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Topic Review
Combination Therapy in Methicillin-Resistant Staphylococcus aureus Bacteremia
Combination therapy with daptomycin plus ceftaroline to treat methicillin-resistant Staphylococcus aureus bacteremia has been reported to reduce methicillin-resistant Staphylococcus aureus bacteremia-related mortality. The combination therapy group had an in-hospital mortality, duration of bacteremia, and adverse event rate similar to those patients who had monotherapy. There was less bacteremia recurrence in the combination group. Initial combination therapy with ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus bacteremia showed a trend of reducing the risk of in-hospital mortality. 
  • 998
  • 16 Sep 2022
Topic Review
Insights and Strategies of Melanoma Immunotherapy
Despite the successes and durable responses with immune checkpoint inhibitors (ICI), many cancer patients, including those with melanoma, do not derive long-term benefits from ICI therapies. The lack of predictive biomarkers to stratify patients to targeted treatments has been the driver of primary treatment failure and represents an unmet medical need in melanoma and other cancers. Understanding genomic correlations with response and resistance to ICI will enhance cancer patients’ benefits. Building on insights into interplay with the complex tumor microenvironment (TME), the ultimate goal should be assessing how the tumor ’instructs’ the local immune system to create its privileged niche with a focus on genomic reprogramming within the TME. It is hypothesized that this genomic reprogramming determines the response to ICI. Furthermore, emerging genomic signatures of ICI response, including those related to neoantigens, antigen presentation, DNA repair, and oncogenic pathways, are gaining momentum. 
  • 996
  • 31 Jan 2023
Topic Review
Genetic Mechanisms Underlying Chronic Intestinal Pseudo-Obstruction
Severe gut motility disorders are characterized by an ineffective propulsion of intestinal contents. As a result, patients develop extremely bothering symptoms, such as nausea and vomiting along with altered bowel habit up to radiologically demonstrable intestinal sub-obstructive episodes. Chronic intestinal pseudo-obstruction (CIPO) is a typical clinical phenotype of severe gut dysmotility due to changes altering the morpho-functional integrity of the intrinsic (enteric) innervation and extrinsic nerve supply (hence neuropathy), interstitial cells of Cajal (ICCs) (mesenchymopathy) and smooth muscle cells (myopathy). In the last years, several genes have been identified in different subsets of CIPO patients. The focus is to cover the most recent update on enteric dysmotility related to CIPO, highlighting: (a) forms with a predominant underlying neuropathy; (b) forms with a predominant myopathy; and (c) mitochondrial disorders with a clear gut dysfunction as part of the clinical phenotype. Researchers will provide a thorough description of the genes that recent evidence showed to cause neuromyopathy thereby leading to the underlying abnormal motor patterns detectable in different types of CIPO.
  • 995
  • 18 Jan 2023
Topic Review
Cellular Senescence in Pulmonary Fibrosis
Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung parenchyma. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. 
  • 992
  • 12 Aug 2021
Topic Review
The MAMs Structure
Mitochondria-associated membranes (MAMs) play a vital role in the complex crosstalk between the ER and mitochondria. MAMs are known to play an important role in lipid synthesis, the regulation of Ca2+ homeostasis, the coordination of ER-mitochondrial function, and the transduction of death signals between the ER and the mitochondria. 
  • 991
  • 10 May 2021
Topic Review
Metabolic Dysfunction in ALS Skeletal Muscle
Defects in mitochondrial structure and function as well as energy metabolism in skeletal muscle contribute to disease pathology and progression, with metabolic dysfunctions appearing long before motor neuron degeneration and death.
  • 991
  • 15 Dec 2022
Topic Review
N-3 PUFAs and Cardiovascular Protection
Polyunsaturated fatty acids (n-3 PUFAs) are long-chain polyunsaturated fatty acids with 18, 20 or 22 carbon atoms, which have been found able to counteract cardiovascular diseases. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in particular, have been found to produce both vaso- and cardio-protective response via modulation of membrane phospholipids thereby improving cardiac mitochondrial functions and energy production. However, antioxidant properties of n-3 PUFAs, along with their anti-inflammatory effect in both blood vessels and cardiac cells, seem to exert beneficial effects in cardiovascular impairment. In fact, dietary supplementation with n-3 PUFAs has been demonstrated to reduce oxidative stress-related mitochondrial dysfunction and endothelial cell apoptosis, an effect occurring via an increased activity of endogenous antioxidant enzymes. On the other hand, n-3 PUFAs have been shown to counteract the release of pro-inflammatory cytokines in both vascular tissues and in the myocardium, thereby restoring vascular reactivity and myocardial performance.
  • 990
  • 07 Jul 2021
Topic Review
Small RNA GcvB
Small non-translated regulatory RNAs control plenty of bacterial vital activities. The small RNA GcvB has been extensively studied, indicating the multifaceted roles of GcvB beyond amino acid metabolism.
