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Background: An association between dietary habits and lung disease has been demonstrated in previous studies. Employing Mendelian randomization, we aimed to explore how different dietary intakes relate to pneumothorax, shedding light on the interplay among gut flora, the lung-gut axis, and pneumothorax., Methods: Employing both two-sample and multi-sample Mendelian randomization (MR) analyses, we investigated 24 dietary intake variables to establish a strong association with pneumothorax. Causal inferences were drawn using the inverse variance weighted (IVW) method. To fortify our findings, we employed a diverse array of methodologies, including Weighted Median Estimator (WME), Weighted Mode, Simple Mode, Mendelian Randomization Pleiotropy Residual Sum and Outlier (MR-PRESSO), MR-Egger regression, and LASSO., Results: Our analysis identified genetic variants reliably predicting dietary intakes, meeting stringent criteria (p < 5 × 10 -8 ) and demonstrating independence (r 2  < 0.001). Causal-effect estimates derived from the IVW model unveiled a statistically significant association, indicating a causal correlation between pneumothorax and three dietary intakes. Specifically, heightened consumption of fresh fruit (OR = 0.196, 95%CI: 0.063-0.606, p = 0.004) and dried fruit (OR = 0.323, 95%CI: 0.114-0.911, p = 0.032) correlated with reduced pneumothorax risk, while increased processed meat intake (OR = 2.705, 95%CI: 1.026-7.128, p = 0.044) showed a positive correlation., Conclusion: In summary, our MR analysis yields robust evidence supporting a causal correlation between dietary elements and pneumothorax. This study significantly advances our comprehension of pneumothorax risk factors, protective agents, and the intricate mechanisms of the lung-gut axis., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Published by Elsevier Ltd.)

Horticultural crops comprising fruit, vegetable, ornamental, beverage, medicinal and aromatic plants play essential roles in food security and human health, as well as landscaping. With the advances of sequencing technologies, genomes for hundreds of horticultural crops have been deciphered in recent years, providing a basis for understanding gene functions and regulatory networks and for the improvement of horticultural crops. However, these valuable genomic data are scattered in warehouses with various complex searching and displaying strategies, which increases learning and usage costs and makes comparative and functional genomic analyses across different horticultural crops very challenging. To this end, we have developed a lightweight universal search engine, HortGenome Search Engine (HSE; http://hort.moilab.net), which allows for the querying of genes, functional annotations, protein domains, homologs, and other gene-related functional information of more than 500 horticultural crops. In addition, four commonly used tools, including 'BLAST', 'Batch Query', 'Enrichment analysis', and 'Synteny Viewer' have been developed for efficient mining and analysis of these genomic data., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Background: Esophageal carcinoma (ESCA) is one of the most prevalent malignant tumors in the world. The prognosis of patients has significantly improved with the development of surgery, targeted therapy and immunotherapy. But the 5-year survival rate of ESCA patients is still incredibly low. Cuproptosis is a type of mitochondrial cell death induced by copper. It is unclear how cuproptosis-related lncRNAs (CRLs) affect ESCA prognosis. Methods: In this study, we obtained the clinical data of ESCA patients, the transcriptome data from TCGA and identified CRLs by co-expression analysis, lasso regression, and cox regression analysis, to build a prognostic model. Then we validated the prognostic model using the Kaplan-Meier curve, cox regression analysis, and ROC, to create a nomogram based on risk score to forecast the prognosis of ESCA. Next, the immune escape of the CRLs was examined using the TIDE algorithm to assess its sensitivity to possible ESCA medications. Results: To predict the prognosis of ESCA patients, we created a predictive model using 6 CRLs (AC034199.1, AC125437.1, AC107032.2, CTBP1-DT, AL024508.1, and AC008610.1), validated by the Kaplan-Meier and ROC curves. The model has a higher diagnostic value compared to other clinical features. The 6 CRLs expressed high in TCGA and ESCA specimens. Enrichment analysis revealed CRLs largely contributed to the interaction between cytokines and their receptors as well as complement coagulation cascades. The immunity escape analysis demonstrated that immunotherapy had a worse effect in the low-risk group than in the high-risk group. Additionally, we screened out potential antineoplastic drugs according to the results of the immunoassay and obtained 5 drugs, including CP-466722, crizotinib, MS-275, KIN001-135, and CP-466722. Conclusion: The prognosis of patients with ESCA can be correctly predicted by the 6 CRLs chosen from this investigation. It lays the groundwork for more investigation into the ESCA mechanism and the identification of novel therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zong, Li, Ning, Zhao, Wang and Wang.)

