Журнал микробного патогенеза

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Объем 4, Проблема 2 (2020)

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Approaches in identification of suitable natural anticancer and anti-inflammatory molecules

V Veena

Statement of the Problem: Several herbal and ayurvedic
preparations are currently used to treat the cancer patients.
Although, several herbs used in such treatment contains
pharmacologically important molecules but they are yet to be
identified and their mode of action is not studied in detail.
Cancer is defined as a wound that never heals due to its
complicated cellular organizations. Thus, the main objective of
present investigation was to identify the herbal leads that
target the inflammatory tumor environment through modern
approaches. Purpose: India is the major country that is rich in
the biodiverse compounds to treat disorders through herbal
and ayurvedic approaches. Several natural lead molecules
are being reported and continuously being investigated
globally. The good examples are being curcurmin and taxol
derivatives of natural origin that is effective against cancer
and inflammatory disorders. Identification of small molecule
drugs from herbs by increasing the selectivity towards tumor
is the prime importance of the study. In this context, we have
investigated several diverse herbal lead molecules that aimed
to increase the selectivity and inflammatory aspects of
heterogenic cancer components. Methodology & Theoretical
Orientation: The major photochemical components of herbs
used in treatment of various disorders was screened to
identify an active components based on preliminary studies.
Further, through virtual screening, the compounds were
identified against cancer specific targets by computational
approaches. The results were validated by in vitro interaction
studies and cell-based studies. Findings: The lead molecules
were obtained that can be used for in vivo studies for
development of anticancer drugs. The findings also enriched
the knowledge regarding mechanistic approach of ayurvedic
drugs being used.

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Effect of a biosurfactant extract obtained from corn in active principles permeation

Rodriguez Lopez L

Nowadays, one of the most important challenges in the
pharmaceutical industry is to find additives for formulations
which improve the permeation and solubility of drugs. Usually,
because of their solubilising and emulsifying properties, it is
common to use surfactants in ointments and creams.
However, some allergies and adverse effects have been
associated with these kinds of substances. In this sense, the
study of biosurfactants as an alternative to synthetic
surfactants is playing a more important role. Biosurfactants
are surface-active compounds, composed of biomolecules,
with some advantages in comparison with their chemical
counterparts, such as biodegradability or low toxicity. For this
reason, the aim of this work was to study the effect of a
biosurfactant extract, obtained from a corn-milling industry
stream, in drug permeation through polydimethylsiloxane
(PDMS). This polymer was chosen as a skin mimic, due to its
good correlation with an in vivo situation in a case whereby
the penetrant lipophilicity was the prime determinant of
compound permeation. During this study, the permeation of
five drugs in the presence of biosurfactant at different
concentrations were determined, in comparison with a control
without the biosurfactant extract.

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Role of regulatory T cells in mother to child transmission of HIV

Peter A Kessler

Mother-to-child transmission of HIV-1 occurs in a minority of
HIV-infected mother-infant pairs, even without any
interventions. The mechanisms that protect the majority of
HIV-exposed infants from infection are unclear. T regulatory
cells (Treg) have important immunomodulatory functions, but
their role in the fetus as well as in mother-to-child
transmission of HIV is understudied. Methods: We studied
available cryopreserved peripheral blood mononuclear cells
from HIV-exposed infants from the breastfeeding,
antiretrovirals and nutrition (BAN) study cohort in Malawi: 64
infants were HIV-uninfected and 28 infants were HIV-infected
at birth. We quantified the frequency of Treg cells
(CD4+CD25+FoxP3+), and activated CD4+ and CD8+ T cells
(CD38+HLADR+) by flow cytometry at birth, 6 weeks and 6, 9
and 12 months of age. Descriptive statistics were performed
to describe the distributions of these lymphocyte markers
according to HIV infection status; and Student’s t-tests and
Wilcoxon-Rank Sum tests to perform comparisons between
HIV- infected and uninfected infants. Results: T cell activation
increased rapidly in the first 6 weeks of life more pronounced
on CD8+T cells; a further increase in activation was observed
at the time of weaning from breastfeeding at 6 months of age.

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The possible role of cytochrome P450s in non-small cell lung cancer therapy

Kitti Andreidesz

Lung cancer is one of the most aggressive forms of cancers
resulting in more than one million deaths yearly. From the two
types of lung cancer, non-small cell lung cancer (NSCLC)
represents about 88% of all lung cancer cases. NSCLC can
be further defined by recurrent driver mutations. The most
common mutations are KRAS and EGFR. Susceptibility to
lung cancer can be influenced by the metabolic capacity of
the lung which strongly relies on cytochrome P450 (CYP)
enzymes. Therapeutic drug response is influenced by these
enzymes also, as they metabolize many of those drugs. In
this study the expression of drug metabolizing CYPs were
measured with qPCR in primary, normal human lung
fibroblasts (NHLF) and primary, small airway epithelial cells
(SAEC) and compared to two adenocarcinoma cell lines
carrying different mutations: KRAS mutant A549 and EGFR
mutant PC9. For their role in drug metabolism CYPs may
contribute to drug resistance beside ABC transporters. For
this reason adenocarcinoma cell lines were treated with
cisplatin, a frequently used chemotherapeutic agent, then the
CYP expressions were measured and compared to the nontreated
cell lines.

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Immobilization of therapeutic agents on magnetic iron oxide nanoparticles decreases binding to blood serum proteins and increases resistance to enzymatic cleavage

Julia Nowak Jary

A drug’s affinity for binding blood serum proteins, such as
albumin, determines a primary interaction affecting its
biological activity. Only the free unbound fraction of a drug
can induce a therapeutic effect. A range of effective
antimicrobial agents, such as peptides containing N3-(4-
methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP), are
known to be powerful inhibitors of fungal and bacterial growth
in vitro; nevertheless, the use of these compounds in clinics
has proven intractable due to their irreversible binding of
blood serum proteins, causing complete loss of their biological
activity. Nanoparticles are now widely tested as drug carriers.
The main purpose of the work was to investigate the
differences in physicochemical properties (solubility,
penetration capacity, lipophilicity) between acid-soluble drugs
in magnetic iron oxide nanoparticles and similar drugs in their
unprotected form. The synthesis of Fe3O4 magnetic iron
oxide nanoparticles containing (3-aminopropyl) triethoxysilane
(APTES) is made with selected adhesive drugs. The detected
nanostructures were detected using IR spectroscopy, atomic
force microscopy (AFM), vibrating sample magnetometry
(VSM) and dynamic light distribution techniques (DLS), as
well as the physicochemical properties of untreated drugs
were studied. Drug deficiency was measured using a flasksaturation
filling method. The discovery was measured using
dialysis membrane, a MWCO 50 kD with pores <10 nm.
Lipophilicity was measured separately by octanol. Drugs
showed better solubility and low pH values (pH 2.0 and 5.0)
and lower solubility and higher pH values (pH 6.5 and 7.5)
compared to compatible non-compliant drugs.

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