Zobrazení zdroje stránky Martinsenodgaard1396

Overall, our findings suggest that KDM4B plays complex roles in regulating multiple cancer processes, providing a useful resource for the future development of cancer therapies that target KDM4B expression.Neutrophils are essential components of the immune system and have vital roles in the pathogenesis of autoimmune disorders. As effector cells, neutrophils promote autoimmune disease by releasing cytokines and chemokines cascades that accompany inflammation, neutrophil extracellular traps (NETs) regulating immune responses through cell-cell interactions. More recent evidence has extended functions of neutrophils. Accumulating evidence implicated neutrophils contribute to tissue damage during a broad range of disorders, involving rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary sjögren's syndrome (pSS), multiple sclerosis (MS), crohn's disease (CD), and gout. A variety of studies have reported on the functional role of neutrophils as therapeutic targets in autoimmune diseases. However, challenges and controversies in the field remain. Enhancing our understanding of neutrophils' role in autoimmune disorders may further advance the development of new therapeutic approaches.As of August 27, 2021, the ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread to over 220 countries, areas, and territories. Thus far, 214,468,601 confirmed cases, including 4,470,969 deaths, have been reported to the World Health Organization. To combat the COVID-19 pandemic, multiomics-based strategies, including genomics, transcriptomics, proteomics, and metabolomics, have been used to study the diagnosis methods, pathogenesis, prognosis, and potential drug targets of COVID-19. In order to help researchers and clinicians to keep up with the knowledge of COVID-19, we summarized the most recent progresses reported in omics-based research papers. [https://www.selleckchem.com/products/CI-1040-(PD184352).html click here] This review discusses omics-based approaches for studying COVID-19, summarizing newly emerged SARS-CoV-2 variants as well as potential diagnostic methods, risk factors, and pathological features of COVID-19. This review can help researchers and clinicians gain insight into COVID-19 features, providing direction for future drug development and guidance for clinical treatment, so that patients can receive appropriate treatment as soon as possible to reduce the risk of disease progression.Mesenchymal stromal/stem cells (MSCs) have a great potential to proliferate, undergo multi-directional differentiation, and exert immunoregulatory effects. There is already much enthusiasm for their therapeutic potentials for respiratory inflammatory diseases. Although the mechanism of MSCs-based therapy has been well explored, only a few articles have summarized the key advances in this field. We hereby provide a review over the latest progresses made on the MSCs-based therapies for four types of inflammatory respiratory diseases, including idiopathic pulmonary fibrosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and asthma, and the uncovery of their underlying mechanisms from the perspective of biological characteristics and functions. Furthermore, we have also discussed the advantages and disadvantages of the MSCs-based therapies and prospects for their optimization.Lung cancer is the most malignant tumor in the worldwide. About 3%-5% non-small cell lung cancer (NSCLC) patients carry anaplastic lymphoma kinase (ALK) gene fusions and receive great benefits from ALK-targeted therapy. However, drug resistance inevitably occurs even with the most potent inhibitor drug lorlatinib. About half of the resistance are caused by alteration in ALK proteins for earlier ALK TKI drugs and near one-third of loratinib resistant cases are caused by compound mutations without current effective treatment strategy in clinic. Novel strategies are in great need to overcome drug resistance. Lately, two novel strategies have been developed and attracted great attentions for their potentials to overcome drug resistance problems (1) developed small compact macrocyclic ALK kinase inhibitors and (2) developed ALK targeted proteolysis-targeting chimera (PROTAC) drugs. The macrocyclic molecules are small and compact in size, brain barrier permeable, and highly potent against lorlatinib-resistant compound mutations. Developed ALK targeted PROTAC molecules could degrade oncogenic ALK driver proteins. Some showed superiority in killing ALK positive cancer cells and inhibiting the growth of cells expressing G1202R resistant ALK proteins comparing to inhibitor drugs. The update on these two treatment strategies was reviewed.Cancer is a leading cause of death worldwide. Surgery is the primary treatment approach for cancer, but the survival rate is very low due to the rapid progression of the disease and presence of local and distant metastasis at diagnosis. Adjuvant chemotherapy and radiotherapy are important components of the multidisciplinary approaches for cancer treatment. However, resistance to radiotherapy and chemotherapy may result in treatment failure or even cancer recurrence. Radioresistance in cancer is often caused by the repair response to radiation-induced DNA damage, cell cycle dysregulation, cancer stem cells (CSCs) resilience, and epithelial-mesenchymal transition (EMT). Understanding the molecular alterations that lead to radioresistance may provide new diagnostic markers and therapeutic targets to improve radiotherapy efficacy. Patients who develop resistance to chemotherapy drugs cannot benefit from the cytotoxicity induced by the prescribed drug and will likely have a poor outcome with these