Brain Transcriptome Analysis Reveals Exercise Improves Methamphetamine‐Induced Impairments in Mouse Learning and Memory Abilities

Objective Silt diaphragm is the most important and bioactive membrane structure in the filtration barrier of kidney, and the root cause of proteinuria is the structural and functional abnormalities of Silt diaphragm. So far, there is little literature on the changes of silt diaphragm caused by overtraining. This research establishes a model of rats with exercise-induced proteinuria with long-term intensitive treadmill exercise, and it simulates the progressive-load training in the cycle of athletes. Histological and ultrastructural changes of kidney immediately and 24 h after exercise are observed, and it aims to analyze the change law of silt diaphragm during the occurrence of persistent proteinuria.
 Methods this study selects 36 Sprague-Dawley rats, which are randomly divided into 3 groups: a control group (group C, 12), a group drawn immediately after exercise(group EI, 12), a group drawn 24 h after exercise(group EA, 12). Group C does not train. The rats in group EI and EA train on the treadmill with an increasing load for 6 weeks(10% grade, 6 d/w): in the first week, the rats run for 10 min at 10 m/min. Starting from the second week, the running speed increases by 5m/min/w, and the training time increases by 30min/w. In the last week the rats run to exhaustion if they could not maintain the target intensity. Record the exhausting time of rats, then group EI and group EA are respectively drawn immediately and 24 hours after exercise. Observe the histological changes of renal glomerulus by optical microscope, and the ultrastructure of silt diaphragm by TEM. Detect urine total protein by BCA, serum and urine creatinine by Jaffe, serum testosterone and corticosterone by radioimmunoassay, serum urea by two-point dynamic method, and the expression of Nephrin by western-blot.
 Results The rats in group EI and EA gradually lose weight at the first weekend of training, and their weight drop significantly from the third weekend to the end, it shows a significant difference compared with group C(p<0.01). There is no significant difference between the exercise group. Glomerular morphology, group C: The structure of glomerulus is compact, the boundary between vascular sphere and the wall of capsule is obvious, and the distribution of erythrocytes in vessels is regular; Group EI: The thickness of glomerulus membrane is uneven, the structure of the podocyte is incomplete, part of the foot process is fused, and SD is discontinuous; Group EA: Part of the glomerular endodermis is abnormal, part of the foot process is fused, detached, and unevenly distributed, and SD is discontinuous. Total protein/ creatinine in urine of rats 30 min and 24 h after exercise is significantly higher than that of group C(p<0.01), and group EA is slightly retuned and lower than group EI(p<0.05). Compared with group C, Serum Testosterone/Corticosterone of rats in group EI and EA is significantly decreased, and there is a significant difference (p<0.01). However, there is a significant decrease in EA group but it is still significantly lower than group EI(p<0.01). Serum corticosterone is significanty decreased in group EI and EA, and there is a significant difference (p<0.01), while group EA is significantly decreased but still significantly lower than that in group EI(p<0.01). Serum urea and espression of Nephrin are significantly decreased in group EI and EA(p<0.01), but there are no significant difference between group EI and EA(p>0.05).
 Conclusions The rats suffer from overtraining syndrome caused by intensitive training, and with persistent proteinuria, their renal function is disordered and cannot be effectively recovered after 24 h rest. Meanwhile, the renal morphology and ultrastructure of silt diaphragm in rats undergo "pathogenical-like" changes, which do not significantly decrease with the extension of recovery time. It is revealed that the injury of renal structure and ultrastructure of silt diaphragm caused by overtraining are the structural basis of continuous exercise-induced proteinuria.

