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- | Journal: Tendon-derived extracellular matrix induces mesenchymal stem cell tenogenesis via an integrin/transforming growth factor-β crosstalk-mediated mechanism. (Pubmed Central) - Jan 16, 2021
Together, these findings suggest that the strong pro-tenogenic bioactivity of tECM is regulated via integrin/TGF-β signaling crosstalk. Understanding how integrins interact with signaling by TGF-β and/or other growth factors (GFs) within the tendon ECM microenvironment will provide a rational basis for an ECM-based approach for tendon repair.
- | Cilcane (cilengitide) / Iceni Pharma
Preclinical, Journal: The iron-regulated surface determinant B (IsdB) protein from Staphylococcus aureus acts as a receptor for the host protein vitronectin. (Pubmed Central) - Jan 15, 2021
Furthermore, IsdB-expressing bacterial cells bound significantly higher amounts of Vn from human plasma than did an isdB mutant. Adherence to and invasion of epithelial and endothelial cells by IsdB-expressing S. aureus cells was promoted by Vn, and an αβ integrin-blocking monoclonal antibody or cilengitide inhibited adherence and invasion by staphylococci, suggesting that Vn acts as a bridge between IsdB and host αβ integrin.
- | Journal, PARP Biomarker: Inhibition of p70 isoforms of S6K1 induces anoikis to prevent transformed human hepatocyte growth. (Pubmed Central) - Jan 15, 2021
Our results suggested that p70-S6K1 inhibition alters orchestration of cell cycle progression, induces cell detachment, and sensitizes hepatocyte growth impairment. Targeting p70 isoform of S6K1 by inhibitor may prove to be a promising approach together with other therapies for hepatocellular carcinoma (HCC) treatment.
- | digoxin / Generic mfg.
Preclinical, Journal: Multifaceted anti-colorectal tumor effect of digoxin on HCT8 and SW620 cells in vitro. (Pubmed Central) - Jan 15, 2021
Furthermore, digoxin significantly reversed ABCB1-mediated multidrug resistance on SW620/Ad300 cells. Our findings suggest that digoxin has the potential to be applied as an antitumor drug via inhibiting proliferation and metastasis as well as reversing the ABCB1-mediated multidrug resistance of colorectal cancer.
- | Journal: Insect Cuticular Chitin Contributes to Form and Function. (Pubmed Central) - Jan 13, 2021
Mutations in integrins and their ligands, as well as depletion of chitin deacetylases, result in defective locomotion and muscle detachment from the ECM. Thus, chitin in the cuticle and chitin deacetylases strongly influence the shape and functions of the exoskeleton as well as locomotion of insects.
- | Journal: Multiple differentiation potential of human periodontal ligament stem cells expressing stromal cell antigen 1 (STRO-1) sorted by MACS (Pubmed Central) - Jan 13, 2021
STRO-1 cells were demonstrated to have osteogenic and adipogenic differentiation potential. Conclusion STRO-1 cells isolated by MACS are human periodontal ligament stem cells with stem cell characteristics.
- | Journal: [Corrigendum] Downregulation of β3 integrin by miR-30a-5p modulates cell adhesion and invasion by interrupting Erk/Ets‑1 network in triple-negative breast cancer. (Pubmed Central) - Jan 13, 2021
4D, appeared to show an overlap with a Figure included in the following paper that also featured some of the same authors, published in 2011 [Li W, Liu C, Tang Y, Li H, Zhou F and Lv S: Overexpression of Snail accelerates adriamycin induction of multidrug resistance in breast cancer cells...The authors are grateful to the Editor of International Journal of Oncology for granting them the opportunity to publish this Corrigendum, and all the authors agree to the publication of this Corrigendum. The authors sincerely apologize for the errors presented in this figure, and apologize to the readership for any inconvenience caused.[the original article was published in International Journal of Oncology 48: 1155‑1164, 2016; DOI: 10.3892/ijo.2016.3319].
- | Journal: Genetic encoding of targeted MRI contrast agents for tumor imaging. (Pubmed Central) - Jan 13, 2021
Specifically, we investigate their potential for enhanced binding and tumor imaging both in vitro and in vivo. Our experiments indicate that these tailored magnetosomes retain their magnetic properties, making them well-suited as T2 contrast agents, while exhibiting increased binding compared to wild-type magnetosomes.
