Melittin: A Natural Peptide with Expanded Therapeutic Applications

2020 ◽  
Vol 10 ◽  
Author(s):  
Ruchi Tiwari ◽  
Gaurav Tiwari ◽  
Akanksha Lahiri ◽  
Vadivelan Ramachandran ◽  
Awani Rai
Keyword(s):  
Bee Venom ◽  
Research Progress ◽  
Cellular Functions ◽  
Venom Component ◽  
Therapeutic Applications ◽  
Therapeutic Uses ◽  
Infected Cells ◽  
Broad Variety ◽  
Natural Peptide ◽  
Therapeutic Activities

Background: Apis mellifera, European honey bee venom (BV) is a complex combination of chemical compounds comprising proteins, peptides, enzymes, and other small molecules. Melittin (MEL), which is the key component of BV is considered as an alternative for treatment of various infections. MEL is an amphipathic, cell-penetrating, 26-residue, ahelical anti-hepatoma peptide derived from BV. However, owing to its initial conformational strength and poor stability, melittin is constrained in use as a medication. Objective: The study focused on collective data of therapeutic activities of Bee venom component, MEL. Method: Regardless of its broad variety of biological and possible therapeutic uses, there has been increasing concern in the use of MEL. According to literature, MEL revealed range of activities started from Anti- cancer activity, Anti- microbial activity, Anti- viral activity, Anti-inflammatory activity to Anti- diabetic activity. Present review article summarized therapeutic applications of MEL, their mechanism of action along with recent research progress in field of its delivery. Conclusion: It could be concluded that MEL exerts multiple effects on cellular functions of infected cells.

scholarly journals Sex Dolls in the Swedish Media Discourse: Intimacy, Sexuality, and Technology

2021 ◽  
Author(s):  
Robin Björkas ◽  
Mariah Larsson
Keyword(s):  
Critical Discourse Analysis ◽  
Critical Discourse ◽  
Sexual Practices ◽  
Media Discourse ◽  
Positive Effects ◽  
Therapeutic Uses ◽  
Broad Variety ◽  
The Media ◽  
Definition Of ◽  
The Relationship

AbstractSex dolls are a complex phenomenon with several diverse possible emotional, sexual and therapeutic uses. They can be part of a broad variety of sexual practices, and also function as a sexual aid. However, the media discourse on sex dolls first and foremost concerns how we perceive the relationship between intimacy and technology. A critical discourse analysis of the Swedish media discourse on sex dolls reveals six themes which dominate the discourse: (a) the definition of what a human being is; (b) a discourse on the (technological and existential) future; (c) a social effort; (d) a loveless phenomenon; (e) men’s violence against women; and (f) pedophilia. Accordingly, this discourse is very conservative and normative in its view of sexuality, technology, and humanity. Overall, the dominant themes do not provide any space for positive effects of technology on human sexuality, and if they do, it is usually as a substitute for something else.

scholarly journals Research Progress of the Antiviral Bioactivities of Natural Flavonoids

2020 ◽  
Vol 10 (5) ◽  
pp. 271-283
Author(s):  
Lin Wang ◽  
Junke Song ◽  
Ailin Liu ◽  
Bin Xiao ◽  
Sha Li ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Research Progress ◽  
Future Perspectives ◽  
Therapeutic Applications ◽  
Pharmaceutical Applications ◽  
Antiviral Activities

Abstract Flavonoids are now considered as an indispensable component in a variety of nutraceutical and pharmaceutical applications. Most recent researches have focused on the health aspects of flavonoids for humans. Especially, different flavonoids have been investigated for their potential antiviral activities, and several natural flavonoids exhibited significant antiviral properties both in vitro and in vivo. This review provides a survey of the literature regarding the evidence for antiviral bioactivities of natural flavonoids, highlights the cellular and molecular mechanisms of natural flavonoids on viruses, and presents the details of most reported flavonoids. Meanwhile, future perspectives on therapeutic applications of flavonoids against viral infections were discussed.

scholarly journals Intracellular HIV-1 Tat protein represses constitutive LMP2 transcription increasing proteasome activity by interfering with the binding of IRF-1 to STAT1

2006 ◽  
Vol 396 (2) ◽  
pp. 371-380 ◽  
Author(s):  
Anna L. Remoli ◽  
Giulia Marsili ◽  
Edvige Perrotti ◽  
Eleonora Gallerani ◽  
Ramona Ilari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mhc Class I ◽  
Consensus Sequence ◽  
Class I ◽  
Tat Protein ◽  
Cellular Functions ◽  
Infected Cells ◽  
Cryptic Epitopes ◽  
Hiv 1

