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Topic Review
JNKs in Development of Disease
c-Jun N-terminal kinases (JNKs) have emerged as suitable therapeutic strategies. In fact, it has been demonstrated that some unspecific JNK inhibitors exert antidiabetic and neuroprotective effects, albeit they usually show high toxicity or lack therapeutic value. In this sense, natural specific JNK inhibitors, such as Licochalcone A, are promising candidates. Nonetheless, research on the understanding of the role of each of the JNKs remains mandatory in order to progress on the identification of new selective JNK isoform inhibitors. In the present review, a summary on the current gathered data on the role of JNKs in pathology is presented, as well as a discussion on their potential role in pathologies like epilepsy and metabolic-cognitive injury. Moreover, data on the effects of synthetic small molecule inhibitors that modulate JNK-dependent pathways in the brain and peripheral tissues is reviewed.
  • 1.5K
  • 23 Oct 2020
Topic Review
Structure of the MRN Complex
The MRE11, RAD50, and NBN genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair with the p53-dependent cell cycle checkpoint arrest. Carriers of homozygous germline pathogenic variants in the MRN complex genes or compound heterozygotes develop phenotypically distinct rare autosomal recessive syndromes characterized by chromosomal instability and neurological symptoms. 
  • 1.5K
  • 06 Apr 2023
Topic Review
Immune-Mediated Drug-Induced Liver Injury
Drug-induced liver injury (DILI) is a challenging clinical event in medicine, particularly because of its ability to present with a variety of phenotypes including that of autoimmune hepatitis or other immune mediated liver injuries.
  • 1.5K
  • 12 Oct 2021
Topic Review
WNT Signalling in Dental Pathologies
Great efforts have been made over the past decades to discover new therapeutic targets for a big variety of human pathologies. Most of the studies dealing with severe pathological conditions such as cancers and tissue malformations are focused on the role of either widely recognized master controlling genes such as ras and myc or pivotal components of key signalling pathways, among which Wnt and Notch. However, these genes and molecules are fundamental for paired embryogenesis as well as for tissue and organ homeostasis and regeneration, where they regulate cell proliferation, migration, differentiation and apoptosis. The precise timing and localization of their activation are important to ensure the appropriate cellular functions in physiological conditions. Thus, their indiscriminate targeting is not desirable, due to both the high risk of severe side effects and the certainty of broad phenotypic consequences. On the contrary, optimal therapeutic targets should be selected based on their tissue, time and pathology specific roles. Here, we suggest a paradigmatic example of such target molecules that could be represented by the Wnt/b-catenin signalling components Bcl9 and Bcl9l. 
  • 1.5K
  • 05 Nov 2020
Topic Review
Lipid Metabolism and Acylglycerolphosphate Acyltransferases (AGPATs) in Cancer
Alter lipid metabolism is an emerging hallmark of cancer. The conversion of fatty acids to neutral triacylglycerides (TAG), plays a central role in this adaptive process.  Acylglycerolphosphate acyltransferases (AGPATs)/lysophosphatidic acid acyltransferases (LPAATs) are a family of enzymes that catalyze the synthesis of phosphatidic acid (PA), an intermediate in TAG synthesis, a signaling molecule, and a precursor of phospholipids. Importantly, the expression of AGPATs has been linked to diverse physiological and pathological phenotypes, including cancer.
  • 1.5K
  • 20 Jan 2022
Topic Review
Cardioprotective Role of Vascular Endothelial Growth Factor B
Coronary heart disease (CHD) is the leading cause of death around the world. Based on the roles of vascular endothelial growth factor (VEGF) family members to regulate blood and lymphatic vessels and metabolic functions, several therapeutic approaches have been attempted. However proangiogenic therapies based on classical VEGF-A have been disappointing. Therefore, it has become important to focus on other VEGFs, like VEGF-B, which is a novel member of the VEGF family. 
  • 1.5K
  • 03 Jan 2023
Topic Review
Vascularization and Cancer Biology
Vascularization is another hallmark of cancer, whereby cancer cells promote the formation of blood vessels to deliver nutrients for fast-growing solid tumors. The most well-known process of vascularization is angiogenesis. In normal cells and tissues, the angiogenesis is a controlled process that is turned on or off depending on the needs of the cells; however, in cancerous cells and tumors, the angiogenesis process is continuous and there is a dysregulation of pro- and antiangiogenesis factors . This continuous activation of angiogenesis allows the cancer cells to form blood vessels to obtain sufficient nutrients for continuous growth and proliferation. There are other ways tumors can achieve vascularization, such as vascular co-option, intussusceptive microvascular growth and vasculogenic mimicry.
