Identification of potential key molecules and signaling pathways for psoriasis based on weighted gene co-expression network analysis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, the pathogenesis of which is more complicated and often requires long-term treatment. In particular, moderate to severe psoriasis usually requires systemic treatment. Psoriasis is also associated with many diseases, such as cardiometabolic diseases, malignant tumors, infections, and mood disorders. Psoriasis can appear at any age, and lead to a substantial burden for individuals and society. At present, psoriasis is still a treatable, but incurable, disease. Previous studies have found that microRNAs (miRNAs) play an important regulatory role in the progression of various diseases. Currently, miRNAs studies in psoriasis and dermatology are relatively new. Therefore, the identification of key miRNAs in psoriasis is helpful to elucidate the molecular mechanism of psoriasis. AIM: To identify key molecular markers and signaling pathways to provide potential basis for the treatment and management of psoriasis. METHODS: The miRNA and mRNA data were obtained from the Gene Expression Omnibus database. Then, differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) were screened out by limma R package. Subsequently, DEmRNAs were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomics functional enrichment. The "WGCNA" R package was used to analyze the co-expression network of all miRNAs. In addition, we constructed miRNA-mRNA regulatory networks based on identified hub miRNAs. Finally, in vitro validation was performed. All experimental procedures were approved by the ethics committee of Chinese PLA General Hospital (S2021-012-01). RESULTS: A total of 639 DEmRNAs and 84 DEmiRNAs were identified. DEmRNAs screening criteria were adjusted P (adj. P) value < 0.01 and |logFoldChange| (|logFC|) > 1. DEmiRNAs screening criteria were adj. P value < 0.01 and |logFC| > 1.5. KEGG functional analysis demonstrated that DEmRNAs were significantly enriched in immune-related biological functions, for example, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, and chemokine signaling pathway. In weighted gene co-expression network analysis, turquoise module was the hub module. Moreover, 10 hub miRNAs were identified. Among these 10 hub miRNAs, only 8 hub miRNAs predicted the corresponding target mRNAs. 97 negatively regulated miRNA-mRNA pairs were involved in the miRNA-mRNA regulatory network, for example, hsa-miR-21-5p-claudin 8 (CLDN8), hsa-miR-30a-3p-interleukin-1B (IL-1B), and hsa-miR-181a-5p/hsa-miR-30c-2-3p-C-X-C motif chemokine ligand 9 (CXCL9). Real-time polymerase chain reaction results showed that IL-1B and CXCL9 were up-regulated and CLDN8 was down-regulated in psoriasis with statistically significant differences. CONCLUSION: The identification of potential key molecular markers and signaling pathways provides potential research directions for further understanding the molecular mechanisms of psoriasis. This may also provide new research ideas for the prevention and treatment of psoriasis in the future.

Nonstationary El Niño teleconnection on the post-summer upwelling off Vietnam.

Summer upwelling has often been observed off Vietnam in the South China Sea (SCS). Occasional disappearance of the upwelling has attracted much attention because it modulates the regional climate and harms surrounding fisheries. Fluctuations of the East Asian monsoon associated with El Niño are considered responsible for the weakened or abolished upwelling. However, analyses of observations performed in the present study were equivocal in terms of the dominant influence of El Niño. Based on long-term sea surface temperature data, we demonstrated that weak upwelling off Vietnam occurs more frequently during periods of accelerated global warming compared to warming hiatus periods. Warming signals in the Indian Ocean vanished relatively quickly during the hiatus period. The accompanying easterly anomalies south of the anomalous anticyclone (AAC) in the northwestern Pacific were also weakened, reducing the impact of the El Niño teleconnection on the SCS summer monsoon and thus preserving the regular post-summer upwelling off Vietnam during warming hiatus periods.

An Atlantic-driven rapid circulation change in the North Pacific Ocean during the late 1990s.