Gas sensors based on organic molecules are attractive for their tailored molecular structures and controllable functions, but weak interfacial adhesion between sensing materials and supporting substrates has severely hampered their practical applications, particularly in harsh environments. Here, inspired by the combined anchoring-recognizing feature of natural olfactory systems, an adhesive-integrated-agent strategy to integrate the adhesive unit (poly(dimethylsiloxane)) with the sensing unit (organoplatinum(II)) into one chemistry entity, creating robust and sensitive nanobelt array gas sensors is demonstrated. Systematic theoretical and experimental studies reveal that incorporating adhesive units significantly enhances the interfacial adhesion of the array sensors and gas-bridged super-exchange electronic couplings of sensing units ensure their efficient gas-sensing performance. The high shear strength of ≈7.05 × 10 6 N m -2 allows these arrays to resist aggressive ultrasonication, tape peeling, or repeated bending without compromising their sensing performance. This molecular engineering strategy opens a new guideline to develop robust gas sensors., (© 2021 Wiley-VCH GmbH.)

Background: Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD)., Methods: The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models., Results: ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis., Conclusions: ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD.

As diabetic macroangiopathy is becoming increasingly prevalent, it is urgent to explore preventive and therapeutic drugs and study the mechanism. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ)for five consecutive days. Diabetic mice were divided into diabetic and allicin groups. After sacrifice, frozen aortic root sections were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2) and inflammation cytokine-tumor necrosis factor α (TNF-α), and the remaining aortic tissues were analyzed by Western blot for the expression of proinflammation genes. In vitro, Nrf2 and inflammatory relative protein expression levels in Human Umbilical Vein Endothelial Cells (HUVECs) were examined. HUVECs proliferation and apoptosis were measured. TNF-α expression was increased in diabetic group compared to that in control group; this effect was alleviated in allicin-treated mice. Inflammation relative protein expression of Vascular Cell Adhesion Molecule 1(VCAM-1), Matrix metalloproteinase 2 (MMP-2), Inducible Nitric Oxide Synthase (iNOS), and monocyte chemotactic protein 1 (MCP-1) was higher in the diabetic group than in the control group; however, allicin treatment inhibited these diabetes-induced increase. In vitro, allicin treatment reversed the hyperglycemia-induced reduction in proliferation, and decreased the apoptosis induced by high glucose. Inflammation relative protein expression was consistent with that in vivo. Additionally, the expression of nuclear factor kappa-B (NF-κB)and Nrf2 was increased in both DM mice and HUVECs; allicin treatment induced a significant reduction in NF-κB level and improvement in Nrf2 level. Allicin alleviates inflammation caused by diabetic macroangiopathy, and the mechanism may occur via increasing Nrf2 and decreasing NF-κB., Competing Interests: Declaration of competing interest No conflicts of interest are declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Two novel heptanornemoralisin-type diterpenoids nornemoralisins A (1) and B (2), together with two known compounds nemoralisin (3) and nemoralisin A (4), were isolated from the stem bark and leaves of Aphanamixis polystachya (Wall.) R. Parker. Their structures were established through comprehensive analyses of NMR spectroscopic data and high resolution mass spectrometric (HR-ESI-MS) data. The absolute configurations of carbon stereocenters were elucidated by circular dichroism (CD) analyses. The four compounds were tested for their potential cytotoxic effects against ACHN, HeLa, SMMC-7721, and MCF-7 cell lines. Nornemoralisins A (1) and B (2) exhibited significant cytotoxicity on ACHN with an IC 50 value of 13.9 ± 0.8 and 10.3 ± 0.4 μM, respectively, and other compounds failed to reveal obvious cytotoxicity on the tested cell lines, compared to positive control vinblastine (IC 50 , 28.0 ± 0.9 μM)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Treatment of chronic hepatitis B with pegylated-interferon-α-2a (PegIFNα) in pediatric patients can lead to a higher rate of hepatitis B virus (HBV) surface antigen (HBsAg) loss than in adults. However, the mechanism of underlying immune response is not clear. The aim of this study was to explore innate and adaptive immunity, especially HBV-specific T cell responses in hepatitis B e antigen (HBeAg)-positive pediatric patients, who have experienced HBsAg loss. Isolated lymphocytes of 20 HBeAg-positive pediatric patients were collected every 12 weeks until treatment was stopped. The phenotype of T/natural killer (NK) cells and function of HBV-specific T cells were analyzed by flow cytometry. The frequency of CD69 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expressed on T cells and TRAIL on CD56 hi NK cells in patients with HBsAg loss was remarkably higher compared with nonresponse patients. Furthermore, in vitro peptide stimulation of HBV-specific T cell responses was increased in patients with HBsAg loss when compared with week 0 and 48, and correlated with decline of viral load. The PegIFNα therapy in pediatric patients triggered T/NK cell activation and HBV-specific T cell responses, thereby contributing to successful viral control.