  • 1.5K
  • 22 Apr 2022
Topic Review
Metabolisms Responsive to Nutrient Deficiencies in Crops
Crop growth and yield often face sophisticated environmental stresses, especially the low availability of mineral nutrients in soils, such as deficiencies of nitrogen, phosphorus, potassium, and others. Thus, it is of great importance to understand the mechanisms of crop response to mineral nutrient deficiencies, as a basis to contribute to genetic improvement and breeding of crop varieties with high nutrient efficiency for sustainable agriculture. 
  • 1.5K
  • 26 Aug 2022
Topic Review
C/EBPs
CCAAT-enhancer-binding proteins (C/EBPs) is a family of six structurally homologous transcription factors that promote the expression of genes involved in different cellular responses, such as proliferation, growth, and differentiation. These transcription factors control the differentiation of several cell types, and have key roles in regulating cellular proliferation, through interaction with cell cycle proteins. The molecular structure of C/EBPs and their ability to interact with a multitude of factors determine their complex functions in different cells. In fact, C/EBPs can be activated or inhibited by a variety of intracellular or extracellular signals. In addition, post-translational modifications and interaction with other proteins can regulate their expression and activity in a complex manner. C/EBPs can activate or repress several classes of genes implicated in cell differentiation, metabolism, inflammation, and immune response. Moreover, C/EBPs play an important role in cancer progression and metastasis, showing both pro-oncogenic and onco-suppressor functions. Interestingly, the same isotype of C/EBP can exhibit both of these opposite functions. This “Janus” role of C/EBPs in cancer could depend on their particular position at the crossroads between proliferation and differentiation. Specific conditions such as cell type, microenvironment, type of heterodimerization, or interaction with different regulatory proteins can tip the balance towards pro- or anti-oncogenic action.
  • 1.5K
  • 13 Sep 2021
Topic Review
Exposome
The “exposome” is the cumulative exposures (diet, exercise, environmental exposure, vaccination, genetics, etc.) an individual has experienced and provides a mechanism for the establishment of immune training or immunotolerance. It is becoming increasingly clear that trained immunity constitutes a delicate balance between the dose, duration, and order of exposures. Upon innate stimuli, trained immunity or tolerance is shaped by epigenetic and metabolic changes that alter hematopoietic stem cell lineage commitment and responses to infection. Due to the immunomodulatory role of the exposome, understanding innate immune training is critical for understanding why some individuals exhibit protective phenotypes while closely related individuals may experience immunotolerant effects (e.g., the order of exposure can result in completely divergent immune responses). Research on the exposome and trained immunity may be leveraged to identify key factors for improving vaccination development, altering inflammatory disease development, and introducing potential new prophylactic treatments, especially for diseases such as COVID-19, which is currently a major health issue for the world. Furthermore, continued exposome research may prevent many deleterious effects caused by immunotolerance that frequently result in host morbidity or mortality. 
  • 1.5K
  • 09 Dec 2020
Topic Review
The Identity of Thrombosis
Since “two-path unifying theory” of hemostasis was published, it has been confirmed that hemostasis is blood clotting mechanism forming “hemostatic plug” in bleeding from external and internal bodily injury, and is also thrombosis promoting mechanism in intravascular injury by producing “thrombus”.
  • 1.5K
  • 10 Nov 2022
Topic Review
The HMOX1 Pathway
Heme oxygenase (HMOX1) is a key enzyme that catalyzes the rate-limiting first step in the heme degradation process, generating carbon monoxide, ferrous, and biliverdin, and therefore HMOX1 has a cytoprotective role as excess free heme has been shown to induce apoptosis. HMOX1 is expressed at high levels in the lungs and has been shown to mediate the anti-inflammatory effect of interleukin-10 (IL-10) in mice. Given these functions of HMOX1, it has been implicated in a variety of pathological states, including myocardial infarction, diabetes, chronic obstructive pulmonary disease (COPD). The upregulation of HMOX1 has been shown to have a protective role against the oxidative stress produced upon HIV, DENV, HCV, and IAV infections.
  • 1.5K
  • 26 Oct 2020
Topic Review
FTO Intronic SNP
Browning of white adipose tissue shifts adipocytes from energy storage white to energy expenditure beige types. The balance between the two adipocyte populations in white adipose tissue is highly determined by noncoding variants of the Fat mass and obesity-associated (FTO) locus which has the strongest association with obesity. The rs1421085 FTO risk allele results in a loss of ARID5B repression of IRX3 and IRX5 which promotes excess white adipocyte formation. Recent studies have revealed the presence of brown adipose tissues at several anatomical sites in humans including the deep-neck (DN).  We found that the characteristic gene expression profile and associated pathways of DN brown adipocytes were determined by partially overlapping effects of tissue site specific commitments of the stem cells, PPARγ stimulation and the FTO status of donors. The presence of FTO rs1421085 risk alleles had a strong influence, manifested during differentiation, on browning resulting in compromised expression of metabolic and mitochondrial genes as well as pathways which are decisive in thermogenesis.
