Colorectal cancer (CRC) is one of the most common cancers and a major cause of mortality. The present study aimed to identify potential biomarkers for CRC metastasis and uncover the mechanisms ...underlying the etiology of the disease. The five datasets GSE68468, GSE62321, GSE22834, GSE14297 and GSE6988 were utilized in the study, all of which contained metastatic and non-metastatic CRC samples. Among them, three datasets were integrated via meta-analysis to identify the differentially expressed genes (DEGs) between the two types of samples. A protein-protein interaction (PPI) network was constructed for these DEGs. Candidate genes were then selected by the support vector machine (SVM) classifier based on the betweenness centrality (BC) algorithm. A CRC dataset from The Cancer Genome Atlas database was used to evaluate the accuracy of the SVM classifier. Pathway enrichment analysis was carried out for the SVM-classified gene signatures. In total, 358 DEGs were identified by meta-analysis. The top ten nodes in the PPI network with the highest BC values were selected, including cAMP responsive element binding protein 1 (CREB1), cullin 7 (CUL7) and signal sequence receptor 3 (SSR3). The optimal SVM classification model was established, which was able to precisely distinguish between the metastatic and non-metastatic samples. Based on this SVM classifier, 40 signature genes were identified, which were mainly enriched in protein processing in endoplasmic reticulum (e.g., SSR3), AMPK signaling pathway (e.g., CREB1) and ubiquitin mediated proteolysis (e.g., FBXO2, CUL7 and UBE2D3) pathways. In conclusion, the SVM-classified genes, including CREB1, CUL7 and SSR3, precisely distinguished the metastatic CRC samples from the non-metastatic ones. These genes have the potential to be used as biomarkers for the prognosis of metastatic CRC.
BMAL1 is a core component of the circadian clock loop, which directs the sophisticated circadian expression of clock-controlled genes. Skeletal Bone development is a complex biological process ...involving intramembranous ossification, endochondral ossification and bone remodeling, as well as specific cells, such as mesenchymal cells, osteoblasts, osteoclasts, chondrocytes, etc. Growing evidences suggest that BMAL1 is indispensable for hard tissue development, including bone, cartilage and teeth. Loss of BMAL1 in animals can inhibit bone and cartilage development, and result in abnormal bone mass. In mesenchymal cells, BMAL1 defect inhibits osteoblastic and chondrocytic differentiation. Inactivation of BMAL1 also can promote the differentiation and formation of osteoclasts and increase bone resorption. Specifically, preclinical data demonstrate that the abnormity of BMAL1 expression is associated with skeletal disorders such as skeletal mandibular hypoplasia, osteoarthritis, osteoporosis, etc. In this review, we systemically describe the impact of BMAL1 in skeletal development and homeostasis, and devote to searching new therapy strategies for bone disorders.
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•BMAL1 participates in multiple biological processes of skeleton development.•Circadian rhythm can interact with mechanical and metabolic stimuli regulating bone remodeling.•BMAL1 abnormality is associated with human skeletal disorders.•BMAL1 may be the therapeutic and preventive target of skeletal diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bacteria identified in the oral cavity are highly complicated. They include approximately 1000 species with a diverse variety of commensal microbes that play crucial roles in the health status of ...individuals. Epidemiological studies related to molecular pathology have revealed that there is a close relationship between oral microbiota and tumor occurrence. Oral microbiota has attracted considerable attention for its role in in‐situ or distant tumor progression. Anaerobic oral bacteria with potential pathogenic abilities, especially Fusobacterium nucleatum and Porphyromonas gingivalis, are well studied and have close relationships with various types of carcinomas. Some aerobic bacteria such as Parvimonas are also linked to tumorigenesis. Moreover, human papillomavirus, oral fungi, and parasites are closely associated with oropharyngeal carcinoma. Microbial dysbiosis, colonization, and translocation of oral microbiota are necessary for implementation of carcinogenic functions. Various underlying mechanisms of oral microbiota‐induced carcinogenesis have been reported including excessive inflammatory reaction, immunosuppression of host, promotion of malignant transformation, antiapoptotic activity, and secretion of carcinogens. In this review, we have systemically described the impact of oral microbial abnormalities on carcinogenesis and the future directions in this field for bringing in new ideas for effective prevention of tumors.
