Antimicrobial Properties of Apis mellifera’s Bee Venom

Bee venom (BV) is a rich source of secondary metabolites from honeybees (Apis mellifera L.). It contains a variety of bioactive ingredients including peptides, proteins, enzymes, and volatile metabolites. The compounds contribute to the venom’s observed biological functions as per its anti-inflammatory and anticancer effects. The antimicrobial action of BV has been shown in vitro and in vivo experiments against bacteria, viruses, and fungi. The synergistic therapeutic interactions of BV with antibiotics has been reported. The synergistic effect contributes to a decrease in the loading and maintenance dosage, a decrease in the side effects of chemotherapy, and a decrease in drug resistance. To our knowledge, there have been no reviews on the impact of BV and its antimicrobial constituents thus far. The purpose of this review is to address the antimicrobial properties of BV and its compounds.

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Antibacterial properties of thioridazine

Farmatsevtychnyi zhurnal ◽

10.32352/0367-3057.4.19.11 ◽

2019 ◽

pp. 96-104

Author(s):

N. Hrynchuk ◽

N. Vrynchanu

Keyword(s):

Antibacterial Activity ◽

Ex Vivo ◽

Antibacterial Properties ◽

Antimicrobial Properties ◽

Antibiotic Resistant ◽

In Vivo Experiments ◽

Antistaphylococcal Activity ◽

The Impact

The emergence and spread of antibiotic-resistant strains of microorganisms reduces the effectiveness of antibiotic therapy and requires finding solutions to problems, one of which is the study of antimicrobial properties in drugs of various pharmacological groups. The purpose of the work was to summarize the data on the antibacterial activity of thioridazine and its derivatives to determine the feasibility and prospects of creating new antibacterial drugs on their basis. The paper presents literature data on the effects of thioridazine on the causative agent of tuberculosis, antistaphylococcal activity, susceptibility of plasmodium and trypanosoma. The antibacterial activity of the drug was established within in vitro studies with the determination of MIC towards gram-positive and gram-negative microorganisms, ex vivo using macrophage lines, as well as within in vivo experiments on mice. It is established that the neuroleptic thioridazine is characterized by pronounced anti-tuberculosis activity, the mechanism of action is associated with the impact on the cell membrane of M. tuberculosis, inactivation by calmodulin and inhibition of specific NADH-dehydrogenase type II. The literature data indicate that thioridazine is able to increase the activity of isoniazid against the strains of mycobacteria that are susceptible and resistant to its action. It has been established that resistance to thioridazine in antibiotic-resistant M. tuberculosis strains is not formed. The drug is characterized by its ability to inhibit the growth and reproduction of both methicylin-sensitive (MSSA) and methicilin-resistant (MRSA) strains of Staphylococcus aureus, which has been proven within in vitro experiments. The effectiveness of thioridazine has been proven within in vivo experiments in case of skin infection and sepsis caused by S. aureus. Antimicrobial effect of the drug is also observed towards to plasmodium (P. falciparum) and trypanosomes (Trypanosoma spp.). Currently, the synthesis of thioridazine derivatives is carried out to identify compounds with a pronounced antibacterial effect. Some of the first synthesized compounds are not inferior or superior to thioridazine by the inhibitory effect. Thus, these data suggest that drugs of different pharmacological groups, including drugs that affect the nervous system - thioridazine and its derivatives, can be a source of replenishment of the arsenal of antimicrobial drugs to control such threatening infections as tuberculosis and diseases caused by polyresistant strains of microorganisms.

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Combination of in vivo phage therapy data with in silico model highlights key parameters for treatment efficacy

10.1101/2021.03.04.433924 ◽

2021 ◽

Author(s):

Raphaelle Delattre ◽

Jeremy Seurat ◽

Feyrouz Haddad ◽

Thu-Thuy Nguyen ◽

Baptiste Gaborieau ◽

...

Keyword(s):

Phage Therapy ◽

Biological Properties ◽

General Strategy ◽

In Vivo Experiments ◽

Bacterial Dynamics ◽

Optimal Dosing ◽

Dosing Regimens ◽

The Impact

The clinical (re)development of phage therapy to treat antibiotic resistant infections requires grasping specific biological properties of bacteriophages (phages) as antibacterial. However, identification of optimal dosing regimens is hampered by the poor understanding of phage-bacteria interactions in vivo. Here we developed a general strategy coupling in vitro and in vivo experiments with a mathematical model to characterize the interplay between phage and bacterial dynamics during pneumonia induced by a pathogenic strain of Escherichia coli. The model estimates some key parameters for phage therapeutic efficacy, in particular the impact of dose and route of administration on phage dynamics and the synergism of phage and the innate immune response on the bacterial clearance rate. Simulations predict a low impact of the intrinsic phage characteristics in agreement with the current semi-empirical choices of phages for compassionate treatments. Model-based approaches will foster the deployment of future phage therapy clinical trials.

