Lipidomics has been proving that membrane lipids play a crucial role in several cell functions and are involved in several pathologies, including cancer. In fact, beyond a scaffold where proteins and ...other components are embedded, the cell membrane can also act as a barrier or a target for anticancer drugs. From this point of view, the development of new chemotherapeutic agents should also take into account the role of the membrane in their activity. This Review aims to highlight the importance of anticancer drug-membrane interactions as a powerful strategy to improve cancer therapy. Biophysical techniques emerge, therefore, as essential tools to unveil such interactions.
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•Cancer cells present changes in phospholipid constitution, surface charge and membrane fluidity.•The structural, biophysical and functional differences between cancer and normal cell membranes can modulate drug activity.•Mimetic models have been developed to overcome membrane's complexity and used to study anticancer drug-membrane interactions.•Research of new cancer therapies using membrane biophysics may be a path to overcome the problems found in clinical practice.
Human papillomaviruses (HPV) are the causative agents of the most common sexually transmitted infection worldwide. While infection is generally asymptomatic and can be cleared by the host immune ...system, when persistence occurs, HPV can become a risk factor for malignant transformation. Progression to cancer is actually an unintended consequence of the complex HPV life cycle. Different antiviral defence mechanisms recognize HPV early in infection, leading to the activation of the innate immune response. However, the virus has evolved several specific strategies to efficiently evade the antiviral immune signalling. Here, we review and discuss the interplay between HPV and the host cell innate immunity. We further highlight the evasion strategies developed by different HPV to escape this cellular response and focus on the correlation with HPV-induced persistence and tumorigenesis.
Human-animal relations have been a fruitful research topic worldwide. The importance of deer in hunter-gatherer societies is undeniable, with cervids being commonly found in archaeological and past ...artistic records, with a notable amount of information recovered in the Iberian Peninsula. This relevance continues during Late Prehistory, but the attempt to discuss cervids under broader perspectives and based on different types of data is not as common. We intend to approach human-deer relations in Central and Southern Portuguese Late Prehistory by considering the zooarchaeological records, both deer abundance in faunal spectra and their presence in "meaningful" assemblages and structured depositions, as well as the use of deer and deer body parts in other socio-cultural and ideological practices. The synthesis of available data shows that human-deer relations changed through time and space, with different abundances related to hunting depending on chronology and geography. The use of deer or their body parts as a resource of symbolic nature also varied, being included in food-sharing events, offerings, structured depositions, and graphic representations. Changeability is part of the different relationships, ontologies, and cosmogonies that humans and deer developed in the Late Prehistoric relational world.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
As the human ovarian follicle enlarges in the course of a regular cycle or following controlled ovarian stimulation, the changes in its structure reveal the oocyte environment composed of cumulus ...oophorus cells and the follicular fluid (FF).In contrast to the dynamic nature of cells, the fluid compartment appears as a reservoir rich in biomolecules. In some aspects, it is similar to the plasma, but it also exhibits differences that likely relate to its specific localization around the oocyte. The chemical composition indicates that the follicular fluid is able to detect and buffer excessive amounts of reactive oxygen species, employing a variety of antioxidants, some of them components of the intracellular milieu.An important part is played by albumin through specific cysteine residues. But the fluid contains other molecules whose cysteine residues may be involved in sensing and buffering the local oxidative conditions. How these molecules are recruited and regulated to intervene such process is unknown but it is a critical issue in reproduction.In fact, important proteins in the FF, that regulate follicle growth and oocyte quality, exhibit cysteine residues at specific points, whose untoward oxidation would result in functional loss. Therefore, preservation of controlled oxidative conditions in the FF is a requirement for the fine-tuned oocyte maturation process. In contrast, its disturbance enhances the susceptibility to the establishment of reproductive disorders that would require the intervention of reproductive medicine technology.
Introduction/objectives
To evaluate rituximab (RTX) effectiveness and safety in patients with interstitial lung disease (ILD) related to connective tissue diseases (CTD).
Methods
Retrospective ...multicenter cohort study, including patients with CTD-ILD, followed in six Portuguese rheumatology departments until November 2018. ILD diagnosis was based on high-resolution CT (HRCT) and/or lung biopsy. Results of HRCT, pulmonary function tests, and 6-min walking test before and after RTX were compared using the Wilcoxon matched pair test. Safety, including adverse events during treatment and reasons for RTX discontinuation, was also analyzed.
Results
A total of 49 patients were included, with rheumatoid arthritis being the commonest CTD (61.2%). The median interval between CTD onset and ILD diagnosis was 4 years (IQR 1–9.5) and median ILD duration at first RTX administration was 1 year (IQR 0–4). The median RTX treatment duration until the last follow-up was 3 years (IQR 1–6). Usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) were the commonest patterns, occurring in 20 and 18 patients, respectively. One year after RTX first administration, there was a stabilization in carbon monoxide diffusing capacity (DLCO; mean + 5.4%,
p
= 0.12) and improvement in forced vital capacity (FVC; mean + 4.3%,
p
= 0.03), particularly in patients with NSIP. Patients with UIP had less promising results, but at 1 year, pulmonary function tests remained stable (DLCO + 2.5%,
p
= 0.77; FVC + 4.2%,
p
= 0.16). Infection was the main reason for RTX discontinuation and led to two deaths.
Conclusions
RTX seems to be a promising treatment for CTD-ILD patients, particularly when NSIP pattern is present.
Key points
•
The use of rituximab in patients with interstitial lung disease related to connective tissue disease is associated with long-standing disease stability in a wide range of systemic rheumatic diseases.
• Efficacy results were particularly impressive in patients with non-specific interstitial pneumonia pattern, although in a subgroup of patients with usual interstitial pneumonia pattern, disease progression was also hold with this treatment.
•
In a large number of patients, rituximab was used in monotherapy and as first-line treatment.
Colorectal cancer is a major health problem worldwide with urgent need for new and effective anti-cancer approaches that allow treating, increasing survival and improving life quality of patients. At ...pharmacological concentrations, ascorbic acid (AA) exerts a selective cytotoxic effect, whose mechanism of cytotoxicity remains unsolved. It has been suggested that it depends on the production of extracellular hydrogen peroxide, using ascorbate radical as an intermediate. The aim of this study was to evaluate the effects induced by AA in three colon cancer cell lines, as well as, possible cell death mechanisms involved.
Our results showed that pharmacological concentrations of AA induce anti-proliferative, cytotoxic and genotoxic effects on three colon cancer cell lines under study. We also found that AA can induce cell death by an increment of oxidative stress, but also mediating a ROS-independent mechanism, as observed in LS1034 cells. This work explores AA anti-tumoral effects and highlights its applicability in the treatment of CC, underlying the importance of proceeding to clinical trials.
Background: Several gastroenterology societies have created recommendations in order to reduce nonessential exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Our aim ...is to evaluate the national gastroenterologists’ perspective on the impact of COVID-19 and the impact of reorganization of a gastroenterology department during the COVID-19 pandemic. Methods: For the first purpose, an online survey was distributed to gastroenterologists nationwide. For the second purpose, the authors conducted an analysis of some endoscopic procedures performed at the Gastroenterology Department of the Centro Hospitalar Vila Nova de Gaia/Espinho (CHVNG/E) between March 16 and May 8 during the years 2019 and 2020. Results: Sixty-seven gastroenterologists answered our survey. Only 14.9% were residents and 86.6% worked in a hospital with COVID-19 patients, with 16.4% assigned to assist those patients. All of the departments suffered modifications. Ninety percent of the residents affirmed that their activity had changed. Ninety-four percent declared having nonessential endoscopic procedures postponed, and 85.1% maintained in-person medical visits, 88.1% were already having remote consultations, and 11.9% did not have any clinical visit. In our gastroenterology unit, the number of endoscopic procedures decreased by 73.1% from 2019 to 2020. In 2020, the proportion of urgent procedures was higher compared to 2019. Conclusion: The advent of COVID-19 has led to important changes in gastroenterology activities in Portugal, and national gastroenterology units are complying with the recommendations. Furthermore, Portuguese gastroenterologists believed that the decrease in endoscopic activity can compromise residents’ education and training. The gastroenterology department at CHVNG/E has shown a significant reduction in the number of endoscopic procedures.
Background: As human longevity continues to increase, age-related diseases are more common, which leads to a higher use of gastroenterology services. Endoscopic procedures are generally considered to ...be of higher risk in the elderly with multiple comorbidities. However, some endoscopic techniques have already been proved to be well tolerated in the elderly. Summary: Enteroscopy enables the nonsurgical diagnosis and therapeutic management of a wide variety of small bowel diseases. Although it has been shown to be safe and effective, with high diagnostic yield and therapeutic success rate in the general population, its safety and efficacy in the elderly is largely unknown, and there are still some concerns about its use in these patients. Key Messages: This review will focus on enteroscopy in elderly people, taking into account patient and procedure characteristics, indications, findings, yield, and complication rate.
Food allergies are becoming ever more prevalent around the world. This pathology is characterized by the breakdown of oral tolerance to ingested food allergens, resulting in allergic reactions in ...subsequent exposures. Due to the possible severity of the symptoms associated with this pathology, new approaches to prevent it and reduce associated symptoms are of utmost importance. In this framework, dietary phenolic compounds appear as a tool with a not fully explored potential. Some phenolic compounds have been pointed to with the ability to modulate food allergies and possibly reduce their symptoms. These compounds can modulate food allergies through many different mechanisms, such as altering the bioaccessibility and bioavailability of potentially immunogenic peptides, by modulating the human immune system and by modulating the composition of the human microbiome that resides in the oral cavity and the gastrointestinal tract. This review deepens the state-of-the-art of the modulation of these mechanisms by phenolic compounds. While this review shows clear evidence that dietary supplementation with foods rich in phenolic compounds might constitute a new approach to the management of food allergies, it also highlights the need for further research to delve into the mechanisms of action of these compounds and decipher systematic structure/activity relationships.
In monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), the expansion of malignant B cells disrupts the normal homeostasis and interactions between B cells and T cells, ...leading to immune dysregulation. CD20+ T cells are a subpopulation of T cells that appear to be involved in autoimmune diseases and cancer.
Here, we quantified and phenotypically characterized CD20+ T cells from MBL subjects and CLL patients using flow cytometry and correlated our findings with the B-cell receptor mutational status and other features of the disease.
CD20+ T cells were more represented within the CD8+ T cell compartment and they showed a predominant memory Tc1 phenotype. CD20+ T cells were less represented in MBL and CLL patients vs healthy controls, particularly among those with unmutated IGVH gene. The expansion of malignant B cells was accompanied by phenotypic and functional changes in CD20+ T cells, including an increase in follicular helper CD4+ CD20+ T cells and CD20+ Tc1 cells, in addition to the expansion of the TCR Vβ 5.1 in CD4+ CD20+ T cells in CLL.
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