Current Drug Targets - Volume 21, Issue 12, 2020

Background: Corneal neovascularization (CN) is a clue feature of different ocular pathological conditions and can lead to corneal edema and opacification with subsequent vision loss. Vascular endothelial growth factor (VEGF), which plays a key role in new vessels formation, proliferation and migration, was found to be up-regulated in these conditions. Nowadays, it is possible to downregulate the angiogenic process by using anti-VEGF agents administered by different routes. Objective: To evaluate the efficacy, safety and possible future directions of anti-VEGF agents used for the treatment of CNV owing to different aetiologies. Methods: A computerized search of articles dealing with the topic of anti-VEGF therapy in CN was conducted in PubMed, Scopus and Medline electronic databases. The following key phrases were used: anti-VEGF agents, corneal neovascularization, bevacizumab, ranibizumab, vascular endothelial growth factor, angiogenesis. Results: The use of anti-VEGF therapy in the treatment of CN reduced pathological vessel density without causing significant side effects. Various administration routes such as topical, subconjunctival and intrastromal ones are available, and the choice depends on patient and disease characteristics. Much more effectiveness is achieved in case of early administration before mature and wellestablished vessels take place. A combined approach between various drugs including anti-VEGF agents should be adopted in those cases at higher risk of neovascularization recurrence such as chronic long-standing diseases where ischemic and inflammatory stimuli are not definitively reversed. Conclusion: The efficacy and safety of anti-VEGF agents support their adoption into the daily clinical practice for the management of CN.

Retinal vein occlusion (RVO) is one of the most prevalent causes of visual loss in the Western World. Its pathogenesis is still not completely known. Chronic macular edema and ischemia compromise the functional and anatomical status of the retina. Antivascular endothelial growth factor (anti-VEGF) injections have demonstrated better results than other previous options, including observation or laser therapy. This narrative review aims to analyze the current aspects related to these drugs.

This review focuses on 5 new anti-VEGF drugs in the advanced stage of clinical development (i.e., phase 3): conbercept, brolucizumab, port delivery system with ranibizumab, abicipar pegol and faricimab. Results of clinical trials and the advantages of each drug compared to the available molecules are discussed in detail.

The therapeutic approach based on anti-vascular endothelial growth factor (anti-VEGF) molecules can be used to treat two important complications of retinal dystrophies: choroidal neovascularization and macular edema. The macular involvement in retinal dystrophies can lead to further visual deterioration in patients at a young age and already affected by functional limitations. The study reports the effect of anti-VEGF treatment in several subforms of retinal dystrophies, critically discussing advantages and limitations.

Retinal diseases affect an increasing number of patients worldwide because of the aging population. Request for diagnostic imaging in ophthalmology is ramping up, while the number of specialists keeps shrinking. Cutting-edge technology embedding artificial intelligence (AI) algorithms are thus advocated to help ophthalmologists perform their clinical tasks as well as to provide a source for the advancement of novel biomarkers. In particular, optical coherence tomography (OCT) evaluation of the retina can be augmented by algorithms based on machine learning and deep learning to early detect, qualitatively localize and quantitatively measure epi/intra/subretinal abnormalities or pathological features of macular or neural diseases. In this paper, we discuss the use of AI to facilitate efficacy and accuracy of retinal imaging in those diseases increasingly treated by intravitreal vascular endothelial growth factor (VEGF) inhibitors (i.e. anti-VEGF drugs), also including integration and interpretation features in the process. We review recent advances by AI in diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity that envision a potentially key role of highly automated systems in screening, early diagnosis, grading and individualized therapy. We discuss benefits and critical aspects of automating the evaluation of disease activity, recurrences, the timing of retreatment and therapeutically potential novel targets in ophthalmology. The impact of massive employment of AI to optimize clinical assistance and encourage tailored therapies for distinct patterns of retinal diseases is also discussed.

Noise exposure (NE) has been recognized as one of the causes of sensorineural hearing loss (SNHL), which can bring about irreversible damage to sensory hair cells in the cochlea, through the launch of oxidative stress pathways and inflammation. Accordingly, determining the molecular mechanism involved in regulating hair cell apoptosis via NE is essential to prevent hair cell damage. However, the role of microRNAs (miRNAs) in the degeneration of sensory cells of the cochlea during NE has not been so far uncovered. Thus, the main purpose of this study was to demonstrate the regulatory role of miRNAs in the oxidative stress pathway and inflammation induced by NE. In this respect, articles related to noise-induced hearing loss (NIHL), oxidative stress, inflammation, and miRNA from various databases of Directory of Open Access Journals (DOAJ), Google Scholar, PubMed; Library, Information Science & Technology Abstracts (LISTA), and Web of Science were searched and retrieved. The findings revealed that several studies had suggested that up-regulation of miR-1229-5p, miR-451a, 185-5p, 186 and down-regulation of miRNA-96/182/183 and miR-30b were involved in oxidative stress and inflammation which could be used as biomarkers for NIHL. There was also a close relationship between NIHL and miRNAs, but further research is required to prove a causal association between miRNA alterations and NE, and also to determine miRNAs as biomarkers indicating responses to NE.

