Tools for assessing quality of life in people with stroke-induced aphasia: a literature review.

BACKGROUND: The quality of life (QOL) of individuals with stroke-induced aphasia is significantly impacted by the condition. Clinicians and researchers are increasingly focusing on QOL assessments for people with aphasia (PWA) to gauge the effects of aphasia and the effectiveness of interventions. While several QOL assessment tools are utilized for PWA, there is limited literature comparing and evaluating their suitability for this population. This review aimed to explore the QOL measurement tools used with PWA, their aphasia-friendly characteristics, their applicability to severe aphasia, and the technical aspects of these questionnaires. SUMMARY: The review process involved two stages. Initially, a search was conducted to identify the tools used for assessing the QOL of PWA in studies published between 1975 and 2022. Various databases such as Google Scholar, PubMed, Scopus, and Web of Science were searched using specific keywords related to stroke, aphasia, QOL, questionnaires, outcome measurements, tools, scales, and instruments. Subsequently, hand searching was employed to gather additional information on the identified tools, including technical properties, communication and language domains, and crucial factors for QOL assessment in PWA. Results revealed that 28 articles met the inclusion criteria, identifying 26 tools for QOL assessment in PWA, comprising 11 generic, 9 stroke-specific, and 6 aphasia-specific tools. Technical details such as research country distribution, publication years (ranging from 1972 to 2015), completion time, administration methods (self-reporting), item formats (question or statement), response types (all tools, except SIP-136, NHP, and SA-SIP30 used Likert type scale for ratings), scoring methods (sum of score or using an algorithm), translation/adaptation status (EQ-5D-3L among generic tools, SIS-16 among stroke-specific questionnaires, and SAQOL-39 among aphasia-specific instruments received the most amount of translation/ adaptation), respondent characteristics (almost all the tools except aphasia-specific tests excluded people with severe aphasia), number of dimensions (ranged 1-12), item numbers (6-136), and coverage of communication/language domains (BOSS, CDP, ALA, AIQ-21 covered all language domains) were analysed. Notably, ALA emerged as the most suitable tool for assessing QOL in PWA due to its alignment with the desired features. KEY MESSAGES: Based on the review findings, clinicians and researchers are advised to prioritize the following features when selecting a QOL questionnaire for PWA: aphasia-specific and aphasia-friendly design, comprehensive coverage of QOL dimensions, inclusion of all language domains, and provision of self-reporting opportunities for PWA across all severity levels. ALA stands out as the preferred tool for QOL assessment in PWA based on its adherence to these criteria.

In silico and experimental potentials of 6-shogaol and meglumine antimoniate on Leishmania major: multiple synergistic combinations through modulation of biological properties.

Conventional therapeutic agents are no longer adequate against leishmaniasis. This complex condition continues to have a high mortality rate and public health impact. The present study aimed to explore an extensive array of experiments to monitor the biological activities of 6-shogaol, a major component of ginger, and meglumine antimoniate (MA or Glucantime®). The binding affinity of 6-shogaol and inducible nitric oxide synthase (iNOS), a major enzyme catalyzing nitric oxide (NO) from L-arginine was the source for the docking outline. The inhibitory effects of 6-shogaol, MA, and mixture were assessed using colorimetric and macrophage assays. Antioxidant activity was inferred by UV-visible spectrophotometry. Variably expressed genes were measured by quantifiable real-time polymerase chain reaction. Apoptotic and cell cycle profiles were analyzed by flow cytometry. Moreover, a DNA fragmentation assay was performed by electrophoresis and antioxidant metabolites include superoxide dismutase (SOD), catalase (CAT), and also nitric oxide (NO) by enzyme-linked immunosorbent assay. 6-shogaol and MA exhibited multiple synergistic mechanisms of action. These included a remarkable leishmanicidal effect, potent antioxidative activity, a high safety index, upregulation of M1 macrophages/Th1-associated cytokines (including, γ-interferon, interleukin-12p40, tumor necrotizing factor-alpha, and associated iNOS), significant cell division capture at the sub-G0/G1 phase, a high profile of apoptosis through DNA fragmentation of the nuclear components. In addition, the activity of NO was substantially elevated by treated intracellular amastigotes, while SOD and CAT activities were significantly diminished. This study is exclusive because no similar investigation has inclusively been conducted before. These comprehensive mechanistic actions form a logical foundation for additional advanced study.

Assessment of the antileishmanial activity of diallyl sulfide combined with meglumine antimoniate on Leishmania major: Molecular docking, in vitro, and animal model.

