The 26S proteasome degrades the majority of cellular proteins and affects all aspects of cellular life. Therefore, the 26S proteasome abundance, proper assembly, and activity in different life contexts need to be precisely controlled. Impaired proteasome activity is considered a causative factor in several serious disorders. Recent advances in proteasome biology have revealed that the proteasome can be activated by different factors or small molecules. Thus, activated ubiquitin-dependent proteasome degradation has effects such as extending the lifespan in different models, preventing the accumulation of protein aggregates, and reducing their negative impact on cells. Increased 26S proteasome-mediated degradation reduces proteotoxic stress and can potentially improve the efficacy of engineered degraders, such as PROTACs, particularly in situations characterized by proteasome malfunction. Here, emerging ideas and recent insights into the pharmacological activation of the proteasome at the transcriptional and posttranslational levels are summarized.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper summarizes the ERA Registry Annual Report 2022, with a special focus on comparisons by sex. The supplement of this paper contains the complete ERA Registry Annual Report 2022. Data was collected from 53 national and regional KRT registries from 35 countries. Using this data, incidence, and prevalence of KRT, kidney transplantation rates, survival probabilities, and expected remaining lifetimes were calculated. In 2022, 530 million people of the European general population were covered by the ERA Registry. The incidence of KRT was 152 per million population (pmp). In incident patients, 54% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes mellitus (22%). At KRT initiation, 83% of patients received haemodialysis, 12% received peritoneal dialysis, and 5% underwent pre-emptive kidney transplantation. On 31 December 2022, the prevalence of KRT was 1074 pmp. In prevalent patients, 48% were 65 years or older, 62% were male, the most common PRD was of miscellaneous origin (18%), 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. In 2022, the kidney transplantation rate was 40 pmp, with most kidneys coming from deceased donors (66%). For patients starting KRT between 2013 to 2017, 5-year survival probability was 52%. Compared with the general population, the expected remaining lifetime was 66% and 68% shorter for males and females, respectively, receiving dialysis, and 46% and 49% shorter for males and females, respectively, living with a functioning graft.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE OF REVIEW: Upper tract urothelial carcinoma (UTUC) is a rare malignancy posing significant diagnostic and management challenges. This review provides an overview of the evidence supporting various imaging modalities and offers insights into future innovations in UTUC imaging. RECENT FINDINGS: With the growing use of advancements in computed tomography (CT) technologies for both staging and follow-up of UTUC patients, continuous innovations aim to enhance performance and minimize the risk of excessive exposure to ionizing radiation and iodinated contrast medium. In patients unable to undergo CT, magnetic resonance imaging serves as an alternative imaging modality, though its sensitivity is lower than CT. Positron emission tomography, particularly with innovative radiotracers and theranostics, has the potential to significantly advance precision medicine in UTUC. Endoscopic imaging techniques including advanced modalities seem to be promising in improved visualization and diagnostic accuracy, however, evidence remains scarce. Radiomics and radiogenomics present emerging tools for noninvasive tumor characterization and prognosis. SUMMARY: The landscape of imaging for UTUC is rapidly evolving, with significant advancements across various modalities promising improved diagnostic accuracy, patient outcomes, and safety.
- MeSH
- karcinom z přechodných buněk * diagnóza diagnostické zobrazování terapie patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- nádory ledvin diagnostické zobrazování terapie diagnóza patologie MeSH
- nádory močovodu diagnostické zobrazování diagnóza terapie patologie MeSH
- počítačová rentgenová tomografie metody MeSH
- pozitronová emisní tomografie metody MeSH
- staging nádorů MeSH
- urologické nádory diagnóza diagnostické zobrazování terapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVES: Nonpharmacologic interventions (NPIs) constitute an important part of treatment for older adults, cover a broad and diverse range of interventions, and have advantages over pharmacologic interventions (eg, limited adverse side effects). However, an unambiguous definition of NPIs is still lacking. Defining NPIs may facilitate research on this topic and enhance comparability of results between studies, and might help to face the challenges of recognition, acceptation, funding, and implementation. Therefore, the aim of this review was to provide an overview and comparison of the definitions of NPIs used in the current literature on older adults. DESIGN: A systematic review was performed to provide an overview of the definitions of NPIs that are used in the current literature on older populations and to organize the characteristics involved in the definitions. SETTING AND PARTICIPANTS: People ≥60 years of age were included, not limited to a specific setting. METHODS: A systematic search was performed in the following 5 databases: PubMed, Embase, Clarivate Analytics/Web of Science Core Collection, Cumulative Index to Nursing and Allied Health Literature, and Wiley/Cochrane Library. The time frame within the databases was from inception to December 4, 2023. Review articles, editorials and consensus papers were included. RESULTS: We included 28 articles. We organized the definitions of NPI according to 4 different aspects: types of interventions involved, target population, goals the interventions addressed, and requirements of the interventions. Definitions in the current literature can generally be divided into 2 groups: NPIs described as not involving medication, and more elaborated multidomain definitions. Based on the results, we formulated criteria for types of interventions that can be considered an NPI. CONCLUSIONS AND IMPLICATIONS: Using current descriptions and characteristics, elements for a new definition for NPIs were proposed. To improve research in this field, consensus needs to be reached regarding elements covered by a definition of NPIs.
