Immunoinformatics approach for design novel multiepitope prophylactic and therapeutic vaccine based on capsid proteins L1 and L2 and oncoproteins E6 and E7 of human papillomavirus 16 and human papillomavirus 18 against cervical cancer.

Objectives: This study aimed to identify the optimal protein construction for designing a multi-epitope vaccine with both prophylactic and therapeutic effects against cervical cancer, utilizing an immunoinformatics approach. The construction process involved using capsid epitopes L1 and L2, as well as oncoproteins E5, E6, and E7 from human papillomavirus (HPV) types 16 and 18. Methods: An experimental in silico analysis with an immunoinformatics approach was used to develop 2 multi-epitope vaccine constructs (A and B). Further analysis was then conducted to compare the constructs and select the one with the highest potential against cervical cancer. Results: This study produced 2 antigenic, non-allergenic, and nontoxic multi-epitope vaccine constructs (A and B), which exhibited the ideal physicochemical properties for a vaccine. Further analysis revealed that construct B effectively induced both cellular and humoral immune responses. Conclusion: The multi-epitope vaccine construct B for HPV 16 and 18, designed for both prophylactic and therapeutic purposes, met the development criteria for a cervical cancer vaccine. However, these findings need to be validated through in vitro and in vivo experiments.

Anti-inflammatory activities of flavonoid derivates.

Background and purpose: Flavonoids are a group of phytochemicals found abundantly in various plants. Scientific evidence has revealed that flavonoids display potential biological activities, including their ability to alleviate inflammation. This activity is closely related to their action in blocking the inflammatory cascade and inhibiting the production of pro-inflammatory factors. However, as flavonoids typically have poor bioavailability and pharmacokinetic profile, it is quite challenging to establish these compounds as a drug. Nevertheless, progressive advancements in drug delivery systems, particularly in nanotechnology, have shown promising approaches to overcome such challenges. Review approach: This narrative review provides an overview of scientific knowledge about the mechanism of action of flavonoids in the mitigation of inflammatory reaction prior to delivering a comprehensive discussion about the opportunity of the nanotechnology-based delivery system in the preparation of the flavonoid-based drug. Key results: Various studies conducted in silico, in vitro, in vivo, and clinical trials have deciphered that the anti-inflammatory activities of flavonoids are closely linked to their ability to modulate various biochemical mediators, enzymes, and signalling pathways involved in the inflammatory processes. This compound could be encapsulated in nanotechnology platforms to increase the solubility, bioavailability, and pharmacological activity of flavonoids as well as reduce the toxic effects of these compounds. Conclusion: In Summary, we conclude that flavonoids and their derivates have given promising results in their development as new anti-inflammatory drug candidates, especially if they formulate in nanoparticles.

Designing multi-epitope based peptide vaccine candidates against SARS-CoV-2 using immunoinformatics approach.

Introduction: The current incidence of the novel coronavirus disease has shown only small reductions of cases and has become a major public health challenge. Development of effective vaccines against the virus is still being encouraged such as multi-epitope vaccines designed from the components of SARS-CoV-2 including its spike, nucleocapsid and ORF1a proteins. Since the addition of adjuvants including HABA protein and L7/L12 ribosomal are considered helpful to increase the effectiveness of the designed vaccine, we proposed to design multiepitope vaccines by two different adjuvants. Methods: We used the IEDB server to predict BCL and TCL epitopes that were characterized using online tools including VaxiJen, AllPred and IL-10 Prediction. The selected epitopes were further constructed into multiepitope vaccines. We also added two different adjuvants to the vaccine components in order to increase the effectiveness of the vaccines. The 3D-structured vaccines were built using trRosetta. They were further docked with different Toll-like-receptors (TLR 3, 4 and 8) and the entry receptor of SARS-CoV-2, ACE2 using ClusPro, PatchDock and refined by FireDock. All structures were visualized by USCF Chimera and PyMOL. Results: In this study, we succeeded in designing two different candidate vaccines by the addition of HABA protein and L7/L12 ribosomal as adjuvants. The two vaccines were almost equally good in terms of their physicochemical properties and characteristics. Likewise, their strong interactions with TLR3 4, 8 and ACE2 show the lowest energy level of both was estimated at more than -1,000. Interactions of vaccines with ACE2 and TLRs are essential for activation of immune responses and production of antibodies. Conclusion: The two designed and constructed multiepitope vaccine have good characteristics and may have the potential to activate humoral and cellular immune responses against SARS-CoV-2. Further research is worth considering to confirm the findings of this study.

