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Topic Review
Tumor-Associated Macrophages (TAMs)
Tumor-associated macrophages (TAMs) are a major component of the immune cells of the TME. They play a prominent role by secreting cytokines and chemokines and coordinating with inflammatory mechanisms to promote tumor development, invasion, metastasis, immunosuppression, angiogenesis, and drug tolerance. Different subtypes of TAMs have different functions, which can be dynamically changed in response to various signals from cancer cells or the TME.
  • 1.2K
  • 18 Aug 2021
Topic Review
E3s That Target Wild-Type p53
p53 plays a role in different biological processes such as proliferation, invasion, pluripotency, metabolism, cell cycle control, ROS (reactive oxygen species) production, apoptosis, inflammation and autophagy. In the nucleus, p53 functions as a bona-fide transcription factor which activates and represses transcription of a number of target genes. In the cytoplasm, p53 can interact with proteins of the apoptotic machinery and by this also induces cell death. Despite being so important for the fate of the cell, expression levels of p53 are kept low in unstressed cells and the protein is largely inactive. 
  • 1.2K
  • 27 Feb 2023
Topic Review
Dystroglycanopathy
Dystroglycanopathy is a collective term referring to muscular dystrophies with abnormal glycosylation of dystroglycan. At least 18 causative genes of dystroglycanopathy have been identified, and its clinical symptoms are diverse, ranging from severe congenital to adult-onset limb-girdle types. 
  • 1.2K
  • 12 Jan 2022
Topic Review
Mechanisms of Antibody Uptake into Central Nervous System
Antibodies (mAbs) are attractive molecules for their application as a diagnostic and therapeutic agent for diseases of the central nervous system (CNS). mAbs can be generated to have high affinity and specificity to target molecules in the CNS. Unfortunately, only a very small number of mAbs have been specifically developed and approved for neurological indications. This is primarily attributed to their low exposure within the CNS, hindering their ability to reach and effectively engage their potential targets in the brain.
  • 1.2K
  • 18 Oct 2023
Topic Review
Role of PARP in TNBC
Triple-negative breast cancer is a combative cancer type with a highly inflated histological grade that leads to poor theragnostic value. Gene, protein, and receptor-specific targets have shown effective clinical outcomes in patients with TNBC. Cells are frequently exposed to DNA-damaging agents. DNA damage is repaired by multiple pathways; accumulations of mutations occur due to damage to one or more pathways and lead to alterations in normal cellular mechanisms, which lead to development of tumors. Advances in target-specific cancer therapies have shown significant momentum; most treatment options cause off-target toxicity and side effects on healthy tissues. PARP (poly(ADP-ribose) polymerase) is a major protein and is involved in DNA repair pathways, base excision repair (BER) mechanisms, homologous recombination (HR), and nonhomologous end-joining (NEJ) deficiency-based repair mechanisms. DNA damage repair deficits cause an increased risk of tumor formation. Inhibitors of PARP favorably kill cancer cells in BRCA-mutations. For a few years, PARPi has shown promising activity as a chemotherapeutic agent in BRCA1- or BRCA2-associated breast cancers, and in combination with chemotherapy in triple-negative breast cancer.
  • 1.2K
  • 29 Oct 2021
Topic Review
TRPC, TRPV and Vascular Disease
Ion channels play an important role in vascular function and pathology. In this review we gave an overview of recent findings and discussed the role of TRPC and TRPV channels as major regulators of cellular remodeling and consequent vascular disorders. Here, we focused on their implication in 4 relevant vascular diseases: systemic and pulmonary artery hypertension, atherosclerosis and restenosis.  
