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- | Biomarker, Journal, IO biomarker: COMP (Cartilage Oligomeric Matrix Protein) Neoepitope: A Novel Biomarker to Identify Symptomatic Carotid Stenosis. (Pubmed Central) - Mar 16, 2021
Degradation of COMP may be associated with atherosclerosis progression and generation of a specific COMP fragment-COMPneo. This may represent a novel biomarker that together with COMPtotal and other risk-markers could be used to identify symptomatic carotid stenosis.
- | Journal: Angiopoietin-2 regulates vessels encapsulated by tumor clusters positive hepatocellular carcinoma nest-type metastasis via integrin α5β1 (Pubmed Central) - Mar 16, 2021
VETC (+) HCC could metastasize as a whole in a nested form, and possesses a specific regulatory protein. Ang-2/α5β1/FAK might be potential protein targets in the treatment of VETC (+) HCC nest-type metastasis.
- || Clinical, Journal: miRNA-92a-3p regulates osteoblast differentiation in patients with concomitant limb fractures and TBI via IBSP/PI3K-AKT inhibition. (Pubmed Central) - Mar 16, 2021
Collectively, these results indicate that miRNA-92a-3p overexpression may be a key factor underlying the improved fracture healing observed in TBI patients. Upregulation of miRNA-92a-3p may therefore be a promising therapeutic strategy for promoting fracture healing and preventing nonunion.
- nintedanib / Generic mfg.
[VIRTUAL] Soluble Thy-1 Reverses Established Lung Fibrosis in a Progressive Model () - Mar 14, 2021 - Abstract #ATS2021ATS_5151;
On the other hand, only sThy1 consistently induced resolution of fibrosis in a progressive model. sThy1 can reverse progressive lung fibrosis, underscoring its antifibrotic potential.
- [VIRTUAL] Binding of SARS-CoV-2 to the avb6 Integrins May Promote Severe COVID in Patients with IPF () - Mar 14, 2021 - Abstract #ATS2021ATS_4593;
In IPF patients, ACE2 levels and αvβ6 integrin levels are increased. Increased binding of the SARS-CoV-2 to ACE2 and the αvβ6 integrin within fibrotic lung may explain the increased risk of severe COVID in patients with IPF.
- [VIRTUAL] Differential Gene Expression and Pathway Enrichment May Explain Female Resistance to Emphysema in Murine Models of COPD () - Mar 14, 2021 - Abstract #ATS2021ATS_220;
Increased binding of the SARS-CoV-2 to ACE2 and the αvβ6 integrin within fibrotic lung may explain the increased risk of severe COVID in patients with IPF. This study demonstrates that changes in the extracellular matrix after cigarette smoking are not explained by sex, whereas pathways related to immune response and regulation of protein translation may contribute to the relative resistance against emphysema observed in female C57BL/6 mice.
- | Journal: Signal Transduction: Physical Deformation of the Membrane Activates Integrins. (Pubmed Central) - Mar 13, 2021
This study demonstrates that changes in the extracellular matrix after cigarette smoking are not explained by sex, whereas pathways related to immune response and regulation of protein translation may contribute to the relative resistance against emphysema observed in female C57BL/6 mice. New work describes a novel mechanism of mechanotransduction, whereby force-induced membrane deformation activates integrins by disrupting the association of the transmembrane domains of α and β integrins.
- ||||| Preclinical: This is a cool technique for multiplexed mass cytometry profiling of murine tumors, including mapping of cancer cell - immune cell interactions. The CD29/CD98 “trick” for murine cancer cell lines is a good one. From @DrLizJaffee @wonjinho1 @hopkinskimmel https://t.co/UBEGXp76U3 (Twitter) - Mar 12, 2021
- | Journal: A Specialized Niche in the Pancreatic Microenvironment Promotes Endocrine Differentiation. (Pubmed Central) - Mar 12, 2021
Next, we measured functional conservation between mouse and human pancreatic mesenchyme by testing identified mesenchymal factors in an iPSC-based differentiation model. Our findings provide insights into how lineage-specific crosstalk between epithelium and neighboring mesenchymal cells underpin the generation of different pancreatic cell types.
