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Special emphasis will be given on how RGD-binding integrins can modulate the intricate molecular pathways and regulate the underlying pathological mechanisms. For instance, the interplay between integrins and key molecular players such as growth factors, cytokines and enzymes will be summarized. In addition, recent clinical advances linked to targeting RGD-binding integrins in the context of DME and nvAMD will be discussed alongside future potential for limiting progression of these diseases.Mesenchymal stromal cells, commonly referred to as MSCs, have emerged as a promising cell-based therapy for a range of autoimmune diseases thanks to several therapeutic advantages. Key among these are 1) the ability to modulate innate and adaptive immune responses and to promote tissue regeneration, 2) the ease of their isolation from readily accessible tissues and expansion at scale in culture, 3) their low immunogenicity enabling use as an allogeneic “off-the-shelf” product, and 4) MSC therapy’s safety and feasibility in humans, as demonstrated in more than one thousand clinical trials. Evidence from preclinical studies and early clinical trials indicate the therapeutic potential of MSCs and their derivatives for efficacy in ocular autoimmune diseases such as autoimmune uveoretinitis and Sjögren’s syndrome-related dry eye disease. In this review, we provide an overview of the current understanding of the therapeutic mechanisms of MSCs, and summarize the results from preclinical and clinical studies that have used MSCs or their derivatives for the treatment of ocular autoimmune diseases. We also discuss the challenges to the successful clinical application of MSC therapy, and suggest strategies for overcoming them.This study aimed to analyze the efficacy of the monoclonal antibodies ipilimumab, nivolumab, and pembrolizumab when compared with conventional chemotherapy in the treatment of advanced melanoma. Three authors made the search independently and five articles matched the eligibility criteria. A fourth expert confirmed their quality (κ = 1). The meta-analysis for overall survival and 12-month overall survival was impaired due to remarkably high heterogeneity (I2 = 91 % and 86 %, respectively). However, chemotherapy showed benefits on 24-months overall survival (RR = 1.60; IC95 % 1.29, 1.98; p  less then  0.0001). The interruption by toxicity outcome showed no significant differences between therapies. Some studies used monoclonal antibodies in monotherapy or in combination and some groups of participants showed heterogeneity, which made the analysis difficult. Given the exorbitant costs of monoclonal antibodies in low and middle-income countries, the evidence of its benefits is limited when considering the replacement of conventional therapy with immunotherapy in public health systems.Moyamoya-like vasculopathy, the “puff of smoke”-like small vessels in the brain, is initially identified in patients with Moyamoya disease (MMD), a rare cerebrovascular disease, and later found in patients with various types of neurological conditions, including Down syndrome, Stroke, and vascular dementia. It is thus of interest to understand how this vasculopathy is developed. Here, we provided evidence for cortical astrocytic neogenin (NEO1) deficiency to be a risk factor for its development. NEO1, a member of deleted in colorectal cancer (DCC) family netrin receptors, was reduced in brain samples of patients with MMD. Astrocytic Neo1-loss resulted in an increase of small blood vessels (BVs) selectively in the cortex. These BVs were dysfunctional, with leaky blood-brain barrier (BBB), thin arteries, and accelerated hyperplasia in veins and capillaries, resembled to the features of moyamoya-like vasculopathy. Additionally, we found that both MMD patient and Neo1 mutant mice exhibited altered gene expression in their cortex in proteins critical for not only angiogenesis [e.g., an increase in vascular endothelial growth factor (VEGFa)], but also axon guidance (e.g., netrin family proteins) and inflammation. In aggregates, these results suggest a critical role of astrocytic NEO1-loss in the development of Moyamoya-like vasculopathy, providing a mouse model for investigating mechanisms of Moyamoya-like vasculopathy.Fragile X syndrome (FXS) is a common form of intellectual disability and autism caused by the lack of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in RNA transport and protein synthesis. Upon cellular stress, global protein synthesis is blocked and mRNAs are recruited into stress granules (SGs), together with RNA-binding proteins including FMRP. Activation of group-I metabotropic glutamate (mGlu) receptors stimulates FMRP-mediated mRNA transport and protein synthesis, but their role in SGs formation is unexplored. To this aim, we pre-treated wild type (WT) and Fmr1 knockout (KO) cultured astrocytes with the group-I-mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) and exposed them to sodium arsenite (NaAsO2), a widely used inducer of SGs formation. In WT cultures the activation of group-I mGlu receptors reduced SGs formation and recruitment of FMRP into SGs, and also attenuated phosphorylation of eIF2α, a key event crucially involved in SGs formation and inhibition of protein synthesis. In contrast, Fmr1 KO astrocytes, which exhibited a lower number of SGs than WT astrocytes, did not respond to agonist stimulation. JKE1674 Interestingly, the mGlu5 receptor negative allosteric modulator (NAM) 2-methyl-6-(phenylethynyl)pyridine (MPEP) antagonized DHPG-mediated SGs reduction in WT and reversed SGs formation in Fmr1 KO cultures. Our findings reveal a novel function of mGlu5 receptor as modulator of SGs formation and open new perspectives for understanding cellular response to stress in FXS pathophysiology.

A viable treatment option for young patients with massive, irreparable rotator cuff tears is arthroscopic superior capsule reconstruction (SCR). SCR theoretically improves shoulder stability and function and decreases pain. However, no prospective studies to date have correlated magnetic resonance imaging (MRI) healing with invivo kinematic data. The purpose of this study was to evaluate the association between graft healing and invivo kinematics, range of motion (ROM), strength, and patient-reported outcomes (PROs).

Ten patients (8 men and 2 women; mean age, 63 ± 7 years) with irreparable rotator cuff tears underwent arthroscopic SCR with dermal allograft. Strength was measured with isometric internal rotation and external rotation (ER) at 0° of abduction, ER at 90° of abduction, and scapular-plane abduction, whereas ROM was measured during shoulder flexion, abduction, and ER and internal rotation at 90° of abduction both before and 1 year after SCR. PROs included American Shoulder and Elbow Surgeons, Western Ontario Rotator Cuff Index, and Disabilities of the Arm, Shoulder and Hand surveys that were collected before and 1 year after SCR.