Current Pharmaceutical Design - Volume 28, Issue 29, 2022

Malignant melanoma is one of the most worrisome malignancies due to its fast dissemination and early formation of metastases in multiple sites throughout the body. Despite the intensive efforts made in the last decades, the use of standard therapeutic strategies, including chemotherapy and radiotherapy, has not led to a substantial improvement in clinical outcomes, mainly because of the intrinsic resistance of melanomas to these treatment modalities. Therefore, in recent years, numerous studies have focused on the possibility of boosting the clinical responses of melanoma patients by using novel immunotherapeutic agents. In this review article, a comprehensive survey is presented about the approved immunotherapeutic drugs and their action mechanisms, besides describing the agents that are currently still in clinical trials. Moreover, the combination of immunotherapeutic drugs with conventional approaches, i.e., radiotherapy, chemotherapy, and targeted therapy, is another focal point of this review, providing valuable input for further elaboration of the best treatment regimens to prolong survival and improve the quality of life of melanoma patients.

Coronavirus disease 2019 (COVID-19) is the result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding molecular pathogenesis is an essential factor for the allocation of effective preventive measures and the development of targeted therapeutics against COVID-19. The genome of SARS-CoV-2 encodes structural and nonstructural proteins, which can be targets for compounds with potential therapeutic ability. On the other hand, the virus life cycle has stages susceptible to targeting by drug compounds. Many natural antiviral compounds have been studied and evaluated at the cellular and molecular levels with antiviral potential. Meanwhile, many studies over the past few months have shown that plant polysaccharides have a good ability to target proteins and stages of the virus life cycle. In this regard, in this review study, the virus specifications and infectious process and structural and functional components of SARSCoV- 2 will be reviewed, and then the latest studies on the effect of plant compounds with more focus on polysaccharides on viral targets and their inhibitory potential on the infectious process of COVID-19 will be discussed.

Cancer immunotherapy approaches have progressed significantly during the last decade due to the significant improvement of our understanding of immunologic evasion of malignant cells. Depending on the type, stage, and grade of cancer, distinct immunotherapy approaches are being designed and recommended; each is different in efficacy and adverse effects. Malignant cells can adopt multiple strategies to alter the normal functioning of the immune system in recognizing and eliminating them. These strategies include secreting different immunosuppressive factors, polarizing tumor microenvironment cells to immunosuppressive ones, and interfering with the normal function of the antigen processing machinery (APM). In this context, careful evaluation of immune surveillance has led to a better understanding of the roles of cytokines, including IL-2, IL-12, IL-15, interferon-α (IFN-α), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) in cancer formation and their potential application in cancer immunotherapy. Additionally, monoclonal antibodies (mAbs), adoptive cell therapy approaches, immune checkpoint blockade, and cancer vaccines also play significant roles in cancer immunotherapy. Moreover, the development of clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/CAS9) as an outstanding genome editing tool resolved many obstacles in cancer immunotherapy. In this regard, this review aimed to investigate the impacts of different immunotherapy approaches and their potential roles in the current and future roads of cancer treatment. Whatever the underlying solution for treating highly malignant cancers is, it seems that solving the question is nowhere near an achievement unless the precise cooperation of basic science knowledge with our translational experience.

Background: Aquasomes are novel trilayered non-lipoidal vesicular nanocarriers that demonstrate structural similarity to ceramic nanoparticles with theranostic activity for diseases like ovarian cancer and antigen delivery. Objective: The objective of the present article is to highlight the multifaceted potential of aquasomes over other nanocarriers for the treatment of various treatments like hemophilia A, cancer, and hepatitis. Methods: Aquasomes enter the target cell by modifying the surface chemistry, extending drug release. The solid core of aquasomes provides structural stability whereas their oligomeric coatings protect drugs from dehydration. This vesicular delivery system was successfully utilized for the delivery of acid-labile enzymes, antigens, vaccines, etc. The aquasomes nanocarrier exhibits a larger surface area, volume, and mass ratio that allows the drug to penetrate inside the cells and a prolonged drug release profile. Moreover, aquasomes consist of a high mechanical strength, reduced or no biodegradability during storage, and a good body response that facilitates deeper penetration into capillaries which makes them more special and interesting. Results: Aquasomes are a potential alternative over other nanocarriers for insulin, antigen, and oxygen delivery. Conclusion: In the near future, aquasomes-based nano-drug delivery systems can be a fascinating field for research in nanotechnology.

Background: Coronavirus disease 2019 (COVID128;‘19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is associated with a high level of mortality. Objective: This updated review aims to present the most important traditional medicinal plants and some of their secondary metabolites that have previously and more recently been shown to affect viruses and may represent a beneficial contributory step against SARS-CoV-2 as the cause of COVID-19. Moreover, the mechanism aspects of these secondary metabolites were discussed, which may help find more reliable drugs against SARSCoV- 2. Methods: Articles were searched on scientific websites including Google Scholar, Scopus, Web of Science, PubMed, and IranMedex using the search terms herbal medicine and traditional medicine with coronavirus, SARS-CoV-2, or COVID-19. Human, animal, and in vitro studies were identified in the search. Results: Medicinal plants and their secondary metabolites may possess a potential role in combating this disease, and researchers suggest that some of these plants and their constituent compounds have inhibitory activity on coronaviruses. Numerous medicinal plants, their extracts, and secondary metabolites have been investigated over a period of time for antiviral activity. Among them, kaempferol, silybin, myricitrin, licoleafol, and curcumin are promising agents with potential activity against SARS-CoV-2. Natural compounds can form strong bonds with the active sites of SARS-CoV-2 protease. Structural and non-structural SARS-CoV-2 proteins such as Spike protein, PLpro, and 3CLpro are inhibited by these phytochemicals. Conclusion: Prospective treatments targeted at the life cycle stages of the virus may eventuate from research endeavors, and it must not be discounted that therapy originally derived from plant secondary metabolite sources may potentially have a part to play.

Background: The clinical utility of Adriamycin (ADR) is limited due to its toxicity, particularly cardiotoxicity. Therefore, effective cardioprotective adjuvants to minimize ADR-induced acute cardiotoxicity are urgently needed. Our previous studies have demonstrated the protective roles of fasudil on tissue injury. Here, we further explore whether inhibition of Rho-kinase could alleviate the acute heart injury induced by ADR. Methods: C57BL6 mice were randomly divided into the following four groups: 1 ADR group; 2 low-dose fasudil (ADR+L); 3 high-dose fasudil (ADR+H); and 4 control group (CON). Animals were injected i.p 20 mg/kg ADR once in group 1~3. Animals were injected i.p fasudil (2 or 10 mg/kg/day) daily for consecutive 6 days in groups 2 and 3, respectively. Blood samples and heart tissues were collected for assays. H9C2 cells were treated with fasudil for 30 mins and then incubated with ADR for 24 hours. Cells were collected for immunohistochemistry and western blot study, respectively. Results: In the mouse model, administration of fasudil significantly ameliorated ADR-induced cardiac damage, suppressed cell apoptosis and senescence, and ameliorated redox imbalance and DNA damage. In vitro, fasudil treatment ameliorated ADR-induced immunofluorescence reaction of 8-OHdG, decreased the expression of TUNEL cells and proteins of Bax, Caspase-3 and p53, and increased the expression of proteins of Bcl-2 and SIRT 1. Conclusion: Fasudil has a protective effect on ADR induced acute cardiotoxicity, which is partially attributed to its antioxidant, anti-senescence, and anti-apoptotic effects.