Current Drug Targets - Volume 22, Issue 3, 2021

Background: The Coronavirus Disease 2019 (COVID-19) is becoming the major health issue in recent human history with thousands of deaths and millions of cases worldwide. Newer research and old experience with other coronaviruses highlighted a probable underlying mechanism of disturbance of the renin-angiotensin system (RAS) that is associated with the intrinsic effects of SARS-CoV-2 infection. Objective: In this review, we aimed to describe the intimate connections between the RAS components, the immune system and COVID-19 pathophysiology. Methods: This non-systematic review article summarizes recent evidence on the relationship between COVID-19 and the RAS. Results: Several studies have indicated that the downregulation of membrane-bound ACE2 may exert a key role for the impairment of immune functions and for COVID-19 patients’ outcomes. The downregulation may occur by distinct mechanisms, particularly: (1) the shedding process induced by the SARS-CoV-2 fusion pathway, which reduces the amount of membrane-bound ACE2, stimulating more shedding by the high levels of Angiotensin II; (2) the endocytosis of ACE2 receptor with the virus itself and (3) by the interferon inhibition caused by SARS-CoV-2 effects on the immune system, which leads to a reduction of ACE2 receptor expression. Conclusion: Recent research provides evidence of a reduction of the components of the alternative RAS axis, including ACE2 and Angiotensin-(1-7). In contrast, increased levels of Angiotensin II can activate the AT1 receptor in several organs. Consequently, increased inflammation, thrombosis and angiogenesis occur in patients infected with SARS-COV-2. Attention should be paid to the interactions of the RAS and COVID-19, mainly in the context of novel vaccines and proposed medications.

Tissue engineering is governed by the use of cells and polymers. The cells may be accounted for the type of tissue to be targeted, while polymers may vary from natural to synthetic. The natural polymers have advantages such as non-immunogenic and complex structures that help in the formation of bonds in comparison to the synthetic ones. Various targeted drug delivery systems have been prepared using polymers and cells, such as nanoparticles, hydrogels, nanofibers, and microspheres. The design of scaffolds depends on the negative impact of material used on the human body and they have been prepared using surface modification technique or neo material synthesis. The dermal substitutes are a distinctive array that aims at the replacement of skin parts either through grafting or some other means. This review focuses on biomaterials for their use in tissue engineering. This article shall provide the bird's eye view of the scaffolds and dermal substitutes, which are naturally derived.

Leishmaniasis is a neglected tropical disease affecting more than 1.5 million people annually, with an annual mortality of over 20.000. The drugs used for its treatment are toxic, expensive, require extended treatment times and present variable efficacy. The disease severity and therapy limitations suggest the need for new antileishmanial agents. In this context, in order to identify new options for treatment, a number of studies based on nanotechnological strategies have been carried out. Poloxamers are triblock copolymers very often utilized for nanotherapeutic solutions, resulting in products with better solubility, higher stability, superior therapeutic efficacy and less toxicity. This review will discuss the physicochemical properties of the copolymers, as well as describe the use of poloxamers for the development of therapeutic formulations to treat leishmaniasis.

The prevalence of periodontitis is around 20-50% in the global population. If it is not treated, it can cause tooth loss. Periodontal treatment aims at preserving the patient's teeth from various damages, including infection control and restoring lost periodontal tissue. The periodontium has great biological regenerative potential, and several biomaterials can be used to improve the outcome of periodontal treatment. To achieve the goal of periodontal tissue regeneration, numerous studies have used fibroblast growth factor 2 (FGF2) to stimulate the regeneration of both the soft tissue and bone. FGF2 induced a significant increment in the percentage of bone fill, bone mineral levels of the defect sites, length of the regenerated periodontal ligament, angiogenesis, connective tissue formation on the root surface, formation of dense fibers bound to the alveolar bone and newly synthesized cementum in teeth. This review will open further avenues to better understand the FGF2 therapy for periodontal regeneration.

