Life-Basel最新文献

Cutaneous viral infections result from the complex interaction between viruses and skin structures, influenced by viral tropism and the host immune response. They can generate lesions ranging from transient rashes to chronic or potentially tumorous formations. Cutaneous manifestations are often the first sign of infection and allow for early recognition. The aim of this review is to analyze the role of viruses in skin pathology, the mechanisms of infection, and the clinical impact. A narrative review of the recent literature was performed, including original articles, systematic reviews, and clinical guidelines on cutaneous viral infections. Data on pathogenic mechanisms, types of lesions, evolution, and therapeutic options were evaluated, covering the main viruses involved in dermatology: herpesviruses, papillomaviruses, poxviruses, and viruses associated with acute rashes. Cutaneous viral infections can be self-limited, recurrent, or chronic, and some can promote malignant transformation of skin cells. The variability of clinical manifestations reflects the virus-host interaction and influences diagnosis and management. Recent advances highlight the development of vaccines and targeted antiviral therapies, which improve prognosis and infection control. Viruses play a major role in the etiology of skin diseases, and their early recognition is essential for preventing complications. Understanding the mechanisms of infection and the cutaneous response contributes to the optimization of therapeutic and preventive strategies, strengthening the modern management of viral cutaneous pathology.

Background: Bladder cancer (BC) predominantly affects older patients, and their multidisciplinary treatment often includes surgical intervention. Frailty can influence treatment decisions and is associated with poorer outcomes. This study analyses trends in demographics, treatment patterns and frailty in a large, nationwide, real-world inpatient cohort in Germany.

Methods: This retrospective observational study included a total of 49,139 consecutive patients, who received inpatient care for BC at all HELIOS hospitals in Germany between 2016 and 2022. Frailty was assessed using the Hospital Frailty Risk Score (HFRS) and categorised as low (<5), intermediate (5-15), or high (>15). Trends in HFRS, treatment modalities, and demographic variables were analysed using regression models and compared between the periods 2016-2019 and 2020-2022.

Results: Of the 49,139 patients, 27,979 were treated between 2016-2019 and 21,160 between 2020-2022. Patients treated in the later period were slightly older but had a lower comorbidity index. The proportion of patients with low frailty increased (73.4% vs. 75.5%, p < 0.01), intermediate frailty decreased (23.5% vs. 21.5%, p < 0.01) and the proportion of highly frail patients remained stable at 3.0% (p = 0.95). Rates of transurethral resection declined over time, whereas rates of RC remained stable (p = 0.12). The use of systemic therapy increased (p = 0.003), particularly among low frailty elderly patients. Early intravesical chemotherapy following transurethral resection declined significantly in 2020-2022 (p < 0.001), particularly among elderly patients with high frailty. Mean length of hospital stay decreased by one day, while ICU admission rates and in-hospital mortality remained stable across time periods.

Conclusions: This study shows frailty-specific changes in hospitalisation patterns and inpatient management of BC in Germany, underscoring the value of frailty assessment in population-based research. The proportion of patients classified as having low frailty increased over time. Significant changes in the use of intravesical chemotherapy and systemic therapy were associated with frailty. The decline in early intravesical chemotherapy may have implications for recurrence risk and downstream healthcare utilisation.

Background: Plants represent an important source of photoprotective compounds that are capable of protecting human skin from solar-induced damage. In this study we investigated the suitability of a murine model for estimating the Erythema Protection Efficacy (EPE) of natural compound. Methods: UVB-induced skin erythema in albino BALB/c mice was quantified using a Mexameter MX18 MDD colorimeter. The ARRIVE principle was followed. The Minimum Erythema Dose (MED) was determined based on Log₁₀ dose-erythema response curves. EPE values for UV filters (e.g., titanium dioxide or zinc oxide) and selected plant-derived compounds (apigenin, caffeic acid, epigallocatechin gallate, kaempferol, and pinocembrin) were calculated as the ratio between the MED of protected skin and that of unprotected skin. Results: The UVB-induced erythema in both female and male mouse skin followed a linear response. Erythema intensity varied by sex and by the dorsal skin area examined. MED values ranged from 39 to 57 mJ/cm² in female mice and from 71 to 80 mJ/cm² in male mice. In both sexes, MED increased linearly with the logarithm of the radiation dose. All tested compounds (apigenin, caffeic acid, epigallocatechin gallate, kaempferol, and pinocembrin) provided protection against UV-radiation-induced erythema in mouse skin. Among them, apigenin, caffeic acid, and kaempferol exhibited the highest EPE values, indicating strong potential for incorporation into sunscreen formulations. Conclusions: The murine EPE metric proved to be a useful tool for identifying plant-derived compounds with potential relevance for the photoprotection of human skin.