  • 990
  • 29 Nov 2021
Topic Review
Mycobacterium tuberculosis as Modulators of Cell Death Mechanisms
Mycobacterium tuberculosis (Mtb) modulates diverse cell death pathways to escape the host immune responses and favor its dissemination, a complex process of interest in pathogenesis-related studies. The main virulence factors of Mtb that alter cell death pathways are classified according to their origin as either non-protein (for instance, lipomannan) or protein (such as the PE family and ESX secretion system). The 38 kDa lipoprotein, ESAT-6 (early antigen-secreted protein 6 kDa), and another secreted protein, tuberculosis necrotizing toxin (TNT), induces necroptosis, thereby allowing mycobacteria to survive inside the cell. The inhibition of pyroptosis by blocking inflammasome activation by Zmp1 and PknF is another pathway that aids the intracellular replication of Mtb. Autophagy inhibition is another mechanism that allows Mtb to escape the immune response. The enhanced intracellular survival (Eis) protein, other proteins, such as ESX-1, SecA2, SapM, PE6, and certain microRNAs, also facilitate Mtb host immune escape process. 
  • 987
  • 04 Jul 2023
Topic Review
Mass Spectrometry and Chromatin Compaction
Chromatin accessibility is a major regulator of gene expression. Histone writers/erasers have a critical role in chromatin compaction, as they “flag” chromatin regions by catalyzing/removing covalent post-translational modifications on histone proteins. Anomalous chromatin decondensation is a common phenomenon in cells experiencing aging and viral infection. Moreover, about 50% of cancers have mutations in enzymes regulating chromatin state. Numerous genomics methods have evolved to characterize chromatin state, but the analysis of (in)accessible chromatin from the protein perspective is not yet in the spotlight.
  • 986
  • 04 Aug 2021
Topic Review
The Influence of Dietary Supplementations on Neuropathic Pain
Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system and affects 7–10% of the worldwide population. Neuropathic pain can be induced by the use of drugs, including taxanes, thus triggering chemotherapy-induced neuropathic pain or as a consequence of metabolic disorders such as diabetes. Neuropathic pain is most often a chronic condition, and can be associated with anxiety and depression; thus, it negatively impacts the quality of life. Several pharmacologic approaches exist; however, they can lead to numerous adverse effects. From this perspective, the use of nutraceuticals and diet supplements can be helpful in relieving neuropathic pain and related symptoms.
  • 986
  • 08 Oct 2022
Topic Review
HARE/Stabilin-2
The Stabilin receptors are a two-member family in the type H class of scavenger receptors. These dynamic receptors bind and internalize multiple ligands from the cell surface for the purpose of clearing extracellular material including some synthetic drugs and for sensing the external environment of the cell. Stabilin-1 was the first receptor to be cloned, though the biological activity of Hyaluronic Acid Receptor for Endocytosis (HARE)/Stabilin-2 was observed about 10 years prior to the cloning of Stabilin-1. Stabilin-1 has a more diverse expression profile among the tissues than HARE/Stabilin-2. 
  • 984
  • 28 Jul 2021
Topic Review
Bioactive Based Nanocarriers against SARS-CoV-2
Several plants and essential oils, as well as isolated bioactive compounds, such as phenolic acids, flavonoids, terpenes, lignans, coumarins, alkaloids, or proteins, showed a potential role as anti-viral agents. Nanoparticles have also been utilized in noninvasive imaging techniques to diagnose and monitor illnesses, as well as treatment responses. Nanomaterials can prevent viral binding to the host cell-surface receptor, which is crucial in the context of CoVs. 
  • 984
  • 09 May 2022
Topic Review
Rice Husk Silica Liquid
Type 2 diabetes mellitus is a complex multifactorial disease characterized by insulin resistance and dysfunction of pancreatic β-cells. Rice husk silica liquid (RHSL) is derived from rice husks and has not been explored in diabetes mellitus until now. Previous studies showed that rice husk is enriched with silica, and its silica nanoparticles are higher more biocompatible. To investigate the potential protective role of RHSL on pancreatic β cells, we utilized RIN-m5F pancreatic β cells and explored RHSL effect after streptozotocin (STZ)-stimulation. The recovery effects of RHSL were evaluated using flow cytometry, Western blotting, and immunofluorescence analysis. Results of our study showed that RHSL reversed the cell viability, insulin secretion, reactive oxygen species (ROS) production, and the change of mitochondria membrane potential (ΔΨm) in STZ-treated RIN-m5F cells. Moreover, the expression of phospho-receptor-interacting protein 3 (p-RIP3) and cleaved-poly (ADP-ribose) polymerase (PARP), phospho-mammalian target of rapamycin (p-mTOR), and sequestosome-1 (p62/SQSTM1) were significantly decreased, while the transition of light chain (LC)3-I to LC3-II was markedly increased after RHSL treatment in STZ-induced RIN-m5F cells. Interestingly, using autophagy inhibitors such as 3-methyladenine (3-MA) and chloroquine (CQ) both showed an increase in cleaved-PARP protein level, indicating apoptosis induction. 