Genome-wide analysis in PC6 electroacupuncture to ameliorate carfilzomib-induced cardiotoxicity in mice

Simple SummaryThe molecular mechanisms of skin pigmentation in Andrias davidianus are not clear. In this study, we identified two albino individuals and found that Andrias davidianus had distinct regulatory mechanisms of skin pigmentation that differed from other vertebrates. The key signaling pathway and transcription factors related to melanin synthesis in other vertebrates did not play a significant role in Andrias davidianus. MITF mRNA in Andrias davidianus had a unique splicing form that was not reported in other vertebrates and a unique mutation existed in the SLC24A5 gene in albino Andrias davidianus. The results contributed to understanding the molecular mechanism of skin pigmentation in Andrias davidianus and accelerating the acquisition process of Andrias davidianus species with specific body colors by genetic means, which will help to enrich the aquaculture market of Andrias davidianus.The Chinese giant salamander (Andrias davidianus) has been increasingly popular in the aquaculture market in China in recent years. In the breeding process of Andrias davidianus, we found that some albino individuals were extremely rare and could not be inherited stably, which severely limits their commercialization in the aquaculture market. In this study, we performed transcriptome and small RNA (sRNA) sequencing analyses in the skin samples of wild-type (WT) and albino (AL) Andrias davidianus. In total, among 5517 differentially expressed genes (DEGs), 2911 DEGs were down-regulated in AL, including almost all the key genes involved in melanin formation. A total of 25 miRNAs were differentially expressed in AL compared to WT, of which 17 were up-regulated. Through the integrated analysis, no intersection was found between the target genes of the differentially expressed miRNAs and the key genes for melanin formation. Gene Ontology (GO) and KEGG pathway analyses on DEGs showed that these genes involved multiple processes relevant to melanin synthesis and the key signal pathway MAPK. Interestingly, the transcription factors SOX10 and PAX3 and the Wnt signaling pathway that play a key role in other species were not included, while the other two transcription factors in the SOX family, SOX21 and SOX7, were included. After analyzing the key genes for melanin formation, it was interesting to note an alternative splicing form of the MITF in WT and a critical mutation of the SLC24A5 gene in AL, which might be the main reason for the skin color change of Andrias davidianus. The results contributed to understanding the molecular mechanism of skin pigmentation in Andrias davidianus and accelerating the acquisition process of individuals with specific body colors by genetic means.

A novel ingredients recipe derived from Shugan-Hewei Formula targeting chemical carcinogenesis-ROS signaling pathway treated gastroesophageal reflux disease.

Simple SummarySariNPV is one of the main pathogens of Samia ricini and its infection of Samia ricini sericulture has caused significant economic losses to society. In this study, we aim to reveal the molecular mechanism of pathogen–host interactions in SariNPV-infected S. ricini through transcriptomic and proteomic analyses. Using RNA-sequencing and iTRAQ, we mapped the differentially expressed genes (DEGs) and proteins (DEPs) that are involved in the immune responses of S. ricini upon virus invasion. Based on our analyses, we identified specific DEGs and DEPs that are involved in various essential biological signaling pathways and immune-related pathways upon SariNPV invasion. These DEGs and DEPs play an important role in triggering host immune responses to pathogens. Our study provides molecular insights into host immune responses regarding pathogen invasion, in particular, the immune response mechanism and network of S. ricini in response to SariNPV infection.Samia ricini nucleopolyhedrovirus (SariNPV) is one of the main pathogens of S. ricini sericulture and its infection causes severe impacts on economic sericulture development. To explore and reveal the molecular mechanisms of S. ricini in response to SariNPV infection, we employed RNA sequencing (RNA-seq), adopting isobaric tags for relative and absolute quantitation (iTRAQ), and carried out combination analysis of the obtained differentially expressed genes (DEGs) and proteins (DEPs). Through transcriptome sequencing, a total of 2535 DEGs were detected, and with iTRAQ, 434 DEPs with significant expression difference were identified. Through correlation analysis, we found that the expression trends of 116 differentially expressed proteins were the same as those of differentially expressed genes (including 106 up-regulated and 10 down-regulated). Twenty-five key differentially expressed genes (proteins) involved in several signaling and immune related pathways (mainly involving Toll, Imd, Jak-STAT and Wnt signaling pathways, as well as other immune related pathways) were screened through real-time quantitative PCR. Our results, not only provide insights into the pathogenic mechanism of SariNPV infection in ricin silkworm and the immune response mechanism within the host, but also provide a significant contribution for identifying and preventing diseases caused by SariNPV.

