Abstract During ZIKV the outbreak in Brazil it was observed an increase of almost 20 times the number of reported cases of microcephaly in newborn babies. There is no vaccine or approved drug ...available for the treatment and prevention of infections by this virus. EGCG, a polyphenol present in green tea has been shown to have an antiviral activity for many viruses. In view of the need for the development of a drug against a Brazilian strain of ZIKV, we assessed the effect of EGCG on ZIKV entry in Vero E6 cells. The drug was capable of inhibiting the virus entry by at least 1-log (>90%) at higher concentrations (>100 μM). The pre-treatment of cells with EGCG did not show any effect on virus attachment. This is the first study to demonstrate the effect of EGCG on ZIKV indicating that this drug might be possibility to be used for prevention of Zika virus infections.
Hepatitis C is considered the major cause of cirrhosis and hepatocellular carcinoma. Conventional treatment is not effective against some hepatitis C virus (HCV) genotypes; therefore, new treatments ...are needed. Coffee and, more recently, caffeine, have been found to have a beneficial effect in several disorders of the liver, including those manifesting abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma. Caffeine acts directly by delaying fibrosis, thereby improving the function of liver cellular pathways and interfering with pathways used by the HCV replication cycle. In the current study, the direct relationship between caffeine and viral replication was evaluated. The Huh-7.5 cell line was used for transient infections with FL-J6/JFH-5′C19Rluc2AUbi and to establish a cell line stably expressing SGR-Feo JFH-1. Caffeine efficiently inhibited HCV replication in a dose-dependent manner at non-cytotoxic concentrations and demonstrated an IC
50
value of 0.7263 mM after 48 h of incubation. These data demonstrate that caffeine may be an important new agent for anti-HCV therapies due to its efficient inhibition of HCV replication at non-toxic concentrations.
Conjugate compounds constitute a new class of molecules of important biological interest mainly for the treatment of diseases such as cancer. The N-terminus region of cationic peptides has been ...described as important for their biological activity. The aim of this study was to evaluate the lytic peptide Hecate (FALALKALKKALKKLKKALKKAL) and the effect of conjugating this macromolecule with gallic acid (C₇H₆O₅) in terms of structure, anti-cancer activity, and toxicity. An N-terminus GA-Hecate peptide conjugate was synthesized to provide information regarding the relationship between the amino-terminal region and its charge and the secondary structure and biological activity of the peptide; and the effects of gallic acid on these parameters. Peptide secondary structure was confirmed using circular dichroism (CD). The CD measurements showed that the peptide has a high incidence of α-helical structures in the presence of SDS and LPC, while GA-Hecate presented lower incidence of α-helical structures in the same chemical environment. An evaluation of the anti-cancer activity in HeLa cancer cells indicated that both peptides are active, but that coupling gallic acid at the N-terminus decreased the activity of the free peptide. GA-Hecate showed lower activity in non-tumor keratinocyte cells but higher hemolytic activity. Our findings suggest that the N-terminus of Hecate plays an important role in its activity against cervical cancer by affecting it secondary structure, toxicity, and hemolytic activity. This study highlights the importance of the N-terminus in antitumor activity and could provide an important tool for developing new anti-cancer drugs.
Zika virus (ZIKV) has been associated with serious health conditions, and an intense search to discover different ways to prevent and treat ZIKV infection is underway. Berberine and emodin possess ...several pharmacological properties and have been shown to be particularly effective against the entry and replication of several viruses. We show that emodin and berberine trigger a virucidal effect on ZIKV. When the virus was exposed to 160 µM of berberine, a reduction of 77.6% in the infectivity was observed; when emodin was used (40 µM), this reduction was approximately 83.3%. Dynamic light scattering data showed that both compounds significantly reduce the hydrodynamic radius of virus particle in solution. We report here that berberine and emodin, two natural compounds, have strong virucidal effect in Zika virus.
Heme crystallization in the midgut of triatomine insects Oliveira, Marcus F.; Gandara, Ana Caroline P.; Braga, Cláudia M.S. ...