Chitosan nanoparticle-mediated effect of antimiRNA-324-5p on decreasing the ovarian cancer cell proliferation by regulation of GLI1 expression.

Introduction: MicroRNAs (miRNAs) are short-sequence RNAs that regulate gene expression by targeting messenger RNAs (mRNAs). Recent studies reveal that miRNA-324-5p plays an important role in worsening the ovarian cancer prognosis when the expression is very high. This study aimed to develop a miRNA targeted therapy by targeting the miRNA-324-5p function as a miRNA-324-5p inhibitor. Methods: Chitosan nanoparticles were used for antimiRNA-324-5p delivery into SKOV3 cell lines formulated by ionic gelation method. Antiproliferative effect of CS-NPs-antimiRNA was assessed by the MTT Assay. A mechanism study assessed the anticancer effect of the formula. In silico analysis used miRTar.Human and StarmiRDB combined with Genecard to predict the target genes of antimiR. Hawkdock web server was used to analyze protein-protein interactions that were further validated by quantitative polymerase chain reaction (qPCR). Results: The results of qPCR analysis showed endogenous miRNA-324-5p decreased after 24-hour transfection of antagonist miRNA. Furthermore, the MTT assay results showed that antimiRNA was able to inhibit SKOV3 cell proliferation (80 nM 68.13%, P < 0.05). In silico analysis found miRNA-324-5p can regulate MEN1 and indirectly repress Gli1 mRNA. Validation results confirmed antimiR can decrease GLI1 mRNA expression. Conclusion: Our results showed antimiRNA-324-5p can act as a microRNA-based therapy to inhibit ovarian cancer proliferation by the reduction of GLI1 expression.

Cancer Incidence in Volcanic Areas: A Systematic Review.

BACKGROUND: There are more than 1,000 active volcanoes worldwide with inhabitants within 100 km of them. Volcanoes spill several toxic metals and spew pollution through gasses, causing soil and water contamination. The dangerously active volcanoes place the nearby population at risk for volcanic hazards. This review aimed to determine whether people living in these volcanic areas have higher risk of cancer and more attention should be given to this danger. METHODS: A systematic literature search was conducted of PUBMED, Science Direct, SCOPUS, Proquest, and Google Scholar, and from citation searching. We assessed the quality of the studies and extracted the incidence rate of cancer in the volcanic areas compared to non-volcanic areas. RESULTS: The search identified 360 articles, with 11 studies meeting our selection criteria. The results reported the incidence of cancer in children was predominantly in volcanic areas with girls suffering as much as 1.4 per 100,000 per year. The highest cancer age standardized incidence rates for females, males, and overall calculation in volcanic areas were reported as 31.7/100,000/year in Catania, 10.34/100,000/year in Furnas, and 38.3/100,000/year in Catania-Messina-Enna for thyroid cancer. We observed the increasing incidence of carcinoma for some types of cancer in volcanic areas. CONCLUSION: Cancer incidence in volcanic areas was higher than non-volcanic areas and it is caused by multifactorial conditions. The concentrations of hazardous elements of volcanic products vary among volcanoes and are related to the harmful risk for the inhabitants. The negative effects of volcanic products to human health should be given more consideration.

Emerging mutation in SARS-CoV-2 spike: Widening distribution over time in different geographic areas.

