The control of cutaneous leishmaniasis (CL) is facilitated by knowledge of factors associated with the treatment failures in endemic countries. The aim of this evaluation was to identify the ...potential risk determinants which might affect the significance of demographic and clinical characteristics for the patients with anthroponotic CL (ACL) and the outcome of meglumine antimoniate (MA) (Glucantime) treatment.
This current was executed as a cohort spanning over a period of 5 years which centered in southeastern part of Iran. Altogether, 2,422 participants were evaluated and 1,391 eligible volunteer patients with ACL caused by Leishmania tropica were included. Overall, 1,116 (80.2%) patients received MA intraleisionally (IL), once a week for 12 weeks along with biweekly cryotherapy, while 275 (19.8%) patients received MA alone (20 mg/kg/day for 3 weeks) (intramuscular, IM). The treatment failure rate in ACL patients was 11% using IL combined with cryotherapy plus IM alone, whilst 9% and 18.5% by IL along with cryotherapy or IM alone, respectively. Multivariate logistic regression model predicted 5 major associated-risk determinants including male (odds ratio (OR) = 1.54, confidence interval (CI) = 1.079-2.22, p = 0.018), lesion on face (OR = 1.574, CI = 1.075-2.303, p = 0.02), multiple lesions (OR = 1.446, CI = 1.008-2.075, p = 0.045), poor treatment adherence (OR = 2.041, CI = 1.204-3.46, p = 0.008) and disease duration > 4 months (OR = 2.739, CI = 1.906-3.936, p≤0.001).
The present study is the original and largest cohort of ACL patients who treated with MA. A comprehensive intervention and coordinated action by the health authorities and policy-makers are crucial to make sure that patients strictly follow medical instructions. Early detection and effective therapy < 4 months following the onset of the lesion is critical for successful treatment of the patients. Since a significant number of patients are still refractory to MA, reducing man-vector exposure and development of new effective alternative drugs are essential measures against ACL due to L. tropica.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: The unique properties of silver nanoparticles (Ag-NPs) produced using plant extract make them attractive for use in medical and industrial applications. Bunium persicum from the ...Apiaceae family is native to Iran, Afghanistan, Pakistan, and some Central Asian countries, which is locally known as "Kermanin Black Cumin" in Iran. In this study, Ag-NPs were synthesized using methanol extract of B. persicum as the regenerating and stabilizing agent for the first time and were followed by the characterization and evaluation of its biological potency. Material & Methods: Synthesis of Ag-NPs was conducted using the B. persicum extract. Ultraviolet-visible (UV-VIS) spectroscopy was used to detect the presence of nanoparticles. Scanning Electron Microscope (SEM) was also employed to visualize the surface morphology, shape, and size distribution of nanoparticles. Fourier Transform Infrared Spectroscopy (FTIR) is very sensitive to the chemical surface of nanoparticles and was utilized to identify functional groups in the nanoparticles. Cytotoxicity against cancer cell lines and antileishmanial activities were investigated using MTT assay, and the well diffusion method was used to detect the antibacterial property of the synthesized nanoparticles. Findings: UV-VIS spectrum exhibits an absorption band at around 400-450 nm suggesting the formation of biological Ag-NPs. The size and morphological properties of nanoparticles were assessed by SEM which showed that particles have spherical shapes with a diameter of about 20-70 nm. Ag-NPs showed cytotoxicity against human glioblastoma cancer cell line A-172 (IC50:7.2 µg/ml) and breast cancer cell line MCF-7 (IC50:7.6 µg/ml) after 48 h treatment. Ag-NPs presented antimicrobial activity against Gram-positive and Gram-negative bacteria. The present study confirmed good antileishmanial activity against the promastigote and amastigote stages of Leishmania major. The IC50 values of Ag-NPs and Glucantime® were 73.89 and 16.17μg/mL for promastigote, as well as 171.02 and 398.21 μg/mL for amastigotes assays, respectively. Discussion & Conclusion: The extract of B. persicum has the ability to reduce Ag+ ions to Ag nanoparticles. Moreover, the fabricated Ag-NPs have good cytotoxicity, antibacterial, and antileishmanial activities.
