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Topic Review
Phenothiazines Modified with Pyridine Ring
Azaphenothiazines are the largest and most perspective group of modified phenothiazines, and they exhibit variety of biological activities. The review sums up the current knowledge on the anticancer activity of isomeric pyridobenzothiazines and dipyridothiazines, which are modified azaphenothiazines with one and two pyridine rings, respectively, against 10 types of cancer cell lines. Some 10-substituted dipyridothiazines and even 10-unsubstituted parent compounds, such as 10H-1,9-diazaphenothiazine and 10H-3,6-diazaphenothiazine, exhibited very potent action with the IC50 values less than 1 µg/mL and 1 µM against selected cancer cell lines. The strength of the anticancer action depends both on the tricyclic ring scaffolds and the substituents at the thiazine nitrogen atom.
  • 1.6K
  • 18 Mar 2021
Topic Review
Exosomal-based Drug Delivery
Exosomes are membrane-bound nanovesicles that are typically 30–150 nm in size with various bioactive molecules. They are typically generated by first endocytosing various transmembrane proteins into endosomes within the cell, which are then sorted and form intraluminal vesicles. These vesicles are then released as the endosome merges with the cell membrane and releases its contents outside of the cell. Tetraspanins (CD9, CD63, CD81) are one of the most common proteins expressed on the surface of exosomes and are often used as exosome-specific markers. These proteins have been shown to interact with different proteins such as integrins and major histocompatibility complexes (MHC). Exosomes commonly act as carriers of genetic and proteomic information, and are therefore vital in intercellular communication. In its role as a cellular messenger, exosomes have been implicated in promoting cancer; because of this, they are also being investigated as potential therapeutic targets and delivery vehicles. 
  • 1.6K
  • 06 Jun 2021
Topic Review
Biological Drug Approvals by the FDA in 2015–2021
Despite belonging to a relatively new class of pharmaceuticals, biological drugs have been used since the 1980s, when they brought about a breakthrough in the treatment of chronic diseases, especially cancer. They conquered a large space in the pipeline of the pharmaceutical industry and boosted the innovation portfolio and arsenal of therapeutic compounds available. From 2015 to 2021, the number of drugs included in this class grew over this period, totaling 90 approvals, with an average of 13 authorizations per year.
  • 1.6K
  • 30 Sep 2022
Topic Review
Micro- and Nanosized Carriers for Nose-to-Brain Drug Delivery
The intranasal route of drug administration offers numerous advantages, such as bypassing the intestine, avoiding first-pass metabolism, and reducing systemic side effects. Moreover, it circumvents the BBB, providing direct entrance to the brain through the olfactory and trigeminal nerve pathways.  Micro- and nanotechnological approaches were widely used to overcome these limitations and enhance the availability of drugs in the brain tissue. Micro- and nanoparticulate carriers are composed of natural or synthetic materials that interact with biological structures at the molecular level and lead the treatment of NDs into a new direction. They may induce interaction between target sites, thus minimizing the side effects.
  • 1.6K
  • 22 Aug 2022
Topic Review
HIV-1
The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small molecule inhibitors that now form key components of antiretroviral therapy regimens. Recent discoveries unveiled that IN has an under-studied yet equally vital second function in HIV-1 replication. This involves IN binding to the viral RNA genome in virions, which is necessary for proper virion maturation and morphogenesis. Herein we describe these two functions of IN within the context of the HIV-1 life cycle, how IN binding to the viral genome is coordinated by the major structural protein, Gag, and discuss the value of targeting the second role of IN in virion morphogenesis.
  • 1.6K
  • 17 Sep 2020
Topic Review
AhR, inflammation and breast cancer
AhR, an environmentally sensitive transcription factor, is one of the more evolutionary conserved molecules in living cells.
  • 1.6K
  • 21 Feb 2022
Topic Review
Clinical Trials of Parkinson’s Disease
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that currently has no cure, but treatments are available to improve PD symptoms and maintain quality of life.
  • 1.6K
  • 03 Aug 2021
Topic Review
Lipid-Based Nanocarriers
Nanoparticle-based drug delivery has demonstrated promising results for topical ophthalmic nanotherapies in the treatment of intraocular diseases. Studies have revealed that nanocarriers enhance the intraocular half-life and bioavailability of several therapies including proteins, peptides and genetic material. Amongst the array of nanoparticles available nowadays, lipid-based nanosystems have shown an increased efficiency and feasibility in topical formulations, making them an important target for constant and thorough research in both preclinical and clinical practice.
  • 1.6K
  • 19 Jun 2021
Topic Review
Lipid-Based Nanoparticles as a Versatile Drug Delivery System
Liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid nanocarriers, and lipid–polymer hybrid nanoparticles are developed for cancer treatment which is well confirmed and documented. cancer nanotechnology that overcomes the drawbacks of conventional drug delivery systems starting from small-scale barricades such as intracellular trafficking and site-specific targeting to large-scale barriers such as biodistribution.