Oral microbiota has been playing an important role in the development of cancer throughout human body. Thus we try to summarize the current researches about this topic.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Plasminogen activator, urokinase (uPA) is a secreted serine protease whose Dysregulation is often accompanied by various cancers. However, the biological functions and potential mechanisms of PLAU in ...head and neck squamous cell carcinoma (HNSCC) remain undetermined. Here, the expression, prognosis, function, and coexpression genetic networks of PLAU in HNSCC were investigated by a series of public bioinformatics tools. A Higher PLAU level predicted a poorer clinical outcome. Meanwhile, functional network analysis implied that PLAU and associated genes mainly regulated cell-substrate adhesion, tissue migration, and extracellular matrix binding. The top 4 significantly associated genes are
C10orf55
,
ITGA5
,
SERPINE1
, and
TNFRSF12A
. Pathway enrichment analysis indicated that PLAU might activate the epithelial-to-mesenchymal transition (EMT) process, which could explain the poor prognosis in HNSCC. Besides, genes associated with PLAU were also enriched in EMT pathways. We further validated the bioinformatics analysis results by
in vivo
and
in vitro
experiments. Then, we found that much more PLAU was detected in HNSCC tissues, and the silencing of PLAU inhibit the proliferation, migration, and EMT process of CAL27 cell lines. Notably, the downregulation of PLAU decreased the expression of
TNFRSF12A
. Moreover, knockdown
TNFRSF12A
also inhibits cell proliferation and migration.
In vivo
experiment results indicated that PLAU inhibition could suppress tumor growth. Collectively, PLAU is necessary for tumor progression and can be a diagnostic and prognostic biomarker in HNSCC.
Abstract
Background
SARS-CoV-2, which has brought a huge negative impact on the world since the end of 2019, is reported to invade cells using the spike (S) protein to bind to angiotensin-converting ...enzyme II (ACE2) receptors on human cells while the transmembrane protease serine 2 (TMPRSS2) is the key protease that activates the S protein, which greatly facilitates the entry of SARS-CoV-2 into target cells. In our previous study, it was observed that the positive rate of SARS-CoV-2 nucleic acids in saliva was higher in male and the elderly COVID-19 patients, suggesting that the susceptibility of oral tissues to SARS-CoV-2 may be related to gender and age. This research aimed to further investigate the SARS-CoV-2 susceptibility in oral tissues and influencing factors from the perspective of ACE2 and TMPRSS2, which were two proteins closely associated with SARS-CoV-2 infection.
Methods
Immunofluorescence was used to find the localization of ACE2 and TMPRSS2 in oral mucosal tissues. Transcriptomic sequencing data of several datasets were then collected to analysis the relationship between the expressions of ACE2 and TMPRSS2 with the age and gender of patients. Furthermore, oral tissues from patients with different ages and genders were collected. Immunohistochemistry staining, qRT-PCR and western blot were performed to explore the relationship between expression levels of ACE2 and TMPRSS2 and patient age as well as gender.
Results
The results showed that the two proteins were able to be co-expressed in the epithelial cells of oral tissues, and their expression levels were higher in the relatively elderly group than those in relatively younger group. Male oral epithelial cells exhibited higher level of TMPRSS2.
Conclusions
Our findings comprehensively confirmed the existence of ACE2 and TMPRSS2 in oral tissues and clarify the relationship between the expression levels with human age and gender for the first time, providing evidence for possible entry routes of SARS-CoV-2 and the influencing factors of SARS-CoV-2 colonization in oral cavity. Thus, the oral mucosa might be at potential risk of infection by SARS-CoV-2, especially in male or elderly patients. Using saliva to detect the nucleic acids of SARS-CoV-2 may be more accurate for elder male COVID-19 patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Maternal psychological distress during pregnancy is associated with unfavorable outcomes in infants. Mindfulness-based interventions (MBIs) can effectively alleviate psychological distress, but there ...are often barriers to the access of face-to-face interventions.
This study aimed to investigate the effectiveness of a digital guided self-help (GSH) MBI (GSH-MBI) in reducing maternal psychological distress and improving infant neuropsychological performance.
This was a randomized controlled trial. We recruited 160 women who were 12 to 20 weeks pregnant and exhibited psychological distress. We randomized them into a digital GSH-MBI group and a control group (usual perinatal care). The digital GSH-MBI consisted of a 6-week intervention through a WeChat mini program, with a daily reminder sent to the participants by a research assistant via WeChat. The primary outcomes consisted of maternal psychological distress, including depression, anxiety, and pregnancy-related anxiety symptoms, which were assessed at 6 time points from baseline to 6 months post partum (only pregnancy-related anxiety symptoms were assessed 3 times during pregnancy). The secondary outcomes were infant neuropsychological outcomes, including temperament and developmental behaviors, which were assessed at 6 weeks and 6 months post partum.
Compared with the control group, the digital GSH-MBI group showed a significant reduction in depression, anxiety, and pregnancy-related anxiety symptoms. In addition, the scores of the digital GSH-MBI group were lower than those of the control group for the 3 types of infant temperament at 6 weeks post partum, including quality of mood, distractibility, and adaptability.
Digital GSH-MBIs are effective in alleviating psychological distress among pregnant women and protecting infant outcomes.
