scholarly journals Bio- and Nanotechnology as the Key for Clinical Application of Salivary Peptide Histatin: A Necessary Advance

2020 ◽  
Vol 8 (7) ◽  
pp. 1024
Author(s):  
Carolina Reis Zambom ◽  
Fauller Henrique da Fonseca ◽  
Saulo Santesso Garrido
Keyword(s):  
Drug Targets ◽  
Extracellular Enzymes ◽  
Innate Immune ◽  
Host Protein ◽  
Histatin 5 ◽  
Salivary Peptide ◽  
Current Review ◽  
Adaptive Mechanisms ◽  
Antifungal Peptides ◽  
Near Future

Candida albicans is a common microorganism of human’s microbiota and can be easily found in both respiratory and gastrointestinal tracts as well as in the genitourinary tract. Approximately 30% of people will be infected by C. albicans during their lifetime. Due to its easy adaptation, this microorganism started to present high resistance to antifungal agents which is associated with their indiscriminate use. There are several reports of adaptive mechanisms that this species can present. Some of them are intrinsic alteration in drug targets, secretion of extracellular enzymes to promote host protein degradation and efflux receptors that lead to a diminished action of common antifungal and host’s innate immune response. The current review aims to bring promising alternatives for the treatment of candidiasis caused mainly by C. albicans. One of these alternatives is the use of antifungal peptides (AFPs) from the Histatin family, like histatin-5. Besides that, our focus is to show how nanotechnology can allow the application of these peptides for treatment of this microorganism. In addition, our intention is to show the importance of nanoparticles (NPs) for this purpose, which may be essential in the near future.

Reduce Disease Burden of Human Schistosomiasis in Asia Through Biological Control

2020 ◽  
Vol 20 (12) ◽  
pp. 1118-1132
Author(s):  
Sidra Saleem ◽  
Haroon Ahmed ◽  
Tooba Siddiqui ◽  
Seyma Gunyakti Kilinc ◽  
Aisha Khan ◽  
...  
Keyword(s):  
Biological Control ◽  
Geographical Distribution ◽  
Disease Burden ◽  
Management Practices ◽  
Control Strategies ◽  
Parasitic Disease ◽  
Asian Countries ◽  
Neglected Disease ◽  
Current Review ◽  
Near Future

Schistosomiasis is a chronic parasitic disease caused by a trematode blood fluke of the genus Schistosoma that belongs to the Schistosomatidae family. It is a neglected disease in different regions of Asia. In this review, 218 articles (between 2000 and 2017) related to the topic were collected from PubMed and Google scholar and reviewed. After thoroughly reading collected articles, due to irrelevant topic requirements, 94 articles were excluded. Articles that have data associated with Asian regions are considered. In Asia, the disease is prevalent in China, Philippines, Indonesia, Yemen, Nepal and Laos, etc. While in Pakistan, India and Bangladesh, the disease is not endemic and very few cases were reported. The disease was eliminated from Japan and Iran. The current review highlights the geographical distribution among Asian countries, transmission patterns, diagnosis, control strategies based on the use of anthelmintic plants and management practices implemented in Asia for the control of schistosomiasis. However, new implementations to treat schistosomiasis in humans should be proved to eliminate the disease finally in the future. This review emphasizes the biological control of schistosomiasis for the eradication of the disease from Asia in the near future.

scholarly journals Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3395
Author(s):  
Maria Radanova ◽  
Galya Mihaylova ◽  
Neshe Nazifova-Tasinova ◽  
Mariya Levkova ◽  
Oskan Tasinov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Targets ◽  
Clinicopathological Characteristics ◽  
Circular Rnas ◽  
Diagnostic Biomarkers ◽  
The Third ◽  
Current Review ◽  
Important Challenge ◽  
Prediction Of Metastasis

Colorectal cancer (CRC) is ranked as the second most commonly diagnosed disease in females and the third in males worldwide. Therefore, the finding of new more reliable biomarkers for early diagnosis, for prediction of metastasis, and resistance to conventional therapies is an important challenge in overcoming the disease. The current review presents circular RNAs (circRNAs) with their unique features as potential prognostic and diagnostic biomarkers in CRC. The review highlights the mechanism of action and the role of circRNAs with oncogenic functions in the CRC as well as the association between their expression and clinicopathological characteristics of CRC patients. The comprehension of the role of oncogenic circRNAs in CRC pathogenesis is growing rapidly and the next step is using them as suitable new drug targets in the personalized treatment of CRC patients.