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A Four-Inflow Construction to Ensure Thermal Stability and Uniformity during Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Rats

Cancers ◽

10.3390/cancers12123516 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3516

Author(s):

Daan R. Löke ◽

Roxan F. C. P. A. Helderman ◽

Jan Sijbrands ◽

Hans M. Rodermond ◽

Pieter J. Tanis ◽

...

Keyword(s):

Intraperitoneal Chemotherapy ◽

Computer Aided Design ◽

Hyperthermic Intraperitoneal Chemotherapy ◽

In Vivo Experiments ◽

The One ◽

Aided Design ◽

The Impact ◽

Phosphate Buffered Saline

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) is used for treating peritoneal metastases of various origins. Present HIPEC protocols have rarely been validated for relevant parameters such as optimal agent, duration and perfusate temperature. In vitro experiments are not completely representative of clinical circumstances. Therefore, a good preclinical in vivo HIPEC model is needed in which temperature distributions can be well-controlled and are stable throughout treatments. Methods: We designed a setup able to generate and maintain a homogeneous flow during a 90-min HIPEC procedure using our in-house developed treatment planning tools and computer aided design (CAD) techniques. Twelve rats were treated with heated phosphate-buffered saline (PBS) using two catheter setups (one vs. four- inflows) and extensive thermometry. Simulated and measured thermal distribution and core temperatures were evaluated for the different setups. Results: Overall, the four-inflow resulted in more stable and more homogeneous thermal distributions than the one-inflow, with lower standard deviations (0.79 °C vs. 1.41 °C at the outflow, respectively) and less thermal losses. The average thermal loss was 0.4 °C lower for rats treated with the four-inflow setup. Rat core temperatures were kept stable using occasional tail cooling, and rarely exceeded 39 °C. Conclusion: Increasing the number of inflow catheters from one to four resulted in increased flow and temperature homogeneity and stability. Tail cooling is an adequate technique to prevent rats from overheating during 90-min treatments. This validated design can improve accuracy in future in vivo experiments investigating the impact of relevant parameters on the efficacy of different HIPEC protocols.

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Impact of surface topography and coating on osteogenesis and bacterial attachment on titanium implants

Journal of Tissue Engineering ◽

10.1177/2041731418790694 ◽

2018 ◽

Vol 9 ◽

pp. 204173141879069 ◽

Cited By ~ 45

Author(s):

Laila Damiati ◽

Marcus G Eales ◽

Angela H Nobbs ◽

Bo Su ◽

Penelope M Tsimbouri ◽

...

Keyword(s):

Surface Topography ◽

Dental Implants ◽

Antimicrobial Properties ◽

Bacterial Attachment ◽

Titanium Implants ◽

Premature Failure ◽

Biological Environment ◽

The Impact

Titanium (Ti) plays a predominant role as the material of choice in orthopaedic and dental implants. Despite the majority of Ti implants having long-term success, premature failure due to unsuccessful osseointegration leading to aseptic loosening is still too common. Recently, surface topography modification and biological/non-biological coatings have been integrated into orthopaedic/dental implants in order to mimic the surrounding biological environment as well as reduce the inflammation/infection that may occur. In this review, we summarize the impact of various Ti coatings on cell behaviour both in vivo and in vitro. First, we focus on the Ti surface properties and their effects on osteogenesis and then on bacterial adhesion and viability. We conclude from the current literature that surface modification of Ti implants can be generated that offer both osteoinductive and antimicrobial properties.

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Effects of developed thyme and oregano essential oil formulations on Monilinia laxa and Monilinia fructicola

Pesticidi i fitomedicina ◽

10.2298/pif2001049t ◽

2020 ◽

Vol 35 (1) ◽

pp. 49-56

Author(s):

Brankica Tanovic ◽

Jovana Hrustic ◽

Milica Mihajlovic ◽

Mila Grahovac ◽

Marija Stevanovic ◽

...

