scholarly journals Clofazimine: A Promising Inhibitor of Rabies Virus

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiajing Wu ◽  
Shouchun Cao ◽  
Shan Lei ◽  
Qiang Liu ◽  
Yinghong Li ◽  
...  
Keyword(s):  
Rabies Virus ◽  
High Throughput Screening ◽  
Survival Rates ◽  
Positive Control ◽  
Post Exposure Prophylaxis ◽  
Antiviral Therapies ◽  
Clinical Drugs ◽  
Underlying Mechanisms ◽  
Exposure Prophylaxis

With an almost 100% mortality rate, rabies virus (RABV) infection is a global concern. Limited post-exposure prophylaxis and lack of an effective treatment necessitate novel antiviral therapies against RABV. Here, using a high-throughput screening (HTS) method developed in our lab, 11 candidates with anti-RABV activity were identified from a library of 767 clinical drugs. Clofazimine (CFZ), an anti-leprosy drug, displayed an EC50 of 2.28 μM, and SI over 967 against RABV. Investigations into the underlying mechanisms revealed that CFZ targeted viral membrane fusion at the early stages of virus replication. Moreover, CFZ and Clofazimine salicylates (CFZS) exhibited elevated survival rates in vivo, compared with the positive control T-705. Thus, this study revealed CFZ as a promising drug against RABV infection.

scholarly journals Eradicate Rabies with Mass Parental Vaccination, Human Post-Exposure Prophylaxis, and Gene Therapy: A Systematic Review

2018 ◽  
Author(s):  
Martin L. Nelwan
Keyword(s):  
Gene Therapy ◽  
Human Resource Development ◽  
Rabies Virus ◽  
Neglected Tropical Diseases ◽  
Clinical Signs ◽  
Post Exposure Prophylaxis ◽  
Post Exposure ◽  
Pubmed Database ◽  
Exposure Prophylaxis

Rabies is one of the neglected tropical diseases, almost 100% fatal, but preventable. Rabies virus causes the disease and causes about 59000 human deaths annually. The author searched the Pubmed Database at NCBI for articles on rabies disease published between 2007 and 2018. All articles are open access, free for redistribution and in English. To examine rabies virus, Seller’s test was used. In this article, references written by the author were included and relevant publications were also included. The author reviewed a rabies dog case kept at Nelwan Institution for Human Resource Development. The dog showed clinical signs such as aggressive behavior, in-appetence, and soaking in water. Currently, there are no drugs to treat rabies. Vaccination is the best way to prevent the disease. To eradicate rabies, mass vaccination in dogs, post-exposure prophylaxis, and gene therapy can be used. To prevent rabies disease, minimum 70% of the dog population should receive vaccination. Humans with category II exposure should receive rabies vaccine and rabies immunoglobulin. For treatment, in vivo experiment showed that gene therapy can eliminate rabies from the infected neurons by using rAAV-N796. To fight rabies virus, induced pluripotent cells in combination with CRISPR/Cas9 system can also be beneficial. Furthermore, it needs US$ 8.6 billion to fight rabies annually.

scholarly journals A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1504
Author(s):  
Syuan-Ling Lin ◽  
Yang-Hsiang Lin ◽  
Hsiang-Cheng Chi ◽  
Tzu-Kang Lin ◽  
Wei-Jan Chen ◽  
...  
Keyword(s):  
Human Cancer ◽  
Cyclin E ◽  
Survival Rates ◽  
Negative Regulator ◽  
Vimentin Expression ◽  
Protein Coding ◽  
Tumorigenic Activity ◽  
Underlying Mechanisms

