scholarly journals Rabies Prophylactic and Treatment Options: An In Vitro Study of siRNA- and Aptamer-Based Therapeutics

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 881
Author(s):  
Terence Peter Scott ◽  
Louis Hendrik Nel
Keyword(s):  
Strong Evidence ◽  
Post Infection ◽  
Treatment Options ◽  
In Vitro Study ◽  
Selection Method ◽  
Significant Inhibition ◽  
Human Rabies ◽  
Proof Of Concept ◽  
Effective Prophylaxis

If the goal of eliminating dog-mediated human rabies by 2030 is to be achieved, effective mass dog vaccination needs to be complemented by effective prophylaxis for individuals exposed to rabies. Aptamers and short-interfering RNAs (siRNAs) have been successful in therapeutics, but few studies have investigated their potential as rabies therapeutics. In this study, siRNAs and aptamers—using a novel selection method—were developed and tested against rabies virus (RABV) in a post-infection (p.i.) scenario. Multiple means of delivery were tested for siRNAs, including the use of Lipofectamine and conjugation with the developed aptamers. One siRNA (N53) resulted in an 80.13% reduction in viral RNA, while aptamer UPRET 2.03 demonstrated a 61.3% reduction when used alone at 2 h p.i. At 24 h p.i., chimera UPRET 2.03-N8 (aptamer-siRNA) resulted in a 36.5% inhibition of viral replication. To our knowledge, this is the first study using siRNAs or aptamers that (1) demonstrated significant inhibition of RABV using an aptamer, (2) tested Lipofectamine RNAi-Max as a means for delivery, and (3) produced significant RABV inhibition at 24 h p.i. This study serves as a proof-of-concept to potentially use aptamers and siRNAs as rabies immunoglobulin (RIG) replacements or therapeutic options for RABV and provides strong evidence towards their further investigation.

Chemical profile and antiperiodontal potential of Thymus linearis Benth. Essential oil using ADMET prediction, In silico and in vitro tools

2021 ◽  
pp. 1-16
Author(s):  
Abdul Rafey ◽  
Aqsa Batool ◽  
Muhammad Kamran ◽  
Samiullah Khan ◽  
Muhammad Akram ◽  
...  
Keyword(s):  
Essential Oil ◽  
In Silico ◽  
Treatment Options ◽  
Significant Inhibition ◽  
Bacterial Biofilm ◽  
Health Concern ◽  
Major Constituent ◽  
Antimicrobial Studies ◽  
Development Of Resistance

Periodontitis is an important health concern that is associated with long term complications. Development of resistance to antibiotics limits the treatment options in periodontitis. We investigated Thymus linearis essential oil for treatment of periodontitis. The essential oil was collected using hydrodistillation and characterized using GC-MS. The constituents were further analyzed for druglikeness, ADMET properties and molecular docking using transcription regulators 2UV0 and 3QP5. The GC-MS results revealed that carvacrol was a major constituent (76.26%) followed by caryophyllene oxide (6.83%) and L-borneol (6.08%). The in vitro antimicrobial studies showed significant inhibition against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa (MIC range 0.024 –0.312μg/mL). The essential oil showed a good inhibition of bacterial biofilm produced by S. aureus (72%) and S. epidermidis (70%). Finally, the antiquorum sensing property (30 mm zone of inhibition) was recorded with violacein inhibition (58%). Based on in silico and in vitro findings, it was concluded that T. linearis essential oil can be used for the treatment of periodontal infections.

scholarly journals Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 395 ◽  
Author(s):  
Ylenia Jabalera ◽  
Beatriz Garcia-Pinel ◽  
Raul Ortiz ◽  
Guillermo Iglesias ◽  
Laura Cabeza ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Electrostatic Interactions ◽  
Magnetic Nanoparticle ◽  
In Vitro Study ◽  
Targeted Chemotherapy ◽  
Proof Of Concept ◽  
Therapeutic Approaches ◽  
Ph Values ◽  
Common Cancer

