scholarly journals Current prevention and potential treatment options for dengue infection

2019 ◽  
Vol 22 ◽  
pp. 440-456
Author(s):  
Malina Jasamai ◽  
Wei Boon Yap ◽  
Aurapa Sakulpanich ◽  
Azmath Jaleel
Keyword(s):  
Defense Mechanism ◽  
Treatment Options ◽  
Dengue Infection ◽  
Antiviral Agents ◽  
Supportive Therapy ◽  
Replication Process ◽  
Larvivorous Fish ◽  
Vector Population ◽  
Host Defense Mechanism ◽  
Virus Replication Cycle

Currently, treatments for dengue infection are only symptomatic as no antiviral agents nor vaccines are available to combat this virus. Despite challenges faced by researchers, many efforts are ongoing to reduce cases of dengue infection either by targeting the vector or the virus. Vector population is monitored and reduced by using mechanical, chemical and biological controls. Chemical control is achieved either by using synthetic or natural insecticides where the latter is more preferable. In biological control, bacteria, fungi and larvivorous fish are utilised to reduce the vector population. Moreover, genes of mosquitoes are also explored to produce progenies which are sterile with low survival ability. Vaccines are among the most effective ways to prevent viral infection. Various approaches have been used and are still being explored towards producing vaccines for dengue. These include live attenuated, inactivated, recombinant subunit, nucleic acid and virus-like particles vaccines. The aim is to produce a vaccine which can target all the four serotypes of the virus. Monoclonal antibodies are widely researched on to equip the host defense mechanism against the dengue virus. Deeper understanding of the virus replication cycle warrants the development of antiviral agents which target viral proteins vital for the replication process. Bioactive compounds are also utilised in the development of antiviral agents. The importance of surveillance and supportive therapy are also discussed.

scholarly journals Connecting the dots: Translating the vaginal microbiome into a drug

2020 ◽  
Author(s):  
Laurel A Lagenaur ◽  
Anke Hemmerling ◽  
Charles Chiu ◽  
Steve Miller ◽  
Peter P Lee ◽  
...  
Keyword(s):  
Defense Mechanism ◽  
Treatment Options ◽  
Interesting Case ◽  
Vaginal Microbiota ◽  
Lactobacillus Species ◽  
Obstetric Outcomes ◽  
Urogenital Infections ◽  
Host Defense Mechanism ◽  
Important Host ◽  
New Treatment

Abstract A Lactobacillus-dominated vaginal microbiota (VMB) has been associated with health and considered an important host defense mechanism against urogenital infections. Conversely, depletion of lactobacilli and increased microbial diversity, or dysbiosis, increases the risk of adverse gynecologic and obstetric outcomes. A common clinical condition that exemplifies dysbiosis is bacterial vaginosis (BV). BV is currently treated with antibiotics, but frequently recurs, due in part to persistent dysbiosis and failure of endogenous lactobacilli to repopulate the vagina. New treatment options are therefore needed to address recurrent urogenital infections, including BV. The VMB represents an interesting case study for the development of microbiome-based therapeutics. Compared to the gut, the vaginal microbiota is relatively simple and optimally dominated by one or several species of one genus, i.e. Lactobacillus. Further, hydrogen peroxide (H2O2)-producing species, such as L. crispatus, show the strongest associations with vaginal health and are depleted in dysbiosis. Thus, replenishing the dysbiotic VMB with protective vaginal Lactobacillus species could be a promising approach to prevent recurrent infections and improve women’s health. In this article we discuss confirmation of this approach with the microbiome-based biologic drug, LACTIN-V (Lactobacillus crispatus CTV-05), focusing on prevention of BV recurrence.

scholarly journals The IL-33-ILC2 pathway protects from amebic colitis

2021 ◽  
Author(s):  
Md Jashim Uddin ◽  
Jhansi L. Leslie ◽  
Stacey L. Burgess ◽  
Noah Oakland ◽  
Brandon Thompson ◽  
...  
Keyword(s):  
Tissue Damage ◽  
Cell Injury ◽  
Defense Mechanism ◽  
Protozoan Parasite ◽  
Lymphoid Cells ◽  
Amebic Colitis ◽  
Host Defense Mechanism ◽  
Important Host ◽  
Murine Colon

AbstractEntamoeba histolytica is a pathogenic protozoan parasite that causes intestinal colitis, diarrhea, and in some cases, liver abscess. Through transcriptomics analysis, we observed that E. histolytica infection was associated with increased expression of IL-33 mRNA in both the human and murine colon. IL-33, the IL-1 family cytokine, is released after cell injury to alert the immune system of tissue damage. Treatment with recombinant IL-33 protected mice from amebic infection and intestinal tissue damage; moreover, blocking IL-33 signaling made mice more susceptible to amebiasis. IL-33 limited the recruitment of inflammatory immune cells and decreased the pro-inflammatory cytokine IL-6 in the cecum. Type 2 immune responses were upregulated by IL-33 treatment during amebic infection. Interestingly, administration of IL-33 protected RAG2–/– mice but not RAG2−/−γc−/− mice, demonstrating that IL-33-mediated protection required the presence of innate lymphoid cells (ILCs). IL-33 induced recruitment of ILC2 but not ILC1 and ILC3 in RAG2−/− mice. At baseline and after amebic infection, there was a significantly higher IL13+ILC2s in C57BL/J mice, which are naturally resistant to amebiasis, than CBA/J mice. Adoptive transfer of ILC2s to RAG2−/−γc−/− mice restored IL-33-mediated protection. These data reveal that the IL-33-ILC2 pathway is an important host defense mechanism against amebic colitis.