Interbasin interactions have been increasingly emphasized in recent years due to their roles in shaping climate trends and the global warming hiatus in the northern hemisphere. The profound influence from the North Atlantic on the Tropical Pacific has been a primary focus. In this study, we conducted observational analyses and numerical modeling experiments to show that the North Atlantic has also strongly influenced the Extratropical North Pacific. A rapid and synchronous change in the atmospheric and oceanic circulations was observed in the North Pacific during the late 1990s. The change was driven by the transbasin influence from the Atlantic Ocean. During the positive phase of the Atlantic Multidecadal Oscillation (AMO) since the 1990s, the anomalously warm North Atlantic triggers a series of zonally symmetric and asymmetric transbasin teleconnections involving the Inter-tropical Convergence Zone (ITCZ), Walker and Hadley circulations, and Rossby wave propagation that lead to a decrease in wind stress curls over the Pacific subtropics, resulting in an abrupt weakening in the North Pacific subtropical gyre (NPSG) and the Kuroshio Current.

Comprehensive transcriptome analysis based on RNA sequencing identifies critical genes for lipopolysaccharide-induced epididymitis in a rat model.

Epididymitis is a commonly diagnosed disease associated with male infertility. However, little is known about the molecules that are involved in its development. This study was to identify critical genes associated with lipopolysaccharide-induced epididymitis and analyze the molecular mechanism of epididymitis through RNA sequencing. Experimental epididymitis models were generated by administering male Sprague-Dawley rats' lipopolysaccharide. A total of 1378 differentially expressed genes, including 531 upregulated and 847 downregulated genes, were identified in the epididymitis model rats compared with those in sham-operated rats by RNA sequencing. Functional enrichment analyses suggested that the upregulated genes were markedly enriched in inflammation-related biological processes, as well as in the tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interactions, complement and coagulation cascades, and in the chemokine signaling pathway. Four downregulated genes (collagen type XXVIII alpha 1 chain [Col28α1], cyclin-dependent kinase-like 1 [Cdkl1], phosphoserine phosphatase [Psph], and fatty acid desaturase 2 [Fads2]) and ten upregulated genes (CCAAT/enhancer-binding protein beta [Cebpß], C-X-C motif chemokine receptor 2 [Cxcr2], interleukin 11 [Il11], C-C motif chemokine ligand 20 [Ccl20], nuclear factor-kappa-B inhibitor alpha [Nfkbiα], claudin 4 [Cldn4], matrix metallopeptidase 9 [Mmp9], heat shock 70 kDa protein 8 [Hspa8], intercellular cell adhesion molecule-1 [Icam1], and Jun) were successfully confirmed by real-time polymerase chain reaction. Western blot demonstrated that CDKL1 was decreased, while MMP9 and NFKBIA were increased in the experimental model group compared with those in the sham-operated group. Our study sheds new light on the understanding of the early response of the epididymis during bacterial epididymitis.

East China Sea increasingly gains limiting nutrient P from South China Sea.

The Taiwan Strait (TS) directly connects two of the richest fishing grounds in the world - the East China Sea (ECS) and the South China Sea (SCS). Carbon and nutrient supplies are essential for primary production and the Yangtze River is an important source for the ECS. However the ECS is severely P-limited. The TS transports an order of magnitude more carbon and a factor of two more phosphate (P) to the ECS than the Yangtze River does. To evaluate the temporal variability of these supplies, the total alkalinity (TA), dissolved inorganic carbon (DIC), nitrate plus nitrite (N), P, and silicate (Si) fluxes through the TS were estimated using empirical equations for these parameters and the current velocity, which was estimated using the Hybrid Coordinate Ocean Model (HYCOM). These empirical equations were derived from in situ salinity and temperature and measured chemical concentrations that were collected during 57 cruises (1995-2014) with a total of 2096 bottle samples. The 24-month moving averages of water, carbon, and nutrient fluxes significantly increase with time, so does the satellite chlorophyll a concentration. More importantly, the increased supply of the badly needed P from the TS is more than that from the Yangtze River.