BackgroundEgg production is one of the most important economic traits in the poultry industry. The hypothalamic-pituitary–gonadal (HPG) axis plays an essential role in regulating reproductive activities. However, the key genes and regulatory pathways within the HPG axis dominating egg production performance remain largely unknown in ducks.ResultsIn this study, we compared the transcriptomic profiles of the HPG-related tissues between ducks with high egg production (HEP) and low egg production (LEP) to reveal candidate genes and regulatory pathways dominating egg production. We identified 543, 759, 670, and 181 differentially expressed genes (DEGs) in the hypothalamus, pituitary, ovary stroma, and F5 follicle membrane, respectively. Gene Ontology (GO) analysis revealed that DEGs from four HPG axis-related tissues were enriched in the "cellular component" category. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the neuroactive ligand-receptor interaction pathway was significantly enriched based on DEGs commonly identified in all four HPG axis-related tissues. Gene expression profiles and Protein–Protein Interaction (PPI) network were performed to show the regulatory relationships of the DEGs identified. Five DEGs encoding secreted proteins in the hypothalamus and pituitary have interaction with DEGs encoding targeted proteins in the ovary stroma and F5 follicle membrane, implying that they were these DEGs might play similar roles in the regulation of egg production.ConclusionsOur results revealed that neuroactive ligand-receptor interaction pathway and five key genes(VEGFC, SPARC, BMP2, THBS1, and ADAMTS15) were identified as the key signaling pathways and candidate genes within the HPG axis responsible for different egg production performance between HEP and LEP. This is the first study comparing the transcriptomic profiles of all HPG axis-related tissues in HEP and LEP using RNA-seq in ducks to the best of our knowledge. These data are helpful to enrich our understanding of the classical HPG axis regulating the egg production performance and identify candidate genes that can be used for genetic selection in ducks.

BackgroundThe breeder rooster has played a pivotal role in poultry production by providing high-quality semen. Typically, fertility peaks between 30 and 40 weeks of age and then declines rapidly from 45 to 55 weeks of age. Research into improving fertility in aging roosters is essential to extend their productive life. While progress has been made, enhancing fertility in aging roosters remains a significant challenge.MethodsTo identify the genes related to promoting sperm remodeling in aged Houdan roosters, we combined changes in testis and semen quality with transcriptome sequencing (RNA-seq) to analyze the synchrony of semen quality and testis development. In this study, 350-day-old Houdan breeder roosters were selected for RNA-seq analysis in testis tissues from induced molting roosters (D group) and non-induced molting roosters (47DG group). All analyses of differentially expressed genes (DEGs) and functional enrichment were performed. Finally, we selected six DEGs to verify the accuracy of the sequencing by qPCR.ResultsCompared with the 47DG group, sperm motility (P < 0.05), sperm density (P < 0.01), and testis weight (P < 0.05) were significantly increased in roosters in the D group. Further RNA-seq analysis of the testis between the D group and 47DG group identified 61 DEGs, with 21 up-regulated and 40 down-regulated. Functional enrichment analysis showed that the DEGs were primarily enriched in the cytokine-cytokine receptor interaction, Wnt signaling pathway, MAPK signaling pathway, TGF-β signaling pathway, and focal adhesion pathway. The qRT-PCR results showed that the expression trend of these genes was consistent with the sequencing results. WNT5A, FGFR3, AGTR2, TGFβ2, ROMO1, and SLC26A7 may play a role in testis development and spermatogenesis. This study provides fundamental data to enhance the reproductive value of aging roosters.