Long intergenic non-coding RNAs (lincRNAs) play important roles in human cancer development, including cell differentiation, apoptosis, and tumor progression. However, their underlying mechanisms of action are largely unknown at present. In this study, we focused on a novel suppressor lincRNA that has the potential to inhibit progression of human hepatocellular carcinoma (HCC). Our experiments disclosed long intergenic non-protein coding RNA 1488 (LINC01488) as a key negative regulator of HCC. Clinically, patients with high LINC01488 expression displayed greater survival rates and better prognosis. In vitro and in vivo functional assays showed that LINC01488 overexpression leads to significant suppression of cell proliferation and metastasis in HCC. Furthermore, LINC01488 bound to cyclin E to induce its ubiquitination and reduced expression of vimentin mediated by both miR-124-3p/miR-138-5p. Our results collectively indicate that LINC01488 acts as a tumor suppressor that inhibits metastasis and tumorigenesis in HCC via the miR-124-3p/miR-138-5p/vimentin axis. Furthermore, LINC01488 interacts with and degrades cyclin E, which contributes to its anti-tumorigenic activity. In view of these findings, we propose that enhancement of LINC01488 expression could be effective as a potential therapeutic strategy for HCC.

scholarly journals In Vitro and In Vivo Characterization of Tebipenem (TBP), an Orally Active Carbapenem, against Biothreat Pathogens

2021 ◽  
Author(s):  
Nicholas P. Clayton ◽  
Akash Jain ◽  
Stephanie A. Halasohoris ◽  
Lisa M. Pysz ◽  
Sanae Lembirik ◽  
...  
Keyword(s):  
Survival Rates ◽  
Multidrug Resistant ◽  
Positive Control ◽  
Vehicle Control ◽  
Control Group ◽  
Post Challenge ◽  
Vehicle Control Group ◽  
Tebipenem Pivoxil

Bacillus anthracis and Yersinia pestis, causative pathogens for anthrax and plague, respectively, along with Burkholderia mallei and B. pseudomallei are potential bioterrorism threats. Tebipenem pivoxil hydrobromide (TBP HBr, formerly SPR994), is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing Enterobacterales. We evaluated the in vitro activity and in vivo efficacy of tebipenem against biothreat pathogens. Tebipenem was active in vitro against 30-strain diversity sets of B. anthracis, Y. pestis, B. mallei, and B. pseudomallei with minimum inhibitory concentration (MIC) values of 0.001 – 0.008 μg/ml for B. anthracis, ≤0.0005 – 0.03 μg/ml for Y. pestis, 0.25 – 1 μg/ml for B. mallei, and 1 – 4 μg/ml for B. pseudomallei. In a B. anthracis murine model, all control animals died within 52 h post challenge. The survival rates in the groups treated with tebipenem were 75% and 73% when dosed at 12 h and 24 h post challenge, respectively. The survival rates in the positive control groups treated with ciprofloxacin were 75% and when dosed 12 h and 25% when dosed 24 h post challenge, respectively. Survival rates were significantly (p=0.0009) greater in tebipenem groups treated at 12 h and 24 h post challenge and in the ciprofloxacin group 12 h post-challenge vs. the vehicle-control group. For Y. pestis, survival rates for all animals in the tebipenem and ciprofloxacin groups were significantly (p<0.0001) greater than the vehicle-control group. These results support further development of tebipenem for treating biothreat pathogens.

SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer

2020 ◽  
Author(s):  
Sisi Wei ◽  
Shiping Sun ◽  
Xinliang Zhou ◽  
Cong Zhang ◽  
Xiaoya Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Underlying Mechanisms ◽  
And Function

