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Topic Review
Cannabis and Male Reproductive Health
Cannabis sativa is a cheap hallucinating agent used in different parts of the world from time unknown as a part of various religious as well as social practices. Cannabis which is a special type of Marijuana can provide temporary relief from analgesia, body pain and in some other clinical conditions. But, impacts of Cannabis on reproductive health of males and females are multi-faceted and differentially fatal. In males, Cannabis can cause changes in testicular morphology, sperm parameters (in terms of semen quality, sperm morphology, sperm mortality and sperm motility), male reproductive hormones and finally causing reduced libido. In females, Cannabis can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles.  Current research suggest that cannabis may negatively impact on male and female fertility conditions. However, male sterility considering the Cannabis impact is totally lacking in human as well as in sub-human primates. However, very limited studies are available on Cannabis effect on primate female reproduction considering Rhesus monkeys. Hence, further studies are needed to validate that robust findings in animal models will carry over into human experience.
  • 2.4K
  • 18 Sep 2021
Topic Review
Polyphenols as Antioxidant/Pro-Oxidant Compounds and Donors
Polyphenolic compounds are characterized by having at least one benzene ring with two or more hydroxyl (OH) groups. There are more than 8000 polyphenolic compounds in nature, classified into flavonoids, phenolic acids, lignans, and stilbenes.
  • 2.4K
  • 19 Sep 2023
Topic Review
Bile Acids
Bile acids (BAs) are facial amphiphiles synthesized in the body of all vertebrates.
  • 2.4K
  • 18 Mar 2021
Topic Review
BCR-ABL1 Tyrosine Kinase Complex Signaling Transduction
The constitutively active BCR-ABL1 tyrosine kinase, found in t(9;22)(q34;q11) chromosomal translocation-derived leukemia, initiates an extremely complex signaling transduction cascade that induces a strong state of resistance to chemotherapy. Targeted therapies based on tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib, have revolutionized the treatment of BCR-ABL1-driven leukemia, particularly chronic myeloid leukemia (CML). However, TKIs do not cure CML patients, as some develop TKI resistance and the majority relapse upon withdrawal from treatment. Importantly, although BCR-ABL1 tyrosine kinase is necessary to initiate and establish the malignant phenotype of Ph-related leukemia, in the later advanced phase of the disease, BCR-ABL1-independent mechanisms are also in place. 
  • 2.4K
  • 09 Feb 2022
Topic Review
Bone Morphogenetic Protein-2
Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the Transforming Growth Factor-Beta (TGF-β) superfamily. These proteins are essential to many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Specifically, within the BMP family, Bone Morphogenetic Protein-2 (BMP-2) was the first BMP to be characterized and has been well-studied. BMP-2 has important roles during embryonic development, as well as bone remodeling and homeostasis in adulthood. Some of its specific functions include digit formation and activating osteogenic genes, such as Runt-Related Transcription Factor 2 (RUNX2). Because of its diverse functions and osteogenic potential, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery, tibial shaft repair, and maxillary sinus reconstructive surgery. However, shortly after initial injections of rhBMP-2, several adverse complications were reported, and alternative therapeutics have been developed to limit these side-effects.
  • 2.4K
  • 26 Oct 2020
Topic Review
PDE4 as Therapeutic Targets in Different Diseases
Cyclic nucleotides (cAMP, cGMP) play a major role in normal and pathologic signaling. Beyond receptors, cyclic nucleotide phosphodiesterases; (PDEs) rapidly convert the cyclic nucleotide in its respective 5′-nucleotide to control intracellular cAMP and/or cGMP levels to maintain a normal physiological state. However, in many pathologies, dysregulations of various PDEs (PDE1-PDE11) contribute mainly to organs and tissue failures related to uncontrolled phosphorylation cascade. Among these, PDE4 represents the greatest family, since it is constituted by 4 genes with multiple variants differently distributed at tissue, cellular and subcellular levels, allowing different fine-tuned regulations.
