Current Pharmaceutical Design - Volume 27, Issue 31, 2021

Legumain (LGMN; EC: 3.4.22.34), an asparaginyl endopeptidase (AEP) or asparaginyl carboxypeptidase (ACP), is a member of the C13 family of cysteine proteases. Elevated expression of LGMN is reported not only in the tumor cells of breast, prostate, and liver but also in the macrophages of the tumor microenvironment. Hence, LGMN is considered as a key protein involved in the regulation of tumor angiogenesis, invasion, and metastasis. Targeting LGMN using siRNA or pharmacological agents and peptides was reported to reduce cancer cell proliferation in vitro and shrink tumor size in vivo. Moreover, expression of LGMN is significantly low in normal cells compared to tumor cells or tumor-associated macrophages (TAMs); hence, legumain can be used as a marker for tumor recognition and targeting. Therefore, approaches inhibiting LGMN expression or activity are more viable, less toxic, and help in developing the targeted therapeutics. However, to date, LGMN targeting strategies have not been well reported. In this review, an attempt was made to summarize articles pertaining to LGMN (a) structure and activity; (b) oncogenic nature; (c) pharmacological inhibitors; and (d) targeting approaches that inhibit tumor growth. Furthermore, a list of existing gaps in LGMN research is highlighted, which needs additional studies.

Leukotrienes are one of the major eicosanoid lipid mediators produced due to an oxidative transformation of arachidonic acid. Subsequently, they get converted into various cellular signaling hormones by a series of enzymes of myeloid origin to mediate or debilitate inflammation. Interestingly, the available literature demonstrates the pivotal role of eicosanoids in neurodegenerative, obesity, diabetes, cardiovascular diseases, and cancers as well. The aberrant metabolism of arachidonic acid by the LOX pathway is a common feature of epithelial-derived malignancies and suggests the contributory role of dietary fats in carcinogenesis. The enzymes and receptors of the LOX pathway play a significant role in cell proliferation, differentiation and regulation of apoptosis through multiple signaling pathways and have been reported to be involved in various cancers, including prostate, colon, lung and pancreatic cancers. So far, leukotriene receptor antagonists and 5-LOX inhibitors have reached up to the clinical trials for treating various diseases. Keeping its various roles in cancer, the review highlights the components of the leukotriene synthesizing machinery, emerging opportunities for pharmacological intervention, and the probability of considering lipoxygenases and leukotriene receptors as good candidates for clinical chemoprevention studies.

Coronavirus disease (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), which is a positive single-stranded RNA virus having a large genome ~30 kb. SARSCoV- 2 is zoonotic and highly contagious, causing severe pneumonia-like symptoms. The efficacy of the different potential drug and drug candidates against COVID-19 has been investigated, which are under various stages of clinical trials. The drugs effective against SARS, and Middle east respiratory syndrome (MERS), have been proposed to have a high potential for the treatment of COVID-19. Here, we selected plant-based materials implicated in the prevention and therapy of COVID-19. The plant produces secondary metabolites in response to viral infection. Different classes of secondary metabolites have different mechanisms to counter virus attacks. Many nanomaterials produced by carbohydrates and lipids have been exploited for their in-vitro and in-vivo delivery of antiviral therapeutics. The vaccine has shown impressive results in producing antibodies against SARS-CoV2 and has been evaluated for safety, tolerance, and preliminary immunogenicity. Similarly, DNA/RNA-based therapy has shown high clinical significance. Various forms of vitamins, minerals, herbs, and phytonutrients help to enhance immunity and be implicated in the control of COVID-19. However, such measures should not replace social distancing, quarantine and special care.