Keyword(s):

Essential Oil ◽

Essential Oils ◽

Antimicrobial Properties ◽

Monilinia Fructicola ◽

Monilinia Laxa ◽

Oregano Essential Oil ◽

In Vivo Experiments ◽

Apple Fruits

Essential oils have been well-known for their antimicrobial properties for a very long time. Some of them have been effectively used in human medicine for decades. Our earlier investigation revealed a great potential of thyme and oregano essential oils as crop protectants against some postharvest fruit pathogens. The effects of formulated thyme and oregano essential oils on Monilinia laxa and Monilinia fructicola were studied in vitro and in vivo. In vitro antagonistic assays were performed on solidified PDA medium using a slightly modified agar overlay technique, while in vivo experiments were conducted on inoculated apple fruits. In vitro essays showed that the developed formulations (emulsifiable concentrates - EC) significantly inhibited the mycelial growth of Monilinia spp. Experiments in vivo, performed on inoculated apple fruits, revealed that the developed formulations provided a significant level of Monilinia spp. suppression. To our knowledge, another EC formulation of oregano essential oil intended for use in Monilinia spp. control has never been developed before. The presented results are initial findings and evaluation of the activity of the developed products should therefore proceed under field conditions to determine their efficacy and activity spectrum, and to estimate economic aspects of their use.

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Harnessing tumor immunity with chemotherapy: Mathematical modeling for decision-making in combinatorial regimen with immune-oncology drugs.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e14095 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e14095-e14095

Author(s):

Vesna Cuplov ◽

Guillaume Sicard ◽

Dominique Barbolosi ◽

Joseph Ciccolini ◽

Fabrice Barlesi

Keyword(s):

Mathematical Modeling ◽

T Cells ◽

In Silico ◽

Checkpoint Inhibitors ◽

Cytotoxic T Cells ◽

Model Parameters ◽

In Vivo Experiments ◽

The Impact

e14095 Background: Combining chemotherapy and immune checkpoint inhibitors (ICI) is challenging due to the near-infinite choice of dosing, scheduling and sequencing between drugs. The aim of this work is to develop a phenomenological model that describes the synergistic effect between cytotoxics and immune check point inhibitors in patients with cancer. Methods: Inspired from literature, we have developed an integrative mathematical model that includes tumor cells, cytotoxic T cells (CTLs) and regulatory T cells (TREGs) plus pharmacokinetics (PK) inputs. Loss in tumor mass is due to combined effect of direct chemotherapy-induced cytotoxicity and CTLs immune response, which is in turn inhibited by the tumor and mitigated by TREGs in the tumor micro-environment. The model describes as well the impact of chemotherapy-induced lymphodepletion on immune tolerance, whereas ICIs protect CTLs against tumor inhibition. Identification of model’s parameters and simulations of various scheduling were performed using Mlxplore software and a Python standalone code. In vitro and in vivo experiments using lung cancer models generate experimental data to adjust model parameters. Results: Complex interplays between cytotoxics and immune cells were best described by a 10-parameters model so as to ensure better identifiability. PK/PD relationships were integrated using compartmental modeling. In silico simulations show how changes in dosing and scheduling impact efficacy endpoints, an observation in line with data from the literature. Ongoing in vitro and in vivo experiments with pemetrexed-cisplatin doublet and anti-PD1 pembrolizumab help optimizing the model’s parameters in a self-learning loop. Conclusions: This work is at the frontier between mathematical modeling and experimental therapeutics with ICIs. In silico modeling and simulations could help narrow down the treatment choices and define optimal combinations prior to running clinical trials. Such model will help identify optimal dosing and scheduling, so as to achieve better synergism and efficacy.

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Cryptococcus neoformans Secretes Small Molecules That Inhibit IL-1β Inflammasome-Dependent Secretion

Mediators of Inflammation ◽

10.1155/2020/3412763 ◽

2020 ◽

Vol 2020 ◽

pp. 1-20

Author(s):

Pedro Henrique Bürgel ◽

Clara Luna Marina ◽

Pedro H. V. Saavedra ◽

Patrícia Albuquerque ◽

Stephan Alberto Machado de Oliveira ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Fungal Infections ◽