Zn2+Ions Selectively Induce Antimicrobial Salivary Peptide Histatin-5 To Fuse Negatively Charged Vesicles. Identification and Characterization of a Zinc-Binding Motif Present in the Functional Domain†

Biochemistry ◽  
1999 ◽  
Vol 38 (30) ◽  
pp. 9626-9633 ◽  
Author(s):  
Sonia Melino ◽  
Stefano Rufini ◽  
Marco Sette ◽  
Roberto Morero ◽  
Alessandro Grottesi ◽  
...  
Keyword(s):  
Zinc Binding ◽  
Binding Motif ◽  
Functional Domain ◽  
Histatin 5 ◽  
Salivary Peptide ◽  
Identification And Characterization ◽  
Zinc Binding Motif

scholarly journals Modulation of Innate Immune Responses by the Influenza A NS1 and PA-X Proteins

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 708 ◽  
Author(s):  
Aitor Nogales ◽  
Luis Martinez-Sobrido ◽  
David Topham ◽  
Marta DeDiego
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Defense Mechanisms ◽  
Synergistic Effects ◽  
Viral Proteins ◽  
Economic Problem ◽  
Innate Immune ◽  
Host Protein ◽  
Innate Immune Responses ◽  
Influenza A Viruses

Influenza A viruses (IAV) can infect a broad range of animal hosts, including humans. In humans, IAV causes seasonal annual epidemics and occasional pandemics, representing a serious public health and economic problem, which is most effectively prevented through vaccination. The defense mechanisms that the host innate immune system provides restrict IAV replication and infection. Consequently, to successfully replicate in interferon (IFN)-competent systems, IAV has to counteract host antiviral activities, mainly the production of IFN and the activities of IFN-induced host proteins that inhibit virus replication. The IAV multifunctional proteins PA-X and NS1 are virulence factors that modulate the innate immune response and virus pathogenicity. Notably, these two viral proteins have synergistic effects in the inhibition of host protein synthesis in infected cells, although using different mechanisms of action. Moreover, the control of innate immune responses by the IAV NS1 and PA-X proteins is subject to a balance that can determine virus pathogenesis and fitness, and recent evidence shows co-evolution of these proteins in seasonal viruses, indicating that they should be monitored for enhanced virulence. Importantly, inhibition of host gene expression by the influenza NS1 and/or PA-X proteins could be explored to develop improved live-attenuated influenza vaccines (LAIV) by modulating the ability of the virus to counteract antiviral host responses. Likewise, both viral proteins represent a reasonable target for the development of new antivirals for the control of IAV infections. In this review, we summarize the role of IAV NS1 and PA-X in controlling the antiviral response during viral infection.

scholarly journals Targeting LIN28: a new hope in prostate cancer theranostics

2021 ◽  
Author(s):  
Garima Shrivastava ◽  
Alaa AA Aljabali ◽  
Seyed Hossein Shahcheraghi ◽  
Marzieh Lotfi ◽  
Madhur D Shastri ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Clinical Research ◽  
Recent Work ◽  
Drug Targets ◽  
Molecular Probes ◽  
Mortality And Morbidity ◽  
Remarkable Increase ◽  
Current Review ◽  
Cancer Theranostics

The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.

scholarly journals Core Protein-Directed Antivirals and Importin β Can Synergistically Disrupt HBV Capsids