Metabolic dysfunction has emerged as a central driver of cardiovascular, renal, hepatic, and endocrine disorders, challenging traditional organ-specific disease models. Increasing evidence indicates that conditions such as obesity, type 2 diabetes, chronic kidney disease, heart failure, and metabolic dysfunction-associated steatotic liver disease frequently develop in parallel, reflecting shared upstream metabolic abnormalities rather than isolated pathologies. This narrative review synthesizes recent clinical, epidemiologic, biomarker, and therapeutic evidence to examine metabolic dysfunction as a unifying framework for multisystem disease, with particular focus on the cardiovascular-renal-hepatic-metabolic (CRHM) model. A targeted literature search of major biomedical databases was conducted to identify relevant studies published between 2020 and 2025, encompassing observational cohorts, randomized trials, and integrative reviews addressing cross-organ metabolic interactions. The reviewed evidence highlights consistent clinical overlap across organ systems, stage-dependent risk amplification and the utility of shared metabolic and inflammatory biomarkers in capturing multisystem vulnerability. In parallel, contemporary metabolic therapies demonstrate coordinated benefits across cardiovascular, renal, and hepatic domains, supporting the concept of common modifiable disease drivers. The reviewed evidence supports a shift from organ-based toward metabolic-centric frameworks for risk stratification and prevention. Viewing metabolic dysfunction as the organizing principle of cardiometabolic disease may improve recognition of multisystem risk, facilitate earlier intervention, and provide a more coherent foundation for precision and preventive medicine, in an era of growing cardiometabolic multimorbidity.

Mass spectrometry imaging (MSI) is an innovative analytical technique that integrates chemical analysis with spatial localization, enabling label-free, in situ detection and visualization of diverse biomolecules within tissue sections. This review summarizes the recent advances in the application of MSI to neurological disorders, with a focus on Parkinson's disease, Alzheimer's disease, schizophrenia, and traumatic brain injury. Studies have demonstrated that MSI can delineate the spatial heterogeneity of disease-related molecules-such as neurotransmitters, lipids, and metabolites-thereby providing new perspectives for understanding the pathological mechanisms of neurodegenerative and psychiatric diseases. Platforms including MALDI-MSI and DESI-MSI have been effectively employed for visualizing drug distribution, characterizing lipid metabolic pathways, and identifying spatial biomarkers. Although challenges remain in quantitative accuracy, spatial resolution, and the detection of low-abundance molecules, advances in high-resolution mass spectrometry, single-cell-level imaging, and multi-omics integration are expected to further enhance the utility of MSI in the investigation of brain diseases.

Ischemia-reperfusion injury (IRI) is a mechanism based on inflammatory mediators' release and activation of effectors of damage. Studies showed a correlation between cytokine, severity of damage, and post-operative outcomes. Ex situ perfusion may work as a platform for the treatment of IRI mechanisms, such as the removal of cytokines using cytokine adsorption (CA). We assessed the safety and benefits of an integrated CA during ex situ dual-oxygenated hypothermic (D-HOPE) and normothermic perfusion (NMP). During the period of July 2021-December 2023, 84 octogenarian liver grafts, suitable for transplantation, were considered: 12 were randomized to D-HOPE or NMP with or without CA (D-HOPE + CA, D-HOPE, NMP + CA, NMP groups, n = 3 each) and compared to 72 performed using grafts preserved in static cold storage (SCS). IL-1, IL-6, IL-10, and TNF-a perfusate concentrations were evaluated together with perfusion parameters and post-operative outcomes. Perfusion procedures were unaffected by CA integration. In NMP, cytokine levels were 10-40 times higher than in healthy subjects and 20-50 times higher than D-HOPE. Cytokines were removed both in D-HOPE and NMP, but the concentration-dependent mechanisms of action of CA led to more remarkable removal in NMP. IL-10 and TNF-a concentrations were significantly lower in NMP + CA than in NMP. The application of CA was associated with significantly higher arterial flows both in D-HOPE and NMP, and reduced neutrophil infiltration in NMP. No differences in post-operative outcomes were found among groups. In conclusion, cytokine adsorption during ex situ machine perfusion of liver grafts from elderly donors is safe and feasible and is associated with modulation of inflammatory mediators and perfusion dynamics. These findings are hypothesis-generating, and larger studies are required to determine the clinical impact of this strategy.

