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Topic Review
STAMP2 in Diabetes, Inflammatory Diseases and Cancers
STAMP2 plays a pivotal role in the pathogenesis of  type II diabetes, inflammation and cancers. The six transmembrane protein of prostate 2 (STAMP2), a metalloreductase involved in iron and copper homeostasis, is well known for its critical role in the coordination of glucose/lipid metabolism and inflammation in metabolic tissues. STAMP2 is a critical modulator for coordinating metabolism and inflammation. Although STAMP2 has been widely studied focusing on the inhibitory role in inflammation and metabolism, the underlying mechanism is not fully understood. In addition to its role in metabolism and inflammation, STAMP2 is also associated with tumorigenesis. For example, STAMP2 overexpression may increase ROS, which may contribute to increased mutational rates and further progression of prostate cancer.
  • 819
  • 02 Sep 2022
Topic Review
Tetraoctylammonium
Alkylammonium salts have been used extensively to study the structure and function of potassium channels. Here, we use the long-chain, hydrophobic tetraoctylammonium (TOA+) to shed light on the structure of the inactivated state of KcsA, a tetrameric prokaryotic potassium channel. By the combined use of a thermal denaturation assay and the analysis of homo-Förster resonance energy transfer in a mutant channel containing a single tryptophan (W67) per subunit, we found that TOA+ binds the channel cavity with high affinity, either with the inner gate open or closed. Moreover, bound TOA+ induces a decrease in the affinity for K+ in the two characteristic K+ binding events to the channel selectivity filter at pH 7.0, when the channel inner gate is in the closed conformation. This is similar to that observed in the absence of TOA+ upon acidic-pH-induced channel inactivation. Therefore, this suggests that TOA+ binding by itself causes inactivation at pH 7.0 when the inner gate is closed. Furthermore, in apparent agreement with such conclusion, the presence of bound TOA+ in the pH 4.0 samples has only modest effects on the affinity of the two binding events for K+, likely because the channel is already inactivated. Finally, we also observed that TOA+ bound at the cavity, allosterically modifies the conformation of the pore helices, leading to longer W67-W67 intersubunit distances at any K+ concentration and both at pH 7.0 and pH 4.0. The changes in the pore helix conformation, along with the decreased affinity for K+ at pH 7.0 caused by TOA+, seen in both homo-FRET and thermal denaturation experiments, are very similar to those effects caused by inactivation at pH 4.0.
  • 819
  • 30 Apr 2021
Topic Review
Inflammatory Response Caused by UVR
Skin is the largest and most complex organ in the human body comprised of multiple layers with different types of cells. Different kinds of environmental stressors, for example, ultraviolet radiation (UVR), temperature, air pollutants, smoking, and diet, accelerate skin aging by stimulating inflammatory molecules. Skin aging caused by UVR is characterized by loss of elasticity, fine lines, wrinkles, reduced epidermal and dermal components, increased epidermal permeability, delayed wound healing, and approximately 90% of skin aging. These external factors can cause aging through reactive oxygen species (ROS)-mediated inflammation, as well as aged skin is a source of circulatory inflammatory molecules which accelerate skin aging and cause aging-related diseases.
  • 818
  • 07 May 2021
Topic Review
Chronic Muscle Disuse
Periods of muscle disuse promote diminished muscle quality along with muscle atrophy that is characterized by reductions in muscle fiber cross-sectional area (CSA). Skeletal muscle disuse may be brought about by chronic sedentarism, periods of immobilization due to injury, bed rest as result of illness, or even exposure to microgravity. Such inactivity elicits functional and metabolic derangements in the affected tissue including marked mitochondrial alterations that contribute to the impaired metabolic health and degree of atrophy in the muscle. These impairments within the tissue prompt a net increase in catabolic processes in conjunction with reductions in skeletal muscle protein synthesis. Skeletal muscle mitochondrial decline and atrophy are underlying features of many diseases and they exacerbate disease progression and reduced mobility with aging. Thus, understanding the molecular underpinnings of muscle mitochondrial deficits with prolonged inactivity is of considerable interest.
  • 817
  • 21 May 2021
Topic Review
Role of Estrogen Receptor Status in PRODH/POX-Dependent Apoptosis/Survival
The estrogen receptor (ER) status and the availability of agonists or antagonists of these receptors determine the processes of growth, differentiation, and proliferation of breast cancer cells. Estrogens and anti-estrogenic compounds have been shown to influence breast cancer cell survival/apoptosis via action through the mitochondrial enzyme proline dehydrogenase/proline oxidase (PRODH/POX). 
  • 817
  • 29 Mar 2022
Topic Review
Novel Therapies for T1D
It is well established that genetic and environmental factors contribute to the initiation and progression of type 1 diabetes, but recent studies show that epigenetic modifications are also important.  Key epigenetic modifications associated with type 1 diabetes pathogenesis and the ways to harness epigenetic mechanisms to prevent, reverse, or manage T1D have been discussed in details. 
