No abstract

ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) proteases comprise the most recently discovered branch of the extracellular metalloenzymes. Research during the last 15years, uncovered their association with a variety of physiological and pathological processes including blood coagulation, tissue repair, fertility, arthritis and cancer. Importantly, a frequent feature of ADAMTS enzymes relates to their effects on vascular-related phenomena, including angiogenesis. Their specific roles in vascular biology have been clarified by information on their expression profiles and substrate specificity. Through their catalytic activity, ADAMTS proteases modify rather than degrade extracellular proteins. They predominantly target proteoglycans and glycoproteins abundant in the basement membrane, therefore their broad contributions to the vasculature should not come as a surprise. Furthermore, in addition to their proteolytic functions, non-enzymatic roles for ADAMTS have also been identified expanding our understanding on the multiple activities of these enzymes in vascular-related processes.

The extracellular protease ADAMTS1 (A disintegrin and metalloprotease with thrombospondin repeats 1) has been described as an anti-angiogenic molecule and its role as a putative tumor protective molecule has also been suggested. Here, we have used a tumor xenograft model to determine the role of ADAMTS1 in tumor growth and angiogenesis. Increasing levels of the protease led to the complete inhibition of tumor growth. In an attempt to elucidate the mechanism of action of this protease, we focused our attention on its proteolytic activity on nidogens, one of the main components of the vascular basement membrane. The increased expression of ADAMTS1 was accompanied by increased proteolysis of nidogen-1 and -2 and their almost complete removal from vascular structures, together with major morphological alterations of tumor blood vessels and a decreased vessel density. The clinical relevance of this work is supported by our observations that ADAMTS1 expression is decreased in breast tumor specimens when compared with healthy tissue. Our studies also reveal that the cleavage of nidogen-1 and -2 is partially inhibited in human tumor samples. Moreover, the deposition of both nidogens surrounding vascular structures is drastically altered, implying a possible reduction in the maintenance of vessel integrity. Our studies reflect the requirement to explore the functional interactions between proteases and specific substrates in cancer biology.

Background Falls are the leading cause of injury-related deaths in older adults. Physical exercise is a suitable strategy to reduce the risk of falls, but there is little research on the effectiveness of specific exercise modalities. Objectives To estimate the effectiveness of Pilates compared to habitual or non-exercise on physical performance and the risk of falls in older adults. Data sources Five databases were searched through April 15, 2021. Study selection Randomized controlled trial in people aged ≥60 years. Outcomes: balance, strength, flexibility, functionality, and risk of falls. Data synthesis Pooled standardized mean differences were calculated using a random-effects model. Subgroup analyses based on Pilates' modality, the existence of a detailed exercise protocol, supervision by a certified instructor, and overall risk of bias were performed. Results Thirty-nine studies were included in the systematic review and meta-analyses. The meta-analyses indicated a moderate effect of Pilates on balance (ES = 0.36; 95% CI = 0.21 to 0.50), strength (ES = 0.63; 95% CI = 0.44 to 0.81), flexibility (ES = 0.41; 95% CI = 0.16 to 0.67), and functionality (ES = 0.51; 95% CI = 0.32 to 0.72) as well as a large effect on the risk of falls (ES = 0.90; 95% CI = 0.41 to 1.38) in older adults when compared with control groups. The level of certainty of the findings was low for balance, flexibility, and functionality and moderate for strength and falls. Conclusion and implications of key findingsPilates may promote the autonomy of older people in their daily living activities. Contribution of the Paper• Pilates is an alternative exercise for reducing the risk of falls.• Pilates improves balance, strength, flexibility, and functionality in older people.• Pilates may increase the autonomy of older adults in their daily living activities.

The matrix metalloprotease ADAMTS1 (A Disintegrin And Metalloprotease with ThromboSpondin repeats 1) has been involved in tumorigenesis although its contributions appeared ambiguous. To understand the multifaceted actions of this protease, it is still required a deeper knowledge of its implication in heterogeneous tumor-stroma interactions. Using a syngeneic B16F1 melanoma model in wild type and ADAMTS1 knockout mice we found distinct stroma versus tumor functions for this protease. Genetic deletion of ADAMTS1 in the host microenvironment resulted in a drastic decrease of tumor growth and metastasis. However, the downregulation of tumor ADAMTS1 did not uncover relevant effects. Reduced tumors in ADAMTS1 KO mice displayed a paradoxical increase in vascular density and vascular-related genes; a detailed characterization revealed an impaired vasculature, along with a minor infiltration of macrophages. In addition, ex-vivo assays supported a chief role for ADAMTS1 in vascular sprouting, and melanoma xenografts showed a relevant induction of its expression in stroma compartments. These findings provide the first genetic evidence that supports the pro-tumorigenic role of stromal ADAMTS1.

No abstract

Recent advances have emphasized the relevance of studying the extracellular microenvironment given its main contribution to tissue homeostasis and disease. Within this complex scenario, we have studied the extracellular protease ADAMTS1 (a disintegrin and metalloprotease with thrombospondin motif 1), implicated in vascularization and development, with reported anti- and pro-tumorigenic activities. In this work we performed a detailed study of the vasculature and substrates in adult organs of wild type and Adamts1-deficient mice. In addition to the expected alterations of organs like kidney, heart and aorta, we found that the lack of ADAMTS1 differently affects lymphocyte and myeloid populations in the spleen and bone marrow. The study of the substrate versican also revealed its alteration in the absence of the protease. With such premises, we challenged our mice with subcutaneous B16F1 syngeneic tumours and closely evaluated the immune repertoire in the tumours but also in the distant spleen and bone marrow. Our results confirmed a pro-inflammatory landscape in the absence of ADAMTS1, correlating with tumour blockade, supporting its novel role as a modulator of the immune cell response.

The network meta-analysis and systematic review conducted aim to comparatively assess the effects of tree nuts and peanuts on body weight (BW), body mass index (BMI), waist circumference (WC), and body fat percentage (BF%). A systematic search up to 31 December 2020 was performed. A random-effects network meta-analysis was conducted following the PRISMA-NMA statement. A total of 105 randomized controlled trials (RCTs) with measures of BW (n = 6768 participants), BMI (n = 2918), WC (n = 5045), and BF% (n = 1226) were included. The transitivity assumption was met based on baseline characteristics. In the comparisons of nut consumption versus a control diet, there was no significant increase observed in any of the adiposity-related measures examined except for hazelnut-enriched diets, which raised WC. Moreover, almond-enriched diets significantly reduced WC compared to the control diet and to the pistachio-, mixed nuts-, and hazelnut-enriched diets. In subgroup analyses with only RCTs, designed to assess whether nut consumption affected weight loss, almonds were associated with reduced BMI and walnuts with reduced %BF. The evidence supports that: (1) tree nut and peanut consumption do not influence adiposity, and (2) compared to a control diet, the consumption of almond-enriched diets was associated with a reduced waist circumference.