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Topic Review
Exosomes in Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC) is the most potent metastatic type of breast cancer that can spread to other body parts. Chemotherapy and surgical intervention are the sole treatments for TNBC, owing to the scarcity of therapeutic targets. Manipulation of the membranes as per the desired targets of exosomes has recently gained much attention as a drug delivery method. 
  • 841
  • 28 Feb 2023
Topic Review
Antibacterial Peptides and Their Mechanism of Action
Despite the great strides in healthcare during the last century, some challenges still remained unanswered. The development of multi-drug resistant bacteria, the alarming growth of fungal infections, the emerging/re-emerging of viral diseases are yet a worldwide threat. Since the discovery of natural antimicrobial peptides able to broadly hit several pathogens, peptide-based therapeutics have been under the lenses of the researchers. Antimicrobial peptides generally affect highly preserved structures, e.g., the phospholipid membrane via pore formation or other constitutive targets like peptidoglycans in Gram-negative and Gram-positive bacteria, and glucan in the fungal cell wall. Additionally, some peptides are particularly active on biofilm destabilizing the microbial communities. They can also act intracellularly, e.g., on protein biosynthesis or DNA replication. Their intracellular properties are extended upon viral infection since peptides can influence several steps along the virus life cycle starting from viral receptor-cell interaction to the budding. Besides their mode of action, improvements in manufacturing to increase their half-life and performances are also taken into consideration together with advantages and impairments in the clinical usage. Thus far, the progress of new synthetic peptide-based approaches is making them a promising tool to counteract emerging infections.
  • 840
  • 08 Mar 2022
Topic Review
Metal Ion-Directed Specific DNA Structures
Various DNA structures, including specific metal ion complexes, have been designed based on the knowledge of canonical base pairing as well as general coordination chemistry. The role of metal ions in these studies is quite broad and diverse. Metal ions can be targets themselves in analytical applications, essential building blocks of certain DNA structures that one wishes to construct, or they can be responsible for signal generation, such as luminescence or redox. 
  • 840
  • 29 Jun 2022
Topic Review
ALK+ lung cancer: targeted inhibitors and resistance mechanisms
EML4-ALK is an oncogenic fusion protein that accounts for approximately 5% of non-small cell lung cancer cases. Targeted inhibitors of ALK are now the standard of care treatment often leading to an excellent initial response and increased overall survival. A variety of resistance mechanisms have been identified that eventually lead to relapse highlighting the need for additional treatment options for these patients.
  • 840
  • 01 Aug 2022
Topic Review
Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization
Hsp90 is a ubiquitous molecular chaperone involved in many cell signaling pathways, and its interactions with specific chaperones and cochaperones determines which client proteins to fold. Hsp90 has been shown to be involved in the promotion and maintenance of proper protein complex assembly either alone or in association with other chaperones such as the R2TP chaperone complex. Hsp90-R2TP acts through several mechanisms, such as by controlling the transcription of protein complex subunits, stabilizing protein subcomplexes before their incorporation into the entire complex, and by recruiting adaptors that facilitate complex assembly.
  • 840
  • 05 Aug 2022
Topic Review
Multifunctionality in Microbial Adhesins
Microbial adhesins have multiple functions, and these activities are all evolved and selected. Adhesins can act as enzymes, as assembly scaffolds and components of complex nano-machines. Sometimes, these activities are called secondary because they were discovered secondarily. For instance, microbial type IV pili were first called adhesive. In contrast, phosphoglycerate kinase has its well-known enzymatic activity, but in fungi it also moonlights as an extracellular adhesin.
  • 840
  • 16 Jun 2023
Topic Review
Metabolism and Bone Diseases
Bone, a highly mineralized organ that serves as a skeleton of the body, is continuously depositing and resorbing bone matrix to maintain homeostasis. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. The dysregulation of these metabolic pathways leads to bone disorders.
  • 839
  • 30 Dec 2020
Topic Review
New Horizons in Structural Biology of Membrane Proteins
A third of both pro- and eukaryotic proteomes consist of membrane proteins. Housed in a milieu of hydrophobic molecules, they serve as crucial contacts of communication between the cytoplasm and non-cytosolic environments, making them essential pharmaceutical targets. While membrane proteins are notoriously difficult to investigate at any level, high-resolution structures of these targets only became feasible at the very end of the twentieth century. It was not until robust technological developments in the fields of X-ray crystallography, NMR spectroscopy and cryo-EM, that the scientific community at large, finally gained access to an ever-increasing number of atomic resolution structures, and began to rationalize how membrane proteins accommodate their function. As if the lack of structural information wasn’t enough to hamper progress, a higher level of complexity arose from the modern understanding of “one structure—one function” paradigm, a primitive simplification useful at the dawn of the scientific era, that has promptly lost credence to the complex maneuvers of membrane proteins.