Abstract A substantial fraction of transcripts are known as long noncoding RNAs (lncRNAs), and these transcripts play pivotal roles in the development of cancer. However, little information has been published regarding the functions of lncRNAs in oesophageal squamous cell carcinoma (ESCC) and the underlying mechanisms. In our previous studies, we demonstrated that small nucleolar RNA host gene 5 (SNHG5), a known lncRNA, is dysregulated in gastric cancer (GC). In this study, we explored the expression and function of SNHG5 in development of ESCC. SNHG5 was found to be downregulated in human ESCC tissues and cell lines, and this downregulation was associated with cancer progression, clinical outcomes and survival rates of ESCC patients. Furthermore, we also found that overexpression of SNHG5 significantly inhibited the proliferation, migration and invasion of ESCC cells in vivo and in vitro. Notably, we found that metastasis-associated protein 2 (MTA2) was pulled down by SNHG5 in ESCC cells using RNA pulldown assay. We also found that SNHG5 reversed the epithelial–mesenchymal transition by interacting with MTA2. In addition, overexpression of SNHG5 downregulated the transcription of MTA2 and caused its ubiquitin-mediated degradation. Thus, overexpression of MTA2 partially abrogated the effect of SNHG5 in ESCC cell lines. Furthermore, we found that MTA2 mRNA expression was significantly elevated in ESCC specimens, and a negative correlation between SNHG5 and MTA2 expression was detected. Overall, this study demonstrated, for the first time, that SNHG5-regulated MTA2 functions as an important player in the progression of ESCC and provide a new potential therapeutic strategy for ESCC.

scholarly journals Human exposure to potential rabies virus transmitters in Olinda, State of Pernambuco, between 2002 and 2006

2007 ◽  
Vol 40 (6) ◽  
pp. 617-621 ◽  
Author(s):  
Filipe Dantas-Torres ◽  
Edmilson Ferreira de Oliveira-Filho
Keyword(s):  
Rabies Virus ◽  
Human Exposure ◽  
Nonhuman Primates ◽  
Prophylactic Treatment ◽  
Human Rabies ◽  
Post Exposure Prophylaxis ◽  
Wild Animals ◽  
Health Unit ◽  
Multifaceted Approach ◽  
Exposure Prophylaxis

The aim of the present study was to evaluate the data on human exposure to potential rabies virus transmitters in Olinda, State of Pernambuco, Brazil. Data from 7,062 patients who underwent antirabies prophylactic treatment in Olinda between 2002 and 2006 were analyzed. As expected, dogs and cats were involved in most of the cases; i.e. 82.3 and 16.3%, respectively. Attacks by nonhuman primates, bats and other species (unspecified) were also reported. Among the 7,062 patients who underwent antirabies treatment, 582 patients abandoned the treatment, either by indication from the health unit (195) or by their own decision (387). In conclusion, this study has indicated that prophylaxis for human rabies in this urban area will require a multifaceted approach, including health education, post-exposure prophylaxis, systematic vaccination for dogs and cats, and possibly selective control over wild animals such as hematophagous bats.

scholarly journals Preliminary study of the toxicity and radioprotective effects of zymosan in vitro and in vivo

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yue-zhi Zhang ◽  
Shu-jing Ge ◽  
Qing-zhen Leng ◽  
Jian-jun Ma ◽  
Han-chen Liu
Keyword(s):  
Flow Cytometry ◽  
Protective Effect ◽  
Cell Viability ◽  
Treatment Time ◽  
Survival Rates ◽  
Positive Control ◽  
X Rays ◽  
Spleen Index