- || Review, Journal: Towards understanding the messengers of extracellular space: Computational models of outside-in integrin reaction networks. (Pubmed Central) - Jan 12, 2021
We also discuss how these computational modeling efforts can be helpful in other disciplines such as biomaterial design. As such, this review is a didactic modeling summary for biomaterial researchers interested in complementing their experimental work with computational tools or for seasoned computational scientists that would like to advance current in silico integrin models.
- | Journal: Differential intolerance to loss of function and missense mutations in genes that encode human matricellular proteins. (Pubmed Central) - Jan 9, 2021
Deficits in missense mutations were also observed for other thrombospondin genes and for SPARC, SPOCK1, SPOCK2, TNR, and DSPP. The intolerance of THBS1 to loss of function in humans and elevated pLI values for THBS2, SPARC, SPOCK1, TNR, and CCN1 support important functions for these matricellular protein genes in humans, some of which may relate to functions in reproduction or responding to environmental stresses.
- | Journal, IO biomarker: Semi-synthetic product dihydroartemisinin inhibited fibronectin-1 and integrin-β1 and interfered with the migration of HCCLM6 cells via PI3K-AKT pathway. (Pubmed Central) - Jan 9, 2021
Our findings revealed that DHA could inhibit proliferation and migration of human hepatocellular carcinoma cells targeting FN1 and ITGB1 via the PI3K-AKT pathway. Therefore, DHA might be a novel drug with a potential effect against liver tumorigenesis and metastasis.
- | Preclinical, Journal: Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis. (Pubmed Central) - Jan 8, 2021
Moreover, blockade of TLR2 or ITGα5 but not Marco using specific antibody significantly reduced production of TNF-α in stimulated macrophages by cartilage fragments. Our data suggested that blocking TLR2 or ITGα5 might be promising therapeutic strategy for treating progressive osteoarthritis.
- | Journal: Human Cytomegalovirus Glycoprotein-Initiated Signaling Mediates the Aberrant Activation of Akt. (Pubmed Central) - Jan 7, 2021
In this work, we demonstrate that HCMV glycoproteins gB and gH work in tandem to reroute classical host cellular receptor signaling to aberrantly activate Akt and drive survival of infected monocytes. Deciphering how HCMV modulates the cellular pathway to induce monocyte survival is important to develop a new class of anti-HCMV drugs that could target and prevent spread of the virus by eliminating infected monocytes.
- | Journal: Characterization and Comparison of Human and Ovine Mesenchymal Stromal Cells from Three Corresponding Sources. (Pubmed Central) - Jan 6, 2021
In summary, this side by side comparison defined phenotypic similarities and differences of human and ovine MSCs from three different sources, thereby contributing to a better characterization and standardization of ovine MSCs. The key findings shown in this report demonstrate the utility of ovine MSCs in preclinical studies for MSC-based therapies.
- | OS2966 / Enochian BioSciences
Journal: Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging. (Pubmed Central) - Jan 6, 2021
The key findings shown in this report demonstrate the utility of ovine MSCs in preclinical studies for MSC-based therapies. The present study design leverages multiple innovations including: (1) the latest CED technology, (2) 2-part design including neoadjuvant intratumoral administration, (3) a first-in-class investigational therapeutic, and (4) concentration-based dosing.
- | Preclinical, Journal: Antibodies against nephronectin ameliorate anti-type II collagen-induced arthritis in mice. (Pubmed Central) - Jan 6, 2021
Here, we developed a new ELISA system to detect Npnt in various autoimmune diseases, which revealed that plasma Npnt levels are increased in various mouse autoimmune models. We also report that antibodies against the α8β1 integrin-binding region of Npnt protect mice from anti-type II collagen-induced arthritis, suggesting that Npnt may be a potential therapeutic target molecule for the prevention of autoimmune arthritis.
- | gentamicin sulfate / Generic mfg.
