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
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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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The activation of the angiotensin (Ang) II after acute kidney injury (AKI) triggers oxidative stress and inflammatory cascade which involved not only the kidneys but also the brain. Ang II through ...the Ang II type 1 receptor (AT1R) may have deleterious effects on hippocampal synaptic transmission and cognitive functions under uremic encephalopathy. The present study was conducted to examine the effects of AT1R antagonist on AKI-induced cognitive and synaptic plasticity impairment.
Here, we investigated the effect of AKI and possible pathophysiological roles of AT1R with the selective AT1R antagonist losartan (10 mg/kg/day for consecutive 9 days) on cognitive performance using passive avoidance and Morris water maze tests. In order to understand the synaptic transmission, in vivo short and long-term plasticity were evaluated at the Schaffer collateral-CA1 synapse. Biochemical analysis was also performed to detect possible hippocampal nitric oxide and oxidative stress mechanisms.
Our data provide evidence of hippocampal complication following AKI with increased level of nitrite (P < 0.01 vs. sham) as well as oxidative stress (P < 0.01 vs. sham) that may be responsible for behavioral dysfunction under uremia (spatial memory, P < 0.001; passive avoidance P < 0.01 vs. sham). Losartan treatment effectively protects against cognitive (spatial memory, P < 0.01; passive avoidance P < 0.05 vs. AKI-veh) and synaptic plasticity impairments induced by AKI possibly via modulation of oxidative stress in the hippocampus (P < 0.01 vs. AKI-veh).
The present study conclusively demonstrated a protective role of AT1R antagonist losartan in hippocampal complication and neurocognitive dysfunction after AKI via modulating oxidative stress.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Waste from construction and demolition (also known as CDW) is one of the most harmful environmental issues. This study's primary goal is to produce new mortar and brick materials from recycled ...concrete powder (RCP) and recycled brick powder (RBP), two of the most popular CDW. Geopolymeric mortar and brick samples were produced by passing RCP and RBP through sieve No. 50 (with sand filler if necessary) and combining them with an alkaline solution made of water glass (WG) and NaOH. In this study, the mixture was then cured for three days at 80 °C in an oven. The effects of filler, RBP amount, WG amount, and the concentration of NaOH alkaline solution on the samples' strength were examined. Additionally, XRF and SEM/XRD tests were performed to verify the materials' composition and microstructure. The mechanical strength of the samples showed an increase with the increase of RCP values, so the brick sample with filler showed the highest compressive strength, measuring 59.53 MPa. The study's samples exhibited strong mechanical properties. Additionally, all of the bricks' water absorption fell within the standard range. In summary, according to different standards, both waste concrete and waste brick can be used to produce geopolymer materials especially bricks for construction and paving purposes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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
A microfluidics approach to synthesize core–shell nanocarriers with high pH tunability is described. The sacrificial shell protects the core layer with the drugs and prevents their release in the ...severe pH conditions of the gastrointestinal tract, while allowing for drug release in the proximity of a tumor. The proposed nanoparticulate drug‐delivery system is designed for the oral administration of cancer therapeutics.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In this study, potassium-doped zinc oxide nanoparticles (K-doped ZnO NPs) were green-synthesized using pine pollen extracts based on bioethics principles. The synthesized NPs were analyzed using ...X-ray diffraction (XRD), inductively coupled plasma atomic emission spectroscopy (ICP-AES), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDXA), and transmission electron microscopy (TEM). The cytotoxicity of these nanoparticles (NPs) on normal macrophage cells and cancer cell lines was evaluated. In the same concentrations of K-doped ZnO and pure ZnO NPs, K-doped ZnO NPs demonstrated higher toxicity. The results confirmed that the doped potassium could increase cytotoxicity. The IC
50
of K-doped ZnO NPs, pure ZnO NPs, and the examined control drug were 497 ± 15, 769 ± 12, and 606 ± 19 µg/mL, respectively. Considering the obtained IC
50
of K-doped ZnO NPs, they were more toxic to the cancer cell lines and had less cytotoxicity on normal macrophage cells.
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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
Neurological complications may occur in patients with acute or chronic renal failure; however, in cases of acute renal failure, the signs and symptoms are usually more pronounced, and progressed ...rapidly. Oxidative stress and nitric oxide in the hippocampus, following kidney injury may be involved in cognitive impairment in patients with uremia. Although many women continue taking hormone therapy for menopausal symptom relief, but there are also some controversies about the efficacy of exogenous sex hormones, especially estrogen therapy alone, in postmenopausal women with kidney injury. Herein, to the best of our knowledge for the first time, spatial memory and synaptic plasticity at the CA1 synapse of a uremic ovariectomized rat model of menopause was characterized by estradiol replacement alone.
While estradiol replacement in ovariectomized rats without uremia, promotes synaptic plasticity, it has an impairing effect on spatial memory through hippocampal oxidative stress under uremic conditions, with no change on synaptic plasticity. It seems that exogenous estradiol potentiated the deleterious effect of acute kidney injury (AKI) with increasing hippocampal oxidative stress.
Although, estrogen may have some positive effects on cognitive function in healthy subjects, but its efficacy in menopause subjects under uremic states such as renal transplantation, needs to be further investigated in terms of dosage and duration.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Over the last years, there has been a remarkable increase in the number of unresponsive patients with anthroponotic cutaneous leishmaniasis (ACL) reported worldwide. The primary objective of this ...study was to explore the role of demographic, clinical and environmental risk related-factors in the development of treatment failure, relapse and chronic cases compared to responsive patients with ACL. Moreover, molecular, histopathological and immunohistochemical (IHC) findings between these forms were explored. This work was undertaken as a prospective and case-control study in southeastern Iran. Culture media and nested PCR were used to identify the causative agent. Univariate multinomial and multiple multinomial logistic regression models and the backward elimination stepwise method were applied to analyze the data. A P<0.05 was defined as significant. Also, for different groups, skin punch biopsies were used to study the histopathological and immunohistochemical (IHC) profile. All samples showed that L. tropica was the only etiological agent in all unresponsive and responsive patients with ACL. Data analysis represented that 8 major risk factors including nationality, age groups, occupation, marital status, history of chronic diseases, duration of the lesion, the lesion on face and presence of domestic animals in the house were significantly associated with the induction of unresponsive forms. The histopathological and immunohistochemical findings were different from one form to another. The present findings clearly demonstrated a positive relation between ACL and distinct demographic, clinical and environmental risk determinants. Knowledge of the main risk factors for ACL infection is crucial in improving clinical and public health strategies and monitor such perplexing factors.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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