Thrombosis is a condition of major concern worldwide as it is associated with life-threatening diseases related to the cardiovascular system. The condition affects 1 in 1000 adults annually, whereas 1 in 4 dies due to thrombosis, and this increases as the age group increases. The major outcomes are considered to be a recurrence, bleeding due to commercially available anti-coagulants, and deaths. The side effects associated with available anti-thrombotic drugs are a point of concern. Therefore, it is necessary to discover and develop an improvised benefit-risk profile drug, therefore, in search of alternative therapy for the treatment of thrombosis, marine sources have been used as promising treatment agents. They have shown the presence of sulfated fucans/galactans, fibrinolytic proteases, diterpenes, glycosaminoglycan, glycoside, peptides, amino acids, sterols, polysaccharides, polyphenols, vitamins, and minerals. Out of these marine sources, many chemicals were found to have anti-thrombotic activities. This review focuses on the recent discovery of anti-thrombotic agents obtained from marine algae, sponges, mussels, and sea cucumber, along with their mechanism of action and patents on its extraction process, preparation methods, and their applications. Further, the article concludes with the author's insight related to marine drugs, which have a promising future.

With the recognition of the important role of gut microbiota in both health and disease progression, attempts to modulate its composition, as well as its co-metabolism with the organism, have attracted special attention. Abundant studies have demonstrated that dysfunction or imbalance of gut microbiota is closely related to disease progression, including endocrine diseases, neurodegenerative diseases, tumors, cardiovascular diseases, etc. Herbal medicines have been applied to prevent and treat diseases worldwide for hundreds of years. Although the underlying mechanism seems to be complex, one of the important ones is through modulating gut microbiota. In this review, co-metabolism between herbal medicines and microbiota, as well as the potential pathways are summarized from most recent published papers.

Background: Intestinal fibrosis and subsequent strictures represent an important burden in inflammatory bowel disease (IBD). Both the detection and evaluation of the degree of fibrosis in stricturing Crohn’s disease (CD) are important when deciding the best therapeutic strategy (medical anti-inflammatory therapy, endoscopic dilation, surgery). Ultrasound elastography (USE) is a non-invasive technique that has been proposed in the field of IBD for evaluating intestinal stiffness as a biomarker of intestinal fibrosis. Objective: The aim of this review is to discuss the ability and current role of ultrasound elastography in the assessment of intestinal fibrosis. Results and Conclusion: Data on USE in IBD are provided by pilot and proof-of-concept studies with small sample size. The first type of USE investigated was strain elastography, while shear wave elastography has been introduced recently. Despite the heterogeneity of the methods of the studies, USE has been proven to be able to assess intestinal fibrosis in patients with stricturing CD. However, before introducing this technique in current practice, further studies with larger sample sizes are needed. In addition, the use of homogeneous parameters, the assessment of reproducibility, and the identification of validated cut-off values are essential.

Epilepsy is one of the most common disorders of the central nervous system. Although epilepsy is common worldwide, approximately 80% of epileptic patients live in the developing countries or those with low-middle income. Up until the second decade of the 20th century, epilepsy was treated mostly by traditional remedies. Today, antiepileptic drugs are used as a general treatment instead to prevent and control epileptic seizures. However, patient access to these drugs is hindered due to the healthcare systems of their countries and a number of other reasons, such as cultural, socio-demographic, and financial poverty. In addition, approximately 30-40%of epileptic patients suffer from refractory epilepsy, additionally, AEDs have adverse side-effects that can lead to treatment failure or reduce the patient’s quality of life. Despite recent advances in the treatment of epilepsy, there is still a need for improving medical treatment with a particular focus on efficacy, safety, and accessibility. Since herbal medicines have been used for many centuries around the world for treating epilepsy, it is, therefore, plausible that a rigorous study on herbal medicine and phytochemical components within plants of various species and origin may lead to the discovery of novel AEDs. Nowadays, many medicinal plants used in different cultures and regions of the world have been identified. Most phytochemical components of these plants have been identified and, in some cases, their targets located. Therefore, it is possible that new, effective, and accessible anticonvulsants drugs can be obtained from a medicinal plant.