GP63, also known as Leishmanolysin, is a multifunctional virulence factor abundant on the surface of Leishmania spp. small peptides with anticancer capabilities that are selective and toxic to cancer ...cells are known as anticancer peptides. We aimed to demonstrate the activity of GP63 and its anticancer properties on melanoma using a range of in silico tools and screening methods to identify predicted and designed anticancer peptides.
Various in silico modeling methodologies are used to establish the three-dimensional (3D) structure of GP63. Refinement and re-evaluation of the modeled structures and the built models' quality evaluated using the different docking used to find the interacting amino acids between MMP2 and GP63 and its anticancer peptides. AntiCP2.0 is used for screening anticancer peptides. 2D interaction plots of protein–ligand complexes evaluated by Protein–Ligand Interaction Profiler server. It is for the first time that used anticancer peptides of GP63 and the predicted and designed peptides.
We used 3 peptides of GP63 based on the AntiCP 2.0 server with scores of 0.63, 0.53, and 0.49, and common peptides of GP63/MMP2 (continues peptide: mean the completely selected peptide after docking with non-anticancer effect, predicted with 0.58 score and designed peptides with 0.47 and 0.45 scores by AntiCP 2.0 server).
The antileishmanial and anticancer peptide research topics exemplify the multidisciplinary nature of peptide research. The advancement of therapeutics targeting cancer and/or Leishmania requires an interconnected research strategy shown in this work.
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GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Treatment of leishmaniasis with conventional synthetic drugs is a major global challenge. This study was designed to explore the leishmanicidal activity and apoptotic profile of three leaf extracts ...on Leishmania tropica stages.
The plants of Quercus velutina, Calotropis procera and Nicotiana tabacum were gathered from Anbarabbad county, in the southeastern part of Kerman province and extracted by maceration method using methanol alcohol. Various concentrations of the extracts (1, 10, 100 and 1000 μg/mL) were used against L. tropica stages to evaluate the inhibitory effect by colorimetric assay, macrophage model and flow cytometry. The MTT assay was conducted to determine the IC50 and CC50 values in promastigotes and J774-A1 macrophages, respectively. For intra-macrophage amastigotes, the leishmanicidal activity was evaluated by calculating the mean number of amastigotes in each macrophage and also IC50 values. The promastigote or amastigote stages with no drug and complete medium without organisms were considered as positive and negative controls, respectively. Meglumine antimoniate (Glucantime) was also used as standard drug. Also, annexin V was used to assess the apoptotic profile. All treatment settings were incubated for a standard time of 72 h in triplicates. Data were analyzed by t-test and ANOVA.
The findings showed that all plant extracts inhibited the proliferation rate of promastigotes and amastigotes (P ˂ 0.001); especially, Q. velutina represented the lowest IC50 in both stages. Besides, Q. velutina showed the least number of amastigotes in each macrophage compared to the other groups (4.5 μg/mL). The percentage of parasitic apoptosis at 1000 μg/mL of Q. velutina, C. procera, N. tabacum and Glucantime® were 37.4, 18.6, 8.5 and 52.4, respectively. Amastigotes (clinical stage) were significantly more susceptible to extracts and also Glucantime® than promastigotes (P < 0.001).
This study revealed that all three extracts of Q. velutina, C. procera and N. tabacum exhibited an effective antileishmanial activity and induced apoptosis against the L. tropica promastigotes. Further investigations are essential to isolate and analyze the chemical compositions and their biological properties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Epidemics of cutaneous leishmaniasis (CL) are occurring more frequently and spreading faster and farther than before in many areas of the world. The present study aimed to assess a long-lasting ...emerging epidemic (2005-2019) of 5532 cases with anthroponotic CL (ACL) in peri-urban areas of Kerman city in southeastern Iran.