- | Journal: Tp0136 targets fibronectin (RGD)/Integrin β1 interactions promoting human microvascular endothelial cell migration. (Pubmed Central) - Mar 12, 2021
Additionally, after pretreatment with an anti-fibronectin antibody, an anti-integrin β1 antibody or RGD, the migration of HMEC-1 cells treated with Tp0136 was obviously suppressed. These results show that Tp0136 promots the migration of HMEC-1 cells by inducing CCL2 expression via the interaction of the fibronectin RGD domain with integrin β1 and the CCL2/CCR2 signaling pathway, and these interactions may contribute to the mechanisms that increase the capacity for self-healing syphilis infection.
- || Herceptin (trastuzumab) / Roche
Clinical, Journal: Osteopontin Level and Promoter Polymorphism in Patients with Metastatic Breast Cancer. (Pubmed Central) - Mar 12, 2021
Trastuzumab (in cases of her2-positive disease) was given whenever possible (if government assistance or personal finances permitted)...Concordance between elisa and pcr results indicates that either method can be used for the evaluation of opn. Increased opn gene mutation in triple-negative bca could assist in tailoring the treatment response in this very aggressive tumour subtype and could be considered a targetable molecule in future studies.
- | Journal: Aquaporin-2 and Na /H exchanger isoform 1 modulate the efficiency of renal cell migration. (Pubmed Central) - Mar 11, 2021
NHE1 blockage significantly reduced the rate of cell migration, the number of lamellipodia, and the assembly of F-actin only in AQP2-expressing cells. Our data suggest that AQP2 modulates the activity of NHE1 through its calcium channel partner TRPV4, thereby determining pH-dependent actin polymerization, providing mechanical stability to delineate lamellipodia structure and defining the efficiency of cell migration.
- | Journal: Laminin is the ECM niche for trophoblast stem cells. (Pubmed Central) - Mar 11, 2021
Importantly, when the integrin-binding ability of laminin was genetically ablated in mice, the size of the TSC population was significantly reduced compared with that in control mice. The present findings underscore an ECM niche function of laminin to support tissue stem cell maintenance in vivo.
- | Journal: Role of miR-30a-3p Regulation of Oncogenic Targets in Pancreatic Ductal Adenocarcinoma Pathogenesis. (Pubmed Central) - Mar 11, 2021
The knockdown of ITGA2 expression attenuated the malignant phenotypes of the PDAC cells. Together, results from these microRNA-based approaches can accelerate our understanding of PDAC molecular pathogenesis.
- | Journal: Oral immunization induces a novel CXCR6 β7 intraepithelial lymphocyte subset predominating in the small intestine. (Pubmed Central) - Mar 11, 2021
As β7 exclusively paired with αE on IELs, our results strongly suggest that CXCR6 may cooperate with the heterodimer αEβ7 to preferentially retain intestinally-induced effector IELs in the epithelium. The identification of this novel IEL phenotype has significant implications for the development of vaccines and therapeutic strategies to enhance gut immunity.
- | Journal: Secreted Pyruvate Kinase M2 Promotes Lung Cancer Metastasis through Activating the Integrin Beta1/FAK Signaling Pathway. (Pubmed Central) - Mar 9, 2021
Mechanistically, secreted PKM2 directly bound to integrin β1 and subsequently activated the FAK/SRC/ERK axis to promote tumor metastasis. Collectively, our findings suggest that PKM2 is a potential serum biomarker for diagnosing lung cancer and that targeting the secreted PKM2-integrin β1 axis can inhibit lung cancer development, which provides evidence of a potential therapeutic strategy in lung cancer.
- | cisplatin / Generic mfg.
