A comprehensive survey of the analytical, numerical and experimental methodologies for dynamics of multibody mechanical systems with clearance or imperfect joints

Type 2 diabetes (T2D), which has currently become a global pandemic, is a metabolic disease largely characterised by impaired insulin secretion and action. Significant progress has been made in understanding T2D aetiology and pathogenesis, which is discussed in this review. Extrapancreatic pathology is also summarised, which demonstrates the highly multifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsible for augmenting insulin secretion from pancreatic beta-cells during the postprandial period. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a much longer half-life have been developed, which are currently an effective treatment option for T2D by enhancing insulin secretion in patients. Interestingly, there is continual emerging evidence that these therapies alleviate some of the post-diagnosis complications of T2D. Additionally, these therapies have been shown to induce weight loss in patients, suggesting they could be an alternative to bariatric surgery, a procedure associated with numerous complications. Current GLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R). Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists have been developed for these sites to test their therapeutic potential. Recent studies have also demonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptors including GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1R mechanisms of activation via different agonists, will likely provide better insight into the therapeutic potential of GLP-1-based therapies to treat T2D.

/pdf/a-review-of-current-trends-with-type-2-diabetes-epidemiology-2kb9dckqqk.pdf

A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives.

Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment. The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p. Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy. Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.

/pdf/circular-rna-circfgfr1-promotes-progression-and-anti-pd-1-3dwvgt1ziz.pdf

Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells

Abstract Background One of the most malignant tumors in men is prostate cancer that is still incurable due to its heterogenous and progressive natures. Genetic and epigenetic changes play significant roles in its development. The RNA molecules with more than 200 nucleotides in length are known as lncRNAs and these epigenetic factors do not encode protein. They regulate gene expression at transcriptional, post-transcriptional and epigenetic levels. LncRNAs play vital biological functions in cells and in pathological events, hence their expression undergoes dysregulation. Aim of review The role of epigenetic alterations in prostate cancer development are emphasized here. Therefore, lncRNAs were chosen for this purpose and their expression level and interaction with other signaling networks in prostate cancer progression were examined. Key scientific concepts of review The aberrant expression of lncRNAs in prostate cancer has been well-documented and progression rate of tumor cells are regulated via affecting STAT3, NF-κB, Wnt, PI3K/Akt and PTEN, among other molecular pathways. Furthermore, lncRNAs regulate radio-resistance and chemo-resistance features of prostate tumor cells. Overexpression of tumor-promoting lncRNAs such as HOXD-AS1 and CCAT1 can result in drug resistance. Besides, lncRNAs can induce immune evasion of prostate cancer via upregulating PD-1. Pharmacological compounds such as quercetin and curcumin have been applied for targeting lncRNAs. Furthermore, siRNA tool can reduce expression of lncRNAs thereby suppressing prostate cancer progression. Prognosis and diagnosis of prostate tumor at clinical course can be evaluated by lncRNAs. The expression level of exosomal lncRNAs such as lncRNA-p21 can be investigated in serum of prostate cancer patients as a reliable biomarker. 

/pdf/molecular-landscape-of-lncrnas-in-prostate-cancer-a-focus-on-1ycjea5w.pdf

Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention

Neutrophil extracellular traps (NET) are the extracellular release of decondensed chromatin and granules known for their role in host defense against foreign pathogens. However, a novel and predominantly pro-tumorigenic role of NETs in cancer is emerging. Tumors induce NET formation through the secretion of an array of tumor and infection-derived factors. NET deposition favors tumor cell proliferation, immunosuppression and cancer-associated thrombosis. Moreover, NETs enhance metastasis by contributing to epithelial-to-mesenchymal transition. A mesenchymal transition in tumor cells potentiates their migratory and invasive abilities. Circulating NETs capture circulating tumor cells and increase vascular permeability, thereby promoting tumor cell intravasation and establishment of micrometastasis. NETs present in pre-metastatic niches serve as cytokines in the recruitment of tumor cells through CCDC25. Through NET-mediated laminin remodelling, dormant cells are reawakened favoring metastatic growth. Moreover, post-operative infection results in high NET deposition and exacerbates post-surgical cancer progression and recurrence. Anti-NET therapies are in use for autoimmune diseases and are now being investigated in the context of cancer. The hope is that anti-NET therapies may synergize with existing anti-cancer therapy to increase rate of response given their multi-faceted interplay in several domains of cancer progression.

The role of neutrophil extracellular traps in cancer progression and metastasis.

This study aimed at elucidating the molecular mechanism of miR-381-3p in cervical cancer progression, which may provide a novel therapeutic target for patients with cervical cancer. The expression of miR-381-3p was confirmed by quantitative reverse transcription polymerase chain reaction. Microarray analysis was conducted to screen out differentially expressed genes, and the target gene of microRNA (miRNA) was predicted on TargetScan. Dual-luciferase reporter assay then verified the targeting relationship between miR-381-3p and FGF7. The protein expression of FGF7 was examined via Western blot assay. Colony formation assay was used to detect the cell proliferation, while flow cytometry was used to analyze cell cycle and apoptosis. The influence of miR-381-3p and FGF7 on cell migration and invasion was confirmed by transwell migration/invasion assay. Finally, we demonstrated that miR-381-3p was lowly expressed, while FGF7 was highly expressed in cervical cancer cells. There was a direct target relationship and a negative correlation between miR-381-3p and FGF7. miR-381-3p could downregulate FGF7 expression, inhibiting cell proliferation and metastasis, and inducing cell cycle arrest and apoptosis in cervical cancer.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcb.27438