BACKGROUND: Recently, differences in mortality rates of COVID-19 in different geographic areas have become an important subject of research because these different mortality rates appear to be associated with mutations that appeared in SARS-CoV-2. The part of the viral body called the spike protein plays a critical role in the viral attachment and entry of the virus into the host cell. Accordingly, we hypothesized that mutations in this area will affect viral infectivity. METHODS: A total of 193 sequences of spike SARS-CoV-2 were randomly retrieved from five different geographic areas and collection dates (from December 2019 until July 2020). Multiple sequence alignment for mutation and phylogenetic analyses was conducted using Bioedit, UniProt, and MEGA X. RESULTS: We found 169 total mutations with 37 different mutations across the included samples. The D614G is the first and most frequently established mutation in different regions including Europe, Asia, America, Africa and Australia with the number of mutations of 49, 33, 17, 16 and 4, respectively. Furthermore, we also found mutations in several important domains in this virus including NTD and CTR/RBD of S1 subunit and at S2 subunit area, namely the peptide fusion (FP), and both heptad repetition (HR1 and 2) domains that suggested this could influence virus binding and virus-host cell membrane fusion. CONCLUSION: In summary, we concluded that mutation had generated diversity of spike SARS-CoV-2 sequences worldwide and is still growing. This analysis may provide important evidence that should be considered in vaccine development in different geographic areas.

MicroRNA-155-5p Diminishes in Vitro Ovarian Cancer Cell Viability by Targeting HIF1α Expression.

Purpose: Ovarian cancer is the most lethal of gynecological malignancies. Recently, the development of microRNA (miRNA) -based therapeutics that could impact broad cellular programs, leading to inhibition of cancer cell viability, is gaining attention in the therapeutic landscape. The therapy is based on the presence of aberrant expressions of miRNA in cancer cells. Decreasing of tumor suppressor miRNA expression causes upregulation of oncoprotein, which worsens the prognosis of the ovarian cancer. Methods: miR-155-5p mimics were carried by chitosan nanoparticles using new nanotechnology methods. Cellular uptake of miRNA was assessed by fluorescence microscope while MTT and qPCR assay were used to determine miRNA profile and the effect of CS-NP/miRNA on SKOV3 cells. Results: Results of profiling validated using quantitative realtime-polymerase chain reaction (PCR) found one of the most altered tumor suppressor miRNAs, miR-155-5p was downregulated 892.15-fold. According to bioinformatic analysis we identified the miRNA could recognize and regulate HIF1α expression. Transfection of mimics for miR-155-5p showed significantly increased miR-155-5p endogen SKOV3 expression level compared to the control group. We found differences after transfection mimics for miR-155-5p 31.5 and 63 nanoMolar. Increasing of miR-155-5p endogen lead to diminished SKOV3 viability (by 30%; <0.05 at concentration 80 nanoMolar). These mimics may cause an increase in upregulated miR-155-5p endogen that can reduce HIF1α expression. Here we found 2-fold and 2.8-fold reduction of HIF1α expression level after transfection compared to the control group. Conclusion: According to these findings, the mimics miR-155-5p can inhibit ovarian cancer cell proliferation by regulating HIF1α expression.

The Effects of Combination of Mimic miR-155-5p and Antagonist miR-324-5p Encapsulated Chitosan in Ovarian Cancer SKOV3.

OBJECTIVE: Ovarian cancer is a malignant tumor that attacks reproductive organs of women. MicroRNA is known to have an involvement in the prognosis of ovarian cancer. One of them is miR-155-5p which is down regulated and miR-324-5p which is up regulated. Chitosan is used as microRNA delivery system. The aims of this study is to find out the effects of combination microRNA encapsulated chitosan in cell line SKOV3. METHODS: Cell line SKOV3 obtained from Stem Cell and Cancer Institute (Kalbe). Mimic miR-155-5p and Antagonist miR-324-5p formulated with chitosan. Total RNA was extracted from nine samples (three as control and six as treatment), and prepared for cDNA synthesis. Expression of RNA and mRNA target was measured using q-PCR Biorad CFX96 C.100 and Gen Ex 7 software. Statistics analysis was measured using SPSS 16.0. RESULTS: The administration of combination microRNA encapsulated with chitosan affect the expression of miR-155-5p and miR-324-5p endogen (p <0.05). The expression of mRNA target HIF1α and GLI1 was down regulated after treatment. The correlation between expression of microRNA and mRNA target was strongly (p <0.05). CONCLUSION: This study successfully presented effects of combination of mimic miR-155-5p and antagonist miR-324-5p encapsulated chitosan which be considered as a potential therapy targets for ovarium cancer.