Currently, no safe vaccine against leishmaniasis is available. So far, different control strategies against numerous reservoir hosts and biological vectors have not been environment-friendly and feasible. Hence, employing medicinal components and conventional drugs could be a promising approach to developing novel therapeutic alternatives. This study aimed to explore diallyl sulfide (DAS), a dynamic constituent of garlic, alone and in a mixture with meglumine antimoniate (MAT as standard drug) using in vitro and animal model experiments against Leishmania major stages. The binding affinity of DAS and four major defense elements of the immune system (iNOS, IFN-É£, IL-12, and TNF-α) was used to predict the predominant binding mode for molecular docking configurations. Herein, we conducted a broad range of experiments to monitor and assess DAS and MAT potential treatment outcomes. DAS, combined with MAT, displayed no cytotoxicity and employed a powerful anti-leishmanial activity, notably against the clinical stage. The function mechanism involved immunomodulation through the induction of Th1 cytokine phenotypes, triggering a high apoptotic profile, reactive oxygen species (ROS) production, and antioxidant enzymes. This combination significantly decreased cutaneous lesion diameter and parasite load in BALB/c mice. The histopathological findings performed the infiltration of inflammatory cells associated with T-lymphocytes, particularly CD4+ phenotypes, as determined by biochemical markers in alleviating the amastigote stage and improving the pathological changes in L. major infected BALB/c mice. Therefore, DAS and MAT deserve further advanced therapeutic development and should be considered as possible candidates for treating volunteer cases with cutaneous leishmaniasis in designing an upcoming clinical trial.

Brain -cyst-driven genes expression in Toxoplasma Gondii Tehran strain: a parasitic-immunogenicity assessment by dint of RNA-Seq.

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite of warm-blooded vertebrates. At present, High-throughput RNA sequencing analysis have made it possible to determine the role of effective genes in host immune response. The aim of the present study is to global transcriptome analysis of the brain of mice infected with T. gondii Tehran strain for the first time and also to evaluate the expression of effective genes in the chronic form of infection. RNA was extracted from the samples and the library was prepared and sequenced using the IlluminaNovaSeq 6000 system. After analyzing gene expression changes, the results were confirmed by real-time method. We found 125 genes that were significantly differentially expressed between infected and non-infected samples (p < 0.0005). Gene ontology analysis revealed that the expression of many genes is critical for pathways such as T cell receptor signaling pathway, Natural Killer cell mediated cytotoxicity, Lysosome and Apoptosis of the host. As infection with Tehran strain leads to chronic infection in mice, therefore, we investigated the genes effective in creating the chronic form of Toxoplasma infection. The comparative analysis of genes showed increases in the expression of genes ctla4, ccl4, cd3e, c3, lcn2, gbp5, usp18, cyba, tap1 and samhd1 in the in the infected sample, which highlights their role in causing chronic infection. RNA-seq provides a valuable tool for analyzing host transcriptomes, better understanding the parasite-host interaction, and developing future drug and vaccine targets.

Catalytic Differences between Flavohemoglobins of Giardia intestinalis and E. coli.

The sole known heme enzyme of the parasitic protist Giardia intestinalis is a flavohemoglobin (gFlHb) that acts as a nitric oxide dioxygenase (NOD) and protects the organism from the free radical nitric oxide. To learn more about the properties of this enzyme, we measured its nitric oxide dioxygenase, NADH oxidase, and cytochrome c reductase activities and compared these to the activities of the E. coli flavohemoglobin (Hmp). The turnover number for the NOD activity of gFlHb (23 s-1) is about two-thirds of that of Hmp (34 s-1) at pH 6.5 and 37 °C. The two enzymes differ in their sensitivity towards molecules that act as heme ligands. For both gFlHb and Hmp, inhibition with miconazole, a large imidazole ligand, is adequately described by simple competitive inhibition, with KI = 10 µM and 0.27 µM for gFlHb and Hmp, respectively. Inhibition plots with the small ligand imidazole were biphasic, which is consistent with previous experiments with carbon monoxide as a probe that show that the active site of flavohemoglobins exists in two conformations. Interestingly, the largest difference is observed with nitrite, which, like imidazole, also shows a biphasic inhibition plot; however, nitrite inhibits gFlHb at sub-millimolar concentrations while Hmp is not significantly affected. NADH oxidase activity measured under aerobic conditions in the absence of nitric oxide for Hmp was more than twice the activity of gFlHb. The addition of 1 mM hydrogen peroxide in these assays stimulated the NADH oxidase activity of gFlHb but not Hmp. Both enzymes had nearly identical cytochrome c reductase activities but the extent of the contribution of indirect reduction by flavohemoglobin-generated superoxide was much lower with gFlHb (4% SOD-inhibited) than with Hmp (17% SOD-inhibited). Although the active sites of the two enzymes share the same highly conserved residues that are important for catalysis, differences in the distal ligand binding site may account for these differences in activity and sensitivity towards NOD inhibitors. The differences observed in the NADH oxidase and cytochrome c reductase assays suggest that gFlHb may have evolved to protect the protist, which lacks both superoxide dismutase and catalase, from the damaging effects of superoxide by minimizing its production and from peroxide by actively reducing it.