Coherent Response of Vietnam and Sumatra-Java Upwellings to Cross-Equatorial Winds.

Upwelling off Vietnam in the South China Sea (SCS) and the Sumatra-Java upwelling in the Indian Ocean significantly modulate regional variation in climate. Although located in different hemispheres, these upwellings nearly concur during the boreal summer; both are the result of wind-induced Ekman divergence. Beyond seasonal time scales, the two upwellings were not synchronous in 1998. In the summer of 1998, upwelling off Vietnam was almost absent, generating the warmest summer on record in the SCS. We demonstrated that the El Niño-Southern Oscillation, which was highly correlated with the upwelling in previous studies, was not solely responsible for this variability. Wind trajectory analyses revealed that cross-equatorial winds, which had passed over the Sumatra-Java upwelling site about 2 weeks earlier, were a rapid force acting on SCS summer upwelling. In the summer of 1998, SCS winds were greatly perturbed due to an anomalous wind path that blew toward the SCS through the Sulu Sea. Our findings suggest that not only the resulting weakening but also the perturbation of the SCS winds prevented the formation of summer upwelling off central Vietnam in that year.

Discordant multi-decadal trend in the intensity of the Kuroshio along its path during 1993-2013.

The Kuroshio transports warm water in the Pacific poleward from the tropics and plays a crucial role in modulating surrounding climate. Based on independent data sets, we demonstrated that the Kuroshio weakened downstream east of Taiwan, but intensified upstream east of Luzon Island during 1993-2013. The surface velocity (volume transport) of the Kuroshio has decreased 12.5% (4~5%) off east Taiwan but increased 18% (8~18%) off east Luzon. The discordant upstream-downstream trend was attributable to changes in oceanic eddies and basin surface winds: greater (lesser) cyclonic eddies, lesser (greater) anticyclonic eddies, and positive (negative) tendency in the Pacific Basin wind curl contributed to a weakened (intensified) downstream (upstream) Kuroshio. The difference in water mass between the upstream and downstream Kuroshio was balanced by an anomalous eastward flow, the southern branch of the Subtropical Counter Current which was enhanced and evacuated the redundant water eastward into the Pacific.

Intrusion of the Kuroshio into the South and East China Seas.

The northward-flowing Kuroshio often intrudes westward and modulates the water masses of the South and East China Seas. These intrusions transcend multiple scales in time and space, which we demonstrate here using various independent data sets. There are two hot spots of intrusion, one in the Luzon Strait and the other off northeast Taiwan, which occur synchronously when the upstream Kuroshio weakens during winter. Beyond seasonal time scales, the two intrusions were not synchronous during 1993-2013. While intrusions into the South China Sea echoed the Pacific Decadal Oscillation, the intrusion northeast of Taiwan decreased markedly before 2002 but regularly reached the shelf thereafter. This change was due to the influence of westward impingements of cyclonic eddies from the open ocean on the Kuroshio main stream in place of anticyclonic eddies. During 1993-2001, decreasing cyclonic eddy impingements moved the Kuroshio away from northeast Taiwan, weakening the Kuroshio intrusion onto the East China Sea shelf. Thereafter, enhanced cyclonic eddy impingement during 2002-2013 weakened the Kuroshio transport, moving it closer to the shelf and enhancing its intrusion into the East China Sea.

Identification of lumbar disc disease hallmarks: a large cross-sectional study.