Preclinical, Journal: Reno-protection of Urine-derived Stem Cells in A Chronic Kidney Disease Rat Model Induced by Renal Ischemia and Nephrotoxicity. (Pubmed Central) - Jan 6, 2021
The present study demonstrates the nephron-protective effect of USC on renal function via anti-inflammatory, anti-oxidative stress, and anti-fibrotic activity in a dual-injury CKD rat model. This provides an alternative treatment for CKD in certain clinical situations, such as instances where CKD is due to drug-induced nephrotoxicity and renal ischemia.
- || Review, Journal: β2 Integrins-Multi-Functional Leukocyte Receptors in Health and Disease. (Pubmed Central) - Jan 6, 2021
Consequently, β2 integrins have received growing interest as targets in the treatment of autoimmune diseases. Moreover, β2 integrin activity on leukocytes has been implicated in tumor development.
- | Preclinical, Journal: Evolution of ASC Immunophenotypical Subsets During Expansion In Vitro. (Pubmed Central) - Jan 6, 2021
However, even at passage 8, there were several predominant lineages that differed with respect to the expression of CD34, CD200 and CD271. Although the significance of remaining subpopulations still needs to be elucidated, our results underscore the necessity to fully characterize ASCs prior to clinical use.
- | Preclinical, Journal: Supercritical Carbon Dioxide-decellularized Porcine Acellular Dermal Matrix combined with Autologous Adipose-derived Stem Cells: Its Role in Accelerated Diabetic Wound Healing. (Pubmed Central) - Jan 6, 2021
The intervention comprising ADM decellularized from porcine skin by using scCO and ASCs was proven to improve diabetic wound healing. ADM-ASCs had a positive effect on epidermal regeneration, anti-inflammation, collagen production and processing, and cell proliferation; thus, it accelerated wound healing.
- | Journal: Osteogenic activity of a titanium surface modified with silicon-doped titanium dioxide. (Pubmed Central) - Jan 6, 2021
Further studies in vivo indicated that the Si-TiO microporous coating could improve early stage osseointegration. In conclusion, the Si-TiO microporous coating is a feasible way to improve the osteogenic abilities of Ti implants to potentially promote clinical performance.
- | Journal: Epigenetic regulation of the ITGB4 gene in prostate cancer. (Pubmed Central) - Jan 1, 2021
Furthermore, PC-3 cells expressed two distinct transcripts, using an alternate transcription start site, which was not detected in other cell lines. In prostate tumour biopsy samples, patterns of methylation across the ITGB4 promoter were similar overall in matched primary and metastatic samples (n = 4 pairs), with a trend toward loss of methylation at specific sites in metastatic lesions.
- | Journal: Trophoblast-derived CXCL12 promotes CD56 CD82 CD29 NK cell enrichment in the decidua. (Pubmed Central) - Jan 1, 2021
In prostate tumour biopsy samples, patterns of methylation across the ITGB4 promoter were similar overall in matched primary and metastatic samples (n = 4 pairs), with a trend toward loss of methylation at specific sites in metastatic lesions. Trophoblast cells enhance the adhesive ability of NK cells to DSCs via the CXCL12/CD82/CD29 signaling pathway and contribute to CD56 NK cell enrichment in the uterus.
- | Journal: Interplay Between Degradability and Integrin Signaling on Mesenchymal Stem Cell Function within Poly(ethylene glycol) Based Microporous Annealed Particle Hydrogels. (Pubmed Central) - Jan 1, 2021
Moreover, in degradable MAP hydrogels the integrin-binding peptide c(RRETAWA) was found to increase osteogenic protein expression by hMSCs compared to RGDS-functionalized MAP hydrogels. These results have important implications for the development of a MAP hydrogel-based hMSC delivery system for bone tissue engineering.
- | Preclinical, Journal: Mouse parotid salivary gland organoids for the in vitro study of stem cell radiation response. (Pubmed Central) - Dec 31, 2020
Murine parotid gland organoids harbor stem cells with long-term expansion and differentiation potential. This model is useful for mechanistic studies of stem cell radiation response and suggests similar radiosensitivity for the parotid and submandibular gland organoids.