  • 839
  • 26 Apr 2022
Topic Review
Ribonuclease Inhibitor
Protein synthesis is a highly complex process executed by well-organized translation machinery. Ribosomes, tRNAs and mRNAs are the principal components of this machinery whereas RNA binding proteins and ribosome interacting partners act as accessory factors. Angiogenin (ANG) – Ribonuclease inhibitor (RNH1) system is one such accessory part of the translation machinery that came into focus afresh due to its unconventional role in the translation.
  • 838
  • 07 Feb 2021
Topic Review
CD44 Intracellular Domain
CD44 serves as a cell surface receptor for various extracellular matrix molecules, mainly hyaluronan, and messenger molecules, such as growth factors, and has important functions in normal and disease states, the predominant one being cancer. CD44 coordinates both structural and signaling events through its highly conserved intracellular domain. Although short and devoid of any enzymatic activity, the CD44 intracellular domain possesses structural motifs that promote the interactions with cytoplasmic effectors involved in important cellular pathways, including cell trafficking, transcription, and metabolism, which regulate cellular functions like growth, survival, differentiation, stemness, and therapeutic resistance.
  • 838
  • 22 Jan 2024
Topic Review
Amino Acids and Its Roles in Glioma Pathology
Amino acids (AAs) are indispensable building blocks of diverse bio-macromolecules as well as functional regulators for various metabolic processes. The fact that cancer cells live with a voracious appetite for specific AAs has been widely recognized. Glioma is one of the most lethal malignancies occurring in the central nervous system. The reprogrammed metabolism of AAs benefits glioma proliferation, signal transduction, epigenetic modification, and stress tolerance. Metabolic alteration of specific AAs also contributes to glioma immune escape and chemoresistance. For clinical consideration, fluctuations in the concentrations of AAs observed in specific body fluids provides opportunities to develop new diagnosis and prognosis markers.
  • 837
  • 14 Oct 2022
Topic Review
Auxin's Role in Nitrate-Regulated Plant Growth and Development
As a major component of vital macromolecules such as nucleic acids, amino acids, and chlorophyll, nitrogen is an essential macronutrient for plants. Although nitrogen is one of the most abundant elements in nature, accounting for about 70% of atmospheric gasses, its availability for plant uptake in the soil varies temporally and spatially. Therefore, modern agriculture relies heavily on nitrogen fertilization to maximize crop quality and yield. Auxins are a group of naturally occurring molecules derived from tryptophan, with indole-3-acetic acid (IAA) being the major form of auxin. The biosynthesis of IAA is defined by a two-step metabolic pathway, in which the TAA family of aminotransferases converts tryptophan (Trp) to indole-3-pyruvate (IPA), followed by a YUC flavin monooxygenases-mediated conversion of IPA to IAA. Auxin has extensive regulatory functions in plant development. 
  • 837
  • 10 Jul 2023
Topic Review
E3 Ubiquitin Ligase TRIP12
The Thyroid hormone Receptor Interacting Protein 12 (TRIP12) protein belongs to the 28-member Homologous to the E6-AP C-Terminus (HECT) E3 ubiquitin ligase family. First described as an interactor of the thyroid hormone receptor, TRIP12’s biological importance was revealed by the embryonic lethality of a murine model bearing an inactivating mutation in the TRIP12 gene. Further studies showed the participation of TRIP12 in the regulation of major biological processes such as cell cycle progression, DNA damage repair, chromatin remodeling, and cell differentiation by an ubiquitination-mediated degradation of key protein substrates. Moreover, alterations of TRIP12 expression have been reported in cancers that can serve as predictive markers of therapeutic response. The TRIP12 gene is also referenced as a causative gene associated to intellectual disorders such as Clark–Baraitser syndrome and is clearly implicated in Autism Spectrum Disorder. The aim of the review is to provide an exhaustive and integrated overview of the different aspects of TRIP12 ranging from its regulation, molecular functions and physio-pathological implications.
  • 836
  • 23 Nov 2020
Topic Review
THUMP-Related tRNA Modification Enzymes
The existence of the thiouridine synthetase, methyltransferase and pseudouridine synthase (THUMP) domain was originally predicted by a bioinformatic study. Since the prediction of the THUMP domain, many tRNA modification enzymes containing the THUMP domain have been identified. According to their enzymatic activity, THUMP-related tRNA modification enzymes can be classified into five types, namely 4-thiouridine synthetase, deaminase, methyltransferase, a partner protein of acetyltransferase and pseudouridine synthase. Biochemical, biophysical and structural studies of tRNA 4-thiouridine synthetase, tRNA methyltransferases and tRNA deaminase have established the concept that the THUMP domain captures the 3′-end of RNA (in the case of tRNA, the CCA-terminus).
