Reviews of Physiology Biochemistry and Pharmacology最新文献

The chapter 'Stationary and Nonstationary Ion and Water Flux Interactions in Kidney Proximal Tubule: Mathematical Analysis of Isosmotic Transport by a Minimalistic Model' has now been made available open access under a CC BY 4.0 license.

Familial hypercholesterolemia (FH) is a frequent autosomal genetic disease characterized by elevated concentrations of low-density lipoprotein cholesterol (LDL) from birth with increased risk of premature atherosclerotic complications. Accumulating evidence has shown enhanced inflammation in patients with FH. In vessels, the deposition of modified cholesterol lipoproteins triggers local inflammation. Then, inflammation facilitates fatty streak formation by activating the endothelium to produce chemokines and adhesion molecules. This process eventually results in the uptake of vascular oxidized LDL (OxLDL) by scavenger receptors in monocyte-derived macrophages and formation of foam cells. Further leukocyte recruitment into the sub-endothelial space leads to plaque progression and activation of smooth muscle cells proliferation. Several inflammatory biomarkers have been reported in this setting which can be directly synthetized by activated inflammatory/vascular cells or can be indirectly produced by organs other than vessels, e.g., liver. Of note, inflammation is boosted in FH patients. Inflammatory biomarkers might improve the risk stratification for coronary heart disease and predict atherosclerotic events in FH patients. This review aims at summarizing the current knowledge about the role of inflammation in FH and the potential application of inflammatory biomarkers for cardiovascular risk estimation in these patients.

The cornea, the eye's outermost layer, protects the eye from the environment. The cornea's innermost layer is an endothelium separating the stromal layer from the aqueous humor. A central role of the endothelium is to maintain stromal hydration state. Defects in maintaining this hydration can impair corneal clarity and thus visual acuity. Two endothelial corneal dystrophies, Fuchs Endothelial Corneal Dystrophy (FECD) and Congenital Hereditary Endothelial Dystrophy (CHED), are blinding corneal diseases with varied clinical presentation in patients across different age demographics. Recessive CHED with an early onset (typically age: 0-3 years) and dominantly inherited FECD with a late onset (age: 40-50 years) have similar phenotypes, although caused by defects in several different genes. A range of molecular mechanisms have been proposed to explain FECD and CHED pathology given the involvement of multiple causative genes. This critical review provides insight into the proposed molecular mechanisms underlying FECD and CHED pathology along with common pathways that may explain the link between the defective gene products and provide a new perspective to view these genetic blinding diseases.

Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na+ channel superfamily, are broadly distributed in the mammalian nervous system where they play important roles in a variety of physiological processes, including neurotransmission and memory-related behaviors. In the last few years, we and others have investigated the role of ASIC1a in different forms of synaptic plasticity especially in the CA1 area of the hippocampus. This review summarizes the latest research linking ASIC1a to synaptic function either in physiological or pathological conditions. A better understanding of how these channels are regulated in brain circuitries relevant to synaptic plasticity and memory may offer novel targets for pharmacological intervention in neuropsychiatric and neurological disorders.

Magnesium research has boomed within the last 20 years. The real breakthrough came at the start of the new millennium with the discovery of a plethora of possible Mg homeostatic factors that, in particular, included putative Mg²⁺ transporters. Until that point, Mg research was limited to biochemical and physiological work, as no target molecular entities were known that could be used to explore the molecular biology of Mg homeostasis at the level of the cell, tissue, organ, or organism and to translate such knowledge into the field of clinical medicine and pharmacology. Because of the aforementioned, Mg²⁺ and Mg homeostasis, both of which had been heavily marginalized within the biomedical field in the twentieth century, have become overnight a focal point of many studies ranging from primary biomedical research to translational medicine.The amount of literature concerning cellular Mg²⁺ transport and cellular Mg homeostasis is increasing, together with a certain amount of confusion, especially about the function(s) of the newly discovered and, in the majority of instances, still only putative Mg²⁺ transporters/Mg²⁺ homeostatic factors. Newcomers to the field of Mg research will thus find it particularly difficult to orient themselves.Here, we briefly but critically summarize the status quo of the current understanding of the molecular entities behind cellular Mg²⁺ homeostasis in mammalian/human cells other than TRPM6/7 chanzymes, which have been universally accepted as being unspecific cation channel kinases allowing the flux of Mg²⁺ while constituting the major gateway for Mg²⁺ to enter the cell.