  • 982
  • 24 Aug 2021
Topic Review
Improved P Digestibility in Animal Feed and Limitations
A circular phosphorus (P) bioeconomy is not only worthwhile for conserving limited mineral P reservoirs, but also for minimizing negative environmental impacts caused by human-made alterations. Although P is an essential nutrient, most of the P in concentrates based on cereals, legumes and oilseed byproducts is organically bound to phytate. The latter cannot be efficiently utilized by monogastric animals and is therefore diluted into the environment through the manure pathway.
  • 982
  • 19 May 2022
Topic Review
Thioredoxin-Interacting Protein (TXNIP)
Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. 
  • 982
  • 02 Jul 2021
Topic Review
Phytoremediation of Cadmium
Cadmium (Cd) is one of the most toxic metals in the environment, and has noxious effects on plant growth and production. Cd-accumulating plants showed reduced growth and productivity. Therefore, remediation of this non-essential and toxic pollutant is a prerequisite. Plant-based phytoremediation methodology is considered as one a secure, environmentally friendly, and cost-effective approach for toxic metal remediation. Phytoremediating plants transport and accumulate Cd inside their roots, shoots, leaves, and vacuoles. Phytoremediation of Cd-contaminated sites through hyperaccumulator plants proves a ground-breaking and profitable choice to combat the contaminants. 
  • 982
  • 05 Aug 2021
Topic Review
Zebrafish Kidney's Response to Fasting
Animals obtain nutrition and energy by eating and to achieve a balance between growth and body health. When the nutrient intake is abnormal, the growth status changes, presumably resulting in changes in the intrinsic immune system. The zebrafish (Danio rerio), a well-known fish model organism, can serve as a suitable model to explore the changes happened to the innate immune system. In this study, the zebrafish underwent 3 weeks of fasting and refeeding for 3 to 7day periods. During this period, zebrafish displayed a specific growth phenomenon so called compensatory growth (CG), accompanied by increased susceptibility to pathogens after starvation. The kidneys suffering starvation displayed an increase of the amount of melano-macrophage centers and appeared oxidative stress, and the antioxidant enzymes activity like CAT, GSH-Px and SOD increased after fasting. In addition, the activity of ALP and lysozyme as well as il-1β mRNA expression enhanced after starvation. Taken together, oxidative stress caused by starvation and the danger-associated molecular patterns produced by injured renal tubules may have contributed to inflammation. This study showed that the function of the innate immune system in zebrafish could be influenced by nutrition status. Further study is needed to explore how starvation increases susceptibility and how the metabolic state influences different kinds of immune cells.
  • 980
  • 21 Jun 2021
Topic Review
Soluble Programmed Cell Death Ligand-1
The interaction of programmed cell death ligand-1 (PDL1) with its receptor PD1 inhibits T-cell responses. Blockade of this interaction with monoclonal antibodies leads to major antitumor effects. However, not all cancer patients respond well to anti-(PD-1/PD-L1) immunotherapy. The PD-L1 protein is expressed at the cell plasma membrane (mPD-L1), at the surface of exosomes (exoPD-L1), in cell nuclei (nPD-L1) and as a soluble circulating protein (sPD-L1). The aim of our analysis was to highlight the multiple variants of sPD-L1 generated either by the proteolytic cleavage of m/exoPD-L1 or by the alternative splicing of PD-L1 pre-mRNA. The objective was also to underline the presence and role of circulating sPD-L1 isoforms in multiple cancer indications and many other diseases (including chronic inflammatory and viral diseases), and under non-pathological conditions (pregnancy). sPD-L1 often represents a general marker of an inflammatory status. The pool of sPD-L1 proteins is an integral part of the highly dynamic PD-1/PD-L1 signaling pathway.
  • 980
  • 30 Jun 2021
Topic Review
Transience of the Retinal Output and Circuit Elements
Retinal ganglion cells (RGCs) encrypt stimulus features of the visual scene in action potentials and convey them toward higher visual centers in the brain. Although there are many visual features to encode, the recent understanding is that the ~46 different functional subtypes of RGCs in the retina share this task. In this scheme, each RGC subtype establishes a separate, parallel signaling route for a specific visual feature (e.g., contrast, the direction of motion, luminosity), through which information is conveyed. The efficiency of encoding depends on several factors, including signal strength, adaptational levels, and the actual efficacy of the underlying retinal microcircuits. Upon collecting inputs across their respective receptive field, RGCs perform further analysis (e.g., summation, subtraction, weighting) before they generate the final output spike train, which itself is characterized by multiple different features, such as the number of spikes, the inter-spike intervals, response delay, and the rundown time (transience) of the response. These specific kinetic features are essential for target postsynaptic neurons in the brain in order to effectively decode and interpret signals, thereby forming visual perception.
  • 980
  • 11 Mar 2022
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