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Topic Review
Primary Cilia: Sensory Hubs for Nitric Oxide Signaling
Primary cilia are sensory organelles present on the surface of most polarized cells. Primary cilia have been demonstrated to play many sensory cell roles, including mechanosensory and chemosensory cell functions. It is known that the primary cilia of vascular endothelial cells will bend in response to fluid shear stress, which leads to the biochemical production and release of nitric oxide, and this process is impaired in endothelial cells that lack primary cilia function or structure. In this entry, we will provide an overview of ciliogenesis and the differences between primary cilia and multicilia, as well as an overview of our published work on primary cilia and nitric oxide, and a brief perspective on their implications in health and disease.
  • 657
  • 04 Aug 2022
Topic Review
Oxidative Stress and Reproductive Function
       There are many factors that contribute to the decline of the male reproductive system. In particular, aging is associated with an increase production of reactive oxygen species (ROS) and a decrease in the antioxidant defense system, leading to oxidative stress, which can be harmful to male germ cells. Although sperm quality is thought to decrease with age, studies in humans have not found a definite negative correlation between aging and sperm quality. Further, advanced paternal age (APA), commonly defined as men over the age of 40 years, is associated with an increase in sperm DNA damage, male infertility and negative progeny outcomes. Although limited, studies have found that there may be benefits to antioxidant supplementation in order to reverse the effects of aging and oxidative stress in males. More studies need to be conducted. 
  • 656
  • 26 Oct 2020
Topic Review
Formulation Strategies to Improve Pharmacokinetics Profile
The oral route is the most common and practical means of drug administration, particularly from a patient’s perspective. However, the pharmacokinetic profile of oral drugs depends on the rate of drug absorption through the intestinal wall before entering the systemic circulation. However, the enteric epithelium represents one of the major limiting steps for drug absorption, due to the presence of efflux transporters on the intestinal membrane, mucous layer, enzymatic degradation, and the existence of tight junctions along the intestinal linings. These challenges are more noticeable for hydrophilic drugs, high molecular weight drugs, and drugs that are substrates of the efflux transporters. Another challenge faced by oral drug delivery is the presence of first-pass hepatic metabolism that can result in reduced drug bioavailability. Over the years, a wide range of compounds have been investigated for their permeation-enhancing effect in order to circumvent these challenges. There is also a growing interest in developing nanocarrier-based formulation strategies to enhance the drug absorption.
  • 654
  • 26 Aug 2022
Topic Review
Oral subunit vaccine design
Many pathogens invade the host at the intestinal surface. To protect against these enteropatho-gens, the induction of intestinal secretory IgA (SIgA) responses is paramount. While systemic vaccination provides strong systemic immune responses, oral vaccination is the most efficient way to trigger protective SIgA responses. However, the development of oral vaccines, especially oral subunit vaccines, is challenging due to mechanisms inherent to the gut. Oral vaccines need to survive the harsh environment in the gastrointestinal tract, characterized by low pH and intestinal proteases and need to reach the gut-associated lymphoid tissues, which are protected by chemical and physical barriers that prevent efficient uptake. Furthermore, they need to surmount default tolerogenic responses present in the gut, resulting in suppression of immunity or tolerance. Several strategies have been developed to tackle these hurdles, such as delivery systems that protect vaccine antigens from degradation, strong mucosal adjuvants that induce robust immune responses and targeting approaches that aim to selectively deliver vaccine antigens towards specific immune cell populations.
  • 653
  • 12 Jan 2021
Topic Review
Ultrasound-Mediated Gene Delivery
Recently, various drug and gene delivery systems employing physical energy, such as ultrasound, magnetic force, electric force, and light, have been developed. Ultrasound-mediated delivery has particularly attracted interest due to its safety and low costs. Ultrasound exposure increases cell membrane permeability and facilitates the delivery of drugs or genes into cells. Its delivery effects are also enhanced when combined with microbubbles or nanobubbles that entrap an ultrasound contrast gas. Furthermore, ultrasound-mediated nucleic acid delivery could be performed only in ultrasound exposed area. 
  • 652
  • 07 Dec 2020
Topic Review
Neurogliovascular Unit and Cerebral-microvascular Disease
The distinctive anatomical assemble and functionally discrete multicellular cerebrovasculature dynamics confer varying rheological and blood–brain barrier (BBB) permeabilities to preserve the integrity of cerebral white matter and its neural microenvironment. This homeostasis intricately involves the neurogliovascular unit (NGVU) and glymphatic system that manages the flow of cerebrospinal fluid (CSF), interstitial fluids (ISF), metabolic waste, and clearance through the venous circulation. NGVU refers to the integration of neuronal structures, glial cells (including the microglial), and vasculature (i.e., capillaries, arteries, and/or arterioles) governed by the astrocytes.