miR-381-3p restrains cervical cancer progression by downregulating FGF7

Intra-abdominal infection after curative surgery for colorectal cancer is a serious complication associated with an increased risk of recurrence. Lipopolysaccharides (LPS)—an essential component of the cell wall of Gram-negative bacteria—were found to exert a protumorigenic effect by stimulating the inflammatory pathology and formation of neutrophil extracellular traps (NETs). This study was conducted to test whether LPS-induced formation of NETs promotes the development of cancer and metastasis. The clinical characteristics, incidence of relapse, and serum myeloperoxidase–DNA complexes of 40 patients with infection and 40 patients without infection after curative surgery were analyzed. The effects of LPS on the induction of NETs were evaluated in a mouse model of colorectal cancer and liver metastasis. The toll-like receptor 9 (TLR9)—a DNA receptor—was knocked down to assess its effect on the mitogen-activated protein kinase pathway and activities implicated in the formation of NETs. Analysis of the clinical data obtained from these patients showed the significant relation of the formation of NETs and incidence of metastasis and survival rates. Subsequent in vitro experiments revealed an increased level of citrullinated-histone H3 and myeloperoxidase–DNA in LPS-injected mice with colorectal cancer. In the mimic metastatic model, injection of LPS enhanced the metastatic capacity, which was then attenuated by DNase I. This suggested that the formation of NETs was activated by LPS. Injection of TLR9-knockdown HCT116 cells in mice, followed by induction through LPS, mitigated the level of citrullinated-histone H3 and myeloperoxidase–DNA. This finding implied that the formation of NETs was suppressed. These findings shed light on the mechanism underlying the relationship between the elevated rate of colorectal cancer recurrence in patients who underwent surgery and the incidence of infection. This mechanism involves the protumorigenic activities of LPS-induced formation of NETs. The NETs which could be mediated by the TLR9 and the mitogen-activated protein kinase signaling pathway.

Lipopolysaccharides increase the risk of colorectal cancer recurrence and metastasis due to the induction of neutrophil extracellular traps after curative resection.

Aims: To evaluate anti-tumour effects and mechanism of novel BF-30 derivative via cell-based assays and melanoma-bearing model mice. Main methods: BF-30 derivatives were designed by fusing heptapeptide-palmitic tags to native BF-30 via a protease-cleavable linker and prepared by F-moc solid-phase synthesis. Albumin binding affinity test and in vitro control-released assay were performed to screen these BF-30 derivatives and explore the mechanism of anti-tumour effects. The selected BF-30 derivative was further subjected to the preclinical efficacy study and chronic evaluation of anti-tumour effects melanoma-bearing model mice. Key findings: Twenty-one BF-30 derivatives, termed LBF-1 to LBF-21, were obtained with high purity and accurate molecular weight. Surface plasmon resonance (SPR) measurements, plasma stability test and in vitro control-released assay all showed that LBF-14 exerted better druggability compared with the others. Moreover, LBF-14 was proved to inhibit the proliferation of B16F10 melanoma cell by disrupting the cytoplasmic membrane and binding to genomic DNA to prevent transcription. Furthermore, half-life of intact LBF-14 and released BF-30 in rhesus monkeys were approximately 120.9 h and 136.4 h, respectively, after a single subcutaneous injection of 0.9 mg/kg LBF-14. In addition, chronic treatment of LBF-14 significantly suppressed melanoma growth and improved the survival rate of B16F10-bearing mice with the observed inhibition of 63.5% for 0.3mg/kg and 91.5% for 0.9 mg/kg. Furthermore, results of H&E staining prove that chronic treatment of LBF-30 effectively suppressed metastasis and invasion of B16F10 cells. Significance: LBF-14 holds potential to be developed as a promising once-weekly candidate for the treatment of malignant melanoma.

/pdf/design-and-biological-evaluation-of-novel-bf-30-analogs-for-1wfvf0cz57.pdf

Design and biological evaluation of novel BF-30 analogs for the treatment of malignant melanoma

Objective To investigate the effect of microRNA-137 (miR-137) on the migration and invasion of melanoma cells and its mechanism. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-137 in melanoma tissues and cells. miR-137 mimics, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) small interfering RNA and corresponding controls were transfected into A375 and WM451 cells by lipofection. The expression of PIK3R3 was examined by qRT-PCR and Western blot analysis. The Trans-well assay was conducted to measure cell migration and invasion. Dual luciferase reporter assay was used to detect the interaction between miR-137 and PIK3R3. Results Compared with normal pigmented nevus tissue, miR-137 expression was significantly reduced in melanoma tissues. Compared with keratinous HaCaT cells, the level of miR-137 was significantly decreased in melanoma SK-MEL-1, A375, and WM451 cells. Knockdown of miR-137 significantly reduced the migrated and invasive abilities of melanoma A375 and WM451 cells. Moreover, inhibition of PIK3R3 obviously suppressed the migration and invasion abilities of melanoma A375 and WM451 cells. Luciferase activity assay showed that PIK3R3 was a direct target of miR-137. In addition, overexpression of miR-137-inhibited PIK3R3 expression, while knockdown of miR-137-enhanced PIK3R3 abundance. Restoration of PIK3R3 reversed the regulatory effect of miR-137 on cell migration and invasive in melanoma A375 and WM451 cells. Conclusion miR-137 inhibited melanoma cell migration and invasion by targeting PIK3R3 gene.

Mechanism of miR-137 regulating migration and invasion of melanoma cells by targeting PIK3R3 gene.

Rational design of a GLP-1/GIP/Gcg receptor triagonist to correct hyperglycemia, obesity and diabetic nephropathy in rodent animals

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Wei Chen

Author Tools

Chat about Author