Interferon‐induced transmembrane proteins (IFITMs) are frequently overexpressed in cancer cells, including cervical carcinoma cells, and play a role in the progression of various cancer types. However, their mechanisms of action remain incompletely understood. In the present study, by employing a combination of surface membrane protein isolation and quantitative mass spectrometry, it was comprehensively described how the IFITM1 protein influences the composition of the cervical cancer cell surfaceome. Additionally, the effects of interferon‐γ on protein expression and cell surface exposure were evaluated in the presence and absence of IFITM1. The IFITM1‐regulated membrane and membrane‐associated proteins identified are involved mainly in processes such as endocytosis and lysosomal transport, cell‐cell and cell‐extracellular matrix adhesion, antigen presentation and the immune response. To complement the proteomic data, gene expression was analyzed using reverse transcription‐quantitative PCR to distinguish whether the observed changes in protein levels were attributable to transcriptional regulation or differential protein dynamics. Furthermore, the proteomic and gene expression data are supported by functional studies demonstrating the impact of the IFITM1 and IFITM3 proteins on the adhesive, migratory and invasive capabilities of cervical cancer cells, as well as their interactions with immune cells.
- MeSH
- buněčná adheze MeSH
- diferenciační antigeny * metabolismus genetika MeSH
- fenotyp MeSH
- interferon gama farmakologie metabolismus MeSH
- lidé MeSH
- membránové proteiny * metabolismus genetika MeSH
- nádorové buněčné linie MeSH
- nádory děložního čípku * patologie genetika metabolismus imunologie MeSH
- pohyb buněk MeSH
- proteiny vázající RNA * metabolismus genetika MeSH
- proteom * MeSH
- proteomika metody MeSH
- regulace genové exprese u nádorů MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Full recovery from spinal cord injury requires axon regeneration to re-establish motor and sensory pathways. In mammals, the failure of sensory and motor axon regeneration has many causes intrinsic and extrinsic to neurons, amongst which is the lack of adhesion molecules needed to interact with the damaged spinal cord. This study addressed this limitation by expressing the integrin adhesion molecule α9, along with its activator kindlin-1, in sensory neurons via adeno-associated viral (AAV) vectors. This enabled sensory axons to regenerate through spinal cord injuries and extend to the brainstem, restoring sensory pathways, touch sensation and sensory behaviours. One of the integrin ligands in the injured spinal cord is tenascin-C, which serves as a substrate for α9β1 integrin, a key receptor in developmental axon guidance. However, the adult PNS and CNS neurons lack this receptor. Sensory neurons were transduced with α9 integrin (which pairs with endogenous β1 to form a α9β1 tenascin receptor) together with the integrin activator kindlin-1. Regeneration from sensory neurons transduced with α9integrin and kindlin-1 was examined after C4 and after T10 dorsal column lesions with C6,7 and L4,5 sensory ganglia injected with AAV1 vectors. In animals treated with α9 integrin and kindlin-1, sensory axons regenerated through tenascin-C-expressing connective tissue strands and bridges across the lesions and then re-entered the CNS tissue. Many axons regenerated rostrally to the level of the medulla. Axons grew through the dorsal grey matter rather than their normal pathway the dorsal columns. Growth was slow, axons taking 12 weeks to grow from T10 to the medulla, a distance of 4-5 cm. Functional recovery was confirmed through cFos activation in neurons rostral to the injury after nerve stimulation and VGLUT1/2 staining indicating new synapse formation above the lesion. Behavioural recovery was seen in both heat and mechanical sensation, as well as tape removal tests. This approach demonstrates the potential of integrin-based therapies for long distance sensory axon regeneration and functional recovery following thoracic and partial recovery after cervical spinal cord injury.