  • 1.6K
  • 27 Sep 2022
Topic Review
Paracetamol
Paracetamol (acetaminophen) is one of the most commonly prescribed drugs worldwide. Synthetized over 150 years ago, paracetamol is highly efficient as analgesic and antipyretic and is on the list of the World Health Organization’s essential medicines. Paracetamol is also a hypothermic agent.
  • 1.6K
  • 28 Apr 2022
Topic Review
Exosomes for Drug Delivery
Particular interest among the scientific community is focused on exploring the use of exosomes for several pharmaceutical and biomedical applications. This is due to the identification of the role of exosomes as an excellent intercellular communicator by delivering the requisite cargo comprising of functional proteins, metabolites and nucleic acids. Exosomes are the smallest extracellular vesicles (EV) with sizes ranging from 30–100 nm and are derived from endosomes. Exosomes have similar surface morphology to cells and act as a signal transduction channel between cells. They encompass different biomolecules, such as proteins, nucleic acids and lipids, thus rendering them naturally as an attractive drug delivery vehicle. Like the other advanced drug delivery systems, such as polymeric nanoparticles and liposomes to encapsulate drug substances, exosomes also gained much attention in enhancing therapeutic activity. Exosomes present many advantages, such as compatibility with living tissues, low toxicity, extended blood circulation, capability to pass contents from one cell to another, non-immunogenic and special targeting of various cells, making them an excellent therapeutic carrier. Exosome-based molecules for drug delivery are still in the early stages of research and clinical trials. The problems and clinical transition issues related to exosome-based drugs need to be overcome using advanced tools for better understanding and systemic evaluation of exosomes.
  • 1.6K
  • 21 Nov 2022
Topic Review
Thymoquinone
Thymoquinone (TQ), the chief active constituent of Nigella sativa (NS), shows very valuable biomedical properties such as antioxidant, antimicrobial, anticancer, anti-inflammatory, antihypertensive, hypoglycemic, antiparasitic and anti-asthmatic effects. Several studies have examined the pharmacological actions of TQ in the treatment of oral diseases but its potential role in periodontal therapy and regeneration is not yet fully defined.
  • 1.6K
  • 17 Dec 2020
Topic Review
Protamine-Based Strategies for RNA Transfection
Protamine is a natural cationic peptide mixture mostly known as a drug for the neutralization of heparin and as a compound in formulations of slow-release insulin. Protamine is also used for cellular delivery of nucleic acids due to opposite charge-driven coupling. This year marks 60 years since the first use of Protamine as a transfection enhancement agent. Since then, Protamine has been broadly used as a stabilization agent for RNA delivery. It has also been involved in several compositions for RNA-based vaccinations in clinical development. Protamine stabilization of RNA shows double functionality: it not only protects RNA from degradation within biological systems, but also enhances penetration into cells. A Protamine-based RNA delivery system is a flexible and versatile platform that can be adjusted according to therapeutic goals: fused with targeting antibodies for precise delivery, digested into a cell penetrating peptide for better transfection efficiency or not-covalently mixed with functional polymers.
  • 1.6K
  • 07 Jul 2021
Topic Review
Bacterial Efflux Pump Inhibitors Reduce Antibiotic Resistance
Efflux pump inhibitors, small molecules capable of restoring the effectiveness of existing antibiotics, are considered potential solutions to antibiotic resistance and have been an active area of research in recent years. Efflux pump inhibitors block efflux pumps through one or more processes, which can inactivate drug transport. 
  • 1.6K
  • 05 Feb 2024
Topic Review
Overcoming Multidrug Resistance of Antibiotics via Nanodelivery Systems
Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to overcome such complications, novel drug delivery systems have gained pharmaceutical scientists’ interest. Significant findings have validated the effectiveness of novel drug delivery systems such as polymeric nanoparticles, liposomes, metallic nanoparticles, dendrimers, and lipid-based nanoparticles against severe microbial infections and combating antimicrobial resistance. 
  • 1.6K
  • 18 Mar 2022
Topic Review
Composition of Lipid–Polymer Hybrid Nanoparticles
Lipid nanoparticles (LNPs) are spherical vesicles composed of ionizable lipids that are neutral at physiological pH. Despite their benefits, unmodified LNP drug delivery systems have substantial drawbacks, including a lack of targeted selectivity, a short blood circulation period, and in vivo instability. lipid–polymer hybrid nanoparticles (LPHNPs) are the next generation of nanoparticles, having the combined benefits of polymeric nanoparticles and liposomes. LPHNPs are being prepared from both natural and synthetic polymers with various techniques, including one- or two-step methods, emulsification solvent evaporation (ESE) method, and the nanoprecipitation method. Varieties of LPHNPs, including monolithic hybrid nanoparticles, core–shell nanoparticles, hollow core–shell nanoparticles, biomimetic lipid–polymer hybrid nanoparticles, and polymer-caged liposomes, have been investigated for various drug delivery applications.