  • 836
  • 15 Feb 2023
Topic Review
TOR–PKA Interactions
TOR and PKA signaling are the major growth-regulatory nutrient-sensing pathways in S. cerevisiae. A number of experimental findings demonstrated a close relationship between these pathways: Both are responsive to glucose availability. Both regulate ribosome production on the transcriptional level and repress autophagy and the cellular stress response. Sch9, a major downstream effector of TORC1 presumably shares its kinase consensus motif with PKA, and genetic rescue and synthetic defects between PKA and Sch9 have been known for a long time.
  • 835
  • 16 Feb 2022
Topic Review
Interleukin-4 Promotes Acetylcholine Production
Tuft cells are taste-like chemosensory cells found in the intestinal epithelium involved in the activation of group 2 innate lymphoid cells (ILC2). Although tuft cells in other tissues secrete the neurotransmitter acetylcholine (ACh), their function in the gut remains poorly understood. We investigated changes in the expression of genes and cell differentiation of the intestinal epithelium by stimulation with interleukin-4 (IL-4) or IL-13 in macaque intestinal organoids. This study is the first to demonstrate ACh upregulation by IL-4 induction in primates, suggesting that IL-4 plays a role in Paneth cell granule secretion via paracrine stimulation.
  • 834
  • 25 Aug 2021
Topic Review
Possible Strategy for Colon Carcinoma Cells
Cancer is a major cause of mortality globally. The major reasons for the failure of cancer treatment is the late diagnosis of cancer and multidrug resistance. Colorectal cancer is the world’s third most common cancer. The desire for fast food has increased the risk of colon cancer in the modern era. Because of the various side effects of treatment methods, such as alopecia, gastrointestinal tract irritation, and the possibility of secondary cancer (leukemia), a novel approach to reducing potential side effects became critical. The combination of flavonoids and chemotherapeutic agents offers a safe and effective therapeutic criterion that can address the issues associated with therapy failure while also producing a synergistic effect. 
  • 834
  • 07 Jun 2022
Topic Review
Antitumor Drugs and Their Targets
Through novel methodologies, including both basic and clinical research, progress has been made in the therapy of solid cancer. Recent innovations in anticancer therapies, including immune checkpoint inhibitor biologics, therapeutic vaccines, small drugs, and CAR-T cell injections, mark a new epoch in cancer research, already known for faster (epi-)genomics, transcriptomics, and proteomics. As the long-sought after personalization of cancer therapies comes to fruition, the need to evaluate all current therapeutic possibilities and select the best for each patient is of paramount importance. This is a novel task for medical care that deserves prominence in therapeutic considerations in the future. This is because cancer is a complex genetic disease. In its deadly form, metastatic cancer, it includes altered genes (and their regulators) that encode ten hallmarks of cancer-independent growth, dodging apoptosis, immortalization, multidrug resistance, neovascularization, invasiveness, genome instability, inflammation, deregulation of metabolism, and avoidance of destruction by the immune system. These factors have been known targets for many anticancer drugs and treatments, and their modulation is a therapeutic goal, with the hope of rendering solid cancer a chronic rather than deadly disease. In this article, the current therapeutic arsenal against cancers is reviewed with a focus on immunotherapies.
  • 833
  • 19 Aug 2021
Topic Review
Disease Models in Rats
Rats (Rattus norvegicus) and mice (Mus musculus) belong to the same rodent family and have been the most widely used models in biomedical research for many years. However, there are several differences between these two animals. For example, the rat is larger (roughly about eight- to ten-fold) in size than the mouse, which provides a number of practical advantages, as exemplified by easier and more rapid microsurgery, multiple sampling of larger blood and tissue volumes, and precise injection of substances into blood vessels or the brain (reviewed by Kjell and Olson). Additionally, mice and rats differ in their physiology, behavior, and neurology. 
  • 833
  • 07 Mar 2022
Topic Review
Circadian Oscillations in Skin
The term circadian rhythm, defined by Franz Halberg, a pioneer of chronobiology, in 1959, was originally adapted from Greek. It is a hybrid of the words “circa” and “day”, meaning approximately 24 h or a day. In his later work, Halberg described biological cycles, which are an overlay of oscillations that occur in mammals. Circadian rhythm is closely linked to immunological processes and skin homeostasis, and its desynchrony can be linked to the perturbation of the skin. The interplay between circadian rhythm and annual, seasonal oscillations, as well as the impact of these periodic events on the skin, is described.
  • 833
  • 31 Mar 2023
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