Cutaneous leishmaniasis (CL) is a serious health challenge at the global level due to Leishmania tropica. This study was conducted to evaluate the risk factors associated with anthroponotic CL (ACL) ...in unresponsive (patient who does not heal and remains with an active lesion, despite receiving two courses of intra-lesional Glucantime along with cryotherapy and one cycle of systemic Glucantime) and responsive patients in a major focus in southeastern Iran. A case-control study was conducted from April 2015 to October 2016 in the southeast of Iran. Patients were recruited in a major ACL focus from unresponsive and responsive cases. These patients were compared for environmental, clinical, and demographic characteristic factors. Twenty-five risk related factors were analyzed using multivariate logistic regression and backward elimination stepwise models. P<0.05 was defined to be statistically significant. In general, 340 patients with ACL comprising 72 (21.2%) unresponsive cases and 268 (78.8%) responsive cases with active lesions or scars were analyzed by estimating odds ratio (OR). All isolates from 15 responsive and 15 unresponsive patients were characterized as Leishmania tropica based on the BLAST and phylogenic analyses by PCR sequences of the Hsp70 and ITS1 loci. Among the 25 variables, 4 major risk factors including poor interior housing conditions (OR = 1.99, confidence interval (CI) = 1-3.93, P<0.04), history of chronic diseases (OR = 6.22, CI = 2.51-15.44, P≤0.001), duration of lesion in the patients referred ≥13 months (OR = 74.99, CI = 17.24-326.17, P≤0.001), and 5-12 months (OR = 7.42, CI = 3.07-17.92, P≤0.001) than lesions with ≤4 months of age and age groups ≥51 years (OR = 3.85, CI = 1.04-14.22, P<0.04) than those ≤7 years, were significantly associated with unresponsive forms. Improving interior house construction protecting high risk individuals and those with debilitating diseases from being bitten by sand flies, together with the early detection and effective treatment of older age groups with history of chronic diseases are highly important measures for preventing unresponsive forms in patients with ACL in southeastern Iran.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cutaneous leishmaniasis (CL) imposes a major health burden throughout the tropical and subtropical regions of the globe. Unresponsive cases are common phenomena occurred upon exposure to the standard ...drugs. Therefore, rapid detection, prognosis and classification of the disease are crucial for selecting the proper treatment modality. Using machine learning (ML) techniques, this study aimed to detect unresponsive cases of ACL, caused by Leishmania tropica, which will consequently be used for a more effective treatment modality. This study was conducted as a case-control setting. Patients were selected in a major ACL focus from both unresponsive and responsive cases. Nine unique and relevant features of patients with ACL were selected. To categorize the patients, different classifier models such as k-nearest neighbors (KNN), support vector machines (SVM), multilayer perceptron (MLP), learning vector quantization (LVQ) and multipass LVQ were applied and compared for this supervised learning task. Comparison of the receiver operating characteristic graphs (ROC) and confusion plots for the above models represented that MLP was a fairly accurate prediction model to solve this problem. The overall accuracy in terms of sensitivity, specificity and area under ROC curve (AUC) of MLP classifier were 87.8%, 90.3%, 86% and 0.88%, respectively. Moreover, the duration of the skin lesion was the most influential feature in MLP classifier, while gender was the least. The present investigation demonstrated that MLP model could be utilized for rapid detection, accurate prognosis and effective treatment of unresponsive patients with ACL. The results showed that the major feature affecting the responsiveness to treatments is the duration of the lesion. This novel approach is unique and can be beneficial in developing diagnostic, prophylactic and therapeutic measures against the disease. This attempt could be a preliminary step towards the expansion of ML application in future directions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Grass waste was used for transform an inexpensive waste into health. Silver nanoparticles (AgNPs) have been synthesized using waste material (dried grass). The average size of silver nanoparticles ...observed in transmission electron images was estimated to be about 15 nm. The anticancer, antifungal and antibacterial effect of AgNPs were studied in vitro. The minimum inhibitory concentration of AgNPs against Pseudomonas aeruginosa and Acinetobacter baumannii was calculated about 3 µg/ml. The highest level of inhibitory effect of AgNPs against Fusarium solani was close to 90% at a concentration of 20 μg/ml of AgNPs. An inhibitory effect on the cancer cell growth is reach, by increasing the concentration of AgNPs to 5 µg/ml; the cancer cells' survival decreases about 30%. Western results showed that the expression of Cyclin D1 protein of MCF-7 cell line decreased after treatment with the effective concentration of AgNPs.