2021 ◽  
Author(s):  
Christine Kim ◽  
Lauren Barnes ◽  
Christopher Schlicksup ◽  
Angela Patterson ◽  
Brian Bothner ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Core Protein ◽  
Innate Immune ◽  
Host Protein ◽  
Structural Proteins ◽  
Nuclear Trafficking ◽  
Terminal Domain ◽  
Viral Lifecycle ◽  
Capsid Stability

ABSTRACTViral structural proteins can have multiple activities. Antivirals that target structural proteins have potential to exhibit multiple antiviral mechanisms. Hepatitis B Virus (HBV) core protein (Cp) is involved in most stages of the viral lifecycle: it assembles into capsids, packages viral RNA, is a metabolic compartment for reverse transcription, interacts with nuclear trafficking machinery, and disassembles to release the viral genome into the nucleus. During nuclear localization, HBV capsids bind to host importins (e.g. Impβ) via Cp’s C-terminal domain (CTD); the CTD is localized to the interior of the capsid and is transiently exposed on the exterior. We used HAP12 as a representative Cp Allosteric Modulators (CpAMs), a class of antivirals that inappropriately stimulates and misdirects HBV assembly and deforms capsids. CpAM impact on other aspects of the HBV lifecycle is poorly understood. We investigated how HAP12 influenced the interactions between empty or RNA-filled capsids with Impβ and trypsin in vitro. We showed that HAP12 can modulate CTD accessibility and capsid stability, depending on the saturation of HAP12-binding sites. We demonstrated that Impβ synergistically contributes to capsid disruption at high levels of HAP12 saturation, using electron microscopy to visualize disruption and rearrangement of Cp dimers into aberrant complexes. However, RNA-filled capsids resisted the destabilizing effects of HAP12 and Impβ. In summary, we show host protein-induced catalysis of capsid disruption, an unexpected additional mechanism of action for CpAMs. Potentially, untimely capsid disassembly can hamper the HBV lifecycle and also cause the virus to become vulnerable to host innate immune responses.IMPORTANCEThe HBV core, an icosahedral complex of 120 copies of the homodimeric core (capsid) protein with or without packaged nucleic acid, is transported to the host nucleus by its interaction with host importin proteins. Importin-core interaction requires the core protein C-terminal domain, which is inside the capsid, to “flip” to the capsid exterior. Core-protein directed drugs that affect capsid assembly and stability have been developed recently. We show that these molecules can, synergistically with importins, disrupt capsids. This mechanism of action, synergism with host protein, has potential to disrupt the virus lifecycle and activate the innate immune system.

scholarly journals Asian and African lineage Zika viruses show differential replication and innate immune responses in human dendritic cells and macrophages

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pamela Österlund ◽  
Miao Jiang ◽  
Veera Westenius ◽  
Suvi Kuivanen ◽  
Riia Järvi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Asian American ◽  
Pacific Islands ◽  
Fetal Brain ◽  
Innate Immune ◽  
Host Protein ◽  
Cytokine Gene Expression ◽  
Innate Immune Responses ◽  
African Lineage

Abstract Zika virus (ZIKV) infections in humans are considered to be mild or subclinical. However, during the recent epidemics in the Pacific Islands and the Americas, the infection was associated with Quillain-Barré syndrome and congenital infections with fetal brain abnormalities, including microcephaly. Thus, more detailed understanding of ZIKV-host cell interactions and regulation of innate immune responses by strains of differential evolutionary origin is required. Here, we characterized the infection and immune responses triggered by two epidemic Asian/American lineage viruses, including an isolate from fetal brains, and a historical, low passage 1947 African lineage virus in human monocyte-derived dendritic cells (DCs) and macrophages. The epidemic Asian/American ZIKV replicated well and induced relatively good antiviral responses in human DCs whereas the African strain replicated less efficiently and induced weaker immune responses. In macrophages both the African and Asian strains showed limited replication and relatively weak cytokine gene expression. Interestingly, in macrophages we observed host protein degradation, especially IRF3 and STAT2, at early phases of infection with both lineage viruses, suggesting an early proteasomal activation in phagocytic cells. Our data indicates that ZIKV evolution has led to significant phenotypic differences in the replication characteristics leading to differential regulation of host innate immune responses.