The Tat protein is the transcriptional activator of HIV-1 gene expression, which is not only essential for viral replication, but also important in the complex HIV-induced pathogenesis of AIDS, as both an intracellular and an extracellular released protein. Accordingly, Tat is able to profoundly affect cellular gene expression, regulating several cellular functions, also in non-infected cells. We showed recently that Tat induces modification of immunoproteasomes in that it up-regulates LMP7 (low-molecular-mass polypeptide 7) and MECL1 (multicatalytic endopeptidase complex-like 1) subunits and down-modulates the LMP2 subunit, resulting in a change in the generation and presentation of epitopes in the context of MHC class I. In particular, Tat increases presentation of subdominant and cryptic epitopes. In the present study, we investigated the molecular mechanism responsible for the Tat-induced LMP2 down-regulation and show that intracellular Tat represses transcription of the LMP2 gene by competing with STAT1 (signal transducer and activator of transcription 1) for binding to IRF-1 (interferon-regulatory factor-1) on the overlapping ICS-2 (interferon consensus sequence-2)–GAS (γ-interferon-activated sequence) present in the LMP2 promoter. This element is constitutively occupied in vivo by the unphosphorylated STAT1–IRF-1 complex, which is responsible for the basal transcription of the gene. Sequestration of IRF-1 by intracellular Tat impairs the formation of the complex resulting in lower LMP2 gene transcription and LMP2 protein expression, which is associated with increased proteolytic activity. On the other hand, extracellular Tat induces the expression of LMP2. These effects of Tat provide another effective mechanism by which HIV-1 affects antigen presentation in the context of the MHC class I complex and may have important implications in the use of Tat for vaccination strategies.

scholarly journals Identification of Epstein-Barr Virus RK-BARF0-Interacting Proteins and Characterization of Expression Pattern

2004 ◽  
Vol 78 (23) ◽  
pp. 12848-12856 ◽  
Author(s):  
Natalie J. Thornburg ◽  
Shuichi Kusano ◽  
Nancy Raab-Traub
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Interacting Proteins ◽  
Cellular Functions ◽  
Barr Virus ◽  
Acid Protein ◽  
Infected Cells ◽  
Epstein Barr ◽  
Endoplasmic Reticulum Targeting

ABSTRACT The Epstein-Barr virus (EBV) BamHI A transcripts are a family of transcripts that are differentially spliced and can be detected in multiple EBV-associated malignancies. Several of the transcripts may encode proteins. One transcript of interest, RK-BARF0, is proposed to encode a 279-amino-acid protein with a possible endoplasmic reticulum-targeting sequence. In this study, the properties of RK-BARF0 were examined through identification of cellular-interacting proteins through yeast two-hybrid analysis and characterization of its expression in EBV-infected cells and tumors. In addition to the interaction previously identified with cellular Notch, it was determined that RK-BARF0 also bound cellular human I-mfa domain-containing protein (HIC), epithelin, and scramblase. An interaction between RK-BARF0 and Notch or epithelin induced proteasome-dependent degradation of Notch and epithelin but not of HIC or scramblase. Low levels of endogenous Notch expression in EBV-positive cell lines may correlate with RK-BARF0 expression. However, a screen of EBV-positive cell lines and tumors with an affinity-purified α-RK-BARF0 antiserum did not consistently detect RK-BARF0. These data suggest that while RK-BARF0 may have important cellular functions during EBV infection, and while the phenotype of EBV-positive cells suggest its expression, RK-BARF0 levels may be too low to detect.

scholarly journals A subpopulation of arenavirus nucleoprotein localizes to mitochondria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francesca Baggio ◽  
Udo Hetzel ◽  
Lisbeth Nufer ◽  
Anja Kipar ◽  
Jussi Hepojoki
Keyword(s):  
Mammalian Cells ◽  
Cytoplasmic Inclusion ◽  
Mitochondrial Morphology ◽  
Cellular Functions ◽  
Cellular Defense ◽  
Mitochondrial Functions ◽  
Infected Cells ◽  
Cytoplasmic Inclusion Bodies ◽  
Targeting Signal

