1,721,075 research outputs found
Innovative pH-interfering agents in association with anticancer agents
No full textAlthough the common strategies to efficiently interfere with cellular pH lie in the direct inhibition of the enzymes/transporters/pumps constituting the cooperative system that controls proton concentration, other approaches can be exploited to obtain similar results. In this respect, it is worthwhile to take into account the effects exhibited by drugs that are not usually considered as pH-interfering agents like HDAC inhibitors and H2S releasing compounds
Treatment of Toxoplasmosis: An Insight on Epigenetic Drugs
No full textToxoplasmosis is the parasitic infection caused by the obligate intracellular parasite T. gondii. This pathogen possesses three different stages of life namely (i) sporozoites, (ii) tachyzoites (iii) and bradyzoites, the slow replicating form living in tissue cysts. To date, the clinical therapy of toxoplasmosis is still based on the use of drugs developed more than 50 years ago and endowed with high toxicity and ineffectiveness against bradyzoites, preventing the complete eradication of the parasite. For these reasons, novel and more effective drugs are still necessary. Epigenetics drugs could fulfil this requirement offering novel mechanisms of action also affecting the bradyzoite stage. Here we report the inhibitors of T. gondii affecting epigenetic targets discovered in the last 25 years
Teaching Numerical Groundwater Flow Modeling with Spreadsheets: Unconfined Aquifers and Multilayered Vertical Cross-Sections
No full textThe use of spreadsheets in numerical groundwater flow modeling, although not new,
has yet to be fully exploited in educational settings. This teaching aid complements
the one published earlier, broadening its scope from the numerical solution for a
single-layer confined aquifer to include unconfined aquifers. It covers flow in horizontal
layers and multilayered vertical cross-sections. The new spreadsheets can also
handle hydraulic conductivity anisotropy, provided its principal directions align with
the Cartesian axes. It can also manage irregular aquifer shapes, incorporate all three
types of boundary conditions, and account for pumping and recharge in the modeling
process. However, the flow regime remains at steady state. With the integration
of these new features, the spreadsheet model becomes a versatile tool for simulating
a great number of steady-state groundwater flow situations. This user-friendly platform
enables students to swiftly experiment with diverse configurations, delve into
the underlying mathematical expressions, and gain insight into the workings of more
sophisticated numerical codes likeMODFLOW. As a complement, and for verification
purposes, Python Flopy scripts are provided for all examples in the GitHub repository
where the spreadsheets can be accessed
Identification of groundwater contaminant source characteristics through artificial neural network
Full text linkAngiotensin-converting enzyme
No full textAngiotensin Converting Enzyme (ACE), is a zinc containing metallopeptidase, best known for its
role in the conversion of Ang I in the active peptide Ang II, which plays a pivotal role in the blood
pressure (BP) regulation trough the Renin Angiotensin System (RAS). In the last decades RAS has
been deeply studied in all its aspects and implications. It has been seen that ACE and its substrates
are involved in many other physiological and pathological processes in addition to pressure control,
such as: hematopoiesis, reproduction, renal development and immune response. Its homologous
protein ACE2, critical enzyme in counter-regulatory response to RAS, was studied and its
pharmacological modulation has been evaluated. According to ACE in vivo roles and its
implication in a great number of physiological pathways, several studies focused on the potential
role of classic ACE inhibitors (ACEIs) and new domain-selective compounds for the treatments of
several diseases. This chapter seeks to review the evolution of the physio/pathological roles of
ACEs and their pharmacological modulation, for the treatment of a wide range of pathologies
Physics-Informed Neural Networks for solving transient unconfined groundwater flow
No full textNeural networks excel in various machine learning applications; however, they lack the physical interpretability
and constraints crucial for numerous scientific and engineering problems. This limitation hinders their ability
to accurately capture and predict complex physical systems’ behavior, potentially yielding inaccurate or
unreliable results. Physics-Informed Neural Networks (PINNs) are a class of machine learning models that
integrate the power of neural networks with the physical laws governing natural phenomena. PINNs provide
an effective tool for solving intricate physical problems, ranging from fluid dynamics to materials science, by
incorporating physical constraints into the neural network architecture. PINNs can substantially enhance the
accuracy and efficiency of model predictions, even in data-limited situations. This work offers insight into
recent developments in the PINN field, including their mathematical formulation and training algorithms, and
emphasizes their application in solving transient unconfined groundwater flow. In this context, the phreatic
surface acts as a spatiotemporally varying boundary condition, and properly accounting for its position is
vital for precise predictions of unconfined groundwater flow and related environmental and engineering
applications. The study’s objective is to develop a reliable model for estimating the phreatic surface and the
spatiotemporal distribution of piezometric heads in a vertical cross-section of an unconfined aquifer. Two cases
are examined: the first involves a homogeneous and isotropic aquifer, while the second comprises a mildly
heterogeneous and anisotropic one. The challenges and opportunities arising from this emerging research area
are also explored, and essential directions for future research are underscored
Novel approaches to the discovery of selective human monoamine oxidase-B inhibitors: is there room for improvement?
No full textIntroduction: Selective monoamine oxidase-B (MAO-B) inhibitors are currently used as coadjuvants for the treatment of early motor symptoms in Parkinson’s disease. They can, based on their chemical structure and mechanism of inhibition, be categorized into reversible and irreversible agents. Areas covered: This review provides a comprehensive update on the development state of selective MAO-B inhibitors describing the results, structures, structure–activity relationships (SARs) and Medicinal chemistry strategies as well as the related shortcomings over the past five years. Expert opinion: Researchers have explored and implemented new and old chemical scaffolds achieving high inhibitory potencies and isoform selectivity. Most of them were characterized and proposed as multitarget agents able to act at different levels (including AChE inhibition, H3R or A2AR antagonism, antioxidant and chelating properties, Aβ1-42 aggregation reduction) in the network of aetiologies of neurodegenerative disorders. These results can also be used to avoid ‘cheese-reaction’ effects and the occurrence of serotonergic syndrome in patients
Nitrogen-and Sulfur-Containing Heterocycles as Dual Anti-oxidant and Anti-cancer Agents
No full textCancer derives from a multi-step process in which tumor cells establish the ability to proliferate and disseminate. Other non-oncogenic pathways can be influenced as an adaptive response, being the oxidative stress the most affected. Indeed, reactive oxygen species act as pivotal mediators of oxidative stress and are involved in cancer initiation and development. Medicinal chemists have directed their efforts toward the concurrent inhibition of the cancer cell growth and the modulation of the upregulated oxidative stress level. Furthermore, anti-cancer drugs can exert their cytotoxic effects by displaying pro-oxidative damage in cancer cells. This pleiotropic activity has been largely investigated among the heterocyclic scaffolds with particular interest in those containing both sulfur and nitrogen atoms. In this chapter, we collected an up-to-date overview of this topic demonstrating the importance of these heterocycles categorizing the discussion on acyclic (isothiosemicarbazones), monocyclic (thiazoles, thiazolidines, thiadiazoles, thiazines, thiazepines), bicyclic (benzothiazoles and benzothiazines), and tricyclic (phenothiazines) compounds. Moreover, natural compounds and metal complexes containing such structures were considered and described. Structure-activity relationships and the most promising agents were provided as well as their results in terms of anti-proliferative and antioxidant activities
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