This descriptive-analytical study was carried out for 15 years in Kerman province, southeastern Iran. The data were passively obtained through the health surveillance system and the Kerman Leishmaniasis Research Center. Every subject was diagnosed using direct smear microscopy. The representative causative agent was further examined by ITS1-PCR, PCR-RFLP, 7SL RNA gene sequencing and phylogenetic analyses. For each subject, a case report form designating demographic and clinical data was recorded.
A different pattern of ACL incidence was found in peri-urban areas compared to that in the city of Kerman. The incidence rate of ACL cases has significantly increased (P < 0.001) from 2005 to 2016 in new settlements with a gradual decline after that. The overall average risk of contracting the disease was 7.6 times higher in peri-urban areas compared to Kerman city, an old endemic focus. All isolates consisting of six variants were confirmed to be Leishmania tropica. The overall pattern of the ACL infection indicates that the etiological agent of ACL is propagated and transmitted by the bite of female Phlebotomus sergenti sandflies from person to person from dissimilar clones as reflected by the complexity of the migrants' backgrounds in the province.
The movement of populations and establishment of new settlements in peri-urban areas close to endemic areas are major risk factors for and are directly linked to CL. The underlying factors of this emerging ACL epidemic caused by L. tropica were disasters and droughts, among others. A robust commitment to a multilateral approach is crucial to make improvements in this area. This will require decisive coordinated actions through all governmental factions and non-governmental organizations. Furthermore, active and passive case detection strategies, early diagnosis, and effective treatment could help control the disease.
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Miniaturized culture systems of hepatic cells are emerging as a strong tool facilitating studies related to liver diseases and drug discovery. However, the experimental optimization of various ...parameters involved in the operation of these systems is time-consuming and expensive. Hence, developing numerical tools predicting the function of such systems can significantly reduce the associated cost. In this paper, a perfusion-based three dimensional (3D) bioreactor comprising encapsulated human liver hepatocellular carcinoma (HepG2) spheroids are analyzed. The flow and mass transfer equations for oxygen as well as different metabolites such as albumin, glucose, glutamine, ammonia, and urea were solved in three different domains, i.e., free flow, hydrogel, and spheroid porous media sections. Since the spheroids were encapsulated inside the hydrogel, shear stress imposed on them were found to be less than tolerable thresholds. The predicted cumulative albumin concentration over the 7 days of culture period showed a good agreement with the experimental data. Based on the critical role of oxygen supply to the hepatocytes, a parametric study was performed and the effect of various parameters was investigated. Results illustrated that convection mechanism was the dominant transport mechanism in the main-stream section contrary to the intra spheroids parts where the diffusion was the prevailing transport mechanism. In the hydrogel parts, the rate of diffusion and convection mechanisms were almost identical. As expected, higher perfusion rate would provide high oxygen level for the cells and, smaller spheroids with a diameter of 100 μm were at the low risk of hypoxic conditions due to short diffusive oxygen penetration depth. Numerical results evidenced that spheroids with diameter size >200 μm at low porosities (ε = 0.2–0.3) were at risk of oxygen depletion, especially at locations near the core center. Therefore, these results could be beneficial in preventing hypoxic conditions during
in vitro
experiments. The presented numerical model provides a numerical platform which can help researchers to design and optimize complex bioreactors and obtain numerical indexes of the main metabolites in a very short time prior to any fabrications. Such numerical indexes can be helpful in certifying the outcomes of forensic investigations.
The aim of this study was cost-effective and greener synthesis of barium carbonate (BaCO
3
or witherite) nanoparticles with economic importance, and to evaluate their therapeutic potentials and ...biocompatibility with immune cells. Barium carbonate nanoparticles were biosynthesized using black elderberry extract in one step with non-toxic precursors and simple laboratory conditions; their morphologies and specific structures were analyzed using field emission scanning electron microscopy with energy dispersive X-ray spectroscopy (FESEM-EDX). The therapeutic capabilities of these nanoparticles on the immune cells of murine macrophages J774 and promastigotes
Leishmania tropica
were evaluated. BaCO
3
nanoparticles with IC
50
= 46.6 µg/mL were more effective than negative control and glucantium (positive control) in reducing promastigotes (
P
< 0.01). Additionally, these nanoparticles with a high value of cytotoxicity concentration 50% (CC
50
) were less toxic to macrophage cells than glucantime; however, they were significantly different at high concentrations compared to the negative control.