The rapid evolution and spread of multidrug resistance among bacterial pathogens has significantly outpaced the development of new antibiotics, underscoring the urgent need for alternative therapies. Antimicrobial photodynamic therapy and antimicrobial sonodynamic therapy have emerged as promising treatments. Antimicrobial photodynamic therapy relies on the interaction between light and a photosensitizer to produce reactive oxygen species, which are highly cytotoxic to microorganisms, leading to their destruction without fostering resistance. Antimicrobial sonodynamic therapy, a novel variation, substitutes ultrasound for light to activate the sonosensitizers, expanding the therapeutic reach. To increase the efficiency of antimicrobial photodynamic therapy and antimicrobial sonodynamic therapy, the combination of these two methods, known as antimicrobial photo-sonodynamic therapy, is currently being explored and considered a promising approach. Recent advances, particularly in the application of nanomaterials, have further enhanced the efficacy of these therapies. Nanosensitizers, due to their improved reactive oxygen species generation and targeted delivery, offer significant advantages in overcoming the limitations of conventional sensitizers. These breakthroughs provide new avenues for treating bacterial infections, especially multidrug-resistant strains and biofilm-associated infections. Continued research, including comprehensive clinical studies, is crucial to optimizing nanomaterial-based antimicrobial photo-sonodynamic therapy for clinical use, ensuring their effectiveness in real-world applications.
- MeSH
- antibakteriální látky * farmakologie MeSH
- Bacteria účinky léků MeSH
- bakteriální infekce * farmakoterapie mikrobiologie terapie MeSH
- biofilmy účinky léků MeSH
- fotochemoterapie * metody MeSH
- fotosenzibilizující látky * farmakologie MeSH
- lidé MeSH
- nanočástice chemie MeSH
- nanostruktury chemie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- ultrazvuková terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
With the advent rise is in urbanization and industrialization, heavy metals (HMs) such as lead (Pb) and cadmium (Cd) contamination have increased considerably. It is among the most recalcitrant pollutants majorly affecting the biotic and abiotic components of the ecosystem like human well-being, animals, soil health, crop productivity, and diversity of prokaryotes (bacteria) and eukaryotes (plants, fungi, and algae). At higher concentrations, these metals are toxic for their growth and pose a significant environmental threat, necessitating innovative and sustainable remediation strategies. Bacteria exhibit diverse mechanisms to cope with HM exposure, including biosorption, chelation, and efflux mechanism, while fungi contribute through mycorrhizal associations and hyphal networks. Algae, especially microalgae, demonstrate effective biosorption and bioaccumulation capacities. Plants, as phytoremediators, hyperaccumulate metals, providing a nature-based approach for soil reclamation. Integration of these biological agents in combination presents opportunities for enhanced remediation efficiency. This comprehensive review aims to provide insights into joint action of prokaryotic and eukaryotic interactions in the management of HM stress in the environment.
- MeSH
- Bacteria * metabolismus účinky léků MeSH
- biodegradace * MeSH
- Eukaryota metabolismus účinky léků MeSH
- houby metabolismus MeSH
- kadmium * metabolismus toxicita MeSH
- látky znečišťující půdu * metabolismus MeSH
- olovo * metabolismus toxicita MeSH
- rostliny mikrobiologie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE OF REVIEW: This review explores the design and endpoints of perioperative platforms in clinical trials for muscle-invasive bladder cancer (MIBC). RECENT FINDINGS: The choice of clinical trial design in perioperative platforms for MIBC must align with specific research objectives to ensure robust and meaningful outcomes. Novel designs in perioperative platforms for MIBC integrate bladder-sparing approaches. Primary endpoints such as pathological complete response and disease-free survival are highlighted for their role in expediting trial results in perioperative setting. Incorporating patient-reported outcomes is important to inform healthcare decision makers about the outcomes most meaningful to patients. Given the growing body of evidence, potential biomarkers, predictive and prognostic tools should be considered and implemented when designing trials in perioperative platforms for MIBC. SUMMARY: Effective perioperative platforms for MIBC trials are critical in enhancing patient outcomes. The careful selection and standardization of study designs and endpoints in the perioperative platform are essential for the successful implementation of new therapies and the advancement of personalized treatment approaches in MIBC.