  • 1.6K
  • 08 Sep 2023
Topic Review
Endocannabinoid System Present in the Glioblastoma Tumour Microenvironment
The highly aggressive and invasive glioblastoma (GBM) tumour is the most malignant lesion among adult-type diffuse gliomas, representing the most common primary brain tumour in the neuro-oncology practice of adults. With a poor overall prognosis and strong resistance to treatment, this nervous system tumour requires new, innovative treatment. GBM is a polymorphic tumour consisting of an array of stromal cells and various malignant cells contributing to tumour initiation, progression, and treatment response. Cannabinoids possess anti-cancer potencies against glioma cell lines and in animal models. To improve existing treatment, cannabinoids as functionalised ligands on nanocarriers were investigated as potential anti-cancer agents. The GBM tumour microenvironment is a multifaceted system consisting of resident or recruited immune cells, extracellular matrix components, tissue-resident cells, and soluble factors. 
  • 1.6K
  • 31 Jan 2024
Topic Review
Bacteriophages
Bacteriophages, viruses that infect bacteria, have emerged as a legitimate alternative antibacterial agent with a wide scope of applications which continue to be discovered and refined. However, the potential of some bacteriophages to aid in the acquisition, maintenance, and dissemination of negatively associated bacterial genes, including resistance and virulence genes, through transduction is of concern and requires deeper understanding in order to be properly addressed. In particular, their ability to interact with mobile genetic elements such as plasmids, genomic islands, and integrative conjugative elements (ICEs) enables bacteriophages to contribute greatly to bacterial evolution. Nonetheless, bacteriophages have the potential to be used as therapeutic and biocontrol agents within medical, agricultural, and food processing settings, against bacteria in both planktonic and biofilm environments. Additionally, bacteriophages have been deployed in developing rapid, sensitive, and specific biosensors for various bacterial targets. Intriguingly, their bioengineering capabilities show great promise in improving their adaptability and effectiveness as biocontrol and detection tools.
  • 1.6K
  • 30 Mar 2021
Topic Review
CO2 Pneumoperitoneum
Laparoscopy (LS) has been shown to decrease the inflammatory sequelae of endotoxemia. β-arrestin 2 plays an important function in signal transduction pathway of TLR4. High mobility group box-1 (HMGB-1) is involved in the delayed systemic inflammatory response. We investigated the effects of CO2 insufflation on liver, lung, and kidney expression of both β-arrestin 2 and HMGB-1 during sepsis. Cecal ligation and puncture (CLP) was performed in male rats and 6 h later the animals were randomly assigned to receive a CO2 pneumoperitoneum or laparotomy. Animals were euthanized; liver, lung, and kidney were removed for the evaluation of β-arrestin 2 and HMGB-1 expression. Immunohistochemical detection of myeloperoxidase (MPO) was investigated in lung and liver and bacterial load was determined in the peritoneal fluid. CO2 pneumoperitoneum reduced peritoneal bacterial load, increased the expression of β-arrestin 2, and blunted the expression of the potent proinflammatory HMGB-1 in liver, lung, and kidney compared with laparotomy. Liver and lung MPO was markedly reduced in rats subjected to LS compared with laparotomy. We believe that CO2 exerts an early protective effect by reducing bacterial load and likely toll-like receptor activation which in turn leads to a preserved β-arrestin 2 expression and a reduced HMGB-1 expression.
  • 1.6K
  • 02 Nov 2020
Topic Review
De Novo Synthesized Estradiol
The estrogen estradiol is a potent neuroactive steroid that may regulate brain structure and function. Although the eff ects of estradiol have been historically associated with gonadal secretion, the discovery that this steroid may be synthesized within the brain has expanded this traditional concept. Indeed, it is accepted that de novo synthesized estradiol in the nervous system (nE2) may modulate several aspects of neuronal physiology, including synaptic transmission and plasticity, thereby influencing a variety of behaviors. These modulations may be on a time scale of minutes via non-classical and often membrane-initiated mechanisms or hours and days by classical actions on gene transcription. Besides the high level, recent investigations in the cerebellum indicate that even a low aromatase expression can be related to the fast nE2 eff ect on brain functioning. These pieces of evidence point to the importance of an on-demand and localized nE2 synthesis to rapidly contribute to regulating synaptic transmission. This review is geared at exploring a new scenario for the impact of estradiol on brain processes as it emerges from the nE2 action on cerebellar neurotransmission and cerebellum-dependent learning.
  • 1.6K
  • 30 Oct 2020
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