Chinese Clinical Trial Register ChiCTR2000040717; https://www.chictr.org.cn/showproj.aspx?proj=65376.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The study examined whether overall sleep quality and the sleep components comprising the Pittsburgh Sleep Quality Index (PSQI) have a bi-directional relationship with resilience among adolescents, ...after adjusting for sex, age, depression, and socioeconomic status, and investigated which sleep components have a stronger effect on resilience.
A total of 1299 students (58% females; mean age, 15.79 years) participated at baseline, with 840 finishing all four study waves over the course of 24 months. Data were collected through questionnaires, including socio-demographics, the Pittsburgh Sleep Quality Index, Patient Health Questionnaire 9-item, and the Connor-Davidson Resilience Scale. Cross-lagged models were used to analyze the relationships between sleep and resilience.
Both daytime dysfunction and sleep disturbance had an independent bi-directional relationship with resilience. Higher resilience scores predicted overall better sleep quality and shorter sleep latency, but not vice versa. Sleep disturbance and daytime dysfunction had stronger effects on resilience.
These findings highlight the importance of future school interventions for sleep to improve students' resilience.
•Sleep disturbance is a risk factor for adolescents' mental and physical health.•Adolescent sleep disturbance and resilience influence each other over time.•School interventions for sleep are crucial for improving adolescents' resilience.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Long noncoding RNAs act essential regulators in lung cancer tumorigenesis. Our research aimed to investigate the potential function and molecular mechanisms of MLK7-AS1 in NSCLC (non-small-cell lung ...cancer). QRT-PCR results indicated that the MLK7-AS1 expression level was upregulated in NSCLC cells and tissues. MLK7-AS1 strengthened cell migration and invasion in H1299 and A549 cells. Luciferase reporter assay found that MLK7-AS1 functioned as an endogenous sponge for miR-375-3p. Transwell assay results showed that miR-375-3p suppressed cell migration and invasion in H1299 and A549 cells. YWHAZ was confirmed as a target gene of miR-375-3p by Targetscan. YWHAZ overexpression promoted the invasion of H1299 and A549 cells. MLK7-AS1 upregulated YWHAZ expression and enhanced H1299 and A549 cell invasion by sponging miR-375-3p. MLK7-AS1 improved the metastasis ability of A549
. In conclusion, MLK7-AS1 was identified as a novel oncogenic RNA in NSCLC and can function as a potential therapeutic target for NSCLC treatment.
We investigated differentially expressed proteins (DEPs) in human glioblastoma U87 cells after treatment with hederagenin as a therapeutic screening mechanism and provided a theoretical basis for ...hederagenin in treating glioblastoma.
The Cell Counting Kit 8 assay was used to analyze the inhibitory effect of hederagenin on the proliferation of U87 cells. Protein was identified by tandem mass tags and LC-MS/MS analysis techniques. Annotation of DEPs, Gene Ontology enrichment and function, and Kyoto Encyclopedia of Genes and Genomes pathways and domains were all examined by bioinformatics. According to the TMT results, hub protein was selected from DEPs for WB verification.
Protein quantitative analysis found 6522 proteins in total. Compared with the control group, 43 DEPs (P < 0.05) were involved in the highly enriched signaling pathway in the hederagenin group, among which 20 proteins were upregulated, and 23 proteins were downregulated. These different proteins are mainly involved in the longness regulating pathway-WORM, the hedgehog signaling pathway, Staphylococcus aureus infection, complement, coagulation cascades, and mineral absorption. KIF7 and ATAD2B expression were significantly down-regulated and PHEX and TIMM9 expression were significantly upregulated, according to WB analysis, supporting the TMT findings.
Hederagenin inhibition of GBM U87 cells may be related to KIF7, which is mainly involved in the hedgehog signaling pathway. Our findings lay a foundation for additional study of the therapeutic mechanism of hederagenin.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This paper presents a highly reconfigurable, low-power, and compact directional coupler. The coupler uses varactors and novel active inductors to achieve wide tuning ranges of operating frequencies ...and coupling coefficients. The use of a low-pass circuit architecture with only two inductors minimizes chip area, power consumption, and noise. The coupler is implemented in a 0.13-μm CMOS process. It occupies an area of 350 μm× 340 μm and consumes 40 mW or less power. The obtained 1-dB compression point is -3.2 dBm, and the measured noise figure is ~ 23 dB. These parameters compare favorably with previously published reconfigurable couplers. The measured coupling coefficient can be tuned from 1.3 to 9.0 dB at 4 GHz with 32 dB or better isolation and 15 dB or better return loss. The operating center frequency can be tuned from 2.0 to 6.0 GHz for a nominal 3-dB operation. These results agree with theoretical predictions and simulations reasonably well.
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