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Topic Review
Conditions Determining Male Infertility
The lack of knowledge of the causes of impaired reproductive potential results in an inability to implement specific treatment, which is associated with the lack of positive outcomes (pregnancy). This review will make relevant environmental comparisons. It will allow an understanding of the importance of environmental factors in shaping the body's defense and capabilities in the field of reproductive condition. The results can be used in enhancing diagnosis and deciding on appropriate infertility treatment.
  • 1.2K
  • 23 Mar 2021
Topic Review
Antibody-Drug Conjugate Targeting c-Kit
Lung cancer is the leading cause of cancer-related deaths. Small cell lung cancer (SCLC) accounts for 15–25% of all lung cancers. It exhibits a rapid doubling time and a high degree of invasiveness. Additionally, overexpression of c-Kit occurs in 70% of SCLC patients.
  • 1.2K
  • 29 Mar 2022
Topic Review
Extracellular vesicles in embryo–maternal communication
The establishment of proper conceptus–endometrial communication is essential for conceptus implantation and subsequent successful placentation in mammals including ruminants. Extracellular vesicles (EVs) present in uterine lumen are now considered to play a role in conceptus–endometrial interactions during the preimplantation period. In fact, EV transport a variety of bioactive molecules, including soluble and membrane-bound proteins, lipids, DNA, and RNAs, into target cells. EVs thus regulate gene expression and elicit biological effects including increased cell proliferation, migration, and adhesion in recipient cells. EVs of conceptus as well as endometrial origins are interactive in the uterine microenvironment for improved pregnancy success.
  • 1.2K
  • 06 Aug 2020
Topic Review
Advanced Microsamples
Although the application of microsamples in metabolic phenotyping exists, it is still in its infancy, with whole blood being overwhelmingly the primary biofluid collected through the collection method of dried blood spots. Research into the metabolic phenotyping of microsamples is limited; however, with advances in commercially available microsampling devices, common barriers such as volumetric inaccuracies and the ‘haematocrit effect’ in dried blood spot microsampling can be overcome.
  • 1.2K
  • 02 Aug 2022
Topic Review
Rab Proteins in Mitophagy
Mitochondrial dysfunction and vesicular trafficking alterations have been implicated in the pathogenesis of several neurodegenerative diseases. It has become clear that pathogenetic pathways leading to neurodegeneration are often interconnected. Indeed, growing evidence suggests a concerted contribution of impaired mitophagy and vesicles formation in the dysregulation of neuronal homeostasis, contributing to neuronal cell death. Among the molecular factors involved in the trafficking of vesicles, Ras analog in brain (Rab) proteins seem to play a central role in mitochondrial quality checking and disposal through both canonical PINK1/Parkin-mediated mitophagy and novel alternative pathways. In turn, the lack of proper elimination of dysfunctional mitochondria has emerged as a possible causative/early event in some neurodegenerative diseases.
  • 1.2K
  • 14 Apr 2023
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
Retroviral Genome Packaging
Retroviruses selectively package two copies of their RNA genomes from a cellular milieu that includes a substantial excess of host and non-genomic viral RNAs. Present understanding of the structural determinants and mechanism of retroviral genome packaging has been derived from combinations of genetic experiments, phylogenetic analyses, nucleotide accessibility mapping, in silico RNA structure predictions, and biophysical studies. Genetic experiments provided early clues regarding the protein and RNA elements required for packaging, and nucleotide accessibility mapping experiments provided insights into the secondary structures of functionally important elements in the genome. Three-dimensional structural determinants of packaging were primarily derived by nuclear magnetic resonance (NMR) spectroscopy. A key advantage of NMR, relative to other methods for determining biomolecular structure (such as X-ray crystallography), is that it is well suited for studies of conformationally dynamic and heterogeneous systems—a hallmark of the retrovirus packaging machinery.
  • 1.2K
  • 06 Nov 2020
Topic Review
Cetuximab
Cetuximab is a human/mouse chimeric monoclonal antibody targeting epidermal growth factor receptor (EGFR), first approved in the world.
  • 1.2K
  • 12 Jan 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
Protein-based Subunit Nanovaccine
Protein-based subunit nanovaccines are typically composed of native or altered protein antigens that can self-assemble into nanoparticles, or antigens associated with nanoparticles through covalent or noncovalent interactions. Characteristically, nanovaccines are 1 to 1000 nm in size which generally facilitates the induction of stronger immune responses.
  • 1.2K
  • 18 Oct 2021
Topic Review
Effect of G-Quadruplexes on DNA Mismatch Repair Pathway
DNA G-quadruplexes (G4s) are known to be an integral part of the complex regulatory systems in both normal and pathological cells. Here we studied the effect of G4s on the DNA mismatch repair pathway. To assess the role of the distance between G4 and DNA mismatch on the functioning of the key mismatch repair protein, MutS, from E. coli on G4-containing substrates, a set of DNA duplexes with an embedded intramolecular parallel G4 structure and a monomethylated recognition site for the MutH endonuclease was prepared; the distance between the mismatched G/T pair and the G4 structure varied from 18 to 3 bp. It has been shown that this non-B form structure is not perceived by the E. coli system as damage that needs to be repaired; at the same time, it does not prevent activation of DNA mismatch repair, even when the G4 structure and G/T pair are at the distance of 3 bp. Thus, the preferential binding of MutS to G4 does not correlate with DNA mismatch repair activity, suggesting an unexpected role of these DNA-protein interactions in genome maintenance.