scholarly journals Novel System for the Simultaneous Analysis ofGeminivirus DNA Replication and Plant Interactions in Nicotianabenthamiana

2003 ◽  
Vol 77 (24) ◽  
pp. 13315-13322 ◽  
Author(s):  
Yiguo Hong ◽  
John Stanley ◽  
Rene van Wezel
Keyword(s):  
Defense Mechanism ◽  
Intracellular Localization ◽  
Potato Virus X ◽  
African Cassava Mosaic Virus ◽  
Origin Of Replication ◽  
Amino Acid Residues ◽  
Plant Interactions ◽  
In Planta ◽  
Gfp Fusion Protein ◽  
Host Defense Mechanism

ABSTRACT The origin of replication of African cassava mosaic virus (ACMV) and a gene expression vector based on Potato virus X were exploited to devise an in planta system for functional analysis of the geminivirus replication-associated protein (Rep) in transgenic Nicotiana benthamiana line pOri-2. This line contains an integrated copy of a tandem repeat of the ACMV origin of replication flanking nonviral sequences that can be mobilized and replicated by Rep as an episomal replicon. A Rep-GFP fusion protein can also mobilize and amplify the replicon, facilitating Rep detection in planta. The activity of Rep and its mutants, Rep-mediated host response, and the correlation between Rep intracellular localization and biological functions could be effectively assessed by using this in planta system. Our results indicate that modification of amino acid residues R2, R5, R7 and K11 or H56, L57 and H58 prevent Rep function in replication. This defect correlates with possible loss of Rep nuclear localization and inability to trigger the host defense mechanism resembling a hypersensitive response.

Gene Therapy for Inherited Retinopathies: Update on Development Progress

2018 ◽  
Vol 2 (4) ◽  
pp. 219-226
Author(s):  
Susan Sun ◽  
Sandra R. Montezuma
Keyword(s):  
Gene Therapy ◽  
Genetic Disorders ◽  
Treatment Options ◽  
Genetic Material ◽  
Disease Process ◽  
Supportive Therapy ◽  
The Us ◽  
Retinal Disorders ◽  
The Status ◽  
Therapy Treatment

Inherited retinopathies are a group of genetic disorders that lead to blindness and/or vision impairment. Until now, treatment options for inherited retinopathies largely remained limited to supportive therapy. Gene therapy is an attractive therapeutic technique that allows repair of diseased genes, and it has shown success in vision improvement for patients affected by retinal disorders caused by genetic mutations. The US Food and Drug Administration approved the first gene therapy treatment for the eye, indicated for biallelic RPE65 mutation associated Leber congenital amaurosis (LCA), in December of 2017. Additionally, results from other ongoing clinical trials could further establish gene therapy as the milestone treatment that plays a role in disease process reversal for inherited retinopathies. This review article provides an update on the status of gene therapy for treatment of a variety of retinopathies, including LCA, choroideremia, achromatopsia, Stargardt disease, X-linked retinitis pigmentosa, and X-linked retinoschisis. Furthermore, this article explores transport methods of the genetic material, as well as therapy-delivery approaches used in the clinical setting.

scholarly journals Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 104
Author(s):  
James V. Rogers ◽  
Veronica L. Hall ◽  
Charles C. McOsker
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Defense Mechanism ◽  
Treatment Options ◽  
Bacterial Biofilms ◽  
Host Immune System ◽  
New Antibiotics ◽  
Financial Burdens ◽  
Global Threat

Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship.

scholarly journals Dram1 confers resistance to Salmonella infection

2021 ◽  
Author(s):  
Samrah Masud ◽  
Rui Zhang ◽  
Tomasz K. Prajsnar ◽  
Annemarie H. Meijer
Keyword(s):  
Defense Mechanism ◽  
Early Response ◽  
Protective Role ◽  
Infection Model ◽  
Transgenic Zebrafish ◽  
Functional Link ◽  
Morpholino Knockdown ◽  
Host Defense Mechanism ◽  
Important Host