Abstract Background This study aimed to confirm the cytotoxicity of zymosan in vitro and in vivo and determine the appropriate treatment time and the dose of zymosan. Methods AHH-1 cells and HIECs were administered by 0, 20, 40, 80 or 160 μg/mL zymosan. The CCK-8 assay and flow cytometry were used to evaluate the cell viability and apoptosis 24 h, 48 h, and 72 h after administration. Furthermore, 12 h before irradiation, the cells were treated with 0, 5, 10, or 20 μg/mL zymosan and then irradiated with 4 Gy X-rays. Cell viability and apoptosis were measured by the CCK-8 assay and flow cytometry at 24 h. In addition, the protective effect of zymosan against radiation in vitro was compared to that of 20 μg/mL LPS. In vivo, weight, the spleen index, and the thymus index were measured to evaluate the toxicity of 0, 5, 10, 20, and 10 mg/kg zymosan. In addition, rats were treated with 0, 2, 4, 8, or 10 mg/kg zymosan and then irradiated with 7 Gy X-rays. The survival rate, organ index were evaluated. The protective effect of zymosan against radiation in vivo was compared to that of 10 mg/kg LPS a positive control. Results The viability and apoptosis of cells treated with different doses and treatment times of zymosan were not different from those of control cells (p < 0.05). Furthermore, cell viability and apoptosis were clearly improved after zymosan preadministration (p < 0.05). The radioprotective effect of zymosan was dose-dependent. In addition, the viability of cells pretreated with zymosan was higher than that of cells pretreated with LPS, and the apoptosis rate of zymosan-treated cells was lower than that of cells pretreated with LPS (p < 0.05). In vivo, weight, the spleen index and the thymus index were significantly decreased by zymosan at a concentration of 20 mg/kg (p < 0.05). Further experiments showed that the concentration at which zymosan exerted radioprotective effects was 10 mg/kg. The survival curves in the irradiated rats were barely separated between the LPS treatment and zymosan treatment. Conclusion Zymosan administration before radiation exposure significantly increased cell viability and the survival rates of rats.

scholarly journals Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies

2017 ◽  
Author(s):  
Emma M. Bentley ◽  
Ruqiyo Ali ◽  
Daniel L. Horton ◽  
Davide Corti ◽  
Ashley C. Banyard ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Case Fatality ◽  
High Titre ◽  
The Arctic ◽  
Pseudotyped Virus ◽  
Post Exposure Prophylaxis ◽  
Virus Envelope ◽  
Vesicular Stomatitis ◽  
Exposure Prophylaxis ◽  
Virus Isolates

ABSTRACTRabies viruses have the highest case fatality rate of any known virus and are responsible for an estimated 60,000 deaths each year. This is despite the fact that there are highly efficacious vaccines and postexposure prophylaxis available. However, while it is assumed these biologics provide protection against all rabies virus isolates, there are certain subdivisions of RABV lineages, such as within the Arctic-like RABV (AL rabies virus lineage, where data is limited and thus the potency of existing biologics has not been thoroughly assessed. By fusing the Arctic-like rabies virus envelope glycoprotein ecto- and transmembrane domains with the vesicular stomatitis virus cytoplasmic domain, a high titre (7.7 x 105− 6.1 x 106RLU/ml) pseudotyped virus was generated that was subsequently used in a pseudotyped virus neutralisation assay. These results showed that Arctic-like rabies viruses are neutralised to human, canine and feline vaccines and human post-exposure prophylaxis and this was not influenced by the swapping of the cytoplasmic domains (CVS-11 vs CVS-11etmVSVc;r= 0.99,p< 0.0001). This study supports the concept that rabies virus vaccines and newly identified mAbs are able to neutralise rabies virus variants that cluster in a monophyletic clade, referred to as phylogroup I lyssaviruses.

scholarly journals Preliminary study of the toxicity and radioprotective effects of zymosan in vitro and in vivo

2021 ◽  
Author(s):  
Yue-zhi Zhang ◽  
Shu-jing Ge ◽  
Qing-zhen Leng ◽  
Jian-jun Ma ◽  
Hanchen Liu
Keyword(s):  
Flow Cytometry ◽  
Protective Effect ◽  
Cell Viability ◽  
Treatment Time ◽  
Survival Rates ◽  
Positive Control ◽  
X Rays ◽  
Spleen Index

