β1 integrin inhib 
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  • ||||||||||  PD98059 / Wayne State University
    Journal:  FRET Visualization of Cyclic Stretch-Activated ERK via Calcium Channels Mechanosensation While Not Integrin β1 in Airway Smooth Muscle Cells. (Pubmed Central) -  Jun 8, 2022   
    FRET measurements showed apparent ERK activation by mechanical stretch, which was abolished by ERK inhibitor PD98059 pretreatment...Furthermore, the ER IPR-dependent ERK activation was not dependent on phospholipase C-IP signal, indicating possibly more mechanical mechanism for IPR activation. It is concluded from our study that the mechanical stretch activated intracellular ERK signal in ASM cells through membrane Ca channels mechanosensation but not integrin β1, which was mediated by actin cytoskeleton.
  • ||||||||||  Journal:  Evidence That β1-Integrin Is Required for the Anti-Viability and Anti-Proliferative Effect of Resveratrol in CRC Cells. (Pubmed Central) -  May 21, 2022   
    Similarly, resveratrol-blocked TME-induced p65-NF-kB and its promoted gene markers linked to proliferation (cyclin D1), invasion (focal adhesion kinase, FAK), or apoptosis (caspase-3), were largely abrogated by anti-β1-integrin or RGD peptide, suggesting that β1-integrin is a potential transmission pathway for resveratrol/integrin down-stream signaling in CRC cells. The current results highlight, for the first time, the important gateway role of β1-integrins as signal carriers for resveratrol on the surfaces of HCT116 and SW480 cells, and their functional cooperation for the modulatory effects of resveratrol on TME-promoted tumorigenesis.
  • ||||||||||  Campath (alemtuzumab) / Sanofi
    Journal:  Update on immunosuppressive strategies in intestinal transplantation. (Pubmed Central) -  May 6, 2022   
    New insights into immune pathways associated with rejection and GVHD in intestinal allografts have led to an evolution of therapies from broad-based immunosuppression to more targeted strategies that hold promise for reducing morbidity from infection, rejection, and GVHD. These should be the focus of further study to facilitate their widespread use.
  • ||||||||||  NEW AUTOANTIBODY IN PATIENTS WITH ULCERATIVE COLITIS (Poster Hall - San Diego Convention Center) -  Apr 25, 2022 - Abstract #DDW2022DDW_4473;    
    Furthermore, we found that the autoantibodies inhibited integrin αvβ6-fibronectin binding, suggesting that they may be involved in the pathogenesis of ulcerative colitis. The autoantibodies may serve as a potential diagnostic biomarker with high sensitivity and specificity, and useful disease activity monitoring tool.
  • ||||||||||  Journal:  The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin α5β1 and NF-κB signaling. (Pubmed Central) -  Apr 19, 2022   
    We suggest that the spike protein, through its RGD motif in the receptor-binding domain, binds to integrin ⍺5β1 in ECs to activate the NF-κB target gene expression programs responsible for vascular leakage and leukocyte adhesion. These findings uncover a new direct action of SARS-CoV-2 on EC dysfunction and introduce integrin ⍺5β1 as a promising target for treating vascular inflammation in COVID-19.
  • ||||||||||  Journal:  Puerarin specifically disrupts osteoclast activation via blocking integrin-β3 Pyk2/Src/Cbl signaling pathway. (Pubmed Central) -  Mar 3, 2022   
    Collectively, puerarin prevented the bone loss in OVX rat through suppression of osteoclast activation and bone resorption, by inhibiting integrin-β3-Pyk2/Cbl/Src signaling pathway, without affecting osteoclasts formation or apoptosis. These results demonstrate the unique mechanism of puerarin on bone metabolism and provide a novel agent for prevention of postmenopausal osteoporosis.
  • ||||||||||  Journal:  Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel. (Pubmed Central) -  May 15, 2021   
    In addition, activation can be induced in a dose-dependent manner via both defined cytokine cocktails and low molecular weight hyaluronic acid. This synthetic brain hydrogel is envisioned as a new tool to study the physiological role of astrocytes in health and disease.
