Proteomic Characterization of Ubiquitin Carboxyl-Terminal Hydrolase 19 Deficient Cells Reveals a Role for USP19 in the Secretion of Lysosomal Proteins.

Ubiquitin carboxyl-terminal hydrolase 19 (USP19) is a unique deubiquitinase, characterized by multiple variants generated by alternative splicing. Several variants bear a C-terminal transmembrane domain that anchors them to the endoplasmic reticulum. Other than regulating protein stability by preventing proteasome degradation, USP19 has been reported to rescue substrates from endoplasmic reticulum-associated protein degradation in a catalytic-independent manner, promote autophagy, and address proteins to lysosomal degradation via endosomal microautophagy.

Development of a Proteomic Workflow for the Identification of Heparan Sulphate Proteoglycan-Binding Substrates of ADAM17.

Ectodomain shedding, which is the proteolytic release of transmembrane proteins from the cell surface, is crucial for cell-to-cell communication and other biological processes. The metalloproteinase ADAM17 mediates ectodomain shedding of over 50 transmembrane proteins ranging from cytokines and growth factors, such as TNF and EGFR ligands, to signalling receptors and adhesion molecules. Yet, the ADAM17 sheddome is only partly defined and biological functions of the protease have not been fully characterized.

Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.

Receptor-mediated endocytosis provides a mechanism for the selective uptake of specific molecules thereby controlling the composition of the extracellular environment and biological processes. The low-density lipoprotein receptor-related protein 1 (LRP1) is a widely expressed endocytic receptor that regulates cellular events by modulating the levels of numerous extracellular molecules via rapid endocytic removal. LRP1 also participates in signalling pathways through this modulation as well as in the interaction with membrane receptors and cytoplasmic adaptor proteins.

iRhom2 regulates ectodomain shedding and surface expression of the major histocompatibility complex (MHC) class I.

Proteolytic release of transmembrane proteins from the cell surface, the so called ectodomain shedding, is a key process in inflammation. Inactive rhomboid 2 (iRhom2) plays a crucial role in this context, in that it guides maturation and function of the sheddase ADAM17 (a disintegrin and metalloproteinase 17) in immune cells, and, ultimately, its ability to release inflammatory mediators such as tumor necrosis factor α (TNFα). Yet, the macrophage sheddome of iRhom2/ADAM17, which is the collection of substrates that are released by the proteolytic complex, is only partly known.

Indications, Associated Procedures, and Results of Ankle Plafond-Plasty for Varus Ankle Osteoarthritis: A Systematic Review and Meta-Analysis.

Backgrounds: Plafond-plasty is a joint-preserving procedure to treat varus ankle osteoarthritis (OA) with asymmetrical joint involvement. The aim of this systematic review and meta-analysis was to evaluate indications, different surgical techniques, associated procedures, and results of plafond-plasty in varus ankle OA and to analyze the level of evidence (LOE) and quality of evidence (QOE) of the included studies.

Methods: A systematic review of the literature was performed using MEDLINE, Embase, and Cochrane.

Staged vs concurrent hardware removal in total ankle arthroplasty.

Introduction: Ankle osteoarthritis is more commonly posttraumatic. Consequently, dealing with hardware removal is quite frequent when performing a total ankle arthroplasty (TAA). The purpose of this study is to compare outcomes regarding either a staged or concurrent hardware removal when performing TAA.

Return to sports after total ankle arthroplasty: A systematic review and meta-analysis.

Purpose: Technological developments and implants newer generation allowed to expand the indications for total ankle arthroplasty (TAA) with aim to maintain active lifestyles. This systematic review and meta-analysis examined chance of return to sport, achievable activity level, the type of patients and the sport type after TAA.

Methods: A literature search of PubMed, Scopus, and Cochrane databases was performed.

Probiotics in Orthopedics: From Preclinical Studies to Current Applications and Future Perspective.

In recent years, probiotics have been emerging as an attractive therapeutic strategy for several diseases. In orthopedics, probiotics seem to be a promising supplementation for treatment of osteoporosis, osteoarthritis, muscle loss-related disease, wound and ulcer issues, and prevention of surgical antibiotic prophylaxis side effects. Although probiotics are still not included in guidelines for these conditions, several studies have reported theoretical benefits of their administration.

Custom-made total ankle arthroplasty with patient-specific instrumentation for severe bone loss conditions: a case series.

Purpose: Management of bone loss around the ankle is a challenging condition. This retrospective study describes the design process, the surgical technique, and the preliminary results of custom-made total ankle arthroplasties (TAA) with patient-specific instrumentation (PSI) for different severe bone loss conditions.

Methods: Consecutive patients that underwent custom-made TAA for severe bone loss conditions were included.

First Metatarsal Hemiepiphysiodesis for the Treatment of Juvenile Hallux Valgus: A Systematic Review.

Introduction: Juvenile hallux valgus (JHV) is a pediatric deformity characterized by the varus deviation of the first metatarsal and valgus deviation of the proximal phalanx. Among the several surgical techniques available, hemiepiphysiodesis consists of the unilateral growth arrest of the first metatarsal physis. Despite this technique has been proposed over 70 years ago, only a few studies including clinical and radiological outcomes have been published, making the procedure unclear in terms of results.

Hallux Valgus Plantar Pressure Distribution Before and After Surgery.

Hallux valgus is a common foot deformity that may cause pain and functional limitation, and often requires surgical correction. Clinical and radiographic parameters are typically used to assess postoperative outcomes. Plantar pressure distribution systems represent an innovative additional tool to evaluate hallux functional outcome after surgery.

Identification of membrane proteins regulated by ADAM15 by SUSPECS proteomics.