  • 2.4K
  • 11 Oct 2022
Topic Review
Ras-Associated Protein 1 in Cancer
Metastasis is known as the most life-threatening event in cancer patients. In principle, the immune system can prevent tumor development. However, dysfunctional T cells may fail to eliminate the tumor cells effectively and provide additional survival advantages for tumor proliferation and metastasis. Constitutive activation of Ras-associated protein1 (Rap1) has not only led to T cell anergy, but also inhibited autophagy and supported cancer progression through various oncogenic events. Inhibition of Rap1 activity with its negative regulator, Rap1GAP, impairs tumor progression. However, active Rap1 reduces tumor invasion in some cancers, indicating that the pleiotropic effects of Rap1 signaling in cancers could be cancer-specific. All in all, targeting Rap1 signaling and its regulators could potentially control carcinogenesis, metastasis, chemoresistance and immune evasion. Rap1GAP could be a promising therapeutic target in combating cancer. 
  • 2.4K
  • 23 Sep 2020
Topic Review
RNA-Targeting CRISPR–Cas Systems
Many CRISPR–Cas systems have been used as a backbone for the development of potent research tools, with Cas9 being the most widespread. While most of the utilized systems are DNA-targeting, recently more and more attention is being gained by those that target RNA. Their ability to specifically recognize a given RNA sequence in an easily programmable way makes them ideal candidates for developing new research tools. 
  • 2.4K
  • 23 Dec 2020
Topic Review
Sirtuins
The sirtuin system consists of seven highly conserved regulatory enzymes responsible for metabolism, antioxidant protection, and cell cycle regulation. The great interest in sirtuins is associated with the potential impact on life extension. 
  • 2.4K
  • 05 Jan 2023
Topic Review
Clavulanic Acid
Clavulanic acid is an irreversible β-lactamase enzyme inhibitor with a weak antibacterial activity produced by the filamentous actinomycete Streptomyces clavuligerus (S. clavuligerus) and, in a lesser extent, by other streptomyces species. Clavulanic acid is typically co-formulated with broad-spectrum β‑lactam antibiotics such as amoxicillin and ticarcillin, conferring them high potential to treat infectious diseases caused by β‑lactam-resistant bacteria like Escherichia coli, Staphylococcus aureus, Neisseria gonorrhoeae and Streptococcus pneumonia.
  • 2.4K
  • 22 Sep 2021
Topic Review
1,3,4-Oxadiazole
Compounds containing 1,3,4-oxadiazole ring in their structure are characterised by multidirectional biological activity.
  • 2.3K
  • 13 Sep 2021
Topic Review
Nanopore Sequencing
Nanopore sequencing is a third generation approach used in the sequencing of biopolymers — specifically, polynucleotides in the form of DNA or RNA. Using nanopore sequencing, a single molecule of DNA or RNA can be sequenced without the need for PCR amplification or chemical labeling of the sample. Nanopore sequencing has the potential to offer relatively low-cost genotyping, high mobility for testing, and rapid processing of samples with the ability to display results in real-time. Publications on the method outline its use in rapid identification of viral pathogens, monitoring ebola, environmental monitoring, food safety monitoring, human genome sequencing, plant genome sequencing, monitoring of antibiotic resistance, haplotyping and other applications.
  • 2.3K
  • 16 Nov 2022
Topic Review
Chemical Enzymology of Monoamine Oxidase
Monoamine oxidase (E.C. 1.4.3.4) enzymes MAO A and MAO B are FAD-containing proteins located on the outer face of the mitochondrial inner membrane, retained there by hydrophobic interactions and a transmembrane helix. The redox co-factor (FAD) is covalently attached to a cysteine and buried deep inside the protein behind an aromatic cage that aligns substrates towards the flavin. MAO metabolizes neurotransmitters such as dopamine and serotonin in the nervous system so is a target for drugs to modify amine levels. MAO also metabolizes a wide range of biogenic amines in all tissues. Current accumulated evidence, particularly from theoretical modelling, supports hydride transfer as the chemical mechanism. The long active site cavity accommodates a wide chemical variety of small molecules designed as inhibitors, including coumarins, chromones, triazoles, and more. Inactivators that bind covalently to MAO include hydrazines, cyclopropylamines and propargylamines. This entry is an extract adapted from a review outlining the remaining uncertainties in the understanding of this key drug target.