  • ||||||||||  Journal:  Kindlin Assists Talin to Promote Integrin Activation. (Pubmed Central) -  May 15, 2021   
    Furthermore, kindlin modifies the molecular mechanisms of inside-out activation by decreasing the crossing angle between transmembrane helices of integrin αIIbβ3, which eventually results in parallelization of integrin dimer. In addition, our control simulation featuring integrin in complex with kindlin reveals that kindlin binding is not sufficient for unclasping the inner-membrane and outer-membrane interactions of integrin dimer, thus ruling out the possibility of solitary action of kindlin in integrin activation.
  • ||||||||||  Journal:  Discovery of cyclic guanidine-linked sulfonamides as inhibitors of LMTK3 kinase. (Pubmed Central) -  May 15, 2021   
    We used a homogeneous time resolve fluorescence (HTRF) assay to screen a collection of mixture-based combinatorial chemical libraries containing over 18 million compounds. We identified several cyclic guanidine-linked sulfonamides with sub-micromolar activity and evaluated their binding mode using a 3D homology model of the LMTK3 K.
  • ||||||||||  Journal:  Modification of PLGA Scaffold by MSC-Derived Extracellular Matrix Combats Macrophage Inflammation to Initiate Bone Regeneration via TGF-β-Induced Protein. (Pubmed Central) -  May 15, 2021   
    Furthermore, the PLGA-ECM scaffolds with the knockdown of transforming growth factor-β-induced protein (TGFβI/βig-H3) demonstrate that M2 macrophage accumulation improved by the PLGA-ECM could be attributed to increasing the migration of M2 macrophages and the repolarization of M1 macrophages to M2 phenotype, which are mediated by multiple integrin signaling pathways involving in integrin β7, integrin α9, and integrin β1 in a TGFβI-dependent manner. This study presents an effective surface modification strategy of polymeric scaffolds to initiate tissue regeneration and combat inflammatory response by increasing M2 macrophage accumulation.
  • ||||||||||  Preclinical, Journal:  Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids. (Pubmed Central) -  May 15, 2021   
    Intestinal enteroids, in addition, retain their proliferative capacity, are functionally responsive to basolateral stimulation, express canonical markers of intestinal crypt cells including Paneth cells, and can be serially passaged. The success of this synthetic ECM in supporting human postnatal organoid culture from multiple different donors and from both the intestine and endometrium suggests it may be broadly useful for other epithelial organoid culture.
  • ||||||||||  Journal:  Customized hydrogel substrates for serum-free expansion of functional hMSCs. (Pubmed Central) -  May 15, 2021   
    The identified substrates were compatible with standard thaw, seed, and harvest protocols. Finally, we used MVA on the screening data to reveal the importance of serum and substrate stiffness on hMSC expansion, highlighting the need for customized cell culture substrates in optimal hMSC biomanufacturing processes.
  • ||||||||||  Journal:  Mechanically induced formation and maturation of 3D-matrix adhesions (3DMAs) in human mesenchymal stem cells. (Pubmed Central) -  May 15, 2021   
    Mechanical preconditioning hMSCs with long-term compression loading induces the formation of mature integrin α-dependent 3DMAs and potentiates their osteogenesis. Collectively, this work shows that active mechanical stimulation can modulate cell-matrix interactions significantly at the cell-material interfaces in a dynamic manner, and affects cell fate decisions, demonstrating the significance of loading-based functional tissue engineering.
  • ||||||||||  Journal:  A frog-derived bionic peptide with discriminative inhibition of tumors based on integrin αvβ3 identification. (Pubmed Central) -  May 15, 2021   
    Meanwhile, increased stability and superior therapeutic efficacy are achieved in vivo for the RA3 fusion peptide. Our study highlights that aided by computational simulation technologies, the biomimetic fusion RA3 peptide has been successfully designed, surmounting the poor tumor-selectivity of the natural defensive peptide, serving as a promising therapeutic agent for cancer treatment.
  • ||||||||||  Journal:  Three-Dimensional Bioprinted Hyaluronic Acid Hydrogel Test Beds for Assessing Neural Cell Responses to Competitive Growth Stimuli. (Pubmed Central) -  May 15, 2021   
    Overall, the selected MeHA/collagen-I bioink was bioprintable, improved cell viability compared to molded controls, and was conducive for cell adhesion, growth factor sequestration, and neural cell infiltration. MeHA is a suitable bioink candidate for extrusion-based bioprinting and will be useful in future development of spatially complex test beds to advance in vitro models as an alternative to common in vivo tests for neural repair applications.