ADAM15 is a member of the disintegrin-metalloproteinase family of sheddases, which plays a role in several biological processes including cartilage homeostasis. In contrast with well-characterized ADAMs, such as the canonical sheddases ADAM17 and ADAM10, little is known about substrates of ADAM15 or how the enzyme exerts its biological functions. Herein, we used "surface-spanning enrichment with click-sugars (SUSPECS)" proteomics to identify ADAM15 substrates and/or proteins regulated by the proteinase at the cell surface of chondrocyte-like cells.

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Introduction: Overcorrection is a possible complication of clubfoot treatment, whose prevalence varies from 5 to 67%. Overcorrected clubfoot usually presented as a complex flatfoot with different degrees of hindfoot valgus, flat top talus, dorsal bunion, and dorsal navicular subluxation. The management of clubfoot overcorrection is challenging, and both conservative and surgical treatments are available.

Patient Reported Outcome Measures (PROMs) in Surgery: Evaluation after Minimally Invasive Reduction and Percutaneous K-Wires Fixation for Intra-Articular Calcaneal Fractures.

Background: The optimal surgical treatment of intra-articular calcaneal fractures (IACF) is still under debate. In the literature, results are based on clinical or radiographical findings. Few studies have evaluated the effect of patient expectations on patient-reported outcomes after surgery and little is known about outcomes directly reported by the patient who experienced it.

Retrograde intramedullary nail entry point for tibio-talo-calcaneal arthrodesis: a review of anatomical studies.

Purpose: Tibio-talo-calcaneal arthrodesis (TTCA) is considered a safe and valuable option for end-stage tibiotalar and subtalar arthritis, and usually is performed with a retrograde intramedullary nail. Although the good results reported, potential complications may be related to retrograde nail entry point. Aim of this systematic review is to analyze in cadaveric studies the risk of iatrogenic injuries related to different entry points and different retrograde intramedullary nail design when performing TTCA.

Growth Performance and Recovery of Nosocomial spp. in Blood Culture Bottles.

Theoretically, Aspergillus spp. grow in culture media, but frequently, blood cultures of patients with invasive Aspergillosis are negative, even if until now, the reasons are not clear. This aspect underlines the lack of a good strategy for the cultivation and isolation of Aspergillus spp.

A top-down approach to uncover the hidden ligandome of low-density lipoprotein receptor-related protein 1 in cartilage.

The low-density lipoprotein receptor-related protein 1 (LRP1) is a cell-surface receptor ubiquitously expressed in various tissues. It plays tissue-specific roles by mediating endocytosis of a diverse range of extracellular molecules. Dysregulation of LRP1 is involved in multiple conditions including osteoarthritis (OA) but little information is available about the specific profile of direct binding partners of LRP1 (ligandome) for each tissue, which would lead to a better understanding of its role in disease states.

High-Resolution Secretome Analysis of Chemical Hypoxia Treated Cells Identifies Putative Biomarkers of Chondrosarcoma.

Chondrosarcoma is the second most common bone tumor, accounting for 20% of all cases. Little is known about the pathology and molecular mechanisms involved in the development and in the metastatic process of chondrosarcoma. As a consequence, there are no approved therapies for this tumor and surgical resection is the only treatment currently available.

Quantitative Proteomics Reveals That ADAM15 Can Have Proteolytic-Independent Functions in the Steady State.

A disintegrin and metalloproteinase 15 (ADAM15) is a member of the ADAM family of sheddases. Its genetic ablation in mice suggests that ADAM15 plays an important role in a wide variety of biological functions, including cartilage homeostasis. Nevertheless, while the substrate repertoire of other members of the ADAM family, including ADAM10 and ADAM17, is largely established, little is known about the substrates of ADAM15 and how it exerts its biological functions.

Patient-specific instrumentation in total ankle arthroplasty.

The recent increase in the adoption of total ankle arthroplasty (TAA) reflects the improvements in implant designs and surgical techniques, including the use of preoperative navigation system and patient-specific instrumentation (PSI), such as custom-made cutting guides. Cutting guides are customized with respect to each patient's anatomy based on preoperative ankle computed tomography scans, and they drive the saw intra-operatively to improve the accuracy of bone resection and implant positioning. Despite some promising results, the main queries in the literature are whether PSI improves the reliability of achieving neutral ankle alignment and more accurate implant sizing, whether it is actually superior over standard techniques, and whether it is cost effective.

Quantitative Proteomics Reveals Changes Induced by TIMP-3 on Cell Membrane Composition and Novel Metalloprotease Substrates.

Ectodomain shedding is a key mechanism of several biological processes, including cell-communication. Disintegrin and metalloproteinases (ADAMs), together with the membrane-type matrix metalloproteinases, play a pivotal role in shedding transmembrane proteins. Aberrant shedding is associated to several pathological conditions, including arthritis.

Strategies to Target ADAM17 in Disease: From its Discovery to the iRhom Revolution.

For decades, disintegrin and metalloproteinase 17 (ADAM17) has been the object of deep investigation. Since its discovery as the tumor necrosis factor convertase, it has been considered a major drug target, especially in the context of inflammatory diseases and cancer. Nevertheless, the development of drugs targeting ADAM17 has been harder than expected.

TIMP-3 facilitates binding of target metalloproteinases to the endocytic receptor LRP-1 and promotes scavenging of MMP-1.

Matrix metalloproteinases (MMPs) and the related families of disintegrin metalloproteinases (ADAMs) and ADAMs with thrombospondin repeats (ADAMTSs) play a crucial role in extracellular matrix (ECM) turnover and shedding of cell-surface molecules. The proteolytic activity of metalloproteinases is post-translationally regulated by their endogenous inhibitors, known as tissue inhibitors of metalloproteinases (TIMPs). Several MMPs, ADAMTSs and TIMPs have been reported to be endocytosed by the low-density lipoprotein receptor-related protein-1 (LRP-1).