Negligible data are available following major social activities and environmental changes on leishmaniasis. Therefore, how interactions between these events influence cutaneous leishmaniasis (CL) ...risk is not well-known. This longitudinal study was undertaken to explore the impact of interventions conducted between 1971 and 2020 in Bam county, which has had the highest disease burden in Iran. Only confirmed CL cases during this period were taken into account. Data were analyzed by SPSS 22 using the X2 test to assess the significance of the difference between proportions. Moreover, we used interrupted time series (ITS) to assess the impact of three environmental events during this period. Overall, 40,164 cases of CL occurred in the past five decades. Multiple complex factors were among the leading causes that synergistically induced the emergence/re-emergence of CL outbreaks in Bam. The main factors attributed negatively to CL control were cessation of malaria spraying activity, expansion of the city spaces, and a massive earthquake creating new breeding potentials for the vectors. The highest impact on CL incidence during these years was related to the earthquake coefficient = 17.8 (95% CI: 11.3, 22.7); p-value < 0.001. Many factors can contribute to CL outbreaks in endemic foci. They also can cause new foci in new areas. Since humans are the single reservoir for CL in this area, early detection and effective management significantly contribute to controlling CL to reduce the disease burden. However, essential evidence gaps remain, and new tools are crucial before the disease can ultimately be controlled. Nevertheless, sustained funding and more trained task forces are essential to strengthen surveillance and case management and monitor the interventions' impact.
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A significant barrier to optimal antileishmanial treatment is low efficacy and the emergence of drug resistance. Multiple approaches were used to monitor and assess crocin (a central component of ...saffron) mixed with amphotericin B (AmpB) potential in silico and in vitro consequences. The binding behavior of crocin and iNOS was the purpose of molecular docking. The results showed that crocin coupled with AmpB demonstrated a safe combination, extremely antileishmanial, suppressed Leishmania arginase absorption, and increased parasite death. This natural flower component is a robust antioxidant, significantly promoting the expression of the Th1-connected cytokines (IL12p40, IFN-gamma, and TNF- alpha), iNOS, and transcription factors (Elk-1, c-Fos, and STAT-1). In comparison, the expression of the Th2-associated phenotypes (IL-10, IL-4, and TGF-beta) was significantly reduced. The leishmanicidal effect of this combination was also mediated through programmed cell death (PCD), as confirmed by the manifestation of phosphatidylserine and cell cycle detention at the sub-GO/G1 phase. In conclusion, crocin with AmpB synergistically exerted in vitro antileishmanial action, generated nitric oxide and reactive oxygen species, modulated Th1, and Th2 phenotypes and transfer factors, enhanced PCD profile and arrested the cell cycle of Leishmania major promastigotes. The main action of crocin and AmpB involved wide-ranging mechanistic insights for conducting other clinical settings as promising drug candidates for cutaneous leishmaniasis. Therefore, this combination could be esteemed as a basis for a potential bioactive component and a logical source for leishmanicidal drug development against CL in future advanced clinical settings.
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Cuminaldehyde (CA), an oxidized aldehyde monoterpene, is a major essential oil component in cumin seeds, which has shown different promising medical effects. In this study, we comprehensively ...evaluated the antileishmanial potential of Bunium persicum (Boiss) B. Fedtsch (Apiaceae) and one of its main essential oil constituents, CA, focus on the mechanisms of action.