We present a simplified phenomenological computational framework that integrates the GABA shunt into established metabolic mechanisms underlying pancreatic beta cell insulin secretion. The GABA shunt introduces carbon into the tricarboxylic acid (TCA) cycle via succinate, thereby functioning as an anaplerotic pathway. This anaplerotic input is coupled to oscillatory cataplerotic fluxes, primarily involving α-ketoglutarate, whose effective extrusion requires coordinated counter-fluxes of malate and aspartate. Within the model, these cataplerotic exchanges are facilitated by UCP2-mediated transport processes and necessitate complementary anaplerotic replenishment through pyruvate carboxylase (PC). Based on this functional interdependence, we introduce the Dual Anaplerotic Model (DAM), which conceptually links two anaplerotic routes-the GABA shunt-mediated pathway and the glucose-dependent PC pathway-into a unified metabolic response module. DAM describes a coordinated, breathing-like redistribution of carbon between mitochondrial and cytosolic metabolite pools, while efficient oxidative metabolism of glucose-derived carbon entering the TCA cycle via pyruvate dehydrogenase is maintained. The model is driven by experimentally observed ATP/ADP and Ca²⁺ dynamics and is not intended to generate autonomous oscillations. Instead, it enables qualitative, phase-dependent visualization of how dual anaplerotic fluxes constrain and shape oscillatory metabolic states in beta cells. DAM provides an integrative conceptual scaffold for interpreting experimental observations and for motivating future quantitative modeling and experimental studies addressing metabolic regulation in physiological and pathophysiological contexts.

The huge number of possible permutations of genes, proteins and small molecules make the random emergence of cellular networks problematic. How, therefore, do interactomes come into existence? What selects for their stability and functionality? I hypothesize that interactomes originate from molecularly complementary modules (MCMs) that are selected for stability and retain their interactivity when mixed and matched with other such modules to create novel molecules and complexes displaying emergent properties not present in the individual components of the network. Because evolution can only proceed by working upon existing variants, and these variants emerge from selection of MCMs, the resulting systems must exhibit the characteristics of pleiofunctional, epistatic interactomes (PEIs). The resulting systems should display "molecular paleontology", providing clues as to the historical process by which these MCMs were incorporated into the system. The MCM mechanism of PEI evolution is illustrated here by two case studies. The first concerns the prebiotic emergence of the glutathione-ascorbate anti-oxidant system and its later incorporation into regulation of glucose transport and catecholamine receptor activity. The second concerns the MCM evolution of the ribosome as, perhaps, the first PEI, and its role as a module for the later construction of the first cellular genomes.

The arachidonic acid pathway plays a pivotal role in the biosynthesis of important inflammatory and signal transducing agents such as prostaglandins, leukotrienes and thromboxanes. When this pathway is deregulated, it leads to pathological conditions such as cardiovascular diseases, metabolic diseases, and cancer. Two key enzymes of the pathway are cyclooxygenases (COXs) and lipoxygenases (LOXs), which are responsible for the production of prostaglandins and leukotrienes, respectively. Consequently, these enzymes have long been recognized as key therapeutic targets for the treatment and management of inflammatory disorders and other pathological conditions associated with inflammation. In this review, we describe the new evidence over the last 4 years regarding the arachidonic acid pathway. Moreover, we will pay attention to the structure and function of the COX-2 and 5-LOX enzymes and their role in inflammation, as well as define their active sites. Later, we will discuss the most potent, dual inhibitors of COX-2 and 5-LOX enzymes, based on in vitro and in vivo experiments, from 2020-2024. Structure-activity relationship (SAR) analysis of these compounds revealed four key structural features required for potent dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). We refer to these criteria as "The Rule of Four for Inflammation".

Background/Objectives: The COVID-19 pandemic profoundly disrupted gastric cancer care, reducing access to screening, delaying diagnosis, and altering therapeutic pathways worldwide. Beyond clinical challenges, it exposed structural weaknesses in healthcare systems but also accelerated innovation. Methods: We conducted a narrative review supported by a structured literature search (PubMed/MEDLINE, Scopus, Web of Science; 1 January 2014-30 November 2025), with a narrative synthesis of observational studies, registry analyses, and meta-analyses addressing COVID-19-related changes in gastric cancer epidemiology, diagnosis, treatment, vaccination, and telemedicine. A PRISMA-style flow diagram was used to illustrate study selection. Results: Elective endoscopy volumes fell by up to 80%, leading to diagnostic backlogs and increased proportions of advanced-stage gastric cancer. Surgical postponements, modified chemotherapy and radiotherapy schedules, and reduced molecular/genetic testing further compromised outcomes. Conversely, vaccination, telemedicine, capsule endoscopy, and adaptive triage frameworks enabled partial recovery of services. Geographical variations were observed in the recovery of gastric cancer care services, with regions that had established screening infrastructure generally resuming activity more rapidly, whereas others experienced ongoing delays and diagnostic backlogs. Conclusions: This review integrates epidemiological, diagnostic, and therapeutic evidence to demonstrate how COVID-19 redefined gastric cancer care. By highlighting regional disparities and outlining a conceptual model for oncologic resilience, it provides an innovative framework for future crisis preparedness. The lessons of the pandemic-digital health integration, flexible treatment protocols, and international collaboration-represent a foundation for more robust, equitable gastric cancer management in the post-pandemic era.