MIMIC

The mitochondrial protein IF1 is upregulated in many tumors and acts as a pro-oncogenic protein through its interaction with the ATP synthase and the inhibition of apoptosis. We have recently characterized the molecular nature of the IF1-Oligomycin Sensitivity Conferring Protein (OSCP) subunit interaction; however, it remains to be determined whether this interaction could be targeted for novel anti-cancer therapeutic intervention. We generated mitochondria-targeting peptides to displace IF1 from the OSCP interaction...

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade...

Nowadays, consumers are more aware of the effects of their diet on their health, and thus demand natural or minimally processed food products. Therefore, research has focused on processes that assure safe products without jeopardizing their nutritional properties. In this context, this work aimed to evaluate the effects of high-pressure processing (550 MPa/3 min/15 °C, HPP) on a fruit salad (composed of melon juice and pieces of Golden apple and Rocha pear) throughout 35 days of storage at 4 °C. For the physicochemical properties analysed (browning degree, polyphenol oxidase activity, antioxidant activity (ABTS assay), and volatile profile), a freshly made fruit salad was used, while for the microbiological tests (total aerobic mesophiles, and yeast and moulds) spoiled melon juice was added to the fruit salad to increase the microbial load and mimic a challenge test with a high initial microbial load...

The main objective of this study was to investigate the metabolism of miconazole, an azole antifungal drug. Miconazole was subjected to incubation with human liver microsomes (HLM) to mimic phase I metabolism reactions for the first time. Employing a combination of an HLM assay and UHPLC-HRMS analysis enabled the identification of seven metabolites of miconazole, undescribed so far. Throughout the incubation with HLM, miconazole underwent biotransformation reactions including hydroxylation of the benzene ring and oxidation of the imidazole moiety, along with its subsequent degradation...

The problem of bacterial resistance has become more and more common with improvements in health care. Worryingly, the misuse of antibiotics leads to an increase in bacterial multidrug resistance and the development of new antibiotics has virtually stalled. These challenges have prompted the need to combat bacterial infections with the use of radically different approaches. Taking lessons from the exciting properties of micro-/nano-natural-patterned surfaces, which can destroy cellular integrity, the construction of artificial surfaces to mimic natural functions provides new opportunities for the innovation and development of biomedicine...

The vascularization pattern of the equine stifle joint is insufficiently described in the literature, even though there is a growing need for knowledge of the exact blood supply, as (i) arthroscopy and endoscopic surgery techniques are increasingly performed in horses and (ii) ex vivo models of menisci need nutrient supply that mimic the in vivo situation. The aim of this study was to describe the vessels involved in the stifle joint supply and the exact branching pattern of the popliteal artery. Colored latex was injected into the arteries of nine pelvic limbs of equine cadavers (n = 6) to evaluate the occurrences, variations and approximate diameters of vessels that supplied the stifle joints...

Background : Shortened femoral stems aim to mimic the biomechanical performance of traditional stems while preserving more bone and minimizing soft tissue damage. Our objective is to assess the outcomes of patients treated with a shortened stem (Furlong Evolution, JRI Orthopaedics, Sheffield, UK) to analyze the implant's efficacy and survivorship. Methods : This retrospective observational study included all patients aged 18 to 70 undergoing uncemented shortened stem total hip replacement at Hospital del Mar between 2010 and 2018...

Lentigo maligna (LM) is a melanoma in situ that is prevalent in chronically sun-damaged skin. Characterized by a slow growth pattern and high mutation rates due to chronic UV exposure, LM poses diagnostic and therapeutic challenges, particularly given its tendency to mimic other skin lesions and its occurrence in cosmetically sensitive areas. Its diagnosis is based on an integrated approach using dermoscopy and reflectance confocal microscopy (RCM). Despite its slow progression, LM can evolve into lentigo maligna melanoma (LMM), making its treatment necessary...

Rhabdomyosarcoma is a pediatric cancer associated with aggressiveness and a tendency to develop metastases. Fusion-negative rhabdomyosarcoma (FN-RMS) is the most commonly occurring subtype of RMS, where metastatic disease can hinder treatment success and decrease survival rates. RMS-derived exosomes were previously demonstrated to be enriched with miRNAs, including miR-1246, possibly contributing to disease aggressiveness. We aimed to decipher the functional impact of exosomal miR-1246 on recipient cells and its role in promoting aggressiveness...