BACKGROUND: Lumbar disc disease has a disabling impact on global people with heavy burden on society, mainly consisting of lumbar disc degeneration (LDD) and lumbar disc herniation (LDH). The recently released lumbar disc nomenclature version 2.0 deepens our understandings on the diseases. Consequently, there is an urgent need to clarify the occurrence and distribution features of LDD and LDH in a large-scale sample in terms of the novel version. QUESTION/PURPOSES: We asked: (1) Is there a difference in the occurrence and distribution hallmarks of LDD and LDH in a population-based large-scale sample? (2) Does the novel nomenclature version bring novel vision on lumbar disc disease? METHODS: Five thousand two hundred eighty-eight consecutive cases (26,440 lumbar discs) undergoing lumbar spine MRI were retrospectively included from Jan 2008 to Dec 2010 in a territory university hospital. Five hundred nine cases were excluded. There were 2727 males (51.57%) and 2561 females (48.43%) with a mean age of 43.73 years. Both T1 and T2 weighted lumbar MRI images from L1/2 to L5/S1 were profoundly analyzed in axial and sagittal planes. We classified lumbar discs in terms of version 2.0. RESULTS: The occurrence of LDH and LDD was 14.18 and 44.23% in average, respectively. Notably, lumbar spine discs were more prone to LDD than LDH. L4/5 was the most frequent level in terms of LDH (26.08%) and LDD (56.09%), followed by L5/S1 (LDH: 24.09%; LDD: 55.33%), then L3/4, L2/3 and L1/2 in ranking order. The prevalence of LDH and LDD in upper lumbar discs from L1/2 to L3/4 was significant lower than the average prevalence rate (P < 0.05). The mean age was 24.70 (±14.81) years for normal lumbar discs; 49.76 (±14.95) years for LDD; 37.01 (±12.91) years for LDH; 51.31(±15.00) years for LDD and LDH (P < 0.05). Modic changes, HIZ, spondylosis deformans and decreased disc height were linked with older age; whereas Schmorl node and lumbar disc sequestration were not associated with age (P < 0.05). CONCLUSIONS: The prevalence of LDD is 44.23%, higher than LDH as 14.18%. L4/5 and L5/S1 are the most frequent involved segments for the majority of lumbar disc diseases. Schmorl node occurs (1.6%) more frequently in upper lumbar spine, independent of age. Modic changes (0.87%) are closely related with older age. CLINICAL RELEVANCE: When diagnosing and treating lumbar disc disease, it might be important to consider the updated nomenclature of LDD and LDH. Our study provides additional novel vision on the features of LDD and LDH in a large-scale sample based on the nomenclature of novel version.

Serine/threonine kinases 31(STK31) may be a novel cellular target gene for the HPV16 oncogene E7 with potential as a DNA hypomethylation biomarker in cervical cancer.

BACKGROUND: Cervical cancer (CC) is a leading cause of mortality in females, especially in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (hrHPV), and hrHPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. STK31 gene of which the expression has been proven to be regulated by the methylation status of its promoter, is one of the novel cancer/testis (CT) genes and plays important roles in human cancers. Reasearches have indicated that viral infection is correlated to the methylation statuses of some genes. Herein, we detected methylation status of the STK31 gene in cervical tumors and explored its interaction with HPV16 or/and HPV18 (HPV16/18) infection. METHODS: Bisulfite genomic sequencing PCR (BGS) combined with TA clone, methylation-specific PCR (MSP) were used to analyze methylation statuses of the STK31 gene promoter/exon 1 region in HPV16/18-positive, HPV-negative CC cell lines; ectopically expressed HPV16 E6, -E7, and -E6/E7 CC cells; normal cervical tissues and cervical tumor tissues of different stages. The mRNA and protein expressions of STK31 were detected by RT-PCR and western blotting. RESULTS: The STK31 gene promoter/exon 1 was hypomethylated in the HPV16/18-positive cell lines HeLa, SiHa and CaSki, and the mRNA and protein expression were detected. In contrast, the STK31 gene exhibited hypermethylation and silenced expression in the HPV-negative CC cells C33A and HT-3. Compared with the primary HPV-negative CC cell lines, the STK31 methylation was downregulated, and STK31 expression was induced in the HPV16E7/E67 transfected cells. The methylation statuses and expressions of STK31 were verified in the cervical tumor samples at different stages. Additionally, chemotherapy treatment may influence STK31 expression by regulating its methylation status. CONCLUSIONS: STK31 may be a novel cellular target gene for the HPV16 oncogeneE7. The HPV16 oncogene E7 may affect STK31 expression through a methylation-mediated mechanism. The aberrant methylation of the STK31 promoter/exon 1 region may be a precursor of human cervical carcinogenesis and a potential DNA aberrant methylation biomarker of conditions ranging from precancerous disease to invasive cancer.