  • 1.5K
  • 30 Oct 2020
Topic Review
Wound Healing Material
Dermal wound healing describes the progressive repair and recalcitrant mechanism of damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of wounds. The exact mechanism of material-cellular interaction is a point of immense importance, particularly in pathological conditions such as diabetes. Bioengineered alternative agents will likely continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new products continue to cut costs and improve the wound healing process. 
  • 1.5K
  • 22 Sep 2021
Topic Review
Ribosomal Protein L10
Eukaryotic cytoplasmic ribosomes are highly structured macromolecular complexes made up of four different ribosomal RNAs (rRNAs) and 80 ribosomal proteins (RPs), which play a central role in the decoding of genetic code for the synthesis of new proteins. Over the past 25 years, studies on yeast and human models have made it possible to identify RPL10 (ribosomal protein L10), which is a constituent of the large subunit of the ribosome, as an important player in the final stages of ribosome biogenesis and in ribosome function.
  • 1.5K
  • 30 Nov 2020
Topic Review
Vincristine-Induced Pediatric Peripheral Neuropathy
Vincristine-induced peripheral neurotoxicity (VIPN) is a very common side effect of vincristine chemotherapy among pediatric patients with cancer. 
  • 1.5K
  • 21 May 2021
Topic Review
Colorectal Cancer Treatment Based on Nanomaterials
Colorectal cancer (CRC) is a global health problem responsible for 10% of all cancer incidences and 9.4% of all cancer deaths worldwide. The number of new cases increases per annum, whereas the lack of effective therapies highlights the need for novel therapeutic approaches. Conventional treatment methods, such as surgery, chemotherapy and radiotherapy, are widely applied in oncology practice. Their therapeutic success is little, and therefore, the search for novel technologies is ongoing. Many efforts have focused recently on the development of safe and efficient cancer nanomedicines. Nanoparticles are among them. They are unique with their properties on a nanoscale and hold the potential to exploit intrinsic metabolic differences between cancer and healthy cells. This feature allows them to induce high levels of toxicity in cancer cells with little damage to the surrounding healthy tissues.
  • 1.5K
  • 21 Jul 2022
Topic Review
Lipids and Gut Microbiota Alterations
Advances in sequencing technologies over the past 15 years have led to a substantially greater appreciation of the importance of the gut microbiome to the health of the host. Recent outcomes indicate that aspects of nutrition, especially lipids (exogenous or endogenous), can influence the gut microbiota composition and consequently, play an important role in the metabolic health of the host. Thus, there is an increasing interest in applying holistic analytical approaches, such as lipidomics, metabolomics, (meta)transcriptomics, (meta)genomics, and (meta)proteomics, to thoroughly study the gut microbiota and any possible interplay with nutritional or endogenous components.
  • 1.5K
  • 21 Apr 2022
Topic Review
miRNA Therapeutics
The discovery of the link between microRNAs (miRNAs) and a myriad of human diseases, particularly various cancer types, has generated significant interest in exploring their potential as a novel class of drugs. This has led to substantial investments in interdisciplinary research fields such as biology, chemistry, and medical science for the development of miRNA-based therapies. Furthermore, the recent global success of SARS-CoV-2 mRNA vaccines against the COVID-19 pandemic has further revitalized interest in RNA-based immunotherapies, including miRNA-based approaches to cancer treatment. Consequently, RNA therapeutics have emerged as highly adaptable and modular options for cancer therapy.
  • 1.5K
  • 30 Jan 2024
Topic Review
Phycobilisomes and Phycobiliproteins
Eukaryotic photosynthesis arose in the course of evolution as a result of the incorporation of an unstored cyanobacterium and its transformation into chloroplasts by an ancestral heterotrophic eukaryotic cell. The pigment apparatus of earlier evolved  Archaeplastida algae and other later algal phyla turned out to be arranged in the same way having pigment-protein complexes of photosystem I (PS I), photosystem II (PS II) and antenna complex. PS I and PS II are characterized by uniform structures, while the light-harvesting antennae have undergone a number  of changes.
  • 1.5K
  • 14 Feb 2023
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