Journal: Insight into Cisplatin-Resistance Signaling of W1 Ovarian Cancer Cells Emerges mTOR and HSP27 as Targets for Sensitization Strategies. (Pubmed Central) - Mar 9, 2021
Remarkably, knockdown of HSP27, another downstream MAPK pathway component overcomes intrinsic resistance completely sensitizing W1CR cells to the level of W1 cells for cisplatin cytotoxicity. Our data confirm the independent regulation of matrix-induced and intrinsic chemoresistance in W1 ovarian cancer cells and offer novel targets for sensitization.
- || Review, Journal: Nephronectin as a Matrix Effector in Cancer. (Pubmed Central) - Mar 7, 2021
Integrins have long been desired as therapeutic targets, where low efficiency and receptor redundancy have been major issues. Based on the summarised publications, the enhancer-motif of nephronectin could present a novel therapeutic target.
- | Journal: Substance P-embedded multilayer on titanium substrates promotes local osseointegration via MSC recruitment. (Pubmed Central) - Mar 6, 2021
Consistently, the Ti/LBL-SP implants also significantly enhanced new bone formation according to the results of micro-CT scanning analysis, H&E staining, Masson's trichrome staining and immunohistochemical staining. The obtained results reveal that SP-modified Ti-based substrates were beneficial for bone formation via recruiting endogenous MSCs.
- [VIRTUAL] Human CD4 Th17 cells cause direct damage to oligodendrocytes trough glutamate secretion () - Mar 6, 2021 - Abstract #ACTRIMSForum2021ACTRIMS_Forum_373;
In addition, we discovered that Th17-secreted glutamate could mediate oligodendrocyte cell processes injury. Moreover, our RNA sequencing data highlighted that glutamate influences oligodendrocyte transcriptomic.
- [VIRTUAL] Cspgs Impede Remyelination In Multiple Sclerosis By Promoting Th17 Neuroinflammation () - Mar 6, 2021 - Abstract #ACTRIMSForum2021ACTRIMS_Forum_329;
These results highlight the role oflesion-elevated CSPGs, especially versican V1, in shaping T cell responses which thenimpact remyelination outcomes. We propose CSPG-lowering drugs as dual prongedrepair therapeutics that directly affect OPCs, and that indirectly antagonize Th17 roles ininflammation and oligodendrocyte injury.Objectives:
- | Preclinical, Journal: Spatial survey of non-collagenous proteins in mineralizing and non-mineralizing vertebrate tissues ex vivo. (Pubmed Central) - Mar 6, 2021
The results from this study indicated that osteocalcin was closely involved in mineralization but did not preclude possible additional roles as a hormone. This report provides for the first time a spatial survey and comparison of NCPs from mineralizing and non-mineralizing tissues ex vivo and defines the proteome of turkey leg tendons as a model for vertebrate mineralization.
- || Review, Journal: Molecular structure, expression, and functional role of Clec11a in skeletal biology and cancers. (Pubmed Central) - Mar 5, 2021
To date, however, the mechanisms governing transcription regulation of the Clec11a gene are not known and remain to be uncovered. Understanding the function and mechanism of action of Clec11a will pave the way for the development of Clec11a as a novel therapeutic target for conditions such as cancer, anemia, and skeletal diseases.
- | AXT107 / Asclepix
Journal: Suppression of Ocular Vascular Inflammation through Peptide-Mediated Activation of Angiopoietin-Tie2 Signaling. (Pubmed Central) - Mar 5, 2021
AXT107 also decreased the levels of pro-inflammatory TNF receptor 1 (TNFR1) without affecting levels of the more protective TNFR2. These data suggest that AXT107 may provide multiple benefits in the treatment of retinal/choroidal and other vascular diseases by suppressing inflammation and promoting vascular stabilization.
- | Journal: Establishing a density-based method to separate proliferating and senescent cells from bone marrow stromal cells. (Pubmed Central) - Mar 5, 2021
We confirmed that over 80% of cells from the low-density gradient layer were senescent with SA-β-gal staining and telomere dysfunction-induced foci (TIF) assay. This density-based method, which can separate proliferating and senescent BMSCs, could be used to study mechanisms of physiologic cell aging and may have implications for the use of BMSCs in clinical transplant applications.