- MeSH
- cystektomie metody škodlivé účinky MeSH
- invazivní růst nádoru * MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- nádory močového měchýře * chirurgie patologie terapie mortalita MeSH
- perioperační péče metody normy MeSH
- stanovení cílového parametru MeSH
- výsledek terapie MeSH
- výzkumný projekt MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The soil microbiota exhibits an important function in the ecosystem, and its response to climate change is of paramount importance for sustainable agroecosystems. The macronutrients, micronutrients, and additional constituents vital for the growth of plants are cycled biogeochemically under the regulation of the soil microbiome. Identifying and forecasting the effect of climate change on soil microbiomes and ecosystem services is the need of the hour to address one of the biggest global challenges of the present time. The impact of climate change on the structure and function of the soil microbiota is a major concern, explained by one or more sustainability factors around resilience, reluctance, and rework. However, the past research has revealed that microbial interventions have the potential to regenerate soils and improve crop resilience to climate change factors. The methods used therein include using soil microbes' innate capacity for carbon sequestration, rhizomediation, bio-fertilization, enzyme-mediated breakdown, phyto-stimulation, biocontrol of plant pathogens, antibiosis, inducing the antioxidative defense pathways, induced systemic resistance response (ISR), and releasing volatile organic compounds (VOCs) in the host plant. Microbial phytohormones have a major role in altering root shape in response to exposure to drought, salt, severe temperatures, and heavy metal toxicity and also have an impact on the metabolism of endogenous growth regulators in plant tissue. However, shelf life due to the short lifespan and storage time of microbial formulations is still a major challenge, and efforts should be made to evaluate their effectiveness in crop growth based on climate change. This review focuses on the influence of climate change on soil physico-chemical status, climate change adaptation by the soil microbiome, and its future implications.
Across the globe, significant inequities in brain tumor treatment, care, and support perpetuate. Identifying and addressing these unmet needs in the context of patients' rights is crucial to reducing inequalities and improving outcomes for people living with brain tumors. Brain tumor patient advocacy addresses and influences gaps in healthcare provision, ensuring optimal treatment, care, and support for patients, their caregivers, and families. Therefore, the purpose of this review is to highlight the variety of challenges faced by brain tumor patients, caregivers, and advocates in various parts of the world and set a benchmark for improvements. Twenty-eight leading brain tumor patient/caregiver advocates from 18 countries in Asia Pacific, Sub-Saharan Africa, North America, Eastern Europe, and Western Europe collaborated to explore unmet and met needs in their countries. Virtual meetings were held with the 5 geographic groupings. Through a process of discussion based on a combination of patient advocates' informed expert opinion, published references, a survey (Asia Pacific) and the informal completion of a matrix of challenges by some of the advocacy organizations involved, agreement within the groupings was also reached regarding what rights within The Brain Tumor Patients' Charter of Rights they felt were being met and where there are still gaps. Acknowledging that some rights in The Brain Tumor Patients' Charter of Rights are aspirational, there still remain many areas of the world where even basic patient rights are not yet attainable. Patient advocacy organizations stand ready to help change this to achieve the best possible health and quality of life outcomes for adults and children living with brain tumors.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Foodborne diseases triggered by various infectious micro-organisms are contributing significantly to the global disease burden as well as to increasing mortality rates. Salmonella enterica belongs to the most prevalent form of bacteria accountable for significant burden of foodborne illness across the globe. The conventional therapeutic approach to cater to Salmonella enterica-based infections relies on antibiotic therapy, but the rapid emergence of the antibiotic resistance strains of Salmonella sp. necessitates the development of alternative treatment and prevention strategies. In light of this growing concern, the scientific community is rigorously exploring novel phytochemicals harnessed from medicinally important plants as a promising approach to curb Salmonella enterica infections. A variety of phytochemicals belonging to alkaloids, phenols, flavonoid, and terpene classes are reported to exhibit their inhibitory activity against bacterial cell communication, membrane proteins, efflux pumps, and biofilm formation among drug resistant Salmonella strains. The present review article delves to discuss the emergence of antibiotic resistance among Salmonella enterica strains, various plant sources, identification of phytochemicals, and the current state of research on the use of phytochemicals as antimicrobial agents against Salmonella enterica, shedding light on the promising potential of phytochemicals in the fight against this pathogen.
- MeSH
- antibakteriální látky * farmakologie MeSH
- bakteriální léková rezistence MeSH
- fytonutrienty * farmakologie chemie MeSH
- lidé MeSH
- nemoci přenášené potravou mikrobiologie prevence a kontrola farmakoterapie MeSH
- Salmonella enterica * účinky léků MeSH
- salmonelóza * mikrobiologie farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