  • 652
  • 16 Aug 2021
Topic Review
Accum™ Technology
Compromised activity is a common impediment for biologics requiring endosome trafficking into target cells. In cancer cells, antibody-drug conjugates (ADCs) are trapped in endosomes or subsequently pumped extracellularly, leading to a reduction in intracellular accumulation. In subsets of dendritic cells (DCs), endosome-engulfed antigens face non-specific proteolysis and collateral damage to epitope immunogenicity before proteasomal processing and subsequent surface presentation. Accum™ is a novel biotechnology exemplifying, in its initial concept, the need to circumvent the biological challenges of ADCs.
  • 652
  • 29 Jul 2022
Topic Review
In Silico Models to Predict Drug-Induced Liver Injury
Drug-induced liver injury (DILI) is a major cause of the withdrawal of pre-marketed drugs, typically attributed to oxidative stress, mitochondrial damage, disrupted bile acid homeostasis, and innate immune-related inflammation. DILI can be divided into intrinsic and idiosyncratic DILI with cholestatic liver injury as an important manifestation. The diagnosis of DILI remains a challenge today and relies on clinical judgment and knowledge of the insulting agent. Early prediction of hepatotoxicity is an important but still unfulfilled component of drug development. In response, in silico modeling has shown good potential to fill the missing puzzle. Computer algorithms, with machine learning and artificial intelligence as a representative, can be established to initiate a reaction on the given condition to predict DILI. 
  • 652
  • 29 Dec 2022
Topic Review
Liposomal Amphotericin B for Treatment of Leishmaniasis
The liposomal amphotericin B (AmB) formulation, AmBisome®, still represents the best therapeutic option for cutaneous and visceral leishmaniasis. However, the need for parenteral administration, its side effects and high cost significantly limit its use in developing countries. The recent advances in the development of topical and oral formulations of liposomal AmB are presented, in addition to the current knowledge on the physicochemical and pharmacological features of AmB.
  • 651
  • 24 Jan 2023
Topic Review
Ethnomedicinal Plant Sonapatha: Oroxylum indicum
Oroxylum indicum, Sonapatha is traditionally used to treat asthma, biliousness, bronchitis, diarrhea, dysentery, fevers, vomiting, inflammation, leukoderma, skin diseases, rheumatoid arthritis, wound injury, and deworm intestine. 
  • 650
  • 07 Jun 2021
Topic Review
Biomedical Applications of Modified Dextran
Native DEX (Dextran) exhibits low-cell-adhesive properties and in order to obtain hydrogels with controlled cell-scaffold interactions, specific molecules must be incorporated. Many research groups have chemically modified DEX by introducing functional groups into the molecule through cross-linking reactions, therefore improving mechanical strength and drug-loading ability and increasing the number of compound classes that can be obtained. Furthermore, DEX has been shown to have metal chelating activity and antioxidant properties, as well as antitumour activity by regulating apoptosis and autophagy.
  • 650
  • 10 Feb 2023
Topic Review
Critically Ill Patients Antimicrobial Dosing
In recent years, the knowledge of pharmacokinetics and pharmacodynamics, drug dosing, therapeutic drug monitoring, and antimicrobial resistance in the critically ill patients has greatly improved, fostering strategies to optimize therapeutic efficacy and to reduce toxicity and adverse events. Nonetheless, delivering adequate and appropriate antimicrobial therapy is still a challenge, since pathogen resistance continues to rise, and new therapeutic agents remain scarce. 
  • 649
  • 13 Jul 2021
Topic Review
Classes of Translational Readthrough-Inducing Drugs
Translational Readthrough-Inducing Drugs (TRIDs) can affect various biomolecular targets, leading to different types of readthrough.
  • 649
  • 11 Jan 2022
Topic Review
Applications of Antimicrobial Photodynamic Therapy
Originally discovered as a relatively new anticancer therapeutic technology, photodynamic therapy (PDT) has since evolved and is now used in many therapeutic technologies. For example, it is used against viruses, such as the recently reported antiviral activity against COVID-19, bacteria, fungi, and parasites, in treating neovascular disease, in environmental sanitation and pest control, and in many other applications. 