Background: The rapid eruption of Coronavirus at the end of 2019 has caused global health crisis and significant loss to the economy and social well-being. This created a massive shortage of advanced health facilities with inadequate medicinal supply, further deteriorating human health conditions. On the basis of adverse effects of the ongoing pandemic, this review has been proposed to evaluate the antiviral efficacy of plant- based therapeutics, against SARS-CoV-2 (commonly called COVID-19) infection. It highlights the possible action of the mechanism of phytotherapeutic drugs against coronavirus inhibition, further validated by clinical trials on herbal formulas is reviewed. Though the experimental studies on COVID-19 treatment are limited, the undesirable side effects of herbal drugs and unidentified compounds cannot be ignored. Objective: We have made an effort to study the prospective plant-derived bioactive entities and their effectiveness in the treatment of COVID-19 and also emphasize on safety and regulatory concerns of phytomedicines. Methods: The methodology involves relevant studies on COVID-19 treatment based on herbal extracts and the purified bioactive metabolites. The e-literature survey has been done by downloading research articles available on PubMed (National Library of medicine), Elsevier, and Google scholar search engines. The keywords used are plant metabolites, natural bioactive, phytotherapeutic drugs, clinical trials, SARS-CoV-2, Coronavirus inhibitors and herbal extracts. Results: The review pays particular attention to the etiological study of the COVID-19 virus and its inhibition using medicinal plant metabolites as immunomodulatory agents. The application of valuable bioactives like phenolic compounds, saponins, alkaloids, tannins, flavonoids and terpenoids in preparing herbal formula/drug has been focused on. The drug resistance of bioactive compounds and their side effects on human health were discussed for effective phytomedicine, thus, emphasizing the perspectives of phytotherapeutic drugs as a safe remedy to boost immunomodulatory functions and antiviral activity against COVID-19. Conclusion: Altogether, the review presents the action mechanism of plant extracts rich in bioactive compounds and depicted potential antiviral activity against SARS-CoV-2. These plant bioactive compounds can serve as lead molecules to develop phytomedicine, ensuring all safety regulations in the clinical trials to treat or prevent COVID-19 viral infections.

Background: This review summarizes recent findings in molecular biology and neuroimaging and their applicability to the classification and identification of depression. We discuss whether there is reliable evidence that could become a basis for biomarkers or subtyping that may enhance our understanding of the biological foundations of depression and may be useful for clinical practice with respect to diagnosis and prognosis as well as the selection of treatments. Objective: The purpose of this investigation is to present molecular mechanisms that contribute to different origins of depressions that could prove useful in the daily psychiatric clinic-based practices. Methods: The authors have analyzed and summarized electronic publications available in PubMed, Science Direct, Google Scholar, and Scopus. Results: The introduction of molecular diagnostic methods into medical practice is a promising method to improve the accuracy of the diagnosis of depression in clinical settings. The literature analysis revealed structural changes in some areas of the brain, its neuroplasticity, as well as changes at the molecular, epigenetic, and genetic levels. However, there are no current reliable biomarkers for differential diagnosis of the types and subtypes of depression. Conclusion: Major depressive disorder is a biologically and genetically heterogeneous disorder. Given its complexity, subtyping is worthwhile to identify biological bases of conditions. The literature review provides ample findings that reveal possible underlying biological mechanisms associated with atypical and melancholic depression. Additional focused research should be continued with respect to the molecular and genetic biology of different types of depression. There already are promising findings, but additional research to define biologically based depressive subtypes is needed and worthwhile.

Background: A patient was evaluated with respect to the effects and results of a complex treatment plan for complete dental rehabilitation. Several steps were required. Each step included immunological tests of salivary biomarkers. Clinical and immunological assessments were evaluated on Day 3, Week 2, Month 3, and Month 6 post-surgery. These evaluations guided the decision-making process with regard to preparation of a permanent prosthesis. Objective: The aim of the study is to evaluate the response of tissues and organs of the maxillofacial region in patients during dental rehabilitation after maxillofacial surgery. Methods: Complex treatment and rehabilitation involving cooperation between the specialists in maxillofacial surgery, prosthetic dentistry, and cancer immunology. Results: Long-term monitoring and clinical examination showed a direct relationship between the patient’s clinical and dental status and the changes in oral fluid biomarkers. Conclusion: The data revealed that the oral fluid biomarkers reflected the patient’s adaptation to prosthodontic rehabilitation. Treatment and monitoring of a maxillofacial tumor patient could use biomarkers as a non-invasive indicator.