Virulent Strain ◽

Acanthamoeba Castellanii ◽

Conditioned Media ◽

Inflammasome Activation ◽

In Vivo Experiments ◽

The Impact

Cryptococcus neoformans is an encapsulated yeast that causes disease mainly in immunosuppressed hosts. It is considered a facultative intracellular pathogen because of its capacity to survive and replicate inside phagocytes, especially macrophages. This ability is heavily dependent on various virulence factors, particularly the glucuronoxylomannan (GXM) component of the polysaccharide capsule. Inflammasome activation in phagocytes is usually protective against fungal infections, including cryptococcosis. Nevertheless, recognition of C. neoformans by inflammasome receptors requires specific changes in morphology or the opsonization of the yeast, impairing proper inflammasome function. In this context, we analyzed the impact of molecules secreted by C. neoformans B3501 strain and its acapsular mutant Δcap67 in inflammasome activation in an in vitro model. Our results showed that conditioned media derived from B3501 was capable of inhibiting inflammasome-dependent events (i.e., IL-1β secretion and LDH release via pyroptosis) more strongly than conditioned media from Δcap67, regardless of GXM presence. We also demonstrated that macrophages treated with conditioned media were less responsive against infection with the virulent strain H99, exhibiting lower rates of phagocytosis, increased fungal burdens, and enhanced vomocytosis. Moreover, we showed that the aromatic metabolite DL-Indole-3-lactic acid (ILA) and DL-p-Hydroxyphenyllactic acid (HPLA) were present in B3501’s conditioned media and that ILA alone or with HPLA is involved in the regulation of inflammasome activation by C. neoformans. These results were confirmed by in vivo experiments, where exposure to conditioned media led to higher fungal burdens in Acanthamoeba castellanii culture as well as in higher fungal loads in the lungs of infected mice. Overall, the results presented show that conditioned media from a wild-type strain can inhibit a vital recognition pathway and subsequent fungicidal functions of macrophages, contributing to fungal survival in vitro and in vivo and suggesting that secretion of aromatic metabolites, such as ILA, during cryptococcal infections fundamentally impacts pathogenesis.

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Influence of formic acid on the vitality of Strongyloides papillosus

Regulatory Mechanisms in Biosystems ◽

10.15421/021865 ◽

2018 ◽

Vol 9 (3) ◽

pp. 435-439

Author(s):

О. О. Boyko ◽

O. G. Gavrilina ◽

P. N. Gavrilin ◽

Y. A. Gugosyan ◽

V. V. Brygadyrenko

Keyword(s):

Formic Acid ◽

Laboratory Animals ◽

Pest Species ◽

Non Invasive ◽

In Vivo Experiments ◽

And Control ◽

The Impact ◽

Experimental Group

Formic acid (methanoic acid, HCOOH) is an organic compound which belongs to saturated monobasic acids. In natural conditions, it is secreted from the glands of ants, and also extracted from the leaves of stinging nettles. It is soluble in water in any proportions, which makes it practical to use for making aquatic solutions. It is broadly used as a preservative in the food industry – Е236 food additive (Codex Alimentarius), as a bactericide in medicine and veterinary medicine, and is also used against agricultural pest species of insects and mites. The in vitro and in vivo experiments revealed the anthelmintic properties of the acid against Strongyloides papillosus nematodes, parasites of the gastrointestinal tract of Ruminantia and rabbits. In the conditions of in vitro, 100% of (L1, L2, L3) nematode larvae died from a 1% solution of formic acid (10 g/l) after 24 hours exposure. When exposed to less strong concentrations of the acid (1, 0.1, 0.01, 0.001 g/l), vital forms of L3 S. papillosus were found. Non-invasive stages (L1, L2) are less resistant to the impact of the acid – death of 100% of the larvae was observed under the impact of 0.1% solution and up to 60% of larvae died at 0.01% solution of formic acid in the same conditions. LD50 for L3 invasive larvae of S. papillosus equaled 0.47%, and 0.0076% for L1, L2 non-invasive larvae of S. papillosus. In the conditions of in vivo experiment (with guinea pigs), the effective dose of formic acid was 0.4% ml/kg of the animal`s body weight. The results of the coproscopy after the treatment demonstrated absence of the helminth larvae in the feces of the laboratory animals during 10 days and their occurrence only on days 15–20 with a low intensity (90 larvae/g of feces on average). During an external examination of the corpses of the animals of the experimental group, no pathological changes were found. The intestine, the heart, the lungs and the liver of the animals from this group had no macroscopic changes – they were of natural colour and size. The hepatocytes looked normal and the structure of the liver lobes was maintained. In the tissues of the liver of the animals from the experimental and control groups, we found processes of passive congestion, and an insignificant degree of signs of hepatic steatosis.

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