The development of resistance toward current cancer therapy modalities is an ongoing challenge in gynecological cancers, especially ovarian and cervical malignancies that require further investigations in the context of drug- and irradiation-induced resistance. In this regard, curcumin has demonstrated beneficial and highly pleiotropic actions and increased the therapeutic efficiency of radiochemotherapy. The antiproliferative, anti-metastatic, anti-angiogenic, and anti-inflammatory effects of curcumin have been extensively reported in the literature, and it could also act as a chemopreventive agent which mitigates the out-of-target harmful impact of chemotherapeutics on surrounding normal tissues. The current review discussed the modulating influences of curcumin on some cell and molecular features, including the cell signaling and molecular pathways altered upon curcumin treatment, the expression of target genes involved in the progression of gynecological cancers, as well as the expression of genes accountable for the development of resistance toward common chemotherapeutics and radiotherapy. The cell molecular targets implicated in curcumin's resensitizing effect, when used together with cisplatin, paclitaxel, and irradiation in gynecological cancers, are also addressed. Finally, rational approaches for improving the therapeutic benefits of curcumin, including curcumin derivatives with enhanced therapeutic efficacy, using nanoformulations to advance curcumin stability in physiological media and improve bioavailability have been elucidated.

The affiliation of the 6th author Dr. Abolfazl Mehdizadehkashi was incorrect. It has been corrected to Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran.

Oncotic cell death or oncosis represents a major mechanism of cell death in ischaemic stroke, occurring in many central nervous system (CNS) cell types including neurons, glia and vascular endothelial cells. In stroke, energy depletion causes ionic pump failure and disrupts ionic homeostasis. Imbalance between the influx of Na⁺ and Cl^- ions and the efflux of K⁺ ions through various channel proteins and transporters creates a transmembrane osmotic gradient, with ensuing movement of water into the cells, resulting in cell swelling and oncosis. Oncosis is a key mediator of cerebral oedema in ischaemic stroke, contributing directly through cytotoxic oedema, and indirectly through vasogenic oedema by causing vascular endothelial cell death and disruption of the blood-brain barrier (BBB). Hence, inhibition of uncontrolled ionic flux represents a novel and powerful strategy in achieving neuroprotection in stroke. In this review, we provide an overview of oncotic cell death in the pathology of stroke. Importantly, we summarised the therapeutically significant pathways of water, Na⁺, Cl^- and K⁺ movement across cell membranes in the CNS and their respective roles in the pathobiology of stroke.

Protein tyrosine kinases (PTK), discovered in the 1970s, have been considered master regulators of biological processes with high clinical significance as targets for human diseases. Their actions are countered by protein tyrosine phosphatases (PTP), enzymes yet underrepresented as drug targets because of the high homology of their catalytic domains and high charge of their catalytic pocket. This scenario is still worse for some PTP subclasses, for example, for the atypical dual-specificity phosphatases (ADUSPs), whose biological functions are not even completely known. In this sense, the present work focuses on the dual-specificity phosphatase 3 (DUSP3), also known as VH1-related phosphatase (VHR), an uncommon regulator of mitogen-activated protein kinase (MAPK) phosphorylation. DUSP3 expression and activities are suggestive of a tumor suppressor or tumor-promoting enzyme in different types of human cancers. Furthermore, DUSP3 has other biological functions involving immune response mediation, thrombosis, hemostasis, angiogenesis, and genomic stability that occur through either MAPK-dependent or MAPK-independent mechanisms. This broad spectrum of actions is likely due to the large substrate diversity and molecular mechanisms that are still under scrutiny. The growing advances in characterizing new DUSP3 substrates will allow the development of pharmacological inhibitors relevant for possible future clinical trials. This review covers all aspects of DUSP3, since its gene cloning and crystallographic structure resolution, in addition to its classical and novel substrates and the biological processes involved, followed by an update of what is currently known about the DUSP3/VHR-inhibiting compounds that might be considered potential drugs to treat human diseases.