BACKGROUND: Several PD-1 antibodies approved as anti-cancer therapies work by blocking the interaction of PD-1 with its ligand PD-L1, thus restoring anti-cancer T cell activities. These PD-1 antibodies lack inter-species cross-reactivity, necessitating surrogate antibodies for preclinical studies, which may limit the predictability and translatability of the studies. RESULTS: To overcome this limitation, we have developed an inter-species cross-reactive PD-1 antibody, GNUV201, by utilizing an enhanced diversity mouse platform (SHINE MOUSE™)...

PURPOSE: Invasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality. METHODS: Emulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-h of hypoxemia...

A more optimized culture medium used in vitro to mimic the bacterial composition of original oral flora as similar as possible remains difficult at present, and the goal of this study is to develop a novel oral biofilm medium to restore the original oral microbiome. Firstly, we conducted a systematic literature review by searching PubMed and summarized the current reported culture media in vitro. Seven culture media were found. We used mixed saliva as the origin of oral species to compare the effects of the above media in culturing oral multispecies biofilms...

Advancements in reliable information transfer across biotic-abiotic interfaces have enabled the restoration of lost human function. For example, communication between neuronal cells and electrical devices restores the ability to walk to a tetraplegic patient and vision to patients blinded by retinal disease. These impactful medical achievements are aided by tailored biotic-abiotic interfaces that maximize information transfer fidelity by considering the physical properties of the underlying biological and synthetic components...

Inhibitory neurons embedded within mammalian neural circuits shape breathing, walking, and other rhythmic motor behaviors. At the core of the neural circuit controlling breathing is the preBötzinger Complex (preBötC), where GABAergic (GAD1/2+ ) and glycinergic (GlyT2+ ) neurons are functionally and anatomically intercalated among glutamatergic Dbx1-derived (Dbx1+ ) neurons that generate rhythmic inspiratory drive. The roles of these preBötC inhibitory neurons in breathing remain unclear. We first characterized the spatial distribution of molecularly-defined preBötC inhibitory subpopulations in male and female neonatal double reporter mice expressing either tdTomato or EGFP in GlyT2+ , GAD1+ , or GAD2+ neurons...

Attentional control over sensory processing has been linked to neural alpha oscillations and related inhibition of cerebral cortex. Despite the wide consensus on the functional relevance of alpha oscillations for attention, precise neural mechanisms of how alpha oscillations shape perception and how this top-down modulation is implemented in cortical networks remain unclear. Here, we tested the hypothesis that alpha oscillations in frontal eye fields (FEF) are causally involved in the top-down regulation of visual processing in humans (male and female)...

Myocardial infarction (MI) is serious health threat and impairs the quality of life. It is a major causative factor of morbidity and mortality. MI leads to the necrosis of cardio-myocytes, cardiac remodelling and dysfunction, eventually leading to heart failure. The limitations of conventional therapeutic and surgical interventions and lack of heart donors have necessitated the evolution of alternate treatment approaches for MI. Polysaccharide hydrogel based repair of infarcted myocardium have surfaced as viable option for MI treatment...

In the zebrafish lateral line, non-sensory supporting cells readily re-enter the cell cycle to generate new hair cells and supporting cells during homeostatic maintenance and following damage to hair cells. This contrasts with supporting cells from mammalian vestibular and auditory sensory epithelia which rarely re-enter the cell cycle, and hence loss of hair cells results in permanent sensory deficit. Lateral line supporting cells are derived from multipotent progenitor cells that migrate down the trunk midline as a primordium and are deposited to differentiate into a neuromast...

PTZ kindling induces oxidative stress, neuronal cell degeneration, and neurobehavioral alterations in rodents that mimic neuropsychiatric comorbidities of epilepsy, which could be initiated or aggravated by some antiepileptic drugs. Here, we investigated the effects of the methanol extract of Ficus platyphylla (FP) on severity scores for seizures, neuronal cell degeneration, and neurobehavioral alterations in rats kindled with pentylenetetrazole (PTZ) and probed the involvement of oxidative stress in these ameliorative effects of FP...

Supramolecular chemistry is versatile for developing stimuli-responsive, dynamic and multifunctional structures. In the context of biomedical engineering applications, supramolecular assemblies are particularly useful as coatings for they can closely mimic the natural structure and organisation of the extracellular matrix (ECM), they can also fabricate other complex systems like drug delivery systems and bioinks. In the current context of growing medical device-associated complications and the developments in the controlled drug delivery and regenerative medicine fields,supramolecular assemblies are becoming an indispensable part of the biomedical engineering arsenal...

Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO2 ). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro...