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71.
Natalia Janicka Agnieszka Saek Magdalena Sawiska Ernest Kuchar Anna Wiela-Hojeska Katarzyna Karowicz-Bodalska 《International journal of molecular sciences》2022,23(13)
Skin and gastrointestinal cancer cells are the target of research by many scientists due to the increasing morbidity and mortality rates around the world. New indications for drugs used in various conditions are being discovered. Non-opioid analgesics are worth noting as very popular, widely available, relatively cheap medications. They also have the ability to modulate the membrane components of tumor cells. The aim of this review is to analyze the impact of diclofenac, ibuprofen, naproxen, acetylsalicylic acid and paracetamol on skin and gastrointestinal cancers cell membrane. These drugs may affect the membrane through topical application, at the in vitro and in vivo level after oral or parenteral administration. They can lead to up- or downregulated expression of receptors, transporters and other molecules associated with plasma membrane. Medications may also alter the lipid bilayer composition of membrane, resulting in changes in its integrity and fluidity. Described modulations can cause the visualization of cancer cells, enhanced response of the immune system and the initiation of cell death. The outcome of this is inhibition of progression or reduction of tumor mass and supports chemotherapy. In conclusion, non-opioid analgesics may be used in the future as adjunctive therapy for the treatment of these cancers. 相似文献
72.
Anna N. Boss Abhirup Banerjee Michail Mamalakis Surajit Ray Andrew J. Swift Craig Wilkie Joseph W. Fanstone Bart Vorselaars Joby Cole Simonne Weeks Louise S. Mackenzie 《International journal of molecular sciences》2022,23(13)
Acute kidney injury (AKI) is a prevalent complication in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive inpatients, which is linked to an increased mortality rate compared to patients without AKI. Here we analysed the difference in kidney blood biomarkers in SARS-CoV-2 positive patients with non-fatal or fatal outcome, in order to develop a mortality prediction model for hospitalised SARS-CoV-2 positive patients. A retrospective cohort study including data from suspected SARS-CoV-2 positive patients admitted to a large National Health Service (NHS) Foundation Trust hospital in the Yorkshire and Humber regions, United Kingdom, between 1 March 2020 and 30 August 2020. Hospitalised adult patients (aged ≥ 18 years) with at least one confirmed positive RT-PCR test for SARS-CoV-2 and blood tests of kidney biomarkers within 36 h of the RT-PCR test were included. The main outcome measure was 90-day in-hospital mortality in SARS-CoV-2 infected patients. The logistic regression and random forest (RF) models incorporated six predictors including three routine kidney function tests (sodium, urea; creatinine only in RF), along with age, sex, and ethnicity. The mortality prediction performance of the logistic regression model achieved an area under receiver operating characteristic (AUROC) curve of 0.772 in the test dataset (95% CI: 0.694–0.823), while the RF model attained the AUROC of 0.820 in the same test cohort (95% CI: 0.740–0.870). The resulting validated prediction model is the first to focus on kidney biomarkers specifically on in-hospital mortality over a 90-day period. 相似文献
73.
Eleni Gavriilaki Anna Papakonstantinou Konstantinos A. Agrios 《International journal of molecular sciences》2022,23(13)
Complement-mediated diseases or complementopathies, such as Paroxysmal nocturnal hemoglobinuria (PNH), cold agglutinin disease (CAD), and transplant-associated thrombotic microangiopathy (TA-TMA), demand advanced complement diagnostics and therapeutics be adopted in a vast field of medical specialties, such as hematology, transplantation, rheumatology, and nephrology. The miracle of complement inhibitors as “orphan drugs” has dramatically improved morbidity and mortality in patients with otherwise life-threatening complementopathies. Efficacy has been significantly improved by upstream inhibition in patients with PNH. Different molecules may exert diverse characteristics in vitro and in vivo. Further studies remain to show safety and efficacy of upstream inhibition in other complementopathies. In addition, cost and availability issues are major drawbacks of current treatments. Therefore, further developments are warranted to address the unmet clinical needs in the field of complementopathies. This state-of-the-art narrative review aims to delineate novel insights into factor D inhibition as a promising target for complementopathies. 相似文献
74.
Chiara Rossi Antonio Salvati Mariarosaria Distaso Daniela Campani Francesco Raggi Edoardo Biancalana Domenico Tric Maurizia Rossana Brunetto Anna Solini 《International journal of molecular sciences》2022,23(13)
P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage. 相似文献
75.
Iwona Radziejewska Katarzyna Supruniuk Micha Tomczyk Wiktoria Izdebska Magorzata Borzym-Kluczyk Anna Bielawska Krzysztof Bielawski Anna Galicka 《International journal of molecular sciences》2022,23(15)
Abnormal glycosylation of cancer cells is considered a key factor of carcinogenesis related to growth, proliferation, migration and invasion of tumor cells. Many plant-based polyphenolic compounds reveal potential anti-cancer properties effecting cellular signaling systems. Herein, we assessed the effects of phenolic acid, p-coumaric acid and flavonoids such as kaempferol, astragalin or tiliroside on expression of selected cancer-related glycoforms and enzymes involved in their formation in AGS gastric cancer cells. The cells were treated with 80 and 160 µM of the compounds. RT-PCR, Western blotting and ELISA tests were performed to determine the influence of polyphenolics on analyzed factors. All the examined compounds inhibited the expression of MUC1, ST6GalNAcT2 and FUT4 mRNAs. C1GalT1, St3Gal-IV and FUT4 proteins as well as MUC1 domain, Tn and sialyl T antigen detected in cell lysates were also lowered. Both concentrations of kaempferol, astragalin and tiliroside also suppressed ppGalNAcT2 and C1GalT1 mRNAs. MUC1 cytoplasmic domain, sialyl Tn, T antigens in cell lysates and sialyl T in culture medium were inhibited only by kaempferol and tiliroside. Nuclear factor NF-κB mRNA expression decreased after treatment with both concentrations of kaempferol, astragalin and tiliroside. NF-κB protein expression was inhibited by kaempferol and tiliroside. The results indicate the rationality of application of examined polyphenolics as potential preventive agents against gastric cancer development. 相似文献
76.