- | OvaSave (ovalbumin) / Sangamo Therapeutics
Journal: Orphan nuclear receptor COUP-TFII is an oncogenic gene in renal cell carcinoma. (Pubmed Central) - Dec 30, 2020
This model is useful for mechanistic studies of stem cell radiation response and suggests similar radiosensitivity for the parotid and submandibular gland organoids. In summary, the present study indicated that COUP-TFII is an oncogenic gene in RCC, and a potential therapeutic target for the treatment of the disease.
- | Journal: C-Methionine PET Identifies Astroglia Involvement in Heart-Brain Inflammation Networking after Acute Myocardial Infarction. (Pubmed Central) - Dec 30, 2020
Immunostaining at d3 revealed co-localization of the L-type amino acid transporter with GFAP-positive astrocytes but not CD68-positive microglia. PET imaging with C-methionine specifically identifies an astrocyte component, enabling further dissection of the heart-brain axis in post MI inflammation.
- | Journal: The secreted protein DEL-1 activates a β3 integrin-FAK-ERK1/2-RUNX2 pathway and promotes osteogenic differentiation and bone regeneration. (Pubmed Central) - Dec 30, 2020
We conclude that DEL-1 can activate a β3 integrin-FAK-ERK1/2-RUNX2 pathway in osteoprogenitors and promote new bone formation in mice. These findings suggest that DEL-1 may be therapeutically exploited to restore bone lost due to periodontitis and perhaps other osteolytic conditions.
- | etrolizumab (RG7413) / Roche, Entyvio (vedolizumab) / Takeda
Journal: Vedolizumab and etrolizumab for ulcerative colitis: twins or simple cousins? (Pubmed Central) - Dec 23, 2020
However, the inhibition of αEβ7 integrin by etrolizumab distinguishes the two anti-integrins making them "cousin" drugs. Phase 3 clinical trials are needed to confirm the promising etrolizumab's efficacy data and to resolve any doubts about its safety, allowing a clearer comparison with vedolizumab.
- | Journal: PSMB8 inhibition decreases tumor angiogenesis in glioblastoma through VEGFA reduction. (Pubmed Central) - Dec 22, 2020
In this article, we demonstrated the role of PSMB8 in glioblastoma progression, especially neovascularization in vitro and in vivo. These results may provide a clue target for the anti-angiogenic effect of PSMB8 in glioblastoma therapy in the future.
- | Journal: Integrin beta 4 (ITGB4) and its tyrosine-1510 phosphorylation promote pancreatic tumorigenesis and regulate the MEK1-ERK1/2 signaling pathway. (Pubmed Central) - Dec 20, 2020
Overall, our study showed that ITGB4 and its phosphorylated form promote cell migration and invasion in pancreatic cancer and that p-ITGB4-Y1510 regulates the downstream MEK1-ERK1/2 signaling cascades. Targeting ITGB4 or its phosphorylation at Y1510 may be a novel therapeutic option for pancreatic cancer.
- || Clinical, Journal: Proteomic analysis of CSF from patients with leptomeningeal melanoma metastases identifies signatures associated with disease progression and therapeutic resistance. (Pubmed Central) - Dec 20, 2020
These analyses identified proteomic/transcriptional signatures in the CSF of patients who succumbed to LMM. We further showed that the CSF from LMM patients has the potential to modulate BRAF inhibitor responses and may contribute to drug resistance.
- | Jetrea (ocriplasmin) / Oxurion
Journal: Induction of posterior vitreous detachment (PVD) by non-enzymatic reagents targeting vitreous collagen liquefaction as well as vitreoretinal adhesion. (Pubmed Central) - Dec 20, 2020
Ocriplasmin has been the only FDA-approved clinical reagent so far...Our findings assume significance in light of the fact that synthetic RGD-containing peptides have already been used for inhibition of tumor cell invasion. Proteins such as variants of collagen binding domains could have extended therapeutic uses in the future.
- | Journal: Analysis of genomics and immune infiltration patterns of epithelial-mesenchymal transition related to metastatic breast cancer to bone. (Pubmed Central) - Dec 19, 2020
Based on the weighted co-expression network for breast-cancer-metastasis-related DEGs, we screened hub genes to explore a prognostic model and the immune infiltration patterns of MBC. The results of this study provided a factual basis to bioinformatically explore the molecular mechanisms of the spread of MBC to the bone and the possibility of predicting the survival of patients.