  • 2.3K
  • 19 Oct 2021
Topic Review
Blood-Brain Barrier: Functionalised Chitosan
The major impediment to the delivery of therapeutics to the brain is the presence of the blood-brain barrier (BBB). The BBB allows for the entrance of essential nutrients while excluding harmful substances, including most therapeutic agents; hence, brain disorders, especially tumors, are very difficult to treat. Chitosan is a well-researched polymer that offers advantageous biological and chemical properties, such as mucoadhesion and ease of functionalization. Chitosan-based nanocarriers (CsNCs) establish ionic interactions with the endothelial cells, facilitating the crossing of drugs through the BBB by adsorptive mediated transcytosis. This process is further enhanced by modifications of the structure of chitosan, owing to the presence of reactive amino and hydroxyl groups. Finally, by permanently binding ligands or molecules, such as antibodies or lipids, CsNCs have shown a boosted passage through the BBB, in both in vivo and in vitro studies which will be discussed in this review.
  • 2.3K
  • 21 Nov 2020
Topic Review
Sigma-2 Receptor
Sigma-1 and sigma-2 receptor have different pharmacological profiles. In the past two decades,  the biological and pharmacological properties of the sigma-1 receptor has been well studied, however, little is known about the sigma-2 receptor. The molecular identity of Sigma-2 receptor has been proposed as TMEM97, but more work has to been done to address questions regarding our current knowledge of Sigma-2 pharmacology. Recently, the sigma-2 receptor is recognized as a novel regulator influencing cellular cholesterol homeostasis. Additionally, cholesterol homeostasis was disrupted in tumors and Alzheimer’s disease, and the sigma-2 receptor ligands have showed promise to treat tumors and AD. 
  • 2.3K
  • 08 Dec 2020
Topic Review
Kinesin-1
The most of the transportations in cells are realized through a kind of proteins, the molecular motor. Molecular motor can be classed into three families, myosin, kinesin and dynein. Kinesin-1 (also called conventional kinesin) is the founding member of the kinesin family and mainly exists in the nerve axons to transport membranous organelles along the microtubule lattice. By using the energy stored in the ATP molecule, kinesin-1 can “walk” along the microtubule lattice in a hand-over-hand manner. In the walking process of the kinesin-1, the conformational changes of the compact motor domain transmit and amplify the small changes of the nucleotide-binding site to the force-generation element to produce the processive movement. The chemical cycle and mechanical cycle of kinesin-1 are highly coupled to ensure the processivity of the kinesin-1 and to avoid the futile ATP hydrolysis.
  • 2.3K
  • 27 Oct 2020
Topic Review
Cannabis Sativa Revisited
Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis. One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been noticed. One of the most important is their ability to reduce the biosynthesis of pro-inflammatory mediators and the modulation of immune mechanisms. Different studies have reported that cannabinoids can reduce oxidative stress at mitochondrial and cellular levels. In detail, the entry shows the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression will be presented.
  • 2.3K
  • 04 Jul 2022
Topic Review
The Role of Cytochromes P450 in Plants
Cytochromes P450 are ancient enzymes diffused in organisms belonging to all kingdoms of life, including viruses, with the largest number of P450 genes found in plants. The functional characterization of cytochromes P450 has been extensively investigated in mammals, where these enzymes are involved in the metabolism of drugs and in the detoxification of pollutants and toxic chemicals.
  • 2.3K
  • 29 Mar 2023
Topic Review
Galectin-3 in Cardiovascular Diseases
Galectin-3 (Gal-3) belongs to a lectin family, acting as a galactoside-binding protein involved in many biological processes, such as controlling cell–cell and cell–matrix interactions, adhesion, proliferation, apoptosis, pre-mRNA splicing, immunity and inflammation.
  • 2.3K
  • 22 Dec 2020
Topic Review
Mitochondrial Heteroplasmy and Disease
Given the relevance of mitochondria in numerous physiological and pathological mechanisms, such as adenosine triphosphate (ATP) synthesis, apoptosis, metabolism, cancer progression, and drug resistance, mitochondrial genome (mtDNA) analysis has become of great interest in the study of human diseases, including cancer. A high number of variants and mutations have been identified in different types of tumors, which coexist with normal alleles, a phenomenon named heteroplasmy. This mechanism is considered an intermediate state between the fixation or elimination of the acquired mutations. It is suggested that mutations, which confer adaptive advantages to tumor growth and invasion, are enriched in malignant cells.
  • 2.3K
  • 09 Sep 2022
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