Conventional chemotherapy against colorectal cancer (CRC), the third most common cancer in the world, includes oxaliplatin (Oxa) which induces serious unwanted side effects that limit the efficiency of treatment. Therefore, alternative therapeutic approaches are urgently required. In this work, biomimetic magnetic nanoparticles (BMNPs) mediated by MamC were coupled to Oxa to evaluate the potential of the Oxa–BMNP nanoassembly for directed local delivery of the drug as a proof of concept for the future development of targeted chemotherapy against CRC. Electrostatic interactions between Oxa and BMNPs trigger the formation of the nanoassembly and keep it stable at physiological pH. When the BMNPs become neutral at acidic pH values, the Oxa is released, and such a release is greatly potentiated by hyperthermia. The coupling of the drug with the BMNPs improves its toxicity to even higher levels than the soluble drug, probably because of the fast internalization of the nanoassembly by tumor cells through endocytosis. In addition, the BMNPs are cytocompatible and non-hemolytic, providing positive feedback as a proof of concept for the nanoassembly. Our study clearly demonstrates the applicability of Oxa–BMNP in colon cancer and offers a promising nanoassembly for targeted chemotherapy against this type of tumor.

scholarly journals Posaconazole-Induced Hypertension and Hypokalemia: Mechanistic Evaluation

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S76-S76
Author(s):  
George R Thompson ◽  
Diana Chang ◽  
Rebecca Wittenberg ◽  
Ian Mchardy ◽  
Alison Semrad
Keyword(s):  
Treatment Options ◽  
Vital Signs ◽  
Normal Function ◽  
Significant Inhibition ◽  
Complete Suppression ◽  
Normal Limits ◽  
Liquid Suspension ◽  
Days Of Therapy ◽  
Apparent Mineralocorticoid Excess

Abstract Background Recent studies have shown the new posaconazole delayed-release tablets have superior bioavailability compared with the liquid suspension formulation. As higher serum posaconazole concentrations have been associated with improved clinical responses, this formulation has been a welcome addition to available treatment options. However, higher serum and tissue levels are likely to reveal previously undescribed toxicity as adverse events attributed to “off-target” effects are observed. Methods We prospectively identified two patients with new onset hypertension, hypokalemia, and alkalosis after starting posaconazole tablets. Patient vital signs and laboratory values were within normal limits prior to starting posaconazole; however, following over 30 days of therapy both patients became newly hypertensive (mean systolic BP increase 59 mmHg). Serum posaconazole levels were 4.3–4.6 μg/ml. Complete suppression of renin and aldosterone, with increased 11-deoxycortisol, estradiol levels, and cortisol/cortisone ratios were observed in both patients. The TTKG in both patients was inappropriately elevated. Results Posaconazole-induced disruption of the steroid biosynthesis pathway in patients has not previously been described, but has been suggested by in vitro studies. Our patients’ laboratory results show clinically significant inhibition of 11β-hydroxysteroid dehydrogenase enzyme type 2 isoform (11β-HSD2) as evidenced by: the elevated 11-deoxycortisol (with subsequent suppression of renin and aldosterone), the highly elevated cortisol/cortisone ratio, and the inappropriately elevated TTKG in the setting of hypokalemia. The normal deoxycorticosterone confirms normal function of 11β-hydroxylase and the observed effects in our patients are thus downstream from this enzyme. Conclusion Our findings support in vitro predictions and highlight the clinical sequelae of posaconazole-mediated inhibition of 11β-HSD2. Additional studies are necessary to determine the frequency of posaconazole induced apparent mineralocorticoid excess syndrome and whether other azole antifungals can be associated with this phenomenon. Disclosures All authors: No reported disclosures.

scholarly journals RELATIVE POTENCY OF ANTI-DIABETIC COSTUS SPECIOSUSPLANT EXTRACT IN MOUSE FIBROBLAST CELL LINE

2016 ◽  
Vol 4 (3) ◽  
pp. 99-107
Author(s):  
Bindu ◽  
Rama Bhat ◽  
Girish ◽  
Krishna Prasad
Keyword(s):  
Glucose Uptake ◽  
Biological Activities ◽  
Glycogen Synthesis ◽  
In Vitro Study ◽  
Significant Inhibition ◽  
Mouse Fibroblast ◽  
Relative Potency ◽  
Major Pathway ◽  
Chemical Structures

Plant-derived compounds have been used clinically to treat type 2 diabetes for many years as they also exert additional beneficial effects on various other disorders. PI3K pathway is the major pathway activated by insulin receptor (IR). It induces glucose uptake, glycogen synthesis, protein synthesis, cell growth and differentiation. Hence metabolic assay was employed to assess glucose uptake based on the property of 3T3-L 1 cells to differentiate into adipocytes which can take up the glucose in medium due to the effect of insulin or insulin like molecules. The results of the current study showed that plants extract probably exerts its anti-diabetic properties by stimulating glucose uptake in adipocytes with significant inhibition of adipogenesis demonstrating reliable relative potency in comparision to the commercial insulin.  The ability of existing therapies to target various aspects of the insulin resistance syndrome induces other metabolic abnormalities, chiefly those involved in lipid metabolism. In this preliminary in-vitro study Costusspeciosus plant extract demonstrated to have significant relative potency in comparison to commercial Insulin which can be exploited to treat diabetes using natural herbal extracts Current study leads researchers to elucidate the chemical structures, isolate active ingrediatents in the crude extract for such biological activities in reference to commercial and recombinant insulins.