The effects of L-carnitine supplementation on inflammation, oxidative stress, and clinical outcomes in critically Ill patients with sepsis: a randomized, double-blind, controlled trial.

BACKGROUND: Sepsis, a life-threatening organ dysfunction caused by a host's dysregulated response to infection with an inflammatory process, becomes a real challenge for the healthcare systems. L-carnitine (LC) has antioxidant and anti-inflammatory properties as in previous studies. Thus, we aimed to determine the effects of LC on inflammation, oxidative stress, and clinical parameters in critically ill septic patients. METHODS: A randomized double-blinded controlled trial was conducted. A total of 60 patients were randomized to receive LC (3 g/day, n = 30) or placebo (n = 30) for 7 days. Inflammatory and oxidative stress parameters (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), superoxide dismutase (SOD), malondialdehyde (MDA), total antioxidant capacity (TAC), 28-day mortality rate, and some monitoring variables were evaluated. RESULTS: There was no statistically significant difference between study arms in baseline characteristics and disease severity scores. CRP (p < 0.001) and ESR (p: 0.004) significantly reduced, and SOD (p < 0.001) and TAC (p < 0.001) significantly improved in the LC group after 7 days. Between-group analysis revealed a significant reduction in CRP (p: 0.001) and serum chloride (p: 0.032), an increase in serum albumin (p: 0.036) and platelet (p: 0.004) significantly, and an increase in SOD marginally (p: 0.073). The 28-day mortality rate was also lower in the LC group compared with placebo (7 persons vs. 15 persons) significantly (odds ratio: 0.233, p: 0.010). CONCLUSIONS: L-carnitine ameliorated inflammation, enhanced antioxidant defense, reduced mortality, and improved some clinical outcomes in critically ill patients with sepsis. TRIAL REGISTRATION: IRCT20201129049534N1; May 2021.

In situ synthesis of long tubular water-dispersible polyaniline with core/shell gold and silver@graphene oxide nanoparticles for gas sensor application.

Gold nanoparticles (Au NPs) with graphene oxide (GO) shell (Au@GO), silver nanoparticles (Ag NPs) with GO shell (Ag@GO), and gold silver nanoparticles (AuAgNPs) with GO shell (AuAg@GO) were synthesized employing a cationic surfactant. The prepared core@shell structures were used for in situ synthesis of long tubular polyaniline structures employing cetyl trimethyl ammonium bromide (CTAB) as a soft template. This process led to a notable enhancement in the tubular nanostructure of PANI, extending its length beyond 10 µm, in the case of using core/shell Au@GO, Ag@GO, and AuAg@GO structures. To evaluate their applicability and compatibility, the dispersibility of these nanocomposites was assessed in three distinct solvents: water, dimethyl sulfoxide (DMSO), and N-Methyl-2-pyrrolidone (NMP). Subsequently, the dedoping of PANI within the prepared nanocomposites was scrutinized using UV-Visible (UV-Vis) spectroscopy, which revealed a reduction in the I750/I315 ratio from 1.00 to 0.66 when subjected to water and NMP solvents, respectively. Notably, the dedoping of the AuAg@GO/PANI nanocomposite was predominantly observed in NMP, attributable to the presence of hydrogen bonding interactions and the basic properties of NMP. In terms of ionic conductivity, it was observed that the prepared nanocomposite exhibited its highest conductivity in a water-based medium, registering at 1982 µs. Furthermore, the AuAg@GO/PANI nanocomposite exhibited superior sensing capabilities in comparison to PANI-based gas sensor devices, particularly when exposed to acetone, CO2, NO2, and H2S. Remarkably, at room temperature (25 °C), the AuAg@GO/PANI nanocomposite displayed rapid response and recovery times, with values of 279 s, 431 s, 335 s, and 509 s for 1 ppm concentrations of CO2, NO2, H2S, and acetone, respectively. The sensitivity of these sensors towards acetone, CO2, NO2, and H2S, was quantified by analyzing the slope of the response versus the target gas concentration, revealing the AuAg@GO/PANI nanocomposite to exhibit the highest sensitivity, particularly towards NO2.

Cutaneous Leishmaniasis Hampers COVID-19: A Controlled Cross-Sectional Study in High-Burden Endemic Areas of Iran.