  • 1.2K
  • 09 Oct 2021
Topic Review
Enhancer Regulation of WNT3A
Upon traumatic brain injury, epigenome reprograms allowing gene expressions for injury response and regeneration. Using chromatin immunoprecipitation-sequencing of histone marks, we identify a novel enhancer region for induced WNT3A transcription during regeneration of injured cortical neurons. An increased mono-methylation of histone H3 at lysine 4 (H3K4me1) modification and a topological transformation of this enhancer and with promoter of WNT3A gene orchestrate the transcription of WNT3A gene during neuronal regeneration.
  • 1.2K
  • 02 Nov 2020
Topic Review
Biosynthetic Strategies for Macrocyclic Peptides
Macrocyclic peptides are predominantly peptide structures bearing one or more rings and spanning multiple amino acid residues. Macrocyclization has become a common approach for improving the pharmacological properties and bioactivity of peptides. A variety of ribosomal-derived and non-ribosomal synthesized cyclization approaches have been established.
  • 1.2K
  • 16 Jul 2021
Topic Review
Effect of Anesthetics on Cancer Treatment
Propofol, fentanyl, rocuronium, sugammadex, and dexamethasone are commonly used to induce anesthesia and prevent pain during surgery. The mechanisms of these drugs to induce the state of anesthesia are not yet fully understood, despite their use being considered safe. An association between anesthetic agents and cancer progression has been determined; therefore, it is essential to recognize the effects of all agents during cancer treatment and to evaluate whether the treatment provided to the patients could be more precise. 
  • 1.2K
  • 11 Nov 2022
Topic Review
GSK-3
The serine/threonine kinase, GSK-3, is a promising drug discovery target for treating multiple pathological disorders. Most GSK-3 inhibitors that were developed function as ATP competitive inhibitors, with typical limitations in specificity, safety and drug-induced resistance. In contrast, substrate competitive inhibitors (SCIs), are considered highly selective, and more suitable for clinical practice. The development of SCIs has been largely neglected in the past because the ambiguous, undefined nature of the substrate-binding site makes them difficult to design. In this study, we used our previously described structural models of GSK-3 bound to SCI peptides, to design a pharmacophore model and to virtually screen the “drug-like” Zinc database (~6.3 million compounds). We identified leading hits that interact with critical binding elements in the GSK-3 substrate binding site and are chemically distinct from known GSK-3 inhibitors. Accordingly, novel GSK-3 SCI compounds were designed and synthesized with IC50 values of~1–4 μM. Biological activity of the SCI compound was confirmed in cells and in primary neurons that showed increased β-catenin levels and reduced tau phosphorylation in response to compound treatment. We have generated a new type of small molecule GSK-3 inhibitors and propose to use this strategy to further develop SCIs for other protein kinases.
  • 1.2K
  • 11 Mar 2021
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
Plant Xyloglucan:Xyloglucosyl Transferases
Plant xyloglucan:xyloglucosyl transferases, known as xyloglucan endo-transglycosylases (XETs) are the key players that underlie plant cell wall dynamics and mechanics. These fundamental roles are central for the assembly and modifications of cell walls during embryogenesis, vegetative and reproductive growth, and adaptations to living environments under biotic and abiotic (environmental) stresses. Xyloglucan:xyloglucosyl transferases or xyloglucan endo-transglycosylases (XET), classified under EC 2.4.1.207, transfer the glycosyl groups from one glycoside to another. These enzymes were discovered in 1992 independently in bean epicotyls, nasturtium seeds, and pea, tomato and other plant extracts, and since their discovery, significant knowledge has been accumulated on their mode of action.
  • 1.2K
  • 14 Feb 2022
Topic Review
Thyroid Cancer from the Tumor-Suppressor Genes Perspective
Thyroid cancer is the most frequent endocrine malignancy and accounts for approximately 1% of all diagnosed cancers. A variety of mechanisms are involved in the transformation of a normal tissue into a malignant one. Loss of tumor-suppressor gene (TSG) function is one of these mechanisms. By identifying alterations in these genes and their protein products, people can understand the thyroid cancer-related gene changes for the development of diagnostic, prognostic, and therapeutic strategies for this cancer.
  • 1.2K
  • 31 May 2022
Topic Review
Neurofibromin Functions
Neurofibromin is a large and multifunctional protein encoded by the tumor suppressor gene NF1, mutations of which cause the tumor predisposition syndrome neurofibromatosis type 1 (NF1). Neurofibromatosis type 1 is an autosomal dominant disorder caused by inherited or de novo germline mutations in the NF1 tumor suppressor gene. It is the most common tumor-predisposing disease in humans. It affects approximately one in 3000 live births and patients present widely heterogeneous clinical manifestations, even within the same family.
  • 1.2K
  • 28 Oct 2022
Topic Review
Molecular Microbial Community Analysis
The microbial diversity in anaerobic digestion (AD) is important because it affects process robustness. High-throughput sequencing offers high-resolution data regarding the microbial diversity and robustness of biological systems including AD; however, to understand the dynamics of microbial processes, knowing the microbial diversity is not adequate alone. Advanced meta-omic techniques have been established to determine the activity and interactions among organisms in biological processes like AD. Results of these methods can be used to identify biomarkers for AD states. This can aid a better understanding of system dynamics and be applied to producing comprehensive models for AD. 
  • 1.2K
  • 08 Jun 2021
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