway stenoses and fistulas, managed with Silicone Y stents, and covered SEMS. The clinical details, clinical outcomes and complications up to 6 months were extracted from medical records. The improvement of performance was assessed based on modified British Medical Research Council (mMRC) dyspnea scores (t=6.892, P<0.001), Karnofsky Performance Scores (KPS) (t=-11.653, P<0.001), and performance status (PS) (t=3.503, P<0.001). RESULT: A total of 31 silicon Y stents and 35 covered SEMSs were inserted. Of the 31 patients (M:F 20:11; age: 54.64±9.57), 25/31 (80.6%) experienced immediate relief of symptoms following stent placement. Patients' mMRC dyspnea scores, KPS, and PS showed significant improvement following stenting. The mean duration of stent placement was 146.3±47.7 days, and 17/31 (55%) patients were alive at 6 months. No major complications related to hybrid stenting were observed during the follow-up period. CONCLUSIONS: Hybrid stenting is a feasible and safe palliative treatment for malignant airway stenosis and fistulas to improve quality of life and can be performed without major complications.

Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis.

BACKGROUND AND AIMS: Post-tuberculosis bronchial stenosis (PTBS) is one of the most common complications of tracheobronchial tuberculosis. Silicone stent serves as a major treatment for maintaining airway patency. However, silicone stent placement remains a large challenge in patients with severe cicatricial PTBS. Our objective was to evaluate the efficacy and safety of covered, self-expanding, metallic stents (SEMSs) as a transition to silicone stent implantation for treating severe PTBS. METHODS: We retrospectively reviewed the data of patients with severe PTBS who received airway stenting in the First Affiliated Hospital of Guangdong Medical University between September 2015 and May 2019. The types of the stent, intervention procedures, bronchoscopic findings, clinical outcomes and related complications were collected and analyzed. RESULTS: Fifty-eight cases with severe PTBS were included in this study. Thirteen (22.4%) of the patients received bronchial silicone stent implantation immediately after dilations. For the remaining 45 (77.6%) patients, silicone stents could not be deployed after dilations and SEMSs implantation was implemented as a bridge to silicone stenting. The SEMSs were placed for an interval of 28.4 ± 11.1 days. All of the silicone stents were inserted successfully following the removal of SEMSs. No SEMS-related complication occurred. The subgroup analysis showed that patients who received transitional SEMSs had less luminal caliber but fewer transbronchial dilations before silicone stent implantation (p < 0.05). CONCLUSION: Covered SEMS placement as a transition to silicone stenting could serve as a feasible procedure to reduce complications and improve the success rate of silicone stent implantation in patients with severe PTBS.The reviews of this paper are available via the supplemental material section.

Proteomic analysis of oxidative stress response in human umbilical vein endothelial cells (HUVECs): role of heme oxygenase 1 (HMOX1) in hypoxanthine-induced oxidative stress in HUVECs.

BACKGROUND: Erectile dysfunction (ED) is a well-known complication of diabetes, affecting up to 75% of diabetic men. Although the etiology of diabetic ED is multifactorial, endothelial dysfunction is considered to be a pillar of its pathophysiology. Endothelial dysfunction is caused by the harmful effects of high glucose levels and increased oxidative stress on the endothelial cells that comprise the vascular endothelium. The aim of this study was to identify the proteomic changes caused by high glucose-induced oxidative stress and explore the role of heme oxygenase 1 (HMOX1) in it. METHODS: The cellular proteomic response to hypoxanthine-induced oxidative stress in human umbilical vein endothelial cells (HUVECs) was analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were analyzed through Network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Further validation assays was performed to validate the role of HMOX1. RESULTS: The results showed that 66 and 76 DEPs were markedly upregulated and downregulated, respectively, for HUVECs oxidative stress. Among these proteins, we verified eight dysregulated genes by quantitative reverse transcription PCR, including nucleolin (NCL), X-ray repair cross-complementing protein 6 (XRCC6), ubiquinol-cytochrome C reductase binding protein (UQCRB), non-POU domain containing octamer binding (NONO), heme oxygenase 1 (HMOX1), nucleobindin 1 (NUCB1), DEK, and chromatin target of prmt1 (CHTOP). Further, using overexpression and genetic knockdown approaches, we found that HMOX1 was critical for the oxidative stress response in HUVECs. CONCLUSIONS: We found that HMOX1 was closely related to the oxidative stress response induced by hypoxanthine. To the best of our knowledge, this study is the first overview of the responses of HUVECs to oxidative stress. The findings will contribute to analyses of the detailed molecular mechanisms involved in the pathogenesis of endothelial dysfunction and related molecular mechanisms in ED patients.