- | Journal: Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway. (Pubmed Central) - Dec 18, 2020
Furthermore, osteoblasts transfected with Ad-p38 also significantly upregulated the protein and gene expressions of noncollagens and SIBLINGs members, whereas transfection of p38-rhRNA showed the opposite effect. Our data suggest that osteonectin regulates the extracellular matrix mineralization of osteoblasts through the P38 signaling pathway.
- | Tysabri (natalizumab) / Biogen
Clinical, Journal: Integrin Antibody Decreases Deformability of Patient-Derived Pre-B Acute Lymphocytic Leukemia Cells as Measured by High-Frequency Acoustic Tweezers. (Pubmed Central) - Dec 18, 2020
These results suggest that decreased deformability is associated with an integrin α blockade. Further assessments of the functional roles of deformability and integrin blockades in B-ALL cell drug resistance and deformability, respectively, are necessary.
- | Journal: Tunable hydrogels for mesenchymal stem cell delivery: integrin-induced transcriptome alterations and hydrogel optimization for human wound healing. (Pubmed Central) - Dec 18, 2020
These molecules can promote cell adhesion and direct stem cell function and fate through "outside in" signaling mechanisms. To better understand how the 3D culture environment and integrin-binding attachment sites impact stem cells, we broadly examined the differentially expressed genes induced by the introduction of well-defined 3D hydrogel culture systems with and without tethered integrin-binding small molecules and the impact of these molecules on re-epithelialization upon mesenchymal stem/stromal cell delivery to ex vivo organotypic human wounds.
- || Biomarker, Clinical, Journal: Screening and validating the core biomarkers in patients with pancreatic ductal adenocarcinoma. (Pubmed Central) - Dec 18, 2020
Furthermore, according to the connectivity degree of these DEGs, we selected the top20 hub genes, namely ALB, FN1, EGF, MMP9, COL1A1, COL3A1, FBN1, CXCL12, POSTIN, BGN, VCAN, THBS2, KRT19, MET, MMP14, COL5A2, GCG, MUC1, MMP1 and CPB1, which were expected to be promising therapeutic targets in PAAD. Collectively, our bioinformatics analysis showed that DEGs and hub genes may be defined as new biomarkers for diagnosis and for guiding the therapeutic strategies of PAAD.
- || aspirin / Generic mfg.
Clinical, Journal: Unexpected low expression of platelet fibrinogen receptor in patients with chronic myeloproliferative neoplasms: how does it change with aspirin? (Pubmed Central) - Dec 18, 2020
Surprisingly, we found a very low PAC-1 binding capacity in MPN patients; however, the expression of PAC-1 was almost completely recovered with aspirin intake. We hypothesize that the hypercoagulable states observed in MPN patients could depend on a primarily plasma-driven impairment of fibrin turnover and thrombin generation.
- || Clinical, Journal: The clinical significance and potential molecular mechanism of integrin subunit beta 4 in laryngeal squamous cell carcinoma. (Pubmed Central) - Dec 18, 2020
Moreover, the Protein-Protein Interaction (PPI) network indicated that ITGA3, ITGA5, ITGB4, MET, LAMA3, and COL4A1 might be the core genes of LSCC development related to ITGB4. In conclusion, high ITGB4 expression may lead to the occurrence and development of LSCC via various signaling pathways.
- | Journal: Ceruloplasmin oxidized and deamidated by Parkinson's disease cerebrospinal fluid induces epithelial cells proliferation arrest and apoptosis. (Pubmed Central) - Dec 18, 2020
In human primary choroid plexus epithelial cells, a possible in vivo target of Cp-ox/de generated in pathological CSFs, we found that Cp-ox/de mediated cell adhesion via isoDGR/integrins binding and transduced an intracellular signal, which resulted in cell proliferation inhibition. Thus, the generation of Cp-ox/de in pathological CSFs and the consequent apoptosis induction of epithelial cells facing the liquor, might represent a novel mechanism that contributes to neurodegeneration.