Background: Prediction of biochemical recurrence (BCR) using standard measures to assign risk classification in prostate cancer (PCa) patients at diagnosis is not precise. While in some patients BCR may happen sooner than expected in others, it may take several years before it appears. It is then necessary to devise better tools to predict accurately BCR. Our goal was to identify differentially expressed genes (DEGs) in cases with and without BCR within the risk groups determined by D'Amico (defined by the clinical stage, initial PSA, and Gleason stage in biopsy). Methods: We ran RNA-seq analysis in 52 Hispanic PCa patients with early BCR (within 5 years after the surgery) and 57 with no BCR in the same period of time. The cases were classified as high, intermediate, or low according to the D'Amico classification. Analyses were done using the DESeq2 package. Genes with p value adjusted by False Discovery Rate (padj) less than 0.05 and fold change (FC) &amp;gt; 2 were considered statistically significant. Pathway analysis was performed in MetaCore. Results: We found 4,281 DEGs (padj &amp;lt; 0.05) associated with tumor tissues in the BCR cases (7 of those with a FC &amp;gt; 2). In contrast, 4,647 DEGs were associated with tumor tissues in cases without BCR (16 with FC &amp;gt; 2). Of these genes, nine (CHRM3, CLDN8, ERG, GDF15, LUZP2, OR51E1, PTPRT, TRGC1, TPO) were exclusively found in cases without BCR, and one, ONECUT2, was exclusive for tissues with BCR. All these genes, except TRGC1, have been associated before with PCa: the Cholinergic Receptor Muscarinic 3 (CHRM3) and the Olfactory Receptor Family 51 Subfamily E Member 1 (OR51E1) have a growth-promoting role; Claudin 8 (CLDN8) is transcriptionally activated by the androgen receptor to promote progression of PCa; ETS Trancription Factor (ERG) participates in chromosomal translocation in PCa and is involved in cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis; Growth Differentiation Factor 15 (GDF15) was reported to be part of a circulating tumor cell profile in castration-resistant PCa with high levels associated with poor survival; Leucine Zipper Protein 2 (LUZP2) seems to contribute to enzalutamide resistance in castration-resistant PCa; Protein Tyrosine Phosphatase Receptor Type T (PTPRT) was recently found overexpressed in localized PCa; Thyroid Peroxidase (TPO) promotes resistance to cell death and to chemotherapy in PCa; and ONECUT2 has been associated with different types of cancer and recently with prostate cancer. Pathway analysis of DEGs identified IL-6 signaling pathway via MEK/ERK and PI3K/AKT cascades; PPAR pathway activation (which involves transcription factors belonging to the nuclear hormone receptor superfamily and activated by fatty acids); and Adenosine A2B receptor signaling, which indirectly activates c-Myc, Cyclin D1, PI3K/AKT, and IL-6 in patients with BCR. On the other hand, IL-15 signaling via JAK-STAT cascade, WNT signaling pathway, G-protein signaling, apoptosis, and survival through NGF/TrkA PI3K-mediating signaling and mTORC2 downstream signaling pathways were identified in the group without BCR. These differences show that DEGs in both groups, even though implicated in processes related with tumor development, are involved in specific pathways that can be associated with the grade of aggressiveness of the tumors, and also, under specific circumstances, lead to BCR. In addition, we found that DEGs can separate BCR from no BCR cases within each risk group, suggesting that a genomic signature with DEGs is a better predictor of BCR than the clinically assigned risk groups. Conclusions: Tumor biology and signaling pathways activated in cases with BCR are different from those in cases without BCR, showing that aggressiveness of tumors can be found at the moment of surgery and that biomarkers of prognosis can be identified at this point. Citation Format: Natalia Acosta, Jovanny Zabaleta, Rodolfo Varela, Jorge Mesa, Silvia Serrano, Jone Garay, Melody Baddoo, Cruz Nataly, Alba Lucía Combita, María Carolina Sanabria-Salas. Aggressiveness and tumor biology in prostate cancer patients with and without biochemical recurrence [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B69.