INTRODUCTION: Emerging infectious diseases such as SARS-CoV-2 can cause pandemics and create a critical risk for humans. In a previous pilot study, we reported that the immunological responses induced by cutaneous leishmaniasis (CL) could decrease the incidence and severity of COVID-19. In this large-scale case-control study, we assessed the possible relationship between mortality and morbidity of COVID-19 in healed CL persons suffering scars compared to cases without CL history. METHODS: This controlled cross-sectional study was conducted between July 2020 and December 2022 in the endemic and high-burden areas of CL in southeastern Iran. In the study, 1400 previous CL cases with scars and 1,521,329 subjects who had no previous CL were analyzed. We used R 4.0.2 to analyze the data. Firth's bias reduction approach corresponding to the penalization of likelihood logistic regression by Jeffreys was also employed to influence the variables in the dataset. Also, a Bayesian ordinal logistic regression model was performed to explore the COVID-19 severity in both case and referent groups. RESULTS: The occurrence and severity rate of COVID-19 in CL scar cases are significantly less than in the non-CL control group, while in the CL scar subjects, patients with critical conditions and mortality were not observed. The morbidity (OR = 0.11, CI 0.06-0.20 and P < 0.001) and severity of COVID-19 in previous cases with CL scars were significantly diminished than that in the control group (credible interval - 2.57, - 1.62). CONCLUSIONS: The results represented a durable negative relationship between cured CL and COVID-19 incidence and severity. Additional studies seem necessary and should be designed to further validate the true impact and underlying mechanistic action of CL on COVID-19.

Separation and identification of snuff constituents by using GC-MS and ICP-OES as well as health risk assessment of some existing heavy metals.

The identification of volatile organic components in snuff was accomplished using GC-MS analysis in this study. The findings of the GC-MS analysis revealed the presence of nicotine, its derivatives, and several other toxic chemicals that are hazardous to human health. Furthermore, the content of 34 elements in four brands of snuff consumed in Neyshabur City was determined by ICP-OES analysis (with five repetitions). The health hazards of measured heavy elements were examined from two perspectives: carcinogenic (7 heavy elements were checked) and non-carcinogenic (4 heavy elements were checked). The investigation of non-carcinogenic hazards from inhalation was based on the computation of the hazard quotient (HQ) factor, and the results indicated that inhaling five heavy metals, Cu, Pb, Ni, Zn, and Cd, does not represent a substantial health risk ((HQ < 1). In contrast, the computed HQ factors for Cr and As were relatively high (1 < HQ < 10), indicating a substantial health risk from breathing these two elements. The carcinogenic factor (CR value) results revealed that the degree of carcinogenic risk for Cd was very low (CR value less than 1 × 10-6) and did not pose a concern to the consumer population. However, the risk of As, Cr, and Ni exposure is considerable in the carcinogenic risk range (CR values between 1 × 10-6 and 1 × 10-4).

In silico and in vitro potentials of crocin and amphotericin B on Leishmania major: Multiple synergistic mechanisms of actions.

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-γ, and TNF- α), 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-ß) 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.

The antitumor effect of oncolytic respiratory syncytial virus via the tumor necrosis factor-alpha induction and ROS-bax-mediated mechanisms.

BACKGROUND: Cervical cancer represents one of the most prevalent cancers among women worldwide, particularly in low- and middle-income nations. Oncolytic viruses (OVs) can infect cancer cells selectively and lethally without harming normal cells. Respiratory syncytial virus (RSV) is an oncolytic virus for anticancer therapy because of its propensity to multiply within tumor cells. This research aimed to assess the in vitro antitumor activities and molecular basis processes of the oncolytic RSV-A2 on the TC-1 cancer cells as a model for HPV­related cervical cancers. METHODS: Cellular proliferation (MTT) and lactate dehydrogenase (LDH) release assays were used to investigate the catalytic impacts of RSV-A2 by the ELISA method. Real-time PCR and flow cytometry assays were utilized to assess apoptosis, autophagy, intracellular concentrations of reactive oxygen species (ROS), and cell cycle inhibition. RESULTS: Our MTT and LDH results demonstrated that TC-1 cell viability after oncolytic RSV-A2 treatment was MOI-dependently and altered significantly with increasing RSV-A2 virus multiplicity of infection (MOI). Other findings showed that the RSV-A2 potentially resulted in apoptosis and autophagy induction, caspase-3 activation, ROS generation, and cell cycle inhibition in the TC-1 cell line. Real-time PCR assay revealed that RSV-A2 infection significantly elevated the Bax and decreased the Bcl2 expression. CONCLUSIONS: The results indicated that oncolytic RSV-A2 has cytotoxic and inhibiting effects on HPV-associated cervical cancer cells. Our findings revealed that RSV-A2 is a promising treatment candidate for cervical cancer.

Analysis of factors affecting discharge with the personal consent of hospitalized patients: A cross-sectional study.

Background and Aims: Discharge by personal satisfaction is a condition in which the patient leaves the hospital before completing the care period against medical advice. Thus, this study aims to identify and analyze the reasons for discharge with the personal satisfaction of hospitalized patients. Methods: The study was descriptive-analytical being performed in 2021. The study population was 2869 discharged inpatients with personal satisfaction. Sampling was done by random and census. The data were collected using a checklist and a researcher-made questionnaire whose