- | Entyvio (vedolizumab) / Takeda
Journal: Unraveling the Role of ACE2, the Binding Receptor for SARS-CoV-2, in Inflammatory Bowel Disease. (Pubmed Central) - Dec 18, 2020
Finally, intact membrane-bound or shed soluble ACE2 can also trigger integrin signaling, modulating the response to anti-integrin biologic drugs used to treat IBD (such as vedolizumab) and fibrosis, a long-term complication of IBD. As such, future studies on ACE2 expression/activity in IBD can improve monitoring of the disease and explore an alternative pharmacological target.
- | Journal: Physical disruption of intervertebral disc promotes cell clustering and a degenerative phenotype. (Pubmed Central) - Dec 17, 2020
Results support our hypothesis. Further confirmation will require longitudinal animal experiments.
- | Journal: Dietary Montmorillonite Improves the Intestinal Mucosal Barrier and Optimizes the Intestinal Microbial Community of Weaned Piglets. (Pubmed Central) - Dec 17, 2020
The digesta sample of ileum from piglets in the 0.2% M group contained greater (P < 0.05) intestinal bacterial diversity and abundances of probiotics, such as Streptococcus, Eubacterium_rectale_group, and Lactobacillus, which could promote the synthesis of carbon-containing biomolecules. Overall, dietary supplementation of 0.2% M was shown to have a tendency to improve the growth performance of weaned piglets and may enhance their intestinal mucosal barrier function via altering the gut microbiota.
- | Journal: Atractyloside targets cancer-associated fibroblasts and inhibits the metastasis of colon cancer. (Pubmed Central) - Dec 17, 2020
In addition, transwell cell migration and scratch wound-healing assays proved that atractylosides could significantly inhibit the migration of CCCs. The atractyloside might be a small molecular compound that potentially targets CAFs and inhibits the development as well as metastasis of CC by changing the TME.
- | Journal: Hemovac blood after total knee arthroplasty as a source of stem cells. (Pubmed Central) - Dec 17, 2020
Moreover, SOX9, type II collagen, and aggrecan were significantly upregulated upon chondrogenic differentiation. HVB from TKA patients is a useful source of stem cells for research.
- | Journal: HLA-B influences integrin beta-1 expression and pancreatic cancer cell migration. (Pubmed Central) - Dec 17, 2020
A transmembrane sequence in an S2-013 HLA-B heavy chain matches a corresponding sequence in HLA-B in the BxPC-3 pancreatic cancer cell line, and knockdown of BxPC-3 HLA-B mimics the effect of S2-013 HLA-B knockdown on migration. In total, our findings indicate that HLA-B influences the expression of ITGB1 in pancreatic cancer cells, with concurrent distinctions in transmembrane sequences and effects on the migration of the cells.
- || Clinical, Review, Journal: VLA-4 Expression and Activation in B Cell Malignancies: Functional and Clinical Aspects. (Pubmed Central) - Dec 17, 2020
Here, we review the contribution of VLA-4 to normal B cell differentiation on the one hand, and to the pathophysiology of B cell malignancies on the other hand. We describe its impact as a prognostic marker, its interplay with BCR signaling and its predictive role for novel BCR-targeting therapies, in chronic lymphocytic leukemia and beyond.
- | Journal: Functional and cell surface characteristics of periodontal ligament cells (PDLCs) on RGD-synthetic polypeptide conjugate coatings. (Pubmed Central) - Dec 16, 2020
Our study demonstrates that SAK-c[RGDfC] and AK-c[RGDfC] improved adhesion and migration of PDLCs and supported osteogenic differentiation of PDLCs. These cyclic RGD peptides proved to be applicable biocompatible material in regenerative medicine.
- || Clinical, Journal: Tissue stiffness contributes to YAP activation in bladder cancer patients undergoing transurethral resection. (Pubmed Central) - Dec 16, 2020
Nuclear localization of YAP was higher in recurrent cancerous tissues compared with newly diagnosed and it was positively associated with higher stiffness (P < 0.05). Our results suggest that postsurgery-induced ECM stiffness can influence integrin-FAK-YAP activity and thereby YAP trafficking to the nucleus where it contributes to BC progression and relapse.