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Topic Review
LCA, DCA, and Their Derivatives from Gut Microbiota
A wide variety and large number of bacterial species live in the gut, forming the gut microbiota. Gut microbiota not only coexist harmoniously with their hosts, but they also induce significant effects on each other. The composition of the gut microbiota can be changed due to environmental factors such as diet and antibiotic intake. In contrast, alterations in the composition of the gut microbiota have been reported in a variety of diseases, including intestinal, allergic, and autoimmune diseases and cancer. The gut microbiota metabolize exogenous dietary components ingested from outside the body to produce short-chain fatty acids (SCFAs) and amino acid metabolites. Unlike SCFAs and amino acid metabolites, the source of bile acids (BAs) produced by the gut microbiota is endogenous BAs from the liver. The gut microbiota metabolize BAs to generate secondary bile acids, such as lithocholic acid (LCA), deoxycholic acid (DCA), and their derivatives, which have recently been shown to play important roles in immune cells. 
  • 940
  • 22 Nov 2023
Topic Review
Estrogen Receptors in bone
Estrogens are key regulators of bone turnover in both females and males. These hormones play a major role in longitudinal and width growth throughout puberty as well as in the regulation of bone turnover. Effects of estrogens on bone involve either estrogen receptor alpha (ERα) or beta (ERβ) depending on the type of bone (femur, vertebrae, tibia, mandible), the compartment (trabecular or cortical), cell types involved (osteoclasts, osteoblasts and osteocytes) and the sex.  
  • 940
  • 18 Mar 2021
Topic Review
Nuclear Ubiquitin-Proteasome Pathways
To protect the cell from the accumulation of aberrant proteins, a network of protein quality control (PQC) pathways identifies the substrates and direct them towards refolding or elimination via regulated protein degradation. The main pathway for degradation of misfolded proteins is the ubiquitin-proteasome system. PQC pathways have been first described in the cytoplasm and the endoplasmic reticulum, however, accumulating evidence indicates that the nucleus is an important PQC compartment for ubiquitination and proteasomal degradation of not only nuclear, but also cytoplasmic proteins. 
  • 939
  • 28 Apr 2021
Topic Review
CLL
CLL is a hematological malignancy considered as the most frequent lymphoproliferative disease in the western world. It is characterized by high molecular heterogeneity and despite the available therapeutic options, there are many patient subgroups showing the insufficient effectiveness of disease treatment.
  • 939
  • 23 Jul 2021
Topic Review
Posttranslational Modifications in PD-L1 Turnover and Function
Programmed death-ligand 1 (PD-L1) is one of the most classic immune checkpoint molecules. Cancer cells express PD-L1 to inhibit the activity of effector T cells’ cytotoxicity through programmed death 1 (PD-1) engagement in exposure to inflammatory cytokines. PD-L1 expression levels on cancer cells might affect the clinical response to anti-PD-1/PD-L1 therapies. Hence, understanding molecular mechanisms for regulating PD-L1 expression is essential for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade. Posttranslational modifications (PTMs), including phosphorylation, glycosylation, ubiquitination, and acetylation, regulate PD-L1 stability, cellular translocation, and interaction with its receptor. A coordinated positive and negative regulation via PTMs is required to ensure the balance and function of the PD-L1 protein. 
  • 939
  • 03 Dec 2021
Topic Review
Cysteinyl Leukotrienes as Multifunctional Inflammation Mediators
Montelukast (MTK)—an antagonist of the cysteinyl leukotrienes receptor 1—is widely used in the management of symptoms among adults and children. Initially described as the slow-reacting substances of anaphylaxis, leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid. Its systemic anti-inflammatory actions, which are particularly important in the brain tissues, are at the onset of various clinical studies focused on the repurposing of this drug for various other diseases, aimed particularly at Alzheimer’s and Parkinson’s diseases.
  • 939
  • 21 Sep 2022
Topic Review
Application of Proteomics in Giardia duodenalis
Giardia duodenalis remains a neglected tropical disease. A key feature of the sustained transmission of Giardia is the ability to form environmentally resistant cysts. Valuable information from proteomics analyses of G. duodenalis has been discovered in terms of the pathogenesis and virulence of Giardia, which may provide guidance for the development of better means with which to prevent and reduce the impacts of giardiasis.