- | Journal: UV irradiation of Type I collagen gels changed the morphology of the interconnected brain capillary endothelial cells on them. (Pubmed Central) - Mar 4, 2021
Thick actin filaments were more clearly observed in the cells on the UV-irradiated collagen gel than the unirradiated one by fluorescent microscopy. We conclude that UV irradiation made the collagen gel stiffened and changed the physiological state of bEnd.3 cells including their adhesion, extension, and proliferation.
- | mitoxantrone / Generic mfg., gefitinib / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Journal: Targeting Discoidin Domain Receptor 1 (DDR1) Signaling and Its Crosstalk with β-integrin Emerges as a Key Factor for Breast Cancer Chemosensitization upon Collagen Type 1 Binding. (Pubmed Central) - Mar 3, 2021
Since ITGB1-knockdown also induces upregulation of pEGFR in MDA-MB-231 cells, inhibitory approaches including EGFR inhibitors, such as gefitinib appear promising for pharmacological interference. These findings provide evidence for the highly dynamic adaptation of breast cancer cells in maintaining matrix binding to circumvent cytotoxicity and highlight DDR1 signaling as a target for sensitization approaches.
- | Journal: Podocyte Integrin-β and Activated Protein C Coordinately Restrict RhoA Signaling and Ameliorate Diabetic Nephropathy. (Pubmed Central) - Mar 3, 2021
Pharmacologic inhibition of PAR1, the pivotal thrombin receptor, restricts RhoA activation and nephroprotects RGE-aPC and wild-type mice.Conclusions aPC-integrin-αβ acts as a rheostat, controlling PAR1-dependent RhoA activation in podocytes in diabetic nephropathy. These results identify integrin-αβ as an essential coreceptor for aPC that is required for nephroprotective aPC-PAR signaling in dNP.
- | Preclinical, Journal: Microfluidic-assisted preparation of RGD-decorated nanoparticles: exploring integrin-facilitated uptake in cancer cell lines. (Pubmed Central) - Mar 3, 2021
The strong preference of U87MG for cyclic (vs. linear) peptide-decorated nanoparticles was shown in 2D culture and further demonstrated in spheroids. Our results demonstrate that targeting specific integrin make-ups is possible and may open the way to more precise treatment, but more efforts need to be devoted to a better understanding of the relation between RGD structure and their integrin-binding capacity.
- | Journal: Partial Sperm beta1 Integrin Subunit Deletion Proves its Involvement in Mouse Gamete Adhesion/Fusion. (Pubmed Central) - Mar 3, 2021
Here, we showed for the first time that the deletion, even partial, of the sperm Itgb1 gene makes the sperm unable to normally fertilize oocytes. However, to elucidate the question of the essentiality of its role during fertilization, further investigations using a mouse expressing a recombinase more effective in male germ cells are necessary.
- | dexamethasone / Generic mfg.
Journal: Comparison of Osteogenic Potential of Phenytoin with Dexamethasone in Cultured Dental Pulp Stem Cells. (Pubmed Central) - Mar 3, 2021
Moreover, western blot results of DPH group showed significant increase of ALP, RUNX2 and osteopontin (OSP) in comparison with control. The data of present study showed the osteogenic activity of phenytoin, considering as an alternative of dexamethasone for inducing osteogenic differentiation of dental pulp stem cells.
- | Journal: THBS4 promotes HCC progression by regulating ITGB1 via FAK/PI3K/AKT pathway. (Pubmed Central) - Mar 2, 2021
In-depth, THBS4 regulated EMT progression and interacted with ITG family to modulate FAK/PI3K/AKT pathway. In conclusion, THBS4 as an oncogene interacts with integrinβ1 (ITGB1) to regulate HCC development via FAK/PI3K/AKT pathway.