Downregulation of fatty acid synthase complex suppresses cell migration by targeting phosphor-AKT in bladder cancer.

The aim of the present study was to investigate the effect of fatty acid synthase complex (FASN) on the migration capacity of bladder transitional cell carcinoma (BTCC) cells and the involvement of matrix metalloproteinase­9 (MMP­9) via targeting of phospho­AKT (p­AKT). FASN­specific small­interfering RNA (FASN­siRNA) was used to inhibit FASN gene expression in the 5637 and 253J BTCC cell lines. The knockdown efficiency of FAM­conjugated FASN­siRNA was confirmed by fluorescence microscopy. The migratory abilities of BTCC cells were assessed using a Transwell assay. Furthermore, protein and mRNA expression of FASN, p­AKT, AKT, and migration­associated protein MMP­9 were detected by western blot analysis. Treatment with FASN inhibitor Cer and FASN­siRNA decreased the migratory capacity of bladder cancer cells and reduced the levels of p­AKT as well as the expression of MMP­9. These results indicated that FASN inhibition suppressed the migratory capacity of BTCC cells through suppressing AKT activation and consequently reducing MMP­9 expression. Targeting FASN may represent a promising novel therapeutic strategy for BTCC.

Transvaginal Resection of a Bladder Leiomyoma Misdiagnosed with a Vaginal Mass: A Case Report and Literature Review.

Bladder leiomyoma is a rare benign tumor and it could be easily misdiagnosed with many other pelvic diseases, especially obstetrical and gynecological diseases; abdominal, laparoscopic, and transurethral resection of bladder leiomyoma have been reported. Herein, we present a case of bladder leiomyoma misdiagnosed with a vaginal mass preoperatively; the mass was isolated, enucleated from the bladder neck, and removed transvaginally; to the best of our knowledge, this is the first case of intramural leiomyoma of bladder neck that has been enucleated transvaginally only without cystotomy.

The study of energy metabolism in bladder cancer cells in co-culture conditions using a microfluidic chip.

OBJECTIVES: This study aimed to systematically analyze changes in mitochondrial-related protein expression in bladder cancer cells and tumor-associated fibroblasts and to investigate the characteristics of bladder cancer cell energy metabolism. METHODS: In this study, we utilized the following techniques to achieve the objectives: (1) a co-culture system of bladder tumor cells and fibroblasts was built using a microfluidic chip as a three-dimensional culture system; (2) the concentration of lactic acid in the medium from the different groups was determined using an automatic micro-plate reader; (3) a qualitative analysis of mitochondria-related protein expression was performed by immunofluorescent staining; and (4) a quantitative analysis of mitochondrial-associated protein expression was conducted via Western blot. SPSS software was utilized to analyze the data. RESULTS: (1) Determination of lactic acid concentration: The lactic acid concentration was determined to be highest in the experimental group, followed by the T24 cell control group and then the fibroblast control group. (2) Qualitative results: In the control group, the mitochondrial-related protein fluorescence intensity was higher in the fibroblasts compared with the cancer cells, and the fluorescence intensity of the fibroblasts was reduced compared with the experimental group. The mitochondrial-related protein fluorescence intensity of the cancer cells was higher in the experimental group compared with the control group, and the opposite results were obtained with the fibroblasts. (3) Quantitative results: The expression of mitochondria-related proteins was higher in fibroblasts compared with cancer cells in the control group, and the opposite results were obtained in the experimental group (P<0.05). The expression of mitochondria-related proteins was increased in cancer cells in the experimental group compared with the control group; the opposite results were observed for the fibroblasts (P<0.05). CONCLUSIONS: The energy metabolism of bladder tumor cells does not parallel the "Warburg effect" because even under sufficient oxygen conditions, cancer cells still undergo glycolysis. Bladder cancer cells also have an efficient oxidative phosphorylation process wherein cancer cells promote glycolysis in adjacent interstitial cells, thereby causing increased formation of nutritional precursors. These high-energy metabolites are transferred to adjacent tumor cells in a specified direction and enter the Krebs Cycle. Ultimately, oxidative phosphorylation increases, and sufficient ATP is produced.