AbstractViruses need cells for their replication and, therefore, ways to hijack cellular functions. Mitochondria play fundamental roles within the cell in metabolism, immunity and regulation of homeostasis due to which some viruses aim to alter mitochondrial functions. Herein we show that the nucleoprotein (NP) of arenaviruses enters the mitochondria of infected cells, affecting the mitochondrial morphology. Reptarenaviruses cause boid inclusion body disease (BIBD) that is characterized, especially in boas, by the formation of cytoplasmic inclusion bodies (IBs) comprising reptarenavirus NP within the infected cells. We initiated this study after observing electron-dense material reminiscent of IBs within the mitochondria of reptarenavirus infected boid cell cultures in an ultrastructural study. We employed immuno-electron microscopy to confirm that the mitochondrial inclusions indeed contain reptarenavirus NP. Mutations to a putative N-terminal mitochondrial targeting signal (MTS), identified via software predictions in both mamm- and reptarenavirus NPs, did not affect the mitochondrial localization of NP, suggesting that it occurs independently of MTS. In support of MTS-independent translocation, we did not detect cleavage of the putative MTSs of arenavirus NPs in reptilian or mammalian cells. Furthermore, in vitro translated NPs could not enter isolated mitochondria, suggesting that the translocation requires cellular factors or conditions. Our findings suggest that MTS-independent mitochondrial translocation of NP is a shared feature among arenaviruses. We speculate that by targeting the mitochondria arenaviruses aim to alter mitochondrial metabolism and homeostasis or affect the cellular defense.

Advancement in Pharmacological Activities of Benzothiazole and its Derivatives:An Up to Date Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Sumit ◽  
Arvind Kumar ◽  
Arun Kumar Mishra
Keyword(s):  
Molecular Structures ◽  
Biologically Active ◽  
Future Research ◽  
Thiazole Ring ◽  
Bicyclic Compound ◽  
Pharmacological Activities ◽  
Broad Variety ◽  
Bioactive Heterocycles ◽  
Available Information ◽  
Therapeutic Activities

: Benzothiazole is a heterocyclic aromatic and bicyclic compound in which, benzene ring is attached with thiazole ring. This nucleus is established in marine as well as terrestrial natural compounds. The benzothiazole skeleton is established in a broad variety of bioactive heterocycles and natural products. The benzothiazole nucleus is considered as the principle moiety in several biologically active compounds. Thus, over the decade, chemists are more and more paying attention towards the revision on the biological and therapeutic activities such including antimicrobial, analgesic, antininflammatory, antitubercular, antiviral and antioxidant of benzothiazole containing compounds. Additionally, the molecular structures of a number of potent drugs including Frentizole, Pramipexole, Thioflavin T and Riluzole etc are based on benzothiazole skeleton. The present work is the compilation and presentation of all available information in a systematic manner with an aim to present the findings in a way, which may be beneficial for future research.

scholarly journals Epigenetic reprogramming promotes the antiviral action of IFNα in HBV-infected cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Luc Gailhouste ◽  
Masayuki Sudoh ◽  
Xian-Yang Qin ◽  
Koichi Watashi ◽  
Takaji Wakita ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Sodium Taurocholate ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Epigenetic Reprogramming ◽  
Oligoadenylate Synthetase ◽  
Cellular Functions ◽  
Interferon Stimulated Genes ◽  
Chronic Hepatitis B Virus ◽  
Infected Cells

AbstractChronic hepatitis B virus (HBV) infections remain a health burden affecting ~250 million people worldwide. Thus far, available interferon-alpha (IFNα)-based therapies have shown unsatisfactory cure rates, and alternative therapeutic molecules are still required. However, their development has been hampered because accessible cell models supporting relevant HBV replication and appropriate antiviral activity are lacking. Strategies that reverse epigenetic alterations offer a unique opportunity for cell reprogramming, which is valuable for restoring altered cellular functions in human cell lines. This work aimed to investigate the feasibility of converting HepG2 cells that stably overexpress the HBV entry receptor (sodium/taurocholate cotransporting polypeptide, NTCP) toward IFNα-responsive cells using epigenetic reprogramming. Herein, we showed that an epigenetic regimen with non-cytotoxic doses of the demethylating compound 5-azacytidine restored the anti-HBV action of IFNα in epigenetically reprogrammed HepG2-NTCP-C4 cells, named REP-HepG2-NTCP cells. Thus, a significant inhibition in HBV DNA levels was measured in REP-HepG2-NTCP cells after IFNα treatment. This inhibitory effect was associated with the enhancement of IFNα-mediated induction of critical interferon-stimulated genes (ISGs), which was limited in non-reprogrammed cells. In particular, our data indicated that re-expression of 2’-5’-oligoadenylate synthetase 1 (OAS1) and interferon regulatory factor 9 (IRF9) was the result of an epigenetically driven unmasking of these genes in reprogrammed cells. At last, we evaluated the therapeutic potential of the IFN analog CDM-3008 in REP-HepG2-NTCP cells and demonstrated the efficiency of this chemical compound in triggering ISG induction and HBV inhibition. In summary, this study shows that epigenetic reprogramming promotes the IFNα response in HBV-infected cells and is potentially attractive for cell-based experimental screening of IFN-like compounds.