treatments. Chemotherapy often shows a low response rate due to various drug resistance mechanisms. This review focuses on the molecular mechanisms of radioresistance and chemoresistance in cancer and discusses recent developments in therapeutic strategies targeting chemoradiotherapy resistance to improve treatment outcomes.As key performers in intercellular communication, exosomes released by tumor cells play an important role in cancer development, including angiogenesis, cancer-associated fibroblasts activation, epithelial-mesenchymal transformation (EMT), immune escape, and pre-metastatic niche formation. Meanwhile, other cells in tumor microenvironment (TME) can secrete exosomes and facilitate tumor progression. Elucidating mechanisms regarding these processes may offer perspectives for exosome-based antitumor strategies. In this review, we mainly introduce the versatile roles of tumor or stromal cell derived exosomes in cancer development, with a particular focus on the biological capabilities and functionalities of their diverse contents, such as miRNAs, lncRNAs, and circRNAs. The potential clinical application of exosomes as biomarkers in cancer diagnosis and prognosis is also discussed. Finally, the current antitumor strategies based on exosomes in immunotherapy and targeted delivery for chemotherapeutic or biological agents are summarized.Alveolar epithelial cells (ACEs) gradually senescent as aging, which is one of the main causes of respiratory defense and function decline. Investigating the mechanisms of ACE senescence is important for understanding how the human respiratory system works. NAD+ is reported to reduce during the aging process. Supplementing NAD+ intermediates can activate sirtuin deacylases (SIRT1-SIRT7), which regulates the benefits of exercise and dietary restriction, reduce the level of intracellular oxidative stress, and improve mitochondrial function, thereby reversing cell senescence. We showed that nicotinamide mononucleotide (NMN) could effectively mitigate age-associated physiological decline in the lung of 8-10 months old C57BL/6 mice and bleomycin-induced pulmonary fibrosis in young mice of 6-8 weeks. Besides, the treatment of primary ACEs with NMN can markedly ameliorate cell senescence phenotype in vitro. These findings to improve the respiratory system function and reduce the incidence and mortality from respiratory diseases in the elderly are of great significance.Global lipidomics is of considerable utility for exploring altered lipid profiles and unique diagnostic biomarkers in diseases. We aim to apply ultra-performance liquid chromatography-tandem mass spectrometry to characterize the lipidomics profile in systemic lupus erythematosus (SLE) patients and explore the underlying pathogenic pathways using the lipidomics approach. Plasma samples from 18 SLE patients, 20 rheumatoid arthritis (RA) patients, and 20 healthy controls (HC) were collected. A total of 467 lipids molecular features were annotated from each sample. Orthogonal partial least square-discriminant analysis, K-mean clustering analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated disrupted lipid metabolism in SLE patients, especially in phospholipid, glycerol, and sphingolipid metabolism. The area under curve (AUC) of lipid metabolism biomarkers was better than SLE inflammation markers that ordinarily used in the clinic. Proposed model of monoglyceride (MG) (160), MG (180), phosphatidylethanolamine (PE) (183-160), PE (160-204), and phosphatidylcholine (PC) (O-162-183) yielded AUC 1.000 (95% CI, 1.000-1.000), specificity 100% and sensitivity 100% in the diagnosis of SLE from HC. A panel of three lipids molecular PC (183-181), PE (203-180), PE (160-204) permitted to accurately diagnosis of SLE from RA, with AUC 0.921 (95% CI, 0.828-1.000), 70% specificity, and 100% sensitivity. The plasma lipidomics signatures could serve as an efficient and accurate tool for early diagnosis and provide unprecedented insight into the pathogenesis of SLE.It is difficult to improve the curative effects of cancer immunotherapy on solid tumors. Cytokines, as powerful immune regulators, show potential in activating host antitumor immunity. We have previously found that the administration of certain cytokine combinations induces complete tumor clearance. Here, we constructed cognate fusion cytokines and evaluated their antitumor effects in various mouse tumor models. The in situ induction of the expression of the fusion cytokine IL12IL2GMCSF caused tumor eradication, including that of the tumors at advanced stages. An immune memory against unrelated syngeneic tumors was also elicited. Furthermore, flow cytometry analysis revealed that tumor-infiltrating CD3+ cells were greatly increased in the treated tumors and were accompanied by an elevation of CD8+/CD4+ ratios. This fusion protein exhibited superior immune activating capability compared to that of cytokine mixtures, in the experiments done in vitro. We also induced tumor regression in various immunocompetent tumor models via intratumoral injection. To improve its translational potential for clinical application, a systemically-administered immunocytokine, IL12IL2DiaNFGMCSF, was constructed by inserting a tumor-targeting diabody in the fusion protein. This protein also displayed good immune stimulating activities in vitro. Intravenous infusion of IL12IL2DiaNFGMCSF induced tumor-infiltrating immune cell alterations like IL12IL2GMCSF, with moderate serum IFNγ increment. Therapeutic effects were observed in the various tumor models after systemic administration of IL12IL2DiaNFGMCSF, but with slight toxicity. These results show the feasibility of developing a versatile cancer immunotherapy.