Dram1 is a stress and infection inducible autophagy modulator that functions downstream of transcription factors p53 and NFκB. Using a zebrafish embryo infection model, we have previously shown that Dram1 provides protection against the intracellular pathogen Mycobacterium marinum by promoting the p62-dependent xenophagy of bacteria that have escaped into the cytosol. However, the possible interplay between Dram1 and other anti-bacterial autophagic mechanisms remains unknown. Recently, LC3-associated phagocytosis (LAP) has emerged as an important host defense mechanism that requires components of the autophagy machinery and targets bacteria directly in phagosomes. Our previous work established LAP as the main autophagic mechanism by which macrophages restrict growth of Salmonella Typhimurium in a systemically infected zebrafish host. We therefore employed this infection model to investigate the possible role of Dram1 in LAP. Morpholino knockdown or CRISPR/Cas9-mediated mutation of Dram1 led to reduced host survival and increased bacterial burden during S. Typhimurium infections. In contrast, overexpression of dram1 by mRNA injection curtailed Salmonella replication and reduced mortality of the infected host. During the early response to infection, GFP-Lc3 levels in transgenic zebrafish larvae correlated with the dram1 expression level, showing over two-fold reduction of GFP-Lc3-Salmonella association in dram1 knockdown or mutant embryos and an approximately 30% increase by dram1 overexpression. Since LAP is known to require the activity of the phagosomal NADPH oxidase, we used a Salmonella biosensor strain to detect bacterial exposure to reactive oxygen species (ROS) and found that the ROS response was largely abolished in the absence of dram1. Together, these results demonstrate the host protective role of Dram1 during S. Typhimurium infection and suggest a functional link between Dram1 and the induction of LAP.

scholarly journals The emergence of novel coronavirus disease, global treatment update and its containment strategies in overpopulated countries: A Review

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Fazli Azim ◽  
Md Shahidul Islam ◽  
Hedaeytullah Saju ◽  
Kaniz Fatema ◽  
Aneela Hayat ◽  
...  
Keyword(s):  
Cell Attachment ◽  
Antiviral Treatment ◽  
Treatment Options ◽  
Supportive Therapy ◽  
The Public ◽  
Drug Candidates ◽  
Cell Based Therapy ◽  
Research Activities ◽  
Host Cell Attachment ◽  
Novel Coronavirus

: The ongoing pandemic of the novel coronavirus SARS-CoV-2 (COVID-19), has created a major challenge for the public health worldwide. The reported cases indicate the outbreak is more widespread than initially assumed. Around 18 million people have been infected with 689,000 reported deaths (August 2020; number is increasing daily) by this novel coronavirus, with a high mutation rate this poses even more serious threat worldwide. The actual source of COVID-19 is still unclear, even if the initial reports links it to the Chinese seafood wet markets in Wuhan, other animals such as birds, snakes, and many small mammals including bats are also linked with this novel coronavirus. Structure of the COVID-19 shows distinctive proteins among which, spike proteins have a pivotal role in host cell attachment and virus-cell membrane fusion in order to facilitate virus infection. Currently, no specific antiviral treatment or vaccine is available. Various drug candidates including SARS‐CoV and MERS‐CoV protease inhibitors, neuraminidase inhibitors, RNA synthesis inhibitors, ACE2 inhibitors and lungs supportive therapy are on the trail. Cell-based therapy also appeared with remarkable treatment possibilities. In this article, we endeavored to succinctly cover the current and available treatment options including pharmaceuticals, cell-based therapy, and traditional medicine. We also focused on the extent of damages by this novel coronavirus in India, Pakistan, and Bangladesh, the strategies adopted and the research activities initiated so far by these densely populated countries (neighboring China) are explained in this review.

scholarly journals Obatoclax, Saliphenylhalamide, and Gemcitabine Inhibit Influenza A Virus Infection

2012 ◽  
Vol 287 (42) ◽  
pp. 35324-35332 ◽  
Author(s):  
Oxana V. Denisova ◽  
Laura Kakkola ◽  
Lin Feng ◽  
Jakob Stenman ◽  
Ashwini Nagaraj ◽  
...  
Keyword(s):  
Influenza A ◽  
Treatment Options ◽  
Antiviral Agents ◽  
Cell Type ◽  
Influenza A Viruses ◽  
Novel Host ◽  
Chemical Screen ◽  
Species Specific ◽  
Host Target ◽  
Transcription And Replication

Influenza A viruses (IAVs) infect humans and cause significant morbidity and mortality. Different treatment options have been developed; however, these were insufficient during recent IAV outbreaks. Here, we conducted a targeted chemical screen in human nonmalignant cells to validate known and search for novel host-directed antivirals. The screen validated saliphenylhalamide (SaliPhe) and identified two novel anti-IAV agents, obatoclax and gemcitabine. Further experiments demonstrated that Mcl-1 (target of obatoclax) provides a novel host target for IAV treatment. Moreover, we showed that obatoclax and SaliPhe inhibited IAV uptake and gemcitabine suppressed viral RNA transcription and replication. These compounds possess broad spectrum antiviral activity, although their antiviral efficacies were virus-, cell type-, and species-specific. Altogether, our results suggest that phase II obatoclax, investigational SaliPhe, and FDA/EMEA-approved gemcitabine represent potent antiviral agents.

Sign in / Sign up

Export Citation Format

Share Document