Coilia nasus is an anadromous fish that has been successfully domesticated in the last decade due to its high economic value. The fish exhibits a delayed ovary development during the reproductive season, despite breeding and selection for five to six offspring. The molecular mechanism of the delayed ovary development is still unknown, so the obstacles have not been removed in the large-scale breeding program. This study aims to investigate the key genes regulating ovarian development by comparing the transcriptomes of ovarian-stage IV and stage II brain/pituitary of Coilia nasus. Ovarian stages were validated by histological sections. A total of 75,097,641 and 66,735,592 high-quality reads were obtained from brain and pituitary transcriptomes, respectively, and alternatively spliced transcripts associated with gonadal development were detected. Compared to ovarian Ⅱ- brain, 515 differentially expressed genes (DEGs) were upregulated and 535 DEGs were downregulated in ovarian Ⅳ- brain, whereas 470 DEGs were upregulated and 483 DEGs were downregulated in ovarian Ⅳ- pituitary compared to ovarian Ⅱ- pituitary. DEGs involved in hormone synthesis and secretion and in the GnRH signaling pathway were screened. Weighted gene co-expression network analysis identified gene co-expression modules that were positively correlated with ovarian phenotypic traits. The hub genes Smad4 and TRPC4 in the modules were co-expressed with DEGs including Kiss1 receptor and JUNB, suggesting that ovarian development is controlled by a hypothalamic-pituitary-gonadal axis. Our results have provided new insights that advance our understanding of the molecular mechanism of C. nasus reproductive functions and will be useful for future breeding.

BackgroundThe submandibular glands, as major salivary glands, participate in rumen digestion in goats. Sialic acid, lysozyme, immunoglobulin A (IgA), lactoferrin and other biologically active substances secreted in the submandibular glands were reported in succession, which suggests that the submandibular gland may have immune functions in addition to participating in digestion. The aim of this study was to map the expression profile of differentially expressed genes (DEGs) at three different stages by transcriptome sequencing, screen immune-related genes and pathways by bioinformatics methods, and predict the immune function of submandibular glands at different developmental stages.MethodsNine submandibular gland tissue samples were collected from groups of 1-month-old kids, 12-month-old adolescent goats and 24-month-old adult goats (3 samples from each group), and high-throughput transcriptome sequencing was conducted on these samples. The DEGs among the three stages were screened and analysed. Key genes and signalling pathways were selected via protein-protein interaction (PPI) network analysis.ResultsThe results revealed 2,706, 2,525 and 52 DEGs between 1-month-old and 12-month-old goats, between 1-month-old and 24-month-old goats, and between 12-month-old and 24-month-old goats, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that most of the DEGs were enriched in immune- related GO terms and pathways. Based on functional enrichment analysis and network analysis, 10 genes (PTPRC, CD28, SELL, LCP2, MYC, LCK, ZAP70, ITGB2, SYK and CCR7), two signalling pathways (the T cell receptor signalling pathway and the NF-κβ signalling pathway) and eight GO terms (T cell receptor signalling pathway, neutrophil mediated immunity, B cell mediated immunity, regulation of alpha-beta T cell activation, positive regulation of T cell proliferation, regulation of leukocyte differentiation, positive regulation of antigen receptor-mediated signalling pathway, positive regulation of lymphocyte proliferation) that may play key roles in the immune functions of the goat submandibular glands at different developmental stages were identified. Moreover, we found that eight antibacterial peptide-encoding genes were downregulated in the tuberculosis and salivary secretion pathways, while all immunoglobulins were upregulated in 10 immune system pathways. These findings indicate that the submandibular glands may be important immunological organs during the growth process of goats and that the immune function of these glands gradually weakens with age up to 12 months but remains relatively stable after 12 months of age. Overall, this study will improve our understanding of transcriptional regulation related to goat submandibular gland immune function.