Polymorphism of organic semiconducting materials exerts critical effects on their physical properties such as optical absorption, emission and electrical conductivity, and provides an excellent platform for investigating structure-property relations. It is, however, challenging to efficiently tune the polymorphism of conjugated polymers in aggregated, semi-crystalline phases due to their conformational freedom and anisotropic nature. Here, two distinctly different semi-crystalline polymorphs (β 1 and β 2 ) of a low-bandgap diketopyrrolopyrrole polymer are formed through controlling the solvent quality, as evidenced by spectroscopic, structural, thermal and charge transport studies. Compared to β 1 , the β 2 polymorph exhibits a lower optical band gap, an enhanced photoluminescence, a reduced π-stacking distance, a higher hole mobility in field-effect transistors and improved photocurrent generation in polymer solar cells. The β 1 and β 2 polymorphs provide insights into the control of polymer self-organization for plastic electronics and hold potential for developing programmable ink formulations for next-generation electronic devices.

Objective: Under 50% of type 2 diabetic patients achieve the recommended glycemic control. One barrier to glycemic control is patients' cost-related nonadherence to medications. We hypothesize gender differences in medication nonadherence due to costs among diabetic patients., Methods: US National Health Interview Survey (2011 to 2014) data yielded 5260 males and 6188 females with diabetes for over a year. We applied 2 analytic methods (A and B below) across multiple outcome measures (1 to 4) of medication nonadherence due to cost. The key independent variable was participant's gender., Results: Across methods and measure, females consistently report significantly higher rates of medication nonadherence due to costs. Pearson's χ 2 showed that female patients were more likely to (1) skip medication (13.5%-10.2%; P < .001), take less than prescribed medication (13.9%-10.5%; P < .001), delay filling prescriptions (16.8%-12.5%; P < .001), and ask doctors to prescribe lower-cost alternative medications (31.8%-28.0%; P < .001). Controlling for covariates, logistic regression models found females more likely to skip medication (OR, 1.30; 95% CI, 1.09-1.55), take less than prescribed medication (OR, 1.26; 95%, CI, 1.06-1.50), delay filling prescriptions, (OR, 1.29; 95% CI, 1.11-1.50), and request lower-cost medication (OR, 1.17; 95% CI, 1.04-1.32). Our results report other factors that influence medication adherence, including socioeconomic and health status variables., Conclusions: A significant gender-based disparity exists on cost-related nonadherence of medication among diabetic patients. Health care providers and policy-makers should pay close attention to find ways to address cost-related nonadherence of medication among patients with chronic illness, especially among female patients., Competing Interests: Conflict of interest: none declared., (© Copyright 2018 by the American Board of Family Medicine.)