  • 816
  • 20 Nov 2020
Topic Review
Fascin-1 in Gastrointestinal Cancers
Gastrointestinal (GI) cancers, including esophageal, gastric, colorectal, liver, and pancreatic cancers, remain as one of the leading causes of death worldwide, with a large proportion accounting for fatalities related to metastatic disease. Invasion of primary cancer occurs by the actin cytoskeleton remodeling, including the formation of the filopodia, stereocilia, and other finger-like membrane protrusions. The crucial step of actin remodeling in the malignant cells is mediated by the fascin protein family, with fascin-1 being the most active. Fascin-1 is an actin-binding protein that cross-links filamentous actin into tightly packed parallel bundles, giving rise to finger-like cell protrusions, thus equipping the cell with the machinery necessary for adhesion, motility, and invasion.
  • 816
  • 27 May 2021
Topic Review
Transmembrane Chloride Intracellular Channel 1
Identification of potential pathological biomarkers has proved to be essential for understanding complex and fatal diseases, such as cancer and neurodegenerative diseases. Ion channels are involved in the maintenance of cellular homeostasis. Moreover, loss of function and aberrant expression of ion channels and transporters have been linked to various cancers, and to neurodegeneration. The Chloride Intracellular Channel 1 (CLIC1), CLIC1 is a metamorphic protein belonging to a partially unexplored protein superfamily, the CLICs. In homeostatic conditions, CLIC1 protein is expressed in cells as a cytosolic monomer. In pathological states, CLIC1 is specifically expressed as transmembrane chloride channel. In the following review, we trace the involvement of CLIC1 protein functions in physiological and in pathological conditions and assess its functionally active isoform as a potential target for future therapeutic strategies.
  • 816
  • 11 Oct 2021
Topic Review
Glycoconjugate Vaccine
Glycoconjugate vaccines have been one tool used to fight against diseases caused by a number of bacteria. Carbohydrates (monosaccharides, oligosaccharides, and polysaccharides) play important functional roles in bacteria. Glycoconjugate vaccines contain oligosaccharides that are attached to a carrier protein.
  • 816
  • 19 Oct 2021
Topic Review
PIWI-Interacting RNAs (piRNAs) and Cancers
The P-Element-induced wimpy testis (PIWI)-interacting RNAs(piRNAs) were first described in 2001 in experiments usingDrosophilamodels evidencing their role in fertility. Then, piRNAs were involved in the function of mammalian germ cells. During the last two decades, researchers have described piRNAs as small RNA molecules able to bind PIWI proteins to form piRNA/PIWI complexes, which act as mediators in several processes including transposon silencing, spermiogenesis, genome rearrangement, epigenetic regulation, protein regulation, and germ stem-cell maintenance in both normal and abnormal cells.
  • 816
  • 20 Jan 2022
Topic Review
Consequences of COVID-19 for Pancreas
Coronaviruses are enveloped, single- and positive-stranded RNA viruses that infect birds and mammals. In humans, coronaviruses cause respiratory tract infection, usually the common cold, but they can also cause severe respiratory illness including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), caused by severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV), respectively. Although coronavirus disease 2019 (COVID-19)-related major health consequences involve the lungs, a growing body of evidence indicates that COVID-19 is not inert to the pancreas either. 
  • 816
  • 26 Jan 2022
Topic Review
Elastic Fibre Proteins in Wound Healing
As essential components of people's connective tissues, elastic fibres give tissues such as major blood vessels, skin and the lungs their elasticity. In humans, the fibrillin family is composed of three highly conserved proteins, fibrillin-1, -2 and -3, all of which are engaged in the formation of microfibrils. Fibrillin-2 and -3 are mainly expressed in fetal tissues, while fibrillin-1 is continuously expressed throughout adulthood in tissues such as the heart, aorta, lung, nervous system and skin. Mutations in the FBN1 gene, which encodes fibrillin-1, are associated with MFS, isolated autosomal dominant ectopia lentis 1, mitral valve-aorta-skeleton-skin (MASS) syndrome, Weill–Marchesani syndrome (WMS), stiff skin syndrome, acromicric and geleophysic dysplasias and Marfanoid-progeroid-lipodystrophy syndrome. 
  • 816
  • 26 May 2022
Topic Review
Synthetic Vulnerabilities in the KRAS Pathway
Mutations in Kristen Rat Sarcoma viral oncogene (KRAS) are among the most frequent gain-of-function genetic alterations in human cancer. Most KRAS-driven cancers depend on its sustained expression and signaling. Despite spectacular recent success in the development of inhibitors targeting specific KRAS alleles, the discovery and utilization of effective directed therapies for KRAS-mutant cancers remains a major unmet need.
  • 815
  • 24 Jun 2022
Topic Review
Digital PCR for Single-Cell Analysis
Single-cell analysis provides an overwhelming strategy for revealing cellular heterogeneity and new perspectives for understanding the biological function and disease mechanism. Moreover, it promotes the basic and clinical research in many fields at a single-cell resolution. A digital polymerase chain reaction (dPCR) is an absolute quantitative analysis technology with high sensitivity and precision for DNA/RNA or protein. With the development of microfluidic technology, digital PCR has been used to achieve absolute quantification of single-cell gene expression and single-cell proteins. For single-cell specific-gene or -protein detection, digital PCR has shown great advantages. 