Acetaminophen is a widely used analgesic for pain management, especially useful in chronic diseases, such as rheumatoid arthritis. However, easy access to this medicine has increased the occurrence of episodes of poisoning. Patients often develop severe liver damage, which may quickly lead to death. Consequently, numerous studies have been conducted to identify new biomarkers that allow the prediction of the degree of acetaminophen intoxication and thus intervene in a timely manner to save patients’ lives. This review highlights the main mechanisms of the induction and progression of liver damage arising from acetaminophen poisoning. In addition, we have discussed the possibility of using new clinical biomarkers for detecting acetaminophen poisoning.

Nowadays, natural compounds of plant origin with anticancer effects have gained more attention because of their clinical safety and broad efficacy profiles. Autophagy is a multistep lysosomal degradation pathway that may have a unique potential for clinical benefit in the setting of cancer treatment. To retrieve articles related to the study, the databases of Google Scholar, Web of sciences, Medline and Scopus, using the following keywords: Autophagic pathways; herbal medicine, oncogenic autophagic pathways, tumor-suppressive autophagic pathways, and cancer were searched. Although natural plant compounds such as resveratrol, curcumin, oridonin, gossypol, and paclitaxel have proven anticancer potential via autophagic signaling pathways, there is still a great need to find new natural compounds and investigate the underlying mechanisms, to facilitate their clinical use as potential anticancer agents through autophagic induction.

Background: Lymphatic filariasis is a pervasive and life-threatening disease for human beings. Currently, 893 million people in 49 countries worldwide affected by lymphatic filariasis as per WHO statistics. The concealed aspects of lymphatic diseases such as delayed disease detection, inappropriate disease imaging, the geographical outbreak of infection, and lack of preventive chemotherapy have brought this epidemic to the edge of Neglected Tropical Diseases. Many medications and natural bioactive substances have seen to promote filaricidal activity against the target parasitic species. However, the majority of failures have occurred in pharmaceutical and pharmacokinetic issues. Objective: The purpose of the study is to focus on the challenges and therapeutic issues in the treatment of filariasis. The review brings novel techniques and therapeutic approaches for combating lymphatic filariasis. It also offers significant developments and opportunities for such therapeutic interventions. Conclusion: Through this review, an attempt has made to critically evaluate the avenues of innovative pharmaceuticals and molecular targeting approaches to bring an integrated solution to combat lymphatic filariasis.

Chronic non-healing wounds are estimated to cost the US healthcare $28-$31 billion per year. Diabetic ulcers, arterial and venous ulcers, and pressure ulcers are some of the most common types of chronic wounds. The burden of chronic wounds continues to rise due to the current epidemic of obesity and diabetes and the increase in elderly adults in the population who are more vulnerable to chronic wounds than younger individuals. This patient population is also highly vulnerable to debilitating infections caused by opportunistic and multi-drug resistant pathogens. Reduced microcirculation, decreased availability of cytokines and growth factors that promote wound closure and healing, and infections by multi-drug resistant and biofilm forming microbes are some of the critical factors that contribute to the development of chronic non-healing wounds. This review discusses novel approaches to understand chronic wound pathology and methods to improve chronic wound care, particularly when chronic wounds are infected by multi-drug resistant, biofilm forming microbes.

The immune system plays an important role in the prevention of infection and forms the first line of defense against pathogen attack. Delivering of antigen through mucosal route may elicit mucosal immune system as the mucosal surface is the most common site of pathogen entry. Mucosal immune system will be capable to counter pathogen at mucosal surface. Oral mucosal immunization opens the ways to deliver antigens at gut-associated lymphoid tissue. This can elicit both local and systemic immune response. Mucosal vaccines are economical, highly accessible, non parenteral delivery and capacity to produce mass immunization at the time of pandemics. To deliver antigens on the mucosal surface of the gastrointestinal tract, the immune system relies on specialized epithelial cell i.e. Microfold (M)-cell. An approach to exploit the targeting specific receptors on M-cell for entry of antigens has made a breakthrough in vaccine development. In this review, various strategies have been discussed for the possible entry of antigens through M-cells and an approach to increase the uptake and efficacy of vaccines for oral mucosal immunization.