  • 1.2K
  • 22 Apr 2021
Topic Review
DNA Damage Response (DDR)
DNA damage could occur in cells either endogenously, through normal cellular replication and metabolism, or exogenously through ultraviolet (UV), ionizing radiation (IR) or various genotoxic compounds] that could induce DNA damage. Different stressors will cause different types of DNA damage. Normal DNA replication could induce mismatch of the nucleotide and cause mutations. Stressors such as oxidative stress will produce reactive oxygen species (ROS) from normal cellular metabolism or from external genotoxic compound, which will cause DNA breaks, either single-stranded or double-stranded. Unrepaired DNA damage could cause severe mutations and chromosomal instability, which would have detrimental effects on the cells and lead to cell death, while DNA breaks that are repaired through non-homologous end joining (NHEJ) might cause mutations during the process.The DDR is the response mechanism which will detect any DNA damage that occurs throughout the chromosome and will activate a repair cascade to the damage site. This will help the cells either to proliferate normally if the repair was successful or to activate the cellular programmed cell death if the damage was too extensive and was unable to be repaired. The known DNA damage repair mechanisms include mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR) and non-homologous end joining (NHEJ). Specific types of DNA damage could be fixed by a specific repair factor, such as the ATM kinase, which is the main factor in double-strand break repair through NHEJ. Figure 1 shows the causes and types of DNA damage as well as the response cascade involved in repairing the damages.
  • 1.2K
  • 08 Oct 2021
Topic Review
CYP21A2 Deficiency
Deficiency of 21-hydroxylase enzyme (CYP21A2) represents 90% of cases in congenital adrenal hyperplasia (CAH), an autosomal recessive disease caused by defects in cortisol biosynthesis. Computational prediction and functional studies are often the only way to classify variants to understand the links to disease-causing effects.
  • 1.2K
  • 29 Mar 2022
Topic Review
Cancer Chemoprevention
Carcinogenesis is a multistep process characterized by a progression of molecular changes that ultimately transform a cell to undergo uncontrolled proliferation.
  • 1.2K
  • 02 Apr 2021
Topic Review
Gene annotation for 'Flaviviridae' genomes
Responding to the ongoing and severe public health threat of viruses of the family Flaviviridae, including dengue, hepatitis C, West Nile, yellow fever, and Zika, demands a greater understanding of how these viruses emerge and spread. Updated phylogenies are central to this understanding. Most cladograms of Flaviviridae focus on specific lineages and ignore outgroups, thus hampering the efficacy of the analysis to test ingroup monophyly and relationships. This is due to the lack of annotated Flaviviridae genomes, which has gene content variation among genera. This variation makes analysis without partitioning difficult. Therefore, we developed an annotation pipeline for the genera of Flaviviridae (Flavirirus, Hepacivirus, Pegivirus, and Pestivirus), named “Fast Loci Annotation of Viruses” (FLAVi: flavi-web.com), that combines ab initio and homology-based strategies. FLAVi recovered 100% of the genes in Flavivirus and Hepacivirus genomes. In Pegivirus and Pestivirus, annotation efficiency was 100% except for one partition each. There were no false positives. The combined phylogenetic analysis of multiple genes made possible by annotation has clear impacts over the tree topology compared to phylogenies that we inferred without outgroups or data partitioning. The final tree is largely congruent with previous hypotheses and adds evidence supporting the close phylogenetic relationship between dengue and Zika.
  • 1.2K
  • 27 Oct 2020
Topic Review
LRRK2, Rab GTPases and Parkinson’s Disease
Studies point to the involvement of endolysosomal defects in parkinson’s disease (PD). The endolysosomal system, which tightly controls a flow of endocytosed vesicles targeted either for degradation or recycling, is regulated by a number of Rab GTPases. Their associations with leucine-rich repeat kinase 2 (LRRK2), a major causative and risk protein of PD, has also been one of the hot topics in the field.
  • 1.2K
  • 19 Jan 2024
Topic Review
EVs, Substance Abuse, and HIV
While extracellular vesicles (EVs) have been shown to play a role in CNS disorders, the intersection of EVs, drug use, and HIV is of particular interest. The interactions of HIV and drugs of abuse are a growing concern given the increasing incidence of HIV transmission via shared needles in illicit drug use. As a drug commonly taken through shared needles, METH is being investigated due to its role in exacerbating HIV-mediated inflammation through both increased vesicular shedding and extracellular release. In vivo experiments have shown that cocaine-induced EV release impacts synaptic plasticity through noncoding RNA. Nicotine studies have also highlighted how the differential packaging of antioxidant enzyme cargoes into EVs affects nicotine-mediated HIV pathogenesis. Additionally, studies of both morphine and heroin have demonstrated differences in the miRNA cargoes of EVs, potentially impacting gene expression and exacerbating HIV. Studies of alcohol use in combination with HIV have shown that EV cargoes such as cytokines are affected in HIV-infected subjects who use alcohol. Investigating EV cargo alterations in all forms of substance abuse studies may allow the EV, HIV, and addiction fields to progress towards diagnosis and remedies for substance-abuse-induced toxicity in HIV patients.