Abstract Background: This study aimed to confirm the cytotoxicity of zymosan in vitro and in vivo and determine the appropriate treatment time and dose of zymosan.Methods: AHH-1 cells and HIECs were administered by 0, 20, 40, 80 or 160 μg/mL zymosan. The CCK-8 assay and flow cytometry were used to evaluate the cell viability and apoptosis 24 h, 48 h, and 72 h after administration. Furthermore, 12 h before irradiation, the cells were treated with 0, 5, 10, or 20 μg/mL zymosan and then irradiated with 4 Gy X-rays. Cell viability and apoptosis were measured by the CCK-8 assay and flow cytometry at 24 h. In addition, the protective effect of zymosan against radiation in vitro was compared to that of 20 μg/mL LPS. In vivo, weight, the spleen index and the thymus index were measured to evaluate the toxicity of 0, 5, 10, 20 and 10 mg/kg zymosan. In addition, rats were treated with 0, 2, 4, 8 or 10 mg/kg zymosan and then irradiated with 7 Gy X-rays. The survival rate, organ index were evaluated. The protective effect of zymosan against radiation in vivo was compared to that of 10 mg/kg LPS a positive control. Results: The viability and apoptosis of cells treated with different doses and treatment times of zymosan were not different from those of control cells (p<0.05). Furthermore, cell viability and apoptosis were clearly improved after zymosan preadministration (p<0.05). The radioprotective effect of zymosan was dose-dependent. In addition, the viability of cells pretreated with zymosan was higher than that of cells pretreated with LPS, and the apoptosis rate of zymosan-treated cells was lower than that of cells pretreated with LPS (p<0.05). In vivo, weight, the spleen index and the thymus index were significantly decreased by zymosan at a concentration of 20 mg/kg (p<0.05). Further experiments showed that the concentration at which zymosan exerted radioprotective effects was 10 mg/kg. The survival curves in the irradiated rats were barely separated between the LPS treatment and zymosan treatment. Conclusion: Zymosan administration before radiation exposure significantly increased cell viability and the survival rates of rats.

scholarly journals Chrysophyllum Albidum Accelerates Delayed Gastric Ulcer Healing in Rats Through Oxidative Stress Reversal and Proton Pump Inhibition

2021 ◽  
Vol 16 (2) ◽  
pp. 163-175
Author(s):  
A.T. Salami ◽  
A. D. Famurewa ◽  
T. P Omayone ◽  
T. F. Iyiola ◽  
S. B. Olaleye
Keyword(s):  
Gastric Ulcer ◽  
Proton Pump ◽  
Ulcer Healing ◽  
Positive Control ◽  
Negative Control ◽  
Gastric Ulcer Healing ◽  
Proton Pump Inhibition ◽  
Male Wistar Rats ◽  
Underlying Mechanisms

Background: Chrysophyllum albidum has been documented to exert its gastric ulcer (GU) healing activities by modulating blood inflammatory mediators, however, other probable in-vivo underlying mechanisms are still vague which this study sought to investigate.Materials and Methods: Male Wistar rats (120-130g) divided into 9 groups (n=15 for groups I-VII; n=5 for groups VIII & IX) viz: Groups I- positive control (DUnA); II and III–250 and 500mg/kg methanolic extract of C. albidum (MeCaB) bark respectively; IV, V and VI-100mg/kg fractions A, B and C respectively; VII–30mg/kg omeprazole; VIII-ulcerated untreated (baseline), IX-negative control. Chronic GU was induced experimentally and delayed using indomethacin with 14 days simultaneous drug treatment. Gastric ulcer score, mucin content, antioxidant and proton pump activities were evaluated by days 3, 7 and 14 of treatment. Data were expressed as Mean+SEM and P<0.05 was significant.Results: C. albidum and fractions treated groups significantly decreased gastric ulcer scores and lipid peroxidation compared with DUnA. Negative control, C. albidum and fraction treated groups significantly increased superoxide dismutase, catalase, glutathione levels and mucin content compared with DUnA group by days 3 and 7. C. albidum, Negative and baseline control groups significantly decreased H+K+ATPase activities compared with DUnA by day14.Conclusion: C. albidum and its fractions facilitated the healing of gastric ulcer, probably by enhanced antioxidant levels, mucin content and decreased gastric H+K+ATPase activity. Keywords: C. albidum and chromatographic fractions, gastric ulcer healing, mucin , antioxidant, H+/K+ATPase pump.

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