Objectives: Lower serum uric acid (UA) levels are considered to be related to the risk to develop many neurodegenerative disorders. However, the association between serum UA level and multiple system atrophy (MSA) remains controversial. The aim of this meta-analysis was to evaluate the relationship between serum UA level and MSA., Patients and Methods: PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched for eligible studies. Standardized mean difference (SMD) and 95% confidence intervals (95% CI) were calculated in a fixed-effects model or a random-effects model when appropriate. Subgroup analyses were carried out based on gender. A total of 6 eligible studies involving 547 MSA patients and 637 healthy individuals were identified., Results: Meta-analysis results revealed that individuals with MSA had lower sera levels of UA as compared with healthy controls (pooled SMD is -0.51, 95%CI: -0.88 to -0.14; p = 0.006). The subgroup analysis to detect sex differences showed that the pooled SMD was -0.61 (95% CI: -0.82 to -0.40; p < 0.0001) for males and -0.22 (95% CI: -0.55 to 0.10; p = 0.18) for females compared with healthy controls., Conclusion: Our meta-analysis revealed that lower serum level of UA is associated with an increased risk of MSA and the relationship is significant in men but not in women., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The correlation between hepatitis B surface antigen (HBsAg) seroconversion and the characteristics of HBV quasispecies (QS) before and during pegylated interferon-α-2a (PEG-IFN-α-2a) treatment in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) children has not yet been reported., Methods: 35 patients, including 18 HBsAg seroconverters (SS) and 17 non-seroconverters (SN), were enrolled. Serum samples were collected before treatment and at weeks 12 and 24 of treatment. Sequences within the basal core promoter/pre-core (BCP/PC) and S/reverse transcriptase (S/RT) region were analysed by next-generation sequencing., Results: There was no significant difference in the baseline diversity of HBV QS (Shannon entropy [Sn]; Hamming distance [HD]) in either region between the two groups. The baseline mutations A1762T/G1764A, C1913A, and T2003A/G or C2004T were correlated with non-response to therapy (P=0.025, P=0.036, P=0.032, respectively). After 24 weeks of therapy, HBV diversity within the BCP/PC region in the SS group notably declined (Sn: P=0.002; HD: P=0.011), while that of the SN group was nearly unchanged. As for the S/RT region, 24 weeks of treatment made no significant difference on QS diversity in either group., Conclusions: Our data demonstrated that the baseline viral mutations and dynamic changes in HBV QS diversity within the BCP/PC region were closely related to HBsAg seroconversion in HBeAg-positive CHB children treated with PEG-IFN-α-2a.

Paeonol (Pae) is an herbal extract that has attracted extensive attention for its anti‑cancer effects demonstrated by a number of studies, which have predominantly demonstrated inhibition of cell proliferation and induction of apoptosis. The influence of Pae on cancer cell metastasis has been less widely reported. The present study aimed to investigate the under‑reported effects of Pae on the growth, invasion and migration of poorly differentiated BGC823 gastric cancer cells with strong invasive and metastatic abilities. The anti‑proliferative and pro‑apoptotic effects of Pae on BGC823 cells were verified by Cell Counting kit‑8 and Annexin V‑fluorescein isothiocyanate/propidium iodide assays. Cell scratch‑wound healing and Transwell methods were applied, and it was demonstrated that Pae could exert inhibitory activities on the invasion and migration of BGC823 cells. Furthermore, it was indicated by western blot analysis that Pae could downregulate the protein expression levels of matrix metalloproteinase (MMP)‑2 and ‑9 in a concentration‑dependent manner, which may support a novel potential mechanism accounting for its anti‑cancer effects on gastric cancer.