- || Biomarker, Clinical, Journal: A SEMA3 Signaling Pathway-Based Multi-Biomarker for Prediction of Glioma Patient Survival. (Pubmed Central) - Mar 2, 2021
Seven genes significantly associated with patient overall survival were used for multi-biomarker construction, which showed 64%, 75%, and 68% of accuracy of predicting the survival of 1-, 2-, and 3-year glioma patients, respectively. The results suggest that the seven-gene signature could serve as a novel multi-biomarker for more accurate prognosis of a glioma patient's outcome.
- | Journal, Cancer stem cells: Differential glycosylation of collagen modulates lung cancer stem cell subsets through β1 integrin-mediated interactions. (Pubmed Central) - Mar 2, 2021
We provide evidence suggesting that collagen glycosylation could play an essential role in modulating the creation of a niche favorable for the generation and selection/survival of lung CSCs. Interfering with this cross talk may represent an innovative therapeutic strategy for lung cancer treatment.
- | Journal: ECT2 promotes lung adenocarcinoma progression through extracellular matrix dynamics and focal adhesion signaling. (Pubmed Central) - Mar 2, 2021
Moreover, in LAC cells, ECT2 binds to and stabilizes FAK and to be associated with formation of the focal adhesions. Our findings provide new insights into the underlying role of ECT2 in cell-ECM dynamics during LAC progression and suggest that ECT2 could be a promising therapeutic avenue for lung cancer.
- | Journal: The progression of intracerebral hemorrhage (ICH) is related to the expression of integrin Β1 (ITGB1). (Pubmed Central) - Mar 2, 2021
In summary, the clinical progression of ICH was related to the expression of ITGB1. ITGB1 may be a potential biomarker and contribute to the treatment of ICH.
- | Journal: Isolation and Multiple Differentiation of Rat Pericardial Fluid Cells. (Pubmed Central) - Mar 2, 2021
This study revealed that a subpopulation of cells was isolated from pericardial fluid, which exhibited progenitor cell features and multiple differentiation potency. PFCs could serve as an alternative cell source for myocardial tissue repair, engineering, and reconstruction.
- | naproxen / Generic mfg.
Journal: Synthesis and biological evaluation of RGD conjugated with Ketoprofen/Naproxen and radiolabeled with [Tc] via N4(GGAG) for αβ integrin-targeted drug delivery. (Pubmed Central) - Feb 27, 2021
Provided that NSAID drugs are conjugated to RGD, there will be a selective delivery to target tissues as well as synergetic anti-tumor effects which reduce systemic doses and toxicity. Graphical abstract.
- || Review, Journal: Involvement of Integrin-Activating Peptides Derived from Tenascin-C in Cancer Aggression and New Anticancer Strategy Using the Fibronectin-Derived Integrin-Inactivating Peptide. (Pubmed Central) - Feb 27, 2021
Notably, the detrimental effects of TNIIIA2 can be inhibited by FNIII14. These findings open the possibility for new therapeutic strategies based on the inactivation of β1-integrin by FNIII14.
- | Journal: Bie Jia Jian Pill Combined with Bone Mesenchymal Stem Cells Regulates microRNA-140 to Suppress Hepatocellular Carcinoma Stem Cells. (Pubmed Central) - Feb 27, 2021
Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.
- | Journal: P38 MAPK Promotes Migration and Metastatic Activity of BRAF Mutant Melanoma Cells by Inducing Degradation of PMCA4b. (Pubmed Central) - Feb 26, 2021
Inhibition of the p38 MAPK pathway markedly reduced migration, colony formation and metastatic activity of BRAF mutant cells in vitro partially through an increase in PMCA4b and a decrease in β4 integrin abundance. In conclusion, our data suggest that the p38 MAPK pathway plays a key role in PMCA4b degradation and inhibition of this pathway-by increasing the stability of PMCA4b-may provide a potential therapeutic target for inhibition of melanoma progression and metastasis.