scholarly journals Papain-Like Proteases as Coronaviral Drug Targets: Current Inhibitors, Opportunities, and Limitations

2020 ◽  
Vol 13 (10) ◽  
pp. 277 ◽  
Author(s):  
Anastasiia I. Petushkova ◽  
Andrey A. Zamyatnin
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Genome ◽  
Drug Targets ◽  
Structural Features ◽  
The Third ◽  
Frequent Mutations ◽  
Near Future ◽  
Viral Reproduction

Papain-like proteases (PLpro) of coronaviruses (CoVs) support viral reproduction and suppress the immune response of the host, which makes CoV PLpro perspective pharmaceutical targets. Their inhibition could both prevent viral replication and boost the immune system of the host, leading to the speedy recovery of the patient. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third CoV outbreak in the last 20 years. Frequent mutations of the viral genome likely lead to the emergence of more CoVs. Inhibitors for CoV PLpro can be broad-spectrum and can diminish present and prevent future CoV outbreaks as PLpro from different CoVs have conservative structures. Several inhibitors have been developed to withstand SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). This review summarizes the structural features of CoV PLpro, the inhibitors that have been identified over the last 20 years, and the compounds that have the potential to become novel effective therapeutics against CoVs in the near future.

scholarly journals Identifying novel biomarkers of the pediatric influenza infection by weighted co-expression network analysis

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Mohadeseh Zarei Ghobadi ◽  
Sayed-Hamidreza Mozhgani ◽  
Mahdieh Farzanehpour ◽  
Farida Behzadian
Keyword(s):  
Immune System ◽  
Network Analysis ◽  
Differentially Expressed Genes ◽  
Drug Targets ◽  
Protein Targeting ◽  
Influenza Infection ◽  
Innate Immune ◽  
Differentially Expressed ◽  
Complex Interactions ◽  
Novel Biomarkers

Abstract Background Despite the high yearly prevalence of Influenza, the pathogenesis mechanism and involved genes have not been fully known. Finding the patterns and mapping the complex interactions between different genes help us to find the possible biomarkers and treatment targets. Methods Herein, weighted gene co-expression network analysis (WGCNA) was employed to construct a co-expression network among genes identified by microarray analysis of the pediatric influenza-infected samples. Results Three of the 38 modules were found as the most related modules to influenza infection. At a functional level, we found that the genes in these modules regulate the immune responses, protein targeting, and defense to virus. Moreover, the analysis of differentially expressed genes disclosed 719 DEGs between the normal and infected subjects. The comprehensive investigation of genes in the module involved in immune system and viral defense (yellow module) revealed that SP110, HERC5, SAMD9L, RTP4, C19orf66, HELZ2, EPSTI1, and PHF11 which were also identified as DEGs (except C19orf66) have the potential to be as the biomarkers and also drug targeting for the treatment of pediatric influenza. Conclusions The WGCN analysis revealed co-expressed genes which were involved in the innate immune system and defense to virus. The differentially expressed genes in the identified modules can be considered for designing drug targets. Moreover, modules can help to find pathogenesis routes in the future.

scholarly journals The human salivary peptide histatin 5 exerts its antifungal activity through the formation of reactive oxygen species

2001 ◽  
Vol 98 (25) ◽  
pp. 14637-14642 ◽  
Author(s):  
E. J. Helmerhorst ◽  
R. F. Troxler ◽  
F. G. Oppenheim
Keyword(s):  
Reactive Oxygen Species ◽  
Antifungal Activity ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Histatin 5 ◽  
Salivary Peptide
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