We used a molecular docking approach to examine the capability of CA for binding to IL-12P40 and TNF-α. The colorimetric assay was performed to assess the effect of B. persicum crude extract, essential oil, and CA, against Leishmania major promastigotes and intracellular amastigotes. The expression of IFN-γ, IL-12P40, TNF-α, and IL-10 genes was detected using quantitative real-time polymerase chain reaction qPCR.
Docking analyses in the current study indicated CA binds to IL-12P40 and TNF-α. These products were safe, extremely antileishmanial, and significantly promoted Th1-related cytokines (IFN-γ, IL-12P40, TNF-α), while downregulating the Th2 phenotype (IL-10).
Cumin essential oil and its major component, CA, possessed powerful antileishmanial activity. The primary mechanism of activity involves an immunomodulatory role toward Th1 cytokine response. Therefore, cumin essential oil and CA deserve further explorations as promising medications for treating leishmaniasis.
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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
As effector innate immune cells and as a host to the protozoan parasite Leishmania, macrophages play a dual role in antileishmanial immunoregulation. The 2 key players in this immunoregulation are ...the macrophage-expressed microRNAs (miRNAs) and the macrophage-secreted cytokines. miRNAs, as small noncoding RNAs, play vital roles in macrophage functions including cytokines and chemokines production. In the reverse direction, Leishmania-regulated cytokines alter miRNAs expression to regulate the antileishmanial functions of macrophages. The miRNA patterns vary with the time and stage of infection. The cytokine-regulated macrophage miRNAs not only help parasite elimination or persistence but also regulate cytokine production from macrophages. Based on these observations, we propose a novel immunoregulatory framework as a scientific rationale for antileishmanial therapy.
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Leishmaniasis is one of the biggest concerns of the World Health Organization (WHO) due to its severe side effects, the emergence of resistance, and secondary bacterial infections; therefore, it was ...reported as an epidemic, especially in immunocompromised individuals. The main purpose of this study was to synthesize and characterize the polylactic acid (PLA)/chitosan nanofibers decorated with amphotericin B as a new delivery system for the in vitro treatment of leishmaniasis wounds. The prepared nanofibers were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), X-ray diffraction (XRD), and in vitro drug release test. The anti-leishmanial effect of nanofibers decorated with amphotericin B against Leishmania major promastigotes and its cytotoxicity to macrophages were determined by the flow cytometry test. The in vitro drug release assay indicated that 84% of the amphotericin B loaded in nanofibers was released after 400 min. The average concentration of the amphotericin B loaded in PLA/chitosan nanofibers and the conventional form of amphotericin B that prevented the growth of 50% of the promastigotes of L. major were 1.29 and 4.34 µg/mL, respectively.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IL-27 is a cytokine that exerts diverse effects on the cells of innate and adaptive immune systems. Chiefly expressed in macrophages and dendritic cells during the early phase of Leishmania ...infection, IL-27 contributes to the protection against L. major infection but suppresses the protective Th1 response against L. donovani, L. infantum, L. amazonensis and L. braziliensis infections, suggesting its functional duality. During the late stage of Leishmania infection, IL-27 limits the immunopathogenic reactions and tissue damages. Herein, we analyze the mechanism of the functional duality of IL-27 in the resistance or susceptibility to Leishmania infection, prompting IL-27 for anti-Leishmanial therapy.
Dirofilariasis is a zoonotic parasitic infection transmitted from animals to humans by culicid mosquitoes. Although the disease can be caused by Dirofilaria spp. including Dirofilaria immitis and ...Dirofilaria repens, human ocular dirofilariasis due to D. immitis is relatively rare in the world. This study was aimed to present a case of ocular dirofilariasis caused by D. immitis in southeastern Iran. The present study provides the second report on ocular dirofilariasis caused by D. immitis isolated from a human in southeast Iran. Based on the available evidence, dirofilariasis in dogs has significantly increased in endemic areas such as Iran. Therefore, physicians should be aware of such zoonotic nematodes so as to take proper and timely action and treatment against the disease.
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