Graphic abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The goal of this study was to analyze the antileishmanial and antibacterial activity of
Coffea arabica
green seed biosynthesize silver nanoparticles (
C. arabica
AgNPs), as well as cytotoxicity and ...cytokine gene expression. UV–vis spectroscopy, FTIR, and FESEM methods used to examine the
C. arabica
AgNPs. MTT test was used to assess the antileishmanial and cytotoxicity effects. The gene expression level was assessed in NPs-treated J774 cells by qPCR. The synthesized
C. arabica
AgNPs were in the size range of 20–70 nm, through FESEM pictures. The IC
50
values of the NPs were 65. 4 and 47.70 μg/mL against promastigotes and amastigotes of
Leishmania major
, but these values were 580.1 and 171.1 μg/mL for Glucantime® as the control drug.
C. arabica
AgNPs represented a significant increase in IL-12P40, as a Th1 cytokine, in comparison to Glucantime® at high concentrations (
P
< 0.01), whilst IL-10 expression level showed a significant reduction between NPs-treated and Glucantime®-treated macrophages at 250–1000 μg/mL concentrations (
P
< 0.001). Moreover, the NPs were cytotoxic on cancer cell lines of Hek293, MCF7, and A172 with the CC
50
values of 437.2, 116.8, and 72.9 µg/mL, respectively. It showed a significant effect of these NPs against A172 (
P
< 0.001). Also, the lowest MIC values of the NPs were obtained for
Bacillus subtilis
and
Staphylococcus aureus
(204 µg/mL). According to the antileishmanial, anticancer, and antibacterial activity of these NPs, it can considered a bio-agent drug in the future in endemic countries.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Reverse transcriptases (RTs) are found in different systems including group II introns, Diversity Generating Retroelements (DGRs), retrons, CRISPR-Cas systems, and Abortive Infection (Abi) ...systems in prokaryotes. Different classes of RTs can play different roles, such as template switching and mobility in group II introns, spacer acquisition in CRISPR-Cas systems, mutagenic retrohoming in DGRs, programmed cell suicide in Abi systems, and recently discovered phage defense in retrons. While some classes of RTs have been studied extensively, others remain to be characterized. There is a lack of computational tools for identifying and characterizing various classes of RTs. In this study, we built a tool (called myRT) for identification and classification of prokaryotic RTs. In addition, our tool provides information about the genomic neighborhood of each RT, providing potential functional clues. We applied our tool to predict RTs in all complete and draft bacterial genomes, and created a collection that can be used for exploration of putative RTs and their associated protein domains. Application of myRT to metagenomes showed that gut metagenomes encode proportionally more RTs related to DGRs, outnumbering retron-related RTs, as compared to the collection of reference genomes. MyRT is both available as a standalone software (https://github.com/mgtools/myRT) and also through a website (https://omics.informatics.indiana.edu/myRT/).
Herbal chemicals with a long history in medicine have attracted a lot of attention. Flavonolignans and flavonoids are considered as two classes of the above-mentioned compounds with different ...functional groups which exhibit several therapeutic capabilities such as antimicrobial, anti-inflammatory, antioxidant, antidiabetic, and anticancer activities. Based on the studies, high hydrophobic properties of the aforementioned compounds limit their bioavailability inside the human body and restrict their wide application. Nanoscale formulations such as solid lipid nanoparticles, liposomes, and other types of lipid-based delivery systems have been introduced to overcome the above-mentioned challenges. This approach allows the aforementioned hydrophobic therapeutic compounds to be encapsulated between hydrophobic structures, resulting in improving their bioavailability. The above-mentioned enhanced delivery system improves delivery to the targeted sites and reduces the daily required dosage. Lowering the required daily dose improves the performance of the drug by diminishing its side effects on non-targeted tissues. The present study aims to highlight the recent improvements in implementing lipid-based nanocarriers to deliver flavonolignans and flavonoids.
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