  • 1.2K
  • 27 Sep 2020
Topic Review
Heat Shock Protein 90
Heat shock protein 90 (Hsp90) is a molecular chaperone that could modulate the pain signaling.
  • 1.2K
  • 08 Jan 2021
Topic Review
ADAM9 in Cancers
ADAM9 plays an important role in tumor biology. It is overexpressed in several cancer types and is correlated with tumor aggressiveness and poor prognosis. Through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies.
  • 1.2K
  • 13 Jan 2021
Topic Review
Biomarker Studies in Stress Biology
Endpoints assessed at the population or community level are most often the result of the sum of effects on individuals, arising from the effects at the cellular and molecular levels. Within this framework, these lower biological level endpoints are more responsive at an early stage of exposure, making them potential toolboxes to be used as early-warning markers to address stress. Given this, by linking responses and understanding organisms’ metabolism and physiology, the possibilities for the use of biomarkers in stress biology are vast.
  • 1.2K
  • 10 Jan 2022
Topic Review
Obesity and Lipids
Recently, lipidomics has become an important branch of medical/clinical sciences similar to proteomics and genomics. Due to the much higher lipid accumulation in obese patients and many alterations in the compositions of various groups of lipids, the methods used for sample preparations for lipidomic studies of samples from obese subjects sometimes have to be modified. Appropriate sample preparation methods allow for the identification of a wide range of analytes by advanced analytical methods, including mass spectrometry. This is especially the case in studies with obese subjects, as the amounts of some lipids are much higher, others are present in trace amounts, and obese subjects have some specific alterations of the lipid profile. 
  • 1.2K
  • 01 Dec 2020
Topic Review
Peretinoin
Peretinoin, an retinoid acid (RA), a metabolite of vitamin A and its related analogues (termed retinoids) has been suggested as a promising chemotherapeutic agent in cancer treatment. The synthetic oral retinoid peretinoin is the only agent for the secondary chemoprevention of HCC after curative therapy that is currently well applied into clinical development.
  • 1.2K
  • 12 Oct 2021
Topic Review
S-Glutathionylation and S-Nitrosylation in Mitochondria: Homeostasis and Neurodegeneration
Redox post-translational modifications are derived from fluctuations in the redox potential and modulate protein function, localization, activity and structure. Amongst the oxidative reversible modifications, the S-glutathionylation of proteins was the first to be characterized as a post-translational modification, which primarily protects proteins from irreversible oxidation. S-nitrosylation, another post-translational modification, was identified in the past, but it was re-introduced as a prototype cell-signaling mechanism, one that tightly regulates core processes within the cell’s sub-compartments, especially in mitochondria. S-glutathionylation and S-nitrosylation are modulated by fluctuations in reactive oxygen and nitrogen species and, in turn, orchestrate mitochondrial bioenergetics machinery, morphology, nutrients metabolism and apoptosis.
  • 1.2K
  • 26 Dec 2022
Topic Review
Molecular Diagnosis of COVID-19
COVID-19 is no longer a global pandemic due to development and integration of different technologies for the diagnosis and treatment of the disease, technological advancement in the field of molecular biology, electronics, computer science, artificial intelligence, Internet of Things, nanotechnology, etc. has led to the development of molecular approaches and computer aided diagnosis for the detection of COVID-19. 
  • 1.2K
  • 11 Jan 2023
Topic Review
The Main Protease of SARS-CoV-2 and its inhibitors
Mpro, also known as 3-chymotrypsin-like protease (3CLpro), is a 33.8 kDa, three-domain cysteine protease, essential for proteolytic maturation and viral replication of coronaviruses. This enzyme is an excellent target for a potential drug, as it is essential for viral replication and has no closely related homologues in humans, making its inhibitors unlikely to be toxic. 
  • 1.2K
  • 08 Aug 2022
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