Shanxi, a traditional production area to produce genuine Astragali Radix of high quality, has experienced major changes in the pattern of resources. This area once accounted for half of Astragali Radix industry, but now only serves as the largest supply area of traditional wild Astragali Radix. Furthermore, the strategic position of Shanxi Astragali Radix industry will become more prominent and more important to economic and social development in face of the diversity of market demands, especially for the strong demands of high-end Astragali Radix. In addition, Astragalus industry involves the simultaneous development of the first, second and tertiary industries in many areas, and it is typical and representative in the traditional Chinese medicine industry development. However, the application and industrial development of Shanxi Astragali Radix have been restricted due to the problems such as blind promotion of transplanting cultivation technology, and lack of science and technology including efficacy investigation, safety evaluation, standardization and controllability studies. Therefore, we would analyze the production history, resource structure, the current situation and progress of industry development, scientific research foundation and existing problem in this paper, and put forward countermeasures for development and technical innovation in order to make Astragali Radix industry bigger and stronger through innovation-driven and make benefits for demos. This thought provides a reference for the exploratory development of other large varieties of Chinese medicinal materials., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Essential genes are those genes indispensable for the survival of any living cell. Bacterial essential genes constitute the cornerstones of synthetic biology and are often attractive targets in the development of antibiotics and vaccines. Because identification of essential genes with wet-lab ways often means expensive economic costs and tremendous labor, scientists changed to seek for alternative way of computational prediction. Aiming to help to solve this issue, our research group (CEFG: group of Computational, Comparative, Evolutionary and Functional Genomics, http://cefg.uestc.edu.cn) has constructed three online services to predict essential genes in bacterial genomes. These freely available tools are applicable for single gene sequences without annotated functions, single genes with definite names, and complete genomes of bacterial strains. To ensure reliable predictions, the investigated species should belong to the same family (for EGP) or phylum (for CEG&#95;Match and Geptop) with one of the reference species, respectively. As the pilot software for the issue, predicting accuracies of them have been assessed and compared with existing algorithms, and note that all of other published algorithms have not any formed online services. We hope these services at CEFG will help scientists and researchers in the field of essential genes.

The GC contents of 2670 prokaryotic genomes that belong to diverse phylogenetic lineages were analyzed in this paper. These genomes had GC contents that ranged from 13.5% to 74.9%. We analyzed the distance of base frequencies at the three codon positions, codon frequencies, and amino acid compositions across genomes with respect to the differences in the GC content of these prokaryotic species. We found that although the phylogenetic lineages were remote among some species, a similar genomic GC content forced them to adopt similar base usage patterns at the three codon positions, codon usage patterns, and amino acid usage patterns. Our work demonstrates that in prokaryotic genomes: a) base usage, codon usage, and amino acid usage change with GC content with a linear correlation; b) the distance of each usage has a linear correlation with the GC content difference; and c) GC content is more essential than phylogenetic lineage in determining base usage, codon usage, and amino acid usage. This work is exceptional in that we adopted intuitively graphic methods for all analyses, and we used these analyses to examine as many as 2670 prokaryotes. We hope that this work is helpful for understanding common features in the organization of microbial genomes.

Mutation is the ultimate source of genetic variation and evolution. Mutation accumulation (MA) experiments are an alternative approach to study de novo mutation events directly. We have constructed a resource of Spontaneous Mutation Accumulation Lines (SMAL; http://cefg.uestc.edu.cn/smal), which contains all the current publicly available MA lines identified by high-throughput sequencing. We have relocated and mapped the mutations based on the most recent genome annotations. A total of 5,608 single base mutations and 540 other mutations were obtained and are recorded in the current version of the SMAL database. The integrated data in SMAL provide detailed information that can be used in new theoretical analyses. We believe that the SMAL resource will help researchers better understand the processes of genetic variation and the incidence of disease.

Integrative genomics predictors, which score highly in predicting bacterial essential genes, would be unfeasible in most species because the data sources are limited. We developed a universal approach and tool designated Geptop, based on orthology and phylogeny, to offer gene essentiality annotations. In a series of tests, our Geptop method yielded higher area under curve (AUC) scores in the receiver operating curves than the integrative approaches. In the ten-fold cross-validations among randomly upset samples, Geptop yielded an AUC of 0.918, and in the cross-organism predictions for 19 organisms Geptop yielded AUC scores between 0.569 and 0.959. A test applied to the very recently determined essential gene dataset from the Porphyromonas gingivalis, which belongs to a phylum different with all of the above 19 bacterial genomes, gave an AUC of 0.77. Therefore, Geptop can be applied to any bacterial species whose genome has been sequenced. Compared with the essential genes uniquely identified by the lethal screening, the essential genes predicted only by Gepop are associated with more protein-protein interactions, especially in the three bacteria with lower AUC scores (<0.7). This may further illustrate the reliability and feasibility of our method in some sense. The web server and standalone version of Geptop are available at http://cefg.uestc.edu.cn/geptop/ free of charge. The tool has been run on 968 bacterial genomes and the results are accessible at the website.