In vitro study on immune response modifiers as novel medical treatment options for cholesteatoma

2021 ◽  
Vol 145 ◽  
pp. 110743
Author(s):  
Tankut Uzun ◽  
Hamdi Çaklı ◽  
Didem Turgut Coşan ◽  
Şaziye Armağan İncesulu ◽  
Ercan Kaya ◽  
...  
Keyword(s):  
Immune Response ◽  
Medical Treatment ◽  
Treatment Options ◽  
In Vitro Study ◽  
Vitro Study

scholarly journals IN VITRO STUDY OF AYURVEDIC CONDITIONER W.S.R. TO ANTIDANDRUFF ACTIVITY

2020 ◽  
Vol 8 (10) ◽  
pp. 4748-4752
Author(s):  
Jain Vatsala ◽  
Rao K. Shankar
Keyword(s):  
Antibacterial Activity ◽  
Treatment Options ◽  
Research Work ◽  
In Vitro Study ◽  
Vitro Study ◽  
Diffusion Method ◽  
Herbal Preparation ◽  
Skin Cells ◽  
Agar Well Diffusion Method

Objective: Dandruff is the unusually high shedding of dead skin cells from the scalp. It is a common scalp disorder affecting almost half of the post pubertal population. In the market many treatment options are available but herbal preparation is the best option to treat dandruff. Thus, in the present research work Ayurvedic conditioner prepared with plant extract (decoction) was studied to evaluate antidandruff activity against Staphyllococus aureus & Candida albicans. Method In vitro study was conducted to evaluate the antidandruff effect of Ayurvedic conditioner against S. aureus & C. albicans. The evaluation done by adopting Kirby-Bauer Agar Well diffusion method. Antibacterial activity was compared with the standard references. Result Study revealed that Ayurvedic conditioner was susceptible for the same microbes in less concentration. Conclusion Ayurvedic conditioner was found to be the most effective formulation against dandruff causing factors; s.aureus and c.albicans.

A Proof-of-Concept In Vitro Study to Determine if EndoAnchors Can Reduce Gutter Size in Chimney Graft Configurations

2013 ◽  
Vol 20 (4) ◽  
pp. 498-505 ◽  
Author(s):  
Wouter W. Niepoth ◽  
Jorg L. de Bruin ◽  
Kak K. Yeung ◽  
Rutger J. Lely ◽  
Andrea N. Devrome ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Vitro Study ◽  
Proof Of Concept ◽  
Chimney Graft

scholarly journals Anticancer potential of myricetin bulk and nano forms in vitro in lymphocytes from myeloma patients

2020 ◽  
Author(s):  
Shabana Akhtar ◽  
Mojgan Najafzadeh ◽  
Mohammad Isreb ◽  
Lisa Newton ◽  
Rajendran C. Gopalan ◽  
...  
Keyword(s):  
Tumour Progression ◽  
P53 Protein ◽  
Treatment Options ◽  
In Vitro Study ◽  
Cancer Therapies ◽  
Potential Candidate ◽  
Healthy Individuals ◽  
Study Results ◽  
Stress Dependent

Abstract Evading apoptosis and chemo-resistance are considered as very important factors which help tumour progression and metastasis. Hence, to overcome chemo-resistance, there is an urgent requirement for emergence of more effective treatment options. Myricetin, a naturally occurring flavonoid, is present in various plant-derived foods and shows antitumour potential in different cancers. In the present in vitro study, results from the comet assay demonstrated that myricetin bulk (10 µM) and nano (20 µM) forms exhibited a non-significant level of genotoxicity in lymphocytes from multiple myeloma patients when compared to those from healthy individuals. Western blot results showed a decrease in Bcl-2/Bax ratio and an increase in P53 protein levels in lymphocytes from myeloma patients, but not in lymphocytes from healthy individuals. A significant increase in intracellular reactive oxygen species level was also observed, suggesting that regulation of apoptotic proteins triggered by myricetin exposure in lymphocytes from myeloma patients occurred through P53 and oxidative stress-dependent pathways. The potency of myricetin against lymphocytes from myeloma patients marks it a potential candidate to be considered as an alternative to overcome chemo-resistance in cancer therapies.