- | Legalon (silibinin) / Mylan
Journal: Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat Model. (Pubmed Central) - Feb 26, 2021
However, immunohistochemical (IHC) staining showed no significant change in CXCR4 expression in the BM of the tibias. These results suggest that silibinin increases the expression of CXCR4 in BM, and the increased CXCR4-positive cells could be granulocytes/monocyte-macrophages.
- | Preclinical, Journal: Reversible Growth-Arrest of a Spontaneously-Derived Human MSC-Like Cell Line. (Pubmed Central) - Feb 26, 2021
Thus, expression of proliferation-associated genes was down-modulated in confluent MSC544 and re-expressed following sub-confluent conditions whilst telomerase (hTERT) transcripts remained detectable at similar levels in both, confluent growth-arrested and proliferating MSC544. Together with the capability of connective cell layer formation for potential therapeutic approaches, MSC544 provide a long term reproducible human cell source with constant properties.
- | Journal: Human umbilical cord mesenchymal stromal cells-derived extracellular vesicles exert potent bone protective effects by CLEC11A-mediated regulation of bone metabolism. (Pubmed Central) - Feb 23, 2021
Moreover, CLEC11A was required for the inhibitory effects of hucMSC-EVs on osteoclast formation. Our results suggest that hucMSC-EVs serve as a critical regulator of bone metabolism by transferring CLEC11A and may represent a potential agent for prevention and treatment of osteoporosis.
- | Journal: Quantitative proteomic analysis in serum of Takifugu rubripes infected with Cryptocaryon irritans. (Pubmed Central) - Feb 23, 2021
The proteins identified in our work may serve as candidates for elucidating the molecular mechanism of cryptocaryonosis in T. rubripes. Our collective findings could provide new insights into searching for disease-specific targets and biomarkers, which may be effective indicators of C. irritans infection in T. rubripes.
- | Preclinical, Journal: The Impact of Small Extracellular Vesicles on Lymphoblast Trafficking across the Blood-Cerebrospinal Fluid Barrier In Vitro. (Pubmed Central) - Feb 23, 2021
In addition, only P12-derived exosomes led to facilitated transmigration of the parental leukemia cells. In conclusion, we provide evidence that, to a varying extent, leukemia-derived exosomes may facilitate CNS invasion of ALL across the BCSFB without destruction of the barrier integrity.
- | Journal: E-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1. (Pubmed Central) - Feb 23, 2021
Our findings, for the first time, showed that E-cig promotes BC growth and metastasis. This study highlights the critical role of TAMs via CCL5 and VCAM-1 pathways in E-cig promoted BC tumor development.
- | Preclinical, Journal: Multilineage Differentiation Potential of Human Dental Pulp Stem Cells-Impact of 3D and Hypoxic Environment on Osteogenesis In Vitro. (Pubmed Central) - Feb 23, 2021
DPSCs exhibiting elevated osteogenic potential may serve as potential candidates for a cell-based product for advanced therapy, particularly for bone repair. Novel tissue engineering approaches combining DPSCs, 3D biomaterial scaffolds, and other stimulating chemical factors may represent innovative strategies for pro-regenerative therapies.
- | Journal: Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding. (Pubmed Central) - Feb 20, 2021
Through comparative sequence analysis of kindlin-2 and kindlin-3, we identify kindlin-3 point mutations that decrease self-association and enhance integrin binding, affording mutant kindlin-3 the ability to localize to focal adhesions. Our results support the notion that kindlin self-association negatively regulates integrin binding.
- || Clinical, Journal: Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-β Signaling Overactivation. (Pubmed Central) - Feb 20, 2021
Taken together, these data demonstrate that in our patient, segmental SSS is characterized by the overactivation of multiple TGF-β signaling pathways, which likely results in altered extracellular matrix composition and fibroblast homeostasis. Our results for the first time reported that aberrant TGF-β signaling may drive the pathogenesis of segmental SSS and might open the way to novel therapeutic approaches.