Comparative biochemistry and physiology. Part C, Toxicology & pharmacology/Comparative biochemistry and physiology. Toxicology & pharmacology,
07/2007, Letnik:
146, Številka:
1-2
Journal Article
Recenzirano
Odprti dostop
Hemozoin (Hz) is a heme crystal produced by several blood-feeding organisms in order to detoxify free heme released upon hemoglobin (Hb) digestion. Here we show that heme crystallization also occurs ...in three species of triatomine insects. Ultraviolet-visible and infrared light absorption spectra of insoluble pigments isolated from the midgut of three triatomine species Triatoma infestans, Dipetalogaster maximus and Panstrongylus megistus indicated that all produce Hz. Morphological analysis of T. infestans and D. maximus midguts revealed the close association of Hz crystals to perimicrovillar membranes and also as multicrystalline assemblies, forming nearly spherical structures. Heme crystallization was promoted by isolated perimicrovillar membranes from all three species of triatomine bugs in vitro in heat-sensitive reactions. In conclusion, the data presented here indicate that Hz formation is an ancestral adaptation of Triatominae to a blood-sucking habit and that the presence of perimicrovillar membranes plays a central role in this process.
Inspecting objects in the industry aims to guarantee product quality allowing problems to be corrected and damaged products to be discarded. Inspection is also widely used in railway maintenance, ...where wagon components need to be checked due to efficiency and safety concerns. In some organizations, hundreds of wagons are inspected visually by a human inspector, which leads to quality issues and safety risks for the inspectors. This paper describes a wagon component inspection approach using Deep Learning techniques to detect a particular damaged component: the shear pad. We compared our approach for convolutional neural networks with the state of art classification methods to distinguish among three shear pads conditions: absent, damaged, and undamaged shear pad. Our results are very encouraging showing empirical evidence that our approach has better performance than other classification techniques.
Gedunin is an important limonoid present in several genera of the Meliaceae family, mainly in seeds. Several biological activities have been attributed to gedunin, including antibacterial, ...insecticidal, antimalarial, antiallergic, anti-inflammatory, anticancer, and neuroprotective effects. The discovery of gedunin as a heat shock protein (Hsp) inhibitor represented a very important landmark for its application as a biological therapeutic agent. The current study is a critical literature review based on the several biological activities so far described for gedunin, its therapeutic effect on some human diseases, and future directions of research for this natural compound.
Abstract
Background
This study aimed at improving a real-time polymerase-chain-reaction (qPCR) assay for the detection of
Histoplasma capsulatum
, a fungal pathogen that can cause severe respiratory ...infections in humans, in clinical and soil samples.
Methods
Primer and probes were
in-silico
designed,
in-silico
and
in-vitro
evaluated including clinical biopsy materials and finally subjected to a real-world application with collected soil samples.
Results
Applying the qPCR assay with liver and lung biopsies from 71 patients each, including 59 patients infected with human immunodeficiency virus (HIV), as well as with Sabouraud (SAB) agar culture as the diagnostic reference standard, diagnostic accuracy of the qPCR assay of 100% (5/5) sensitivity and 96% (63/66) specificity for liver samples and 100% (4/4) sensitivity and 94% (63/67) specificity for the lung samples was recorded. When applying the assay with soil samples from caves near of Presidente Figueiredo city, Amazonas, Brazil, one sample from the Maroaga cave was confirmed as positive.
Conclusions
The improved qPCR assessed in this study was successful in detecting
H. capsulatum
with high efficiency and accuracy in
in-vitro
evaluation, including the identification of the target pathogen in both clinical and environmental samples.
Hepatitis C virus (HCV) frequently establishes persistent infections in the liver, leading to the development of chronic hepatitis and, potentially, to liver cirrhosis and hepatocellular carcinoma at ...later stages. The objective of this study was to test the ability of five Dicer substrate siRNAs (DsiRNA) to inhibit HCV replication and to compare these molecules to canonical 21 nt siRNA. DsiRNA molecules were designed to target five distinct regions of the HCV genome - the 5' UTR and the coding regions for NS3, NS4B, NS5A or NS5B. These molecules were transfected into Huh7.5 cells that stably harboured an HCV subgenomic replicon expressing a firefly luciferase/neoR reporter (SGR-Feo-JFH-1) and were also tested on HCVcc-infected cells. All of the DsiRNAs inhibited HCV replication in both the subgenomic system and HCVcc-infected cells. When DsiRNAs were transfected prior to infection with HCVcc, the inhibition levels reached 99.5%. When directly compared, canonical siRNA and DsiRNA exhibited similar potency of virus inhibition. Furthermore, both types of molecules exhibited similar dynamics of inhibition and frequencies of resistant mutants after 21 days of treatment. Thus, DsiRNA molecules are as potent as 21 nt siRNAs for the inhibition of HCV replication and may provide future approaches for HCV therapy if the emergence of resistant mutants can be addressed.
Almost simultaneously, several studies reported the emergence of novel SARS-CoV-2 lineages characterized by their phylogenetic and genetic distinction (1), (2), (3), (4).….
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