  • 939
  • 18 Nov 2022
Topic Review
Oxidative Stress and Aging in Neurodegeneration Disorders
Healthy aging is characterized by a gradual breakdown of physiological systems leading to a reduction in cognitive functions and brain health, but the timing and duration of this decline vary in individule. Oxidative stress (OS) is a crucial factor in the aging process that can cause direct damage to the brain’s cellular organization, causing neurodegenerative disease.
  • 939
  • 08 Mar 2023
Topic Review
Diverse Downstream Effectors of RRAD
Ras-related associated with diabetes (RRAD), a member of the Ras-related GTPase superfamily, is primarily a cytosolic protein that actives in the plasma membrane. RRAD is highly expressed in type 2 diabetes patients and as a biomarker of congestive heart failure. Mounting evidence showed that RRAD is important for the progression and metastasis of tumor cells, which play opposite roles as an oncogene or tumor suppressor gene depending on cancer and cell type. 
  • 939
  • 11 Apr 2023
Topic Review
RNAnalysis for Codeless RNAnalysing Sequencing of Data
In next-generation sequencing experiments, significant obstacles include conducting exploratory data analysis, deciphering trends, pinpointing potential targets/candidates, and presenting results in a clear and intuitive manner. These challenges become more pronounced for researchers lacking expertise in coding, as most analysis tools demand programming skills. Even for adept computational biologists, there is a need for an efficient and reproducible system to produce standardized results.
  • 939
  • 12 Dec 2023
Topic Review
Ion Mobility–Mass Spectrometry for Bioanalysis
This study aims to cover the main strategies based on ion mobility spectrometry (IMS) for the analysis of biological samples. The determination of endogenous and exogenous compounds in such samples is important for the understanding of the health status of individuals. For this reason, the development of new approaches that can be complementary to the ones already established (mainly based on liquid chromatography coupled to mass spectrometry) is welcomed. In this regard, ion mobility spectrometry has appeared in the analytical scenario as a powerful technique for the separation and characterization of compounds based on their mobility. IMS has been used in several areas taking advantage of its orthogonality with other analytical separation techniques, such as liquid chromatography, gas chromatography, capillary electrophoresis, or supercritical fluid chromatography. Bioanalysis is not one of the areas where IMS has been more extensively applied. However, over the last years, the interest in using this approach for the analysis of biological samples has clearly increased.
  • 938
  • 31 Mar 2021
Topic Review
Computational Drug Design on Ion Channels
Ion channels play important roles in fundamental biological processes, such as electric signaling in cells, muscle contraction, hormone secretion, and regulation of the immune response. Targeting ion channels with drugs represents a treatment option for neurological and cardiovascular diseases, muscular degradation disorders, and pathologies related to disturbed pain sensation. While there are more than 300 different ion channels in the human organism, drugs have been developed only for some of them and available drugs lack selectivity. Computational approaches are an indispensable tool for drug discovery and can speed up, especially, the early development stages of lead identification and optimization. The number of molecular structures of ion channels has considerably increased over the last ten years, providing new opportunities for structure-based drug development.
  • 938
  • 09 Jun 2023
Topic Review
Tafazzin in Mitochondrial Function, Development and Disease
Tafazzin, an enzyme associated with the rare inherited x-linked disorder Barth Syndrome, is a nuclear encoded mitochondrial transacylase that is highly conserved across multiple species and plays an important role in mitochondrial function. 
  • 937
  • 15 Jul 2022
Topic Review
Plant Secondary Metabolites and Endothelium
According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time—from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide–cyclic guanosine monophosphate activation, prostacyclin–cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition.
  • 936
  • 19 Mar 2021
Topic Review
Plasma Clearance Receptors of FVIII and VWF
Congenital deficiency in blood coagulation factor (F) VIII (FVIII) results in excessive bleeding. The disease (hemophilia A) is treated with infusions of therapeutic FVIII concentrates, either plasma-derived (pdFVIII) or produced with recombinant DNA technology (rFVIII). Due to the relatively short FVIII plasma half-life (~12 h), such treatment requires frequent FVIII infusions (3–4 per week in prophylaxis) that calls for developing more efficient longer-acting FVIII products, in particular with an extended plasma lifetime, commonly termed half-life (EHL). Relevant protein modifications are performed via genetic and/or chemical modification of rFVIII, and efficient designs require understanding the molecular mechanisms of FVIII plasma clearance.