Altered anxiety and social behaviors in a mouse model of Fragile X syndrome treated with hyperbaric oxygen therapy.

Fragile X syndrome (FXS) is a common mental retardation syndrome. Anxiety and abnormal social behaviors are prominent features of FXS in humans. To better understand the effects of hyperbaric oxygen therapy (HBOT) on these behaviors, we analyzed anxiety-related and social behaviors in Fmr1 knockout mice treated by HBOT. In the open field test, HBOT group mice preferred the periphery to central areas and tended to run or walk along the wall. The results suggested that thigmotaxis was significantly increased in the HBOT group compared with the control group. In the elevated plus maze test, the percentage of distance traveled was significantly increased in the open arm and significantly decreased in the closed arm for HBOT group mice compared with control group mice. These results suggested that HBOT group mice displayed enhanced motor activity in the open arm and exhibited fewer anxiety-related behaviors. In the three-chambered social approach test, the HBOT group mice made more approaches to the wire cup containing an acquaintance mouse than control group mice in the sociability test and made more approaches to the wire cup containing a stranger mouse than control group mice in the social novelty preference test. The results suggested that HBOT group mice showed increased levels of social interaction and decreased "social anxiety" than the control group to partner mice in this test. Our findings indicated that HBOT resulted in altered anxiety and social behavior in Fmr1 knockout mice and could possibly be used as a treatment for FXS.

Evaluation of the Normal Airway Morphology Using Optical Coherence Tomography.

BACKGROUND: The anatomic location of small airways, the distribution of airway cartilage, and their correlation with ageing have not been well elucidated. The objective of this article was to explore the morphologic characteristics of small airways in vivo, and how airway structural changes correlate with age using endobronchial optical coherence tomography (EB-OCT). METHODS: We recruited 112 subjects with peripheral pulmonary nodules. Participants underwent CT scan, spirometry, and EB-OCT measurements. We measured the airway internal diameter, the inner area (Ai), the airway wall area percentage (Aw%), and the thickness of airway cartilage. EB-OCT airway structural characteristics at different age intervals were analyzed, and the association between airway morphology and age was evaluated. RESULTS: Of the small airways, 47.3% originated from the seventh generation of bronchi. Cartilage was uniformly present in the third to sixth generation of bronchi, despite a decreasing proportion of cartilage from the seventh to ninth generation of bronchi (92.4%, 54.5%, and 26.8%, respectively). The thickness of airway cartilage progressively decreased with older age. In subjects 40 to 54 years of age, Ai from the third to sixth generation correlated positively with age (r = 0.577, P < .001). Both Ai from the third to sixth generation and Ai from the seventh to ninth generation correlated negatively with age in subjects 55 to 69 years of age (r = -0.374, P = .021 and r = -0.410, P = .011). Aw% from the third to sixth generation and Aw% from the seventh to ninth generation did not correlate significantly with age. CONCLUSIONS: Small airways are mainly located at the seventh generation, where cartilaginous structures are present despite reduced distribution in more distal airways, and the thickness decreased in older age. Reduction in luminal area of medium-to-small airways might be the morphologic changes associated with ageing (ie, > 55 years of age).