  • ||||||||||  Journal:  Discovery of a Novel Polymer for Xeno-Free, Long-Term Culture of Human Pluripotent Stem Cell Expansion. (Pubmed Central) -  May 15, 2021   
    Analysis of cell-polymer interface interactions through mass spectrometry and integrin blocking studies provides novel mechanistic insight into the role of the E8 proteins in promoting integrin-mediated hPSC attachment and maintaining hPSC signaling, including ability to undergo multi-lineage differentiation. This study therefore identifies a novel substrate for long-term serial passaging of hPSCs in serum-free, commercial chemically-defined E8, which provides a promising and economic hPSC expansion platform for clinical-scale application.
  • ||||||||||  Preclinical, Journal:  Engineered Three-Dimensional Tumor Models to Study Natural Killer Cell Suppression. (Pubmed Central) -  May 15, 2021   
    Relative to conventional 2D cocultures, NK-92 cell mediated cytotoxicity was reduced in the 3D tumor models, suggesting the hydrogel serves to mimic some features of the biophysical barriers in in vivo tumor microenvironments. This study demonstrates the feasibility of a synthetic hydrogel system for investigating the biophysical and biochemical cues impacting NK cell infiltration and NK cell-cancer cell interactions in the solid tumor microenvironment.
  • ||||||||||  Journal:  Differential expression of αVβ3 and αVβ6 integrins in prostate cancer progression. (Pubmed Central) -  May 15, 2021   
    In summary, we demonstrate that αVβ3 integrin is upregulated in NEPrCa primary and metastatic lesions; in contrast, the αVβ6 integrin is confined to adenocarcinoma of the prostate. Our findings suggest that the αVβ3 integrin, but not αVβ6, may promote a shift in lineage plasticity towards a NE phenotype and might serve as an informative biomarker for the early detection of NE differentiation in prostate cancer.
  • ||||||||||  Preclinical, Journal:  In vivo monitoring platform of transplanted human stem cells using magnetic resonance imaging. (Pubmed Central) -  May 15, 2021   
    Furthermore, we verified that intravenously injected MnOHo-Ab specifically targeted human induced pluripotent stem cells (hiPSCs) that were transferred to mice testes and differentiated into various lineages. The new stem cell monitoring method using MnOHo-Ab demonstrates whether the injected human stem cells have migrated and transplanted themselves in the target area during long-term stem cell regenerative therapy.
  • ||||||||||  Journal:  Construction of bioengineered corneal stromal implants using an allogeneic cornea-derived matrix. (Pubmed Central) -  May 15, 2021   
    When the ACM was implanted into rabbit corneal stromal pockets, the rabbit cornea remained transparent throughout the follow-up period. These results indicate that the construction of corneal stromal implants from discarded human corneal tissues may pave the way for the generation of high-quality corneal tissue for transplantation.
  • ||||||||||  Journal:  Enhanced Collagen-like Protein for Facile Biomaterial Fabrication. (Pubmed Central) -  May 15, 2021   
    Moreover, such hydrogels containing the constructs with the RGD integrin-binding sequence are shown to promote the adhesion, spreading, and proliferation of C2C12 and 3T3 cells in vitro. Due to its enhanced solubility, structural stability, fluidity at elevated concentrations, ease of modification, and facility of cross-linking, this eBCL collagen-mimetic system has potential for numerous biomedical material applications, where the ease of processing and fabrication and the facility to tailor the sequence for specific biological functionality are desired.
  • ||||||||||  Journal:  Exosomes secreted by macrophages upon copper ion stimulation can promote angiogenesis. (Pubmed Central) -  May 15, 2021   
    The exosomes have little influence on endothelial adhesion and proliferation, but can upregulate angiogenic ability of endothelial cells in vitro and in vivo, which may be related to trafficking of integrin β1. The results provide insight into the effect of copper ions on immunomodulatory mechanism of macrophages, which is important for implant design from the perspective of material compositions.