Transcriptome sequencing and differential expression analysis in bacterial wilt tolerant and susceptible clones of tomato (Solanum lycopersicum L.) following Ralstonia solanacearum infection

To observe the effect of electroacupuncture (EA) at "Baihui"(GV20) and "Shenshu" (BL23) on the pathological injury of neurons in SAMP8 mice and the anti-inflammatory effect on neuron repair, providing a new experimental basis for EA prevention and treatment of Alzheimer's disease. Twelve 7-month-old SAMP8 mice were randomly divided into model and EA groups, and 6 SAMR1 mice of the same age and genetic background were used as normal group. Mice in the EA group were needled at GV20 and bilateral BL23, and EA (1 mA, 2 Hz) was applied to bilateral BL23 for 15 min, once daily, 10 d as a course for a total of 4 courses, with an interval of 1 d. Mice in the normal and model groups were captured and fixed in the same way as the EA group. The spatial learning and memory ability was detected by Morris water maze test. Neuronal nuclear antigen (NeuN) positive expression and the number of NeuN-positive cells in dentate gyrus (DG) were detected by immunofluorescence staining. The protein expression levels of ionized calcium binding adapter molecule 1(Iba-1), tumor necrosis factor-α(TNF-α), interleukin (IL)-6 and IL-1β in hippocampus were detected by Western blot. The ultrastructure of nerve cells in DG was observed by transmission electron microscopy. Compared with the normal group, the average escape latency was prolonged(P<0.01), the number of platform crossing was significantly reduced (P<0.01), the average fluorescence intensity of NeuN and the number of NeuN-positive cells in hippocampus DG region decreased (P<0.05), the expression levels of Iba-1, TNF-α, IL-6 and IL-1β in hippocampus were increased (P<0.05) in the model group.Compared with the model group, the ave-rage escape latency was shortened (P<0.01), the number of platform crossing times was significantly increased (P<0.01), the average fluorescence intensity of NeuN and the number of NeuN-positive cells in hippocampus DG region increased (P<0.05), the expression levels of Iba-1, TNF-α, IL-6 and IL-1β in hippocampus were decreased (P<0.05) in the EA group. The morphology of nerve cells in the hippocampus DG region was normal， and the organelles in the cytoplasm were clear, complete and regularly distributed in the normal group. However, the morphology of nerve cells in the model group was seriously irregular, which was also irregular in EA group but somewhat relieved compared with model group. EA at GV20 and BL23 can improve the learning and memory ability of SAMP8 mice, which may be related to inhibiting the neuroinflammatory response, increasing the number of neurons and improving the ultrastructure of the DG region of the hippocampus to play the role of neuron protection.

To observe the immunoregulatory effect of electroacupuncture (EA) intervention for muscular dystrophy chronic obstructive pulmonary disease (COPD) rats, so as to investigate its underlying mechanism in improving respiratory function. Forty male SD rats were randomly divided into 5 groups: normal, model, EA, exercise, and EA+ exercise (n=8 in each). The muscular dystrophy COPD model was established by placing the rats in a closed box to be exposed to cigarette smoke (3-10 cigarettes/time) for 60 min, twice daily, 6 days a week for 90 days. The EA, exercise and EA+exercise interventions were given beginning from day 80 after exposure to cigarette smoke. EA (2 Hz/40 Hz, 6 mA) was applied to "Danzhong" (CV 17), "Qihai" (CV 6), "Zhongwan" (CV 12), "Liangmen" (ST 21) and bilateral "Quchi" (LI 11) for 10 min, once every other day, for 20 times. The swimming exercise was conducted by forcing the rat to swim in a water box for 10 min, once every other day, for 20 times. The rat's lung function including the resistance of inspiration (RI), functional residual capacity(FRC), pulmonary dynamic compliance (Cdyn), etc., was detected under anesthesia. Pathological changes of the lung tissue were detected by H.E. staining, and the contents of serum TNF-alpha, IL-6 and IL-1 beta assayed by ELISA. After 80 days' exposure to the cigarette smoke, the rats' body weight values in the model, EA, exercise and EA+exercise groups were significantly lower than that of the normal group(P<0.05). Moreover, the RI and FRC levels were significantly increased, and the Cdyn level was remarkably decreased in the model group relevant to the normal group (P<0.01). Following the intervention, both RI and FRC levels were significantly down-regulated in the EA, exercise and EA+exercise groups relevant to the model group (P<0.05), suggesting an improvement of the lung function. But the decreased Cdyn level had no marked improvement in the 3 treatment groups relevant to the model group (P>0.05). The numbers of monocytes and lymphocytes of the lung tissue, and the contents of serum TNF-α, IL-6 and IL-1 β were significantly higher in the model group than in the normal group (P< 0.01), and significantly lower in the EA, exercise and EA+exercise groups than in the model group (P<0.05), except monocytes in the exercise group (P>0.05). No significant differences were found among the EA, exercise and EA+exercise groups in the levels of RI and FRC, pulmonary monocytes and serum IL-6 and IL-1 β (P>0.05). The body weight was significantly higher in the exercise and EA+exercise groups than in the EA group, and the pulmonary lymphocytes and serum TNF-α obviously lowered in the EA group than in the exercise group (P<0.05). H.E. staining showed deformation of the bronchial tube cavity, detachment and flattening of the bronchial mucosal epithelial cilia, hyperplasia of Goblet cells, infiltration of abundant inflammatory cells in the submucosal layer and muscular layer, more secretions in the bronchovascular cavity, incomplete alveolar structure, thinning and rupture of the alveolar wall, and expansion of the alveolar cavity to form large pulmonary vesicles after modeling, which was obviously milder in the 3 treatment groups. EA intervention can improve the pulmonary function and pathological changes in pulmonary muscular dystrophy COPD rats, which is associated with its effects in reducing pulmonary monocytes and lymphocytes and serum TNF-α, IL-6 and IL-1 β contents, suggesting an enhancement of immunoregulation.