- MeSH
- axony MeSH
- Dependovirus genetika MeSH
- genetické vektory MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nervové receptory * metabolismus fyziologie patologie MeSH
- obnova funkce fyziologie MeSH
- poranění míchy * patologie patofyziologie metabolismus MeSH
- potkani Sprague-Dawley MeSH
- proteiny nervové tkáně metabolismus genetika MeSH
- regenerace nervu * fyziologie MeSH
- tenascin metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
BACKGROUND: Muscle strength and postural control are essential components for performing daily living activities, particularly in older adults, and can therefore serve as screening tools for assessing fall risk in this population. METHODS: The aim of this quasi-experimental study was to evaluate the impact of a 12-week exercise intervention followed by a 2-week detraining period on lower limb strength and postural stability in older adults. The study involved 38 community-dwelling participants of Central European origin over 60 years of age. Participants underwent the measurements consisting of assessments of knee flexors and extensors strength (isokinetic dynamometer, 90° range of motion, 60°/s angular velocity, Humac Norm CSMI, Stoughton MA, USA), toe grip strength (toe grip dynamometer, Takei Scientific Instruments, Niigata, Japan), and postural stability (narrow stand, 30 s, Kistler, Switzerland). Testing was repeated three times during the study (pre-intervention, post-intervention, and post-detraining). Participants were separated into 3 groups according to the type of training: resistance training group (n = 13), proprioceptive training group (n = 14), and endurance training group (n = 11). The intervention program lasted 12 weeks, two 60-min sessions per week. A linear mixed model (LMM) predicted a change in postural stability after the resistance, proprioceptive, and endurance exercise interventions were applied. RESULTS: Results showed that knee extensor strength normalized to body mass significantly increased in the resistance training group post-intervention (p = 0.01). Toe grip strength was significantly higher after the intervention in the endurance training group (p = 0.02). A statistically significant increase in knee flexor strength was observed in the proprioceptive training group (p = 0.01). The 2-weeks detraining period revealed no statistically significant loss in training gains. The LMM found different predictions of postural stability changes related to knee extensor strength after each type of training intervention. The final LMM model explains well the variability of the dependent variable R2 = 0.866. CONCLUSIONS: These results highlight the unique characteristics of specific exercise interventions in enhancing muscular strength and postural stability, which are critical for fall prevention among older adults.
- MeSH
- časové faktory MeSH
- cvičení * fyziologie MeSH
- dolní končetina * fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- odporový trénink * metody MeSH
- posturální rovnováha * fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- svalová síla * fyziologie MeSH
- terapie cvičením * metody MeSH
- úrazy pádem prevence a kontrola MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Toscana virus (TOSV) is an emerging but neglected human pathogen currently circulating around the Mediterranean basin including North Africa. Human illness ranges from asymptomatic or mild flu-like syndromes to severe neurological diseases such as meningitis or meningoencephalitis. Despite its significant impact, understanding of TOSV transmission and epidemiology remains limited. Sand flies (Diptera: Phlebotominae), specifically Phlebotomus perniciosus and Phlebotomus perfiliewi, are believed to be the primary vectors of TOSV. However, the spread of TOSV to new geographical areas and its detection in other sand fly species suggest that additional species play a role in the circulation and transmission of this virus. This study investigated the vector competence of four sand fly species - P. tobbi, P. sergenti, P. papatasi, and Sergentomyia schwetzi - for two TOSV strains: 1500590 (TOSV A lineage) and MRS20104319501 (TOSV B lineage). Sand flies were orally challenged with TOSV via bloodmeals. None of the tested species showed susceptibility to the TOSV A strain. However, for TOSV B strain, P. tobbi demonstrated a high potential as a new vector, exhibiting high infection and dissemination rates. P. sergenti also showed some susceptibility to TOSV B, with the virus dissemination observed in all infected females. These finding suggests that P. tobbi and P. sergenti are new potential vectors for TOSV B. Given that P. tobbi and P. sergenti are the primary vectors of human leishmaniases in the Balkans, Turkey and Middle East, their susceptibility to TOSV could have significant epidemiological consequences. On the other hand, P. papatasi and S. schwetzi appeared refractory to TOSV B infection. Refractoriness of P. papatasi, a highly anthropophilic species distributed from the Mediterranean to the Middle East and India, suggests that this species does not contribute to TOSV circulation.
The IgM-related peripheral neuropathies (IgM-PN) are a group of chronic disorders characterized by the presence of monoclonal IgM that may be associated with one of several diseases affecting the peripheral nerves. In many cases, there is a monoclonal IgM associated with activity against neural targets, leading to progressive peripheral nerve demyelination. Neurological symptoms in this setting can also result from direct invasion of the peripheral or central nervous system by lymphoplasmacytic cells (neurolymphomatosis and Bing-Neel syndrome respectively) or via other mechanisms (for example AL amyloid deposition or cryoglobulinemic vasculitis). There is an expanding array of treatment options, but high-quality data are sparse. Diagnostic accuracy is important and needs collaboration between hematologists and neuromuscular specialists to determine the sequence and intensity of investigations. Appropriate causal attribution to the IgM disorder is essential to enable the correct therapeutic intervention. The aims of treatment intervention should be clear and realistic. Consistent and clinically meaningful measures are needed to capture treatment success. Despite therapeutic advances, many patients experience persistent disability, highlighting the need for further research.
- MeSH
- imunoglobulin M * imunologie MeSH
- lidé MeSH
- management nemoci MeSH
- nemoci periferního nervového systému * terapie diagnóza etiologie imunologie MeSH
- Waldenströmova makroglobulinemie * terapie komplikace diagnóza imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