77.
Elisa Boschetti Leonardo Caporali Roberto DAngelo Carolina Malagelada Anna Accarino Maria Teresa Dotti Roberta Costa Giovanna Cenacchi Loris Pironi Rita Rinaldi Vincenzo Stanghellini Stefano Ratti Lucia Manzoli Valerio Carelli Roberto De Giorgio 《International journal of molecular sciences》2022,23(15)
mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE. 相似文献
78.
Assessing the landscape context and conversion risk of protected areas using satellite data products
Leona K. Svancara J. Michael Scott Anna B. Pidgorna 《Remote sensing of environment》2009,113(7):1357-227
Since the establishment of the first national park (Yellowstone National Park in 1872) and the first wildlife refuge (Pelican Island in 1903), dramatic changes have occurred in both ecological and cultural landscapes across the U.S. The ability of these protected areas to maintain current levels of biodiversity depend, at least in part, on the integrity of the surrounding landscape. Our objective was to quantify and compare the extent and pattern of natural land cover, risk of conversion, and relationships with demographic and economic variables in counties near National Park Service units and U.S. Fish and Wildlife Service refuges with those counties distant from either type of protected area in the coterminous United States. Our results indicate that landscapes in counties within 10 km of both parks and refuges and those within 10 km of just parks were more natural, more intact, and more protected than those in counties within 10 km of just refuges and counties greater than 10 km from either protected area system. However, they also had greater human population density and change in population, indicating potential conversion risk since the percent of landscape protected averaged < 5% in both groups and human population dynamics are primary drivers of change in many landscapes. Conversion outweighed protection by at least two times (Conservation Risk Index > 2) in 76% of counties near both parks and refuges, 81% of counties near just parks, 91% of counties near just refuges, and 93% of distant counties. Thirteen percent of counties in the coterminous U.S. had moderate to high amounts of natural land cover (> 60%), low protection (< 20%), and the greatest change in population (> 20%). Although these areas are not the most critically endangered, they represent the greatest conservation opportunity, need, and urgency. Our approach is based on national level metrics that are simple, general, informative, and can be understood by broad audiences and by policy makers and managers to assess the health of lands surrounding parks and refuges. Regular monitoring of these metrics with satellite data products in counties surrounding protected areas provides a consistent, national level assessment of management opportunities and potentially adverse changes on adjacent lands. 相似文献
79.
Competitive snoopy caching 总被引:8,自引:1,他引:8
In a snoopy cache multiprocessor system, each processor has a cache in which it stores blocks of data. Each cache is connected to a bus used to communicate with the other caches and with main memory. Each cache monitors the activity on the bus and in its own processor and decides which blocks of data to keep and which to discard. For several of the proposed architectures for snoopy caching systems, we present new on-line algorithms to be used by the caches to decide which blocks to retain and which to drop in order to minimize communication over the bus. We prove that, for any sequence of operations, our algorithms' communication costs are within a constant factor of the minimum required for that sequence; for some of our algorithms we prove that no on-line algorithm has this property with a smaller constant.A preliminary and condensed version of this paper appeared in theProceedings of the 27th Annual Symposium on the Foundations of Computer Science, IEEE, 1986.This author received support from an IBM doctoral fellowship, and did part of this work while a research student associate at IBM Almaden Research Center. 相似文献
80.
We propose a new model of restricted branching programs specific to solving GEN problems, which we call incremental branching programs. We show that syntactic incremental branching programs capture previously studied models of computation for the problem GEN, namely marking machines
(Cook, S.A. in J. Comput. Syst. Sci. 9(3):308–316, 1974) and Poon’s extension (Proc. of the 34th IEEE Symp. on the Foundations of Computer Science, pp. 218–227, 1993) of jumping automata on graphs (Cook, S.A., Rackoff, C.W. in SIAM J. Comput. 9:636–652, 1980). We then prove exponential size lower bounds for our syntactic incremental model, and for some other variants of branching
program computation for GEN. We further show that nondeterministic syntactic incremental branching programs are provably stronger
than their deterministic counterpart when solving a natural NL-complete GEN sub-problem. It remains open if syntactic incremental
branching programs are as powerful as unrestricted branching programs for GEN problems.
A preliminary version of this paper appears as (Gál, A., Koucky, M., McKenzie, P., Incremental branching programs, in Proc.
of the 2006 Computer Science in Russia Conference CSR06. Lecture Notes in Computer Science, vol. 3967, pp. 178–190, 2006).
A. Gal supported in part by NSF Grant CCF-0430695 and an Alfred P. Sloan Research Fellowship. M. Koucky did part of this work
while being a postdoctoral fellow at McGill University, Canada and at CWI, Amsterdam, Netherlands. Supported in part by NWO
vici project 2004–2009, project No. 1M0021620808 of MŠMT ČR, grants 201/07/P276, 201/05/0124 of GA ČR, and Institutional Research
Plan No. AV0Z10190503.
P. McKenzie supported by the NSERC of Canada and the (Québec) FQRNT. 相似文献