Most bacterial genomes have one single chromosome. The species Burkholderia cenocepacia, a Gram-negative β-proteobacterium, is one of the exceptions. Genomes of four strains of the species have been sequenced and each has three circular chromosomes. In the genus Burkholderia, there are another seven sequenced strains that have three chromosomes. In this paper, the numbers of essential genes and tRNA genes among the 11 strains of the genus Burkholderia are compared. Interestingly, it is found that the shortest chromosome of B. cenocepacia AU-1054 has much (over three times) more essential genes and tRNA genes than the corresponding chromosomes in the other 10 strains. However, no significant difference has been found on the two longer chromosomes among the 11 strains. Non-homologous chromosomal translocation between chromosomes I and III in the species B. cenocepacia is found to be responsible for the unusual distribution of essential genes. The present work may contribute to the understanding of how the secondary chromosomes of multipartite bacterial genomes originate and evolve. The computer program, DEG&#95;match, for comparatively identifying essential genes in any annotated bacterial genomes is freely available at http://cobi.uestc.edu.cn/resource/AU1054/., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the effect of Shengmai San (SMS), a traditional Chinese herbal medicine, on heatstroke-induced circulatory shock and oxidative damage in the brain in rats. Anesthetized rats were exposed to a high ambient temperature (43 degrees C) to induce heatstroke. After the onset of heatstroke, the values of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of O(2) were all significantly lower than those in normothermic controls. However, the values of intracranial pressure, brain and colonic temperatures, and brain levels of free radicals, lipid peroxidation, and cellular ischemia and damage markers were all greater in heatstroke rats compared with those of normothermic controls. Pretreatment or post-treatment with SMS significantly reduced the hypotension, intracranial hypertension, cerebral hypoperfusion and hypoxia and increased levels of ischemia and damage markers in the brain during heatstroke. The protective effects exerted by SMS pretreatment is superior to those of SMS post-treatment. The results demonstrate that SMS is effective for prevention and repair of circulatory shock and ischemic and oxidative damage in the brain during heatstroke.

Background: Monocytes, macrophages, and antigen-presenting cells (APCs) are key effectors of both innate and acquired immune responses. Such cells have been implicated in the pathogenesis of some inflammatory diseases. Differential gene expression in CD14-positive cells from patients with atomic dermatitis (AD) was studied using real-time quantitative RT-PCR to measure transcription levels of selected genes., Methods: PBMCs were prepared by Ficoll gradient separation from 30 AD patients (the anti-mite-specific IgE RAST score: 0.75 to >100 UA/ml) and 10 healthy adult individuals (the RAST score: <0.34-0.37 UA/ml) and CD14-positive cells were selected. A total of 64 genes was selected for study from groups of genes with different molecular function., Results: Genes involved in MHC class I antigen presentation, such as beta(2)-microglobulin, subunits of an immunoproteasome and ATP-binding cassette transporter TAP2 were expressed at higher levels in the AD patients than in the healthy controls. The genes for Toll-like receptors, CD36 and IFNgamma receptor were also upregulated in the AD patients. These genes are involved in MHC class I antigen presentation, recognition of bacterial pathogens and apoptotic cells., Conclusions: The upregulation of genes suggests that circulating monocytes in AD patients may be primed to differentiate into effector cells by conditions associated with AD. The upregulation of genes may prove to be a useful marker for AD., (Copyright 2003 S. Karger AG, Basel)

