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Topic Review
hIAPP Amyloidosis in Type 2 Diabetes Mellitus
Cases of Type 2 Diabetes Mellitus (T2DM) are increasing at an alarming rate due to the rise in obesity, sedentary lifestyles, glucose-rich diets and other factors. Numerous studies have increasingly illustrated the pivotal role that human islet amyloid polypeptide (hIAPP) plays in the pathology of T2DM through damage and subsequent loss of pancreatic β-cell mass. Here researchers provide an up-to-date summary of recent progress in the field, highlighting factors that contribute to hIAPP misfolding and aggregation which have been linked to β-cell cytotoxicity. Understanding the structure of hIAPP and how these factors affect amyloid formation will help better understand how hIAPP misfolds and aggregates and, importantly, help identify potential therapeutic targets for inhibiting amyloidosis so alternate and more effective treatments for T2DM can be developed.
  • 689
  • 29 Apr 2022
Topic Review
Gestational Factors Throughout Fetal Neurodevelopment
Serotonin (5-HT) is a critical player in brain development and neuropsychiatric disorders. Fetal 5-HT levels can be influenced by several gestational factors, such as maternal genotype, diet, stress, medication, and immune activation. In this review, addressing both human and animal studies, we discuss how these gestational factors affect placental and fetal brain 5-HT levels, leading to changes in brain structure and function and behavior. We conclude that gestational factors are able to interact and thereby amplify or counteract each other’s impact on the fetal 5-HT-ergic system. We, therefore, argue that beyond the understanding of how single gestational factors affect 5-HT-ergic brain development and behavior in offspring, it is critical to elucidate the consequences of interacting factors. Moreover, we describe how each gestational factor is able to alter the 5-HT-ergic influence on the thalamocortical- and prefrontal-limbic circuitry and the hypothalamo-pituitary-adrenocortical-axis. These alterations have been associated with risks to develop attention deficit hyperactivity disorder, autism spectrum disorders, depression, and/or anxiety. Consequently, the manipulation of gestational factors may be used to combat pregnancy-related risks for neuropsychiatric disorders.
  • 688
  • 27 Oct 2020
Topic Review
Flavivirus Genomes
The flavivirus genome consists of a single positive-stranded RNA molecule with just one open reading frame (ORF) flanked by untranslated 5′ and 3′ regions. The ORF encodes a polyprotein that is processed to produce three structural and seven non-structural viral proteins. The RNA genome is endowed with a type I cap structure at the 5′ terminus and lacks a poly A tail at its 3′ end. To store all the information required for their successful propagation, flaviviruses use discrete structural genomic RNA elements to code for functional information by the establishment of dynamic networks of long-range RNA–RNA interactions that promote specific functional folding.
  • 688
  • 20 Apr 2021
Topic Review
Lipidomics
Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. 
  • 688
  • 27 Apr 2021
Topic Review
Virus-Specific Immunity in TMEV-Induced Demyelination
The infection of susceptible mice with Theiler’s murine encephalomyelitis virus (TMEV) establishes persistent viral infections and induces chronic inflammatory demyelinating disease.
  • 688
  • 31 May 2021
Topic Review
Omega-3 PUFA in Pediatric Cancer
Epidemiological literature suggests a protective effect of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) against cancer. They are attributed to have significant anti-inflammatory properties, and are reported to directly inhibit carcinogenesis and tumor expansion, whilst also reducing the risk for secondary complications, thus representing a promising approach for adjunctive chemotherapy treatment. At the same time, the incidence of malnutrition amongst children with cancer is high and both under- and overnutrition are associated with detrimental consequences, including increased risks for morbidity and mortality, early relapse rates, and a higher prevalence of secondary complications during treatment. Taken together with the benefits of n-3 PUFA supplementation, an enhancement of the nutritional status is a potentially modifiable prognostic factor in pediatric oncology.
  • 688
  • 08 Jun 2021
Topic Review
Peptide Human Neutrophil Elastase Inhibitors
Elastases are a broad group of enzymes involved in the lysis of elastin, the main component of elastic fibres. They are produced and released in the human body, mainly by neutrophils and the pancreas.
  • 688
  • 06 Apr 2022
Topic Review
The Gut Microbiota and Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease characterized by increased pulmonary vascular resistance, pulmonary vasoconstriction, and right ventricular hypertrophy. Developments in genomics and metabolomics have gradually revealed the roles of the gut microbiota (GM) and its metabolites in cardiovascular diseases. Accumulating evidence reveals that the GM plays important roles in the occurrence and development of PAH. Gut microbiota dysbiosis directly increases the gut permeability, thereby facilitating pathological bacterial translocation and allowing translocation of bacterial products such as lipopolysaccharides from the gut into circulation. This process aggravates pulmonary perivascular inflammation and exacerbates PAH development through the endothelial–mesenchymal transition. Additionally, a shift in the composition of PAH also affects the gut metabolites. Changes in gut metabolites, such as decreased short-chain fatty acids, increased trimethylamine N-oxide, and elevated serotonin, contribute to pulmonary perivascular inflammation and pulmonary vascular remodeling by activating several signaling pathways. Studies of the intestinal microbiota in treating pulmonary hypertension have strengthened linkages between the GM and PAH. Probiotic therapy and fecal microbiota transplantation may supplement existing PAH treatments.