scholarly journals Evaluation of Predation Capability of Periodontopathogens Bacteria by Bdellovibrio Bacteriovorus HD100. An in Vitro Study

Materials ◽  
2019 ◽  
Vol 12 (12) ◽  
pp. 2008 ◽  
Author(s):  
Romeo Patini ◽  
Paola Cattani ◽  
Simona Marchetti ◽  
Gaetano Isola ◽  
Gianluca Quaranta ◽  
...  
Keyword(s):  
Treatment Options ◽  
Brain Heart Infusion ◽  
In Vitro Study ◽  
Periodontal Pocket ◽  
Oral Microbiota ◽  
Prey Cell ◽  
Liquid Suspension ◽  
Predatory Bacteria ◽  
Predatory Capacity

Treatment options against periodontitis attempt to completely remove oral microbiota even if several species in dental plaque demonstrate protective features. Predatory bacteria that selectively predate solely on Gram-negative bacteria might be a viable therapeutic alternative. Therefore, the aim of this study is to in vitro evaluate the susceptibility of some oral pathogens to predation by B. bacteriovorus HD100 in liquid suspension. Cultures of prey cell were prepared in brain heart infusion broth (BHI) broth incubating overnight at the appropriate conditions for each organism to reach log phase of growth. Predatory activity was assessed by measuring optical density at 600 nm after 12, 24, 48 and 72 hours. Statistical analysis was performed using the Mann–Whitney U test and p values less than 0.05 were considered statistically significant. The study demonstrated that B. bacteriovorus is able to predate on aerobic species and on microaerophilic ones (p < 0.05) but also that its predatory capacity is strongly compromised by the conditions of anaerobiosis. B. bacteriovorus, in fact, was unable to predate the anaerobic species involved in the present study (F. nucleatum and P. gingivalis). The findings of the study suggest that B. bacteriovorus is able to tolerate microaerophilic conditions and that in anaerobiosis it cannot exert its predatory capacity. Such evidence could lead to its use as an agent to prevent recolonization of the periodontal pocket following therapy. Further studies are needed to investigate the activity of B. bacteriovorus against recently recognized periodontopathogens, alone or organized in biofilms of multi-species communities.

scholarly journals Avian antibodies (IgY) targeting spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibit receptor binding and viral replication

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252399
Author(s):  
Chad Artman ◽  
Kyle D. Brumfield ◽  
Sahil Khanna ◽  
Julius Goepp
Keyword(s):  
Viral Replication ◽  
Significant Inhibition ◽  
Respiratory Pathogens ◽  
Proof Of Concept ◽  
Spike Glycoprotein ◽  
Concept Study ◽  
Short Period ◽  
Initial Adhesion ◽  
Protein Receptors

Background The global pandemic of Coronavirus infectious disease 2019 (COVID-19), caused by SARS-CoV-2, has plunged the world into both social and economic disarray, with vaccines still emerging and a continued paucity of personal protective equipment; the pandemic has also highlighted the potential for rapid emergence of aggressive respiratory pathogens and the need for preparedness. Avian immunoglobulins (IgY) have been previously shown in animal models to protect against new infection and mitigate established infection when applied intranasally. We carried out a proof-of-concept study to address the feasibility of using such antibodies as mucosally-applied prophylaxis against SARS-CoV-2. Methods Hens were immunized with recombinant S1 spike glycoprotein of the virus, and the resulting IgY was evaluated for binding specificity, inhibition of glycoprotein binding to angiotensin converting enzyme-2 (ACE2) protein (the requisite binding site for the virus), and inhibition of viral replication in Vero cell culture. Results Titers of anti-S1 glycoprotein IgY were evident in yolks at 14 days post-immunization, peaking at 21 days, and at peak concentrations of 16.8 mg/ml. IgY showed strong and significant inhibition of S1/ACE2 binding interactions, and significantly inhibited viral replication at a concentration of 16.8 mg/ml. Four weeks’ collection from eggs of two hens produced a total of 1.55 grams of IgY. Conclusions In this proof-of-concept study we showed that avian immunoglobulins (IgY) raised against a key virulence factor of the SARS-CoV-2 virus successfully inhibited the critical initial adhesion of viral spike glycoproteins to human ACE2 protein receptors and inhibited viral replication in vitro, in a short period using only two laying hens. We conclude that production of large amounts of IgY inhibiting viral binding and replication of SARS-CoV-2 is feasible, and that incorporation of this or similar material into an intranasal spray and/or other mucosal protecting products may be effective at reducing infection and spread of COVID-19.

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