  • 815
  • 23 Feb 2024
Topic Review
Viper Venom Phospholipase A2
Viper venom phospholipase A2 enzymes (vvPLA2s) and phospholipase A2-like (PLA2-like) proteins are two of the principal toxins in viper venom that are responsible for the severe myotoxic and neurotoxic effects caused by snakebite envenoming, among other pathologies. 
  • 815
  • 22 Feb 2024
Topic Review
S-Denitrosylation in Glutathione and Redoxin Systems
S-nitrosylation of proteins occurs as a consequence of the derivatization of cysteine thiols with nitric oxide (NO) and is often associated with diseases and protein malfunction. Aberrant S-nitrosylation, in addition to other genetic and epigenetic factors, has gained rapid importance as a prime cause of various metabolic, respiratory, and cardiac disorders, with a major emphasis on cancer and neurodegeneration. The S-nitrosoproteome, a term used to collectively refer to the diverse and dynamic repertoire of S-nitrosylated proteins, is relatively less explored in the field of redox biochemistry, in contrast to other covalently modified versions of the same set of proteins. Advancing research is gradually unveiling the enormous clinical importance of S-nitrosylation in the etiology of diseases and is opening up new avenues of prompt diagnosis that harness this phenomenon. Ever since the discovery of the two robust and highly conserved S-nitrosoglutathione reductase and thioredoxin systems as candidate denitrosylases, years of rampant speculation centered around the identification of specific substrates and other candidate denitrosylases, subcellular localization of both substrates and denitrosylases, the position of susceptible thiols, mechanisms of S-denitrosylation under basal and stimulus-dependent conditions, impact on protein conformation and function, and extrapolating these findings towards the understanding of diseases, aging and the development of novel therapeutic strategies. 
  • 815
  • 28 Nov 2022
Topic Review
Cu2+ and Osteoclast
Copper-containing biomaterials are increasingly applied for bone regeneration due to their pro-angiogenetic, pro-osteogenetic and antimicrobial properties. Therefore, the effect of Cu2+ on osteoclasts, which play a major role in bone remodeling was studied in detail. Methods: Human primary osteoclasts, differentiated from human monocytes were differentiated or cultivated in the presence of Cu2+. Osteoclast formation and activity were analyzed by measurement of osteoclast-specific enzyme activities, gene expression analysis and resorption assays. Furthermore, the glutathione levels of the cells were checked to evaluate oxidative stress induced by Cu2+. Results: Up to 8 µM Cu2+ did not induce cytotoxic effects. Activity of tartrate-resistant acid phosphatase (TRAP) was significantly increased, while other osteoclast specific enzyme activities were not affected. However, gene expression of TRAP was not upregulated. Resorptive activity of osteoclasts towards dentin was not changed in the presence of 8 µM Cu2+ but decreased in the presence of extracellular bone matrix. When Cu2+ was added to mature osteoclasts TRAP activity was not increased and resorption decreased only moderately. The glutathione level of both differentiating and mature osteoclasts was significantly decreased in the presence of Cu2+. Conclusions: Differentiating and mature osteoclasts react differently to Cu2+. High TRAP activities are not necessarily related to high resorption.
  • 814
  • 16 Mar 2021
Topic Review
Brain Tissue Respiration in Trauma
The passage of oxygen (O2) from vessels into the cells comprises multiple steps in different volumes (e.g., intracellular erythrocytes, plasma, interstitial tissue, intracellular brain cells) and is influenced by multiple physiological factors (e.g., cerebral blood flow, capillary density, concentration of hemoglobin (Hb), O2 affinity for Hb). The pathogenesis of brain trauma may alter the mechanisms that regulate these steps.
  • 814
  • 10 May 2021
Topic Review
Antimicrobial Compounds from Endolichenic Fungi
A lichen is a symbiotic relationship between a fungus and a photosynthetic organism, which is algae or cyanobacteria. Endolichenic fungi are a group of microfungi that resides asymptomatically within the thalli of lichens. Endolichenic fungi can be recognized as luxuriant metabolic artists that produce propitious bioactive secondary metabolites. 
  • 814
  • 06 Jul 2021
Topic Review
The Gut–Liver Axis of Boar Taint
The gut microbiome is a complex organ that is typically comprised of a couple hundred bacterial species expressing nearly 2 million different genes, which promote the biotransformation of xenobiotics and endogenous compounds and regulate the production of microbial metabolites in response to dietary, genetic, and environmental factors. Microbiota-derived compounds function as signaling molecules between different bacterial species to synchronize bacterial behaviours by altering the microbial population or the gene expression within the gut microbiome, which is known as quorum sensing. Gut-derived compounds also modulate metabolic pathways in the liver and intestines and act as ligands for nuclear receptors and other xenobiotic sensing transcription factors. In response, the liver produces bile to provide feedback to the gut microbiota and regulate further metabolite production. This bidirectional communication between the liver and the gut is referred to as the gut–liver axis and represents an important link between the gut microbiome and nuclear receptor signaling pathways.
  • 814
  • 13 Sep 2022
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