  • 649
  • 13 Apr 2022
Topic Review
Extracellular Vesicles in Lung Disease
The use of MSC-derived EVs as a potential therapy for lung disease is a fairly young but rapidly growing field, with current research covering a wide variety of lung diseases. The majority of the current research evaluating the therapeutic potential of EVs has been performed in in vitro or pre-clinical animal model systems. This review will describe current published research using EVs as a potential therapy for acute lung injury/acute respiratory distress syndrome (ALI/ARDS), bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), asthma, and silicosis.
  • 648
  • 28 Oct 2020
Topic Review
Nano and Microemulsions for Depression and Anxiety Treatment
Most drugs used for the treatment of depression, anxiety and related disorders have low absorption, high metabolism, low brain targeting and/or low water solubility, which can make it hard to formulate them at high strength and can also lead to decreased bioavailability. Incorporating these drugs into nanometric emulsions can solve these issues. Nanometric emulsions were able to increase drug strength up to 20,270-fold (compared to aqueous solubility). The formulations showed droplet size, polydispersity index, zeta potential, viscosity, osmolality, pH, in vitro drug release and ex vivo drug permeation as adequate for the intended effect and administration route.
  • 645
  • 23 Dec 2022
Topic Review
Circadian Clock to Skin /Cancer
Over the years, the circadian regulation of drug metabolism and processing has been employed in the treatment of a range of disease states, including diabetes, hypertension, peptic ulcers, and allergic rhinitis . There is also interest in using chronotherapeutic approaches for skin disease, including psoriasis and atopic dermatitis . Although time-dictated drug administration had been demonstrated many decades ago, its application in cancer treatment was limited due to insufficient mechanistic data supporting experimental results and inconsistency among clinical trials.
  • 644
  • 21 Jun 2021
Topic Review
Antiepileptic Drugs
For drugs, such as antiepileptic drugs (AEDs), whose therapeutic or toxic effects are more closely related to blood levels than to a specific dose, monitoring of plasma levels plays a crucial role. Many drugs used in epilepsy therapy often cause acute poisonings (carbamazepine, oxcarbazepine, valproic acid, lamotrigine). AEDs do not have an ideal pharmacokinetic profile, which at the same time qualifies them to monitor both in the therapeutic and toxic aspects. Currently, a great benefit for patients using various AEDs is adjusting the dosage to their individual needs and monitoring sufficient blood concentrations. There is still a need to develop new, rapid methods that meet the validation criteria. This trend has been observed in the last few years in the bioanalysis of different type of biological samples, not only blood, serum or plasma, but also saliva and blood/serum/plasma dried spots technique.
  • 643
  • 01 Dec 2020
Topic Review
Targeting Gut in Obesity: Signals from Inner Surface
Obesity is caused by prolonged energy surplus. Current anti-obesity medications are mostly centralized around the energy input part of the energy balance equation by increasing satiety and reducing appetite. Our gastrointestinal tract is a key organ for regulation of food intake and supplies a tremendous number of circulating signals that modulate the activity of appetite-regulating areas of the brain by either direct interaction or through the vagus nerve. Intestinally derived messengers are manifold and include absorbed nutrients, microbial metabolites, gut hormones and other enterokines, collectively comprising a fine-tuned signalling system to the brain. After a meal, nutrients directly interact with appetite-inhibiting areas of the brain and induce satiety. However, overall feeding behaviour also depends on secretion of gut hormones produced by highly specialized and sensitive enteroendocrine cells. Moreover, circulating microbial metabolites and their interactions with enteroendocrine cells further contribute to the regulation of feeding patterns. Current therapies exploiting the appetite-regulating properties of the gut are based on chemically modified versions of the gut hormone, glucagon-like peptide-1 (GLP-1) or on inhibitors of the primary GLP-1 inactivating enzyme, dipeptidyl peptidase-4 (DPP-4). The effectiveness of these approaches shows that that the gut is a promising target for therapeutic interventions to achieve significant weigh loss. 
  • 643
  • 24 Jan 2022
Topic Review
Antifungal Drugs against Paracoccidioidomycosis
Paracoccidioidomycosis is a neglected disease that causes economic and social impacts, mainly affecting people of certain social segments, such as rural workers. The limitations of antifungals, such as toxicity, drug interactions, restricted routes of administration, and the reduced bioavailability in target tissues, have become evident in clinical settings. These factors, added to the fact that Paracoccidioidomycosis (PCM) therapy is a long process, lasting from months to years, emphasize the need for the research and development of new molecules.
  • 640
  • 16 Dec 2020
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