Background: Analysis of genes that are differentially expressed in patients with atopic dermatitis (AD) and normal individuals will provide important information on the underlying molecular pathogenetic mechanisms of AD., Methods: Transcript of freshly isolated peripheral blood T cells from 59 individuals were analyzed with a fluorescent differential display (FDD) method. Ninety-two differentially expressed genes were identified in this manner. Additionally, real-time quantitative RT-PCR was employed to investigate the expression of the FDD-selected genes and also genes related to T cell function., Results: A number of genes, including CC chemokine receptor 4, T cell-specific tyrosine kinase (Emt/Itk), integrin beta1, integrin alpha6, IQGAP1 and MAR/SAR DNA-binding protein (SATB1), were shown to be more highly expressed in patients with moderate and/or severe AD than in controls or patients with mild AD. Because the products of these upregulated genes influence chemotaxis, adhesion, migration and Th2 polarization, it is suggested that in more severe AD, circulating T cells may function differently in this regard. Several other genes, the role of which in T cell function is currently unknown, were also found to be differentially expressed in AD. These included the heat shock protein 40 and vasopressin-activated calcium-mobilizing receptor 1., Conclusion: The upregulated genes identified in this work may serve as useful markers for moderate to severe AD as opposed to normal or mild AD and also as markers indicating progression to more severe AD. Further functional characterization will provide a better understanding of the pathophysiology of circulating T cells in AD., (Copyright 2002 S. Karger AG, Basel)

Bronchial asthma is a complex disease characterized by airway inflammation involving interleukin (IL)-4 and IL-13. We have applied microarray analyses to human bronchial epithelial cultures to probe for genes regulated by these cytokines and have identified a subset of disease-relevant genes by comparison with cDNA libraries derived from normal and asthmatic bronchial biopsies. Squamous cell carcinoma antigen-1 (SCCA1) and SCCA2, the cysteine and serine protease inhibitors, respectively, showed the highest expression by IL-4 and IL-13, and particularly, SCCA1 was significantly increased in the asthmatic cDNA library. STAT6 was shown to be involved in expression of SCCA1 and SCCA2 in vitro. Furthermore, serum levels of SCCA were also elevated in asthmatic patients. Taken together, it was supposed that SCCA may play some role in the pathogenesis of bronchia asthma, and measuring its serum level may be relevant for diagnosing or monitoring the status of bronchial asthma. In a complex disorder such as asthma, this combination of in vitro and in vivo genomic approaches is a powerful discriminatory method enabling identification of novel disease-related genes and their mechanisms of regulation.

Cathepsin C/dipeptidyl-peptidase I is a papain-like lysosomal cysteine proteinase implicated in the processing of various proenzymes to their active forms. In this study, we identified an alternative splicing variant of cathepsin C in both human and mouse species for the first time. The variant messenger RNA (mRNA) encodes 137 amino acids corresponding to the first and second exons, followed by additional 31 amino acids. The two newly recognized exons are located in the former intron 2. The variant mRNA is distributed ubiquitously, but predominantly in kidney, placenta, and lymph nodes. Furthermore, both interleukin 4 (IL-4) and IL-13, but not a range of cytokines induce expression of the variant in bronchial epithelial cells. These results indicate that the variant may play a role in regulating the biological activities of cathepsin C, involved in the pathogenesis of bronchial asthma.

To determine the genes responsible for mediating the effects of glucocorticoids (GCs) on leukemic cells, transcriptional changes in GC-sensitive human pre-B leukemia 697 cells during GC-induced apoptosis were monitored using oligonucleotide microarrays. To circumvent the challenge of recovering mRNAs from dying cells, we compared the pattern of gene expression with that of 697 cells protected from apoptosis by transfection with bcl-2. Of the 12,000 genes examined for their response to GC, 93 genes were induced and 28 genes were repressed, many of which are known to be implicated in signal transduction, growth arrest, and transcription. These included the signal transduction-related genes encoding SOCS1, SOCS2, FKBP51, DSCR1, p56lck, and four protein kinase phosphatases. Growth arrest-related genes encoding p19(INK4d) and several Myc inhibitors were induced in response to the GC treatment. Anti-proliferative- or apoptosis-related genes encoding BTG1, BTG2, and granzyme A were also found to be transcriptionally up-regulated by GC. In addition, the regulation of genes encoding the glucocorticoid receptor and steroid receptor coactivator-1 suggested autoregulation of a GC-mediated signaling pathway., ((c) 2002 Elsevier Science (USA).)