Perioperative Blood Transfusion Promotes Worse Outcomes of Bladder Cancer after Radical Cystectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple studies have investigated the effect of perioperative blood transfusion (PBT) for patients with radical cystectomy (RC), but the results have been inconsistent. We conducted a systematic review and meta-analysis to investigate the relationship between PBT and the clinical outcomes of RC patients. METHODS: We searched MEDLINE, EMBASE, the Cochrane library and BIOSIS previews to identify relevant literature for studies that focused on the relationship of PBT and outcomes of patients undergoing RC. A fixed or random effects model was used in this meta-analysis to calculate the pooled hazard ratio (HR) with 95% confidence intervals (CIs). RESULTS: A total of 7080 patients in 6 studies matched the selection criteria. Aggregation of the data suggested that PBT in patients who underwent RC correlated with increased all-cause mortality, cancer-specific mortality and cancer recurrence. The combined HRs were 1.19 (n = 6 studies, 95% CI: 1.11-1.27, Z = 4.71, P<0.00001), 1.17 (n = 4 studies, 95% CI: 1.06-1.30, Z = 3.06, P = 0.002), 1.14 (n = 3 studies, 95% CI: 1.03-1.27, Z = 2.50, P = 0.01), respectively. The all-cause mortality associated with PBT did not vary by the characteristics of the study, including number of study participants, follow-up period and the median blood transfusion ratio of the study. CONCLUSION: Our data showed that PBT significantly increased the risks of all-cause mortality, cancer-specific mortality and cancer recurrence in patients undergoing RC for bladder cancer.

Warburg effect or reverse Warburg effect? A review of cancer metabolism.

Cancer is a major threat to human health. A considerable amount of research has focused on elucidating the nature of cancer from its pathogenesis to treatment and prevention. Tumor cell metabolism has been considered a hallmark of cancer. Cancer cells differ from normal cells through unlimited cell division, and show a greater need for energy for their rapid growth and duplication. Research on glycometabolism, as the key point of energy metabolism, has played a unique role. In the 1920s, Warburg found that cancer cells prefer to produce adenosine triphosphate (ATP) by glycolysis, which is a less efficient pathway compared to oxidative phosphorylation. This striking discovery, called 'the Warburg effect', has influenced and guided the study of the mechanism and treatment of tumors for generations, but its causal relationship with cancer progression is still unclear. Some studies have now shown contradicting evidence and a new hypothesis, the reverse Warburg effect, has been put forward, in which cancer cells produce most of their ATP via glycolysis, even under aerobic conditions. In this review we discuss the new points concerning the energy metabolism of a tumor, as well as the current facts and perspectives.

Role of MicroRNAs in Prostate Cancer Pathogenesis.

Prostate cancer (PCa) remains the most commonly diagnosed malignant tumor in men, and is the second highest cause of cancer mortality after lung tumors in the United States. Accumulating research indicates that microRNAs (miRNAs) are increasingly being implicated in PCa. miRNAs are conserved small noncoding RNAs that control gene expression posttranscriptionally. Recent profiling research suggests that miRNAs are aberrantly expressed in PCa, and these have been implicated in the regulation of apoptosis, cell cycle, epithelial to mesenchymal transition, PCa stem cells, and androgen receptor pathway. All of these might provide the basis for new approaches for PCa. Here, we review current findings regarding miRNA research in PCa to provide a strong basis for future study aimed at promising contributions of miRNA in PCa.