Atherosclerosis is a leading cause of cardiovascular morbidity and mortality worldwide. Endothelial disfunction underlying the atherogenesis can be triggered by genotoxic stress in endothelial cells. In the presented research whole transcriptome sequencing (RNA-seq) of human coronary artery (HCAEC) and internal thoracic artery (HITAEC) endothelial cells in vitro exposed to 500 ng/mL mitomycin C (treatment group) or 0.9% NaCl (control group) was performed. Resulting to bioinformatic analysis, 56 upregulated differentially expressed genes (DEGs) and 6 downregulated DEGs with absolute fold change ≥ 2 and FDR p-value < 0.05 were selected in HCAEC exposed to mitomycin C compared to the control group; in HITAEC only one upregulated DEG was found. According to Gene Ontology enrichment analysis, DEGs in HCAEC were classified into 25 functional groups of biological processes, while in HITAEC we found no statistically significant (FDR p-value < 0.05) groups. The four largest groups containing more than 50% DEGs (“signal transduction”, “response to stimulus”, “biological regulation”, and “regulation of biological process”) were identified. Finally, candidate DEGs and pathways underlying the genotoxic stress induced endothelial disfunction have been discovered that could improve our understanding of fundamental basis of atherogenesis and help to justification of genotoxic stress as a novel risk factor for atherosclerosis.

The purpose of the present study was to investigate the molecular mechanisms of myotonic dystrophy (DM) 1 and 2 cataracts using bioinformatics methods. A microarray dataset (E-MEXP-3365) downloaded from the Array Express database included lens epithelial samples of DM1 and DM2 cataract patients (n=3/group) and non-DM lens epithelial samples as a control (n=4). Differentially expressed genes (DEGs) were identified between DM1 and control samples, and between DM2 and control samples. Pathway enrichment analyses were performed for the DEGs. Potential micro (mi)RNAs regulating these DEGs were predicted. An miRNA-target gene network was constructed for DM1 and DM2. The study identified 223 DEGs in DM1, and 303 DEGs in DM2. DM1 and DM2 shared 172 DEGs. The DEGs in DM1 were enriched with calcium, Wnt and axon guidance signaling pathways. The DEGs in DM2 were linked by adherens junction signaling pathways. miRNA (miR)-197, miR-29b and miR-29c were included in the network modules of DM1. miR-197, miR-29c and miR-29a were involved in the network modules of DM2. It is therefore hypothesized that these signaling pathways and miRNAs underlie DM1 and DM2 cataracts, and may represent potential therapeutic targets for the treatment of this disorder.