  • 934
  • 29 May 2023
Topic Review
Targeting Iron-Sulfur Clusters in Cancer
Iron dysregulation is a hallmark of cancer, characterized by an overexpression of genes involved in iron metabolism and iron-sulfur cluster (ISC) biogenesis. Dysregulated iron homeostasis increases intracellular labile iron, which may lead to the formation of excess cytotoxic radicals and make it vulnerable to various types of regulated cell death, including ferroptosis. The inhibition of ISC synthesis triggers the iron starvation response, increasing lipid peroxidation and ferroptosis in cancer cells treated with oxidative stress-inducing agents. Various methods, such as redox operations, iron chelation, and iron replacement with redox-inert metals, can destabilize or limit ISC formation and function, providing potential therapeutic strategies for cancer treatment. Targeting ISCs to induce ferroptosis represents a promising approach in cancer therapy.
  • 934
  • 01 Aug 2023
Topic Review
Role of SCAP/SREBP in Hepatic Steatosis
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a unique, multi-factorial condition with several phases of progression including steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Sterol element binding protein 1c (SREBP1c) is the main transcription factor involved in regulating hepatic de novo lipogenesis. This transcription factor is synthesized as an inactive precursor, and its proteolytic maturation is initiated in the membrane of the endoplasmic reticulum upon stimulation by insulin. SREBP cleavage activating protein (SCAP) is required as a chaperon protein to escort SREBP from the endoplasmic reticulum and to facilitate the proteolytic release of the N-terminal domain of SREBP into the Golgi. SCAP inhibition prevents activation of SREBP and inhibits the expression of genes involved in triglyceride and fatty acid synthesis, resulting in the inhibition of de novo lipogenesis.
  • 934
  • 24 Jan 2024
Topic Review
Integrin β4 as Tumor Marker
Integrin β4 (ITGβ4) is a class of transmembrane adhesion molecules composed of hemidesmosomes (HDs). Its unique long intracellular domain provides intricate signal transduction functions. These signal transduction effects are especially prominent in tumors. Integrin β4 is differentially expressed in various tumors, and it plays a vital role in tumor invasion, proliferation, epithelial–mesenchymal transition, and angiogenesis. In clinical practice, it is described as a diagnostic marker for the targeted treatment of cancer and will be helpful in the clinical diagnosis and treatment of tumors.
  • 933
  • 03 Sep 2021
Topic Review
Metabolomics and Bladder Cancer
In the last decade, metabolomics has tried to assert its value in the bladder cancer field. Due to the current invasive diagnostic techniques, such as cystoscopy and the continuous monitoring patients must undergo, the introduction of non-invasive urinary biomarkers for monitoring this disease would be advantageous. This section represents a collection of all the metabolic information that various studies have obtained in recent years on bladder cancer, with particular attention to discovering biomarkers in urine for the diagnosis of this disease. In principle, they would complement cystoscopy or, at best, replace it. However, evaluating the different degrees of reproducibility that the experiments have shown in the indication of biomarkers, a synthesis was proposed to obtain a consensus list that is more reliable to become a guideline for clinical practice.
  • 933
  • 11 Nov 2021
Topic Review
Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes
Obesity is defined as abnormal and excessive fat accumulation, and it is a risk factor for developing metabolic and neurodegenerative diseases and cognitive deficits. Obesity is caused by an imbalance in energy homeostasis resulting from increased caloric intake associated with a sedentary lifestyle. However, the entire physiopathology linking obesity with neurodegeneration and cognitive decline has not yet been elucidated. During the progression of obesity, adipose tissue undergoes immune, metabolic, and functional changes that induce chronic low-grade inflammation. It has been proposed that inflammatory processes may participate in both the peripheral disorders and brain disorders associated with obesity, including the development of cognitive deficits. In addition, mitochondrial dysfunction is related to inflammation and oxidative stress, causing cellular oxidative damage. 
  • 933
  • 20 Jan 2023
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