scholarly journals Gene 33/Mig6/ERRFI1, an Adapter Protein with Complex Functions in Cell Biology and Human Diseases

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1574
Author(s):  
Dazhong Xu ◽  
Cen Li
Keyword(s):  
Cell Biology ◽  
Research Progress ◽  
Cellular Functions ◽  
Protein Protein Interaction ◽  
Calculated Molecular Weight ◽  
New Findings ◽  
Complex Functions ◽  
Associated Functions ◽  
Multiple Cell ◽  
Multiple Domains

Gene 33 (also named Mig6, RALT, and ERRFI1) is an adapter/scaffold protein with a calculated molecular weight of about 50 kD. It contains multiple domains known to mediate protein–protein interaction, suggesting that it has the potential to interact with many cellular partners and have multiple cellular functions. The research over the last two decades has confirmed that it indeed regulates multiple cell signaling pathways and is involved in many pathophysiological processes. Gene 33 has long been viewed as an exclusively cytosolic protein. However, recent evidence suggests that it also has nuclear and chromatin-associated functions. These new findings highlight a significantly broader functional spectrum of this protein. In this review, we will discuss the function and regulation of Gene 33, as well as its association with human pathophysiological conditions in light of the recent research progress on this protein.

scholarly journals The dual regulation of apoptosis by Flavivirus

2020 ◽  
Author(s):  
Yuhong Pan ◽  
Anchun Cheng ◽  
Mingshu Wang ◽  
Zhong Yin ◽  
Ren-Yong Jia
Keyword(s):  
Immune Response ◽  
Endoplasmic Reticulum ◽  
Signaling Pathways ◽  
Death Receptor ◽  
Scientific Basis ◽  
Research Progress ◽  
Host Defenses ◽  
Host Proteins ◽  
Infected Cells ◽  
Induced Apoptosis

Apoptosis is a form of programmed cell death, which maintains cellular homeostasis by eliminating pathogen-infected cells. It contains three signaling pathways: death receptor pathway, mitochondria-mediated pathway and endoplasmic reticulum pathway. Its importance in host defenses is highlighted by the observation that many viruses evade, hinder or destroy apoptosis, thereby weakening the host’s immune response. Flaviviruses such as Dengue virus, Japanese encephalitis virus and West Nile virus utilize various strategies to activate or inhibit cell apoptosis. This article reviews the research progress of apoptosis mechanism during flaviviruses infection, including flaviviruses proteins to regulate apoptosis by interacting with host proteins, as well as various signaling pathways involved in flaviviruses-induced apoptosis, which provides a scientific basis for understanding the pathogenesis of flaviviruses and helps in developing an effective antiviral therapy.

Resveratrol: A Vital Therapeutic Agent with Multiple Health Benefits

Drug Research ◽  
2021 ◽  
Author(s):  
Arshpreet Kaur ◽  
Ruchi Tiwari ◽  
Gaurav Tiwari ◽  
Vadivelan Ramachandran
Keyword(s):  
Defense Mechanism ◽  
Scientific Development ◽  
Polygonum Cuspidatum ◽  
Cellular Functions ◽  
Activity Data ◽  
Wide Range ◽  
Anti Cancer ◽  
Infected Cells ◽  
Natural Phenolic Compounds ◽  
Multiple Health

AbstractResveratrol (RSV), the most effective stilbene phytoalexin synthesized naturally or induced in plants as part of their defense mechanism, is a key component of natural phenolic compounds and is being considered as a treatment option for a variety of diseases. RSV was discovered in the skin of red grapes, mulberries, peanuts, pines, and Polygonum cuspidatum weed root extracts. It was first extracted from white hellebore (Veratrum grandiflorum O. Loes) roots in 1940, then from Polygonum cuspidatum roots in 1963. However, RSV’s use as a drug is limited due to its initial conformational strength and poor stability. The research focused on a set of RSV biological activity data. RSV has been the subject of growing concern, despite its wide range of biological and therapeutic applications. According to the literature, RSV has antioxidant, anti-cancer, cardioprotective, neuroprotective, anti- inflammatory, anti-microbial, immunomodulatory, and radioprotective properties. The current analysis summarized biological applications of RSV, their mechanisms of action, and recent scientific development in the area of their delivery. It is possible to infer that RSV has many effects on infected cells’ cellular functions.

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