  • 688
  • 04 Nov 2022
Topic Review
Remote Ischemic Preconditioning
Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in RIPC-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by 30 min transient blockade of the left coronary artery to simulate I/R injury. Hindlimb muscle and the heart were excised 24 h post reperfusion. RIPC prior to I/R upregulated autophagy in the rat heart at 24 h post reperfusion. In vitro, autophagy inhibition or stimulation prior to RIPC respectively, either ameliorated or stimulated the cardioprotective effect, measured as improved cell viability to mimic the preconditioning effect. Recombinant IL-6 treatment prior to I/R increased in vitro autophagy in a dose dependent manner activating the JAK-STAT pathway without affecting the other kinase pathways such as p38 MAPK, and GSK-3β pathways. Prior to I/R, in vitro inhibition of the JAK-STAT pathway reduced autophagy upregulation despite recombinant IL-6 pre-treatment. Autophagy is an essential component of RIPC-induced cardioprotection that may upregulate autophagy through an IL-6/JAK-STAT dependent mechanism, thus identifying a potentially new therapeutic option for the treatment of ischemic heart disease.
  • 687
  • 29 Oct 2020
Topic Review
Timing of Metastatic Colorectal Cancer
Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, where ~50% of patients develop metastasis, despite current improved management. Genomic characterisation of metastatic CRC, and elucidating the effects of therapy on the metastatic process, are essential to help guide precision medicine. Multi-region whole-exome sequencing was performed on 191 sampled tumour regions of patient-matched therapy-naïve and treated CRC primary tumours (n = 92 tumour regions) and metastases (n = 99 tumour regions), in 30 patients. Somatic variants were analysed to define the origin, composition, and timing of seeding in the metastatic progression of therapy-naïve and treated metastatic CRC. High concordance, with few genomic differences, was observed between primary CRC and metastases. Most cases supported a late dissemination model, via either monoclonal or polyclonal seeding. Polyclonal seeding appeared more common in therapy-naïve metastases than in treated metastases. Whereby, treatment prompted for the selection of distinct resistant clones, through monoclonal seeding to distant metastatic sites. Overall, this study reinforces the importance of early clinical detection and surgical excision of the CRC tumour, whilst further highlighting the clinical challenges for metastatic CRC with increased intratumour heterogeneity (either due to early dissemination or polyclonal metastatic spread) and the underlying risk of future therapeutic resistance in treated patients.
  • 687
  • 20 Oct 2020
Topic Review
Glaucoma Pathophysiology
Glaucoma is a progressive neurodegenerative disease that represents the major cause of irreversible blindness.
  • 687
  • 31 May 2021
Topic Review
Protein-based Subunit Nanovaccine
Protein-based subunit nanovaccines are typically composed of native or altered protein antigens that can self-assemble into nanoparticles, or antigens associated with nanoparticles through covalent or noncovalent interactions. Characteristically, nanovaccines are 1 to 1000 nm in size which generally facilitates the induction of stronger immune responses.
  • 687
  • 18 Oct 2021
Topic Review
Berbamine
Berbamine is a natural, potent, pharmacologically active biomolecule isolated from Berberis amurensis. Berbamine has been shown to modulate different oncogenic cell-signaling pathways in different cancers.
  • 687
  • 15 Apr 2022
Topic Review
Targeting Mitochondria in Kidney Diseases
Kidney function highly depends on mitochondria, organelles that regulate different metabolic pathways. Mitochondria-altered function and structure are present during acute kidney injury (AKI) and chronic kidney disease (CKD).
  • 687
  • 08 Aug 2022
Topic Review
DNA Methyltransferases
DNA methylation is an epigenetic mark that living beings have used in different environments. The MTases family catalyzes DNA methylation. This process is conserved from archaea to eukaryotes, from fertilization to every stage of development, and from the early stages of cancer to metastasis. The family of DNMTs has been classified into DNMT1, DNMT2, and DNMT3. Each DNMT has been duplicated or deleted, having consequences on DNMT structure and cellular function, resulting in a conserved evolutionary reaction of DNA methylation. DNMTs are conserved in the five kingdoms of life: bacteria, protists, fungi, plants, and animals. 
  • 687
  • 30 Aug 2022
Topic Review
Gap-Juntions in the Oocyte
Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore they do play a fundamental role in the communication between the oocyte and accompanying cells.
  • 686
  • 11 Jun 2021
Topic Review
Entrectinib—An Inhibitor of SARS-CoV-2 Cell Entry
This entry describes entrectinib as an antiviral drug.
  • 686
  • 20 Jan 2022
Topic Review
Phosphatidylinositol 5 Phosphate
Phosphatidylinositol (PI)-related signaling plays a pivotal role in many cellular aspects, including survival, cell proliferation, differentiation, DNA damage, and trafficking. PI is the core of a network of proteins represented by kinases, phosphatases, and lipases which are able to add, remove or hydrolyze PI, leading to different phosphoinositide products. Among the seven known phosphoinositides, phosphatidylinositol 5 phosphate (PI5P) was the last to be discovered. PI5P presence in cells is very low compared to other PIs, but is has been reported to control many cellular outcomes, including cell proliferation, gene expression and chromatin remodeling.
  • 686
  • 11 Aug 2021
Topic Review
Dye Decoloring Peroxidase
Dye decoloring peroxidases (DyPs) were named after their high efficiency to decolorize and degrade a wide range of dyes. DyPs are a type of heme peroxidase and are quite different from known heme peroxidases in terms of amino acid sequences, protein structure, catalytic residues, and physical and chemical properties. DyPs oxidize polycyclic dyes and phenolic compounds.
  • 686
  • 07 Sep 2021
Topic Review
Omega-3 LCPUFAs against Age-Related Cognitive Impairment
Among nutrients to cope with aging in special cognitive decline, the long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have emerged as very promising ones. Due to their neuroinflammatory resolving effects, an increased status of DHA and EPA in the elderly has been linked to better cognitive function and a lower risk of dementia. Recently, supplementation with structured forms of EPA and DHA, which can be derived natural forms or targeted structures, have proven enhanced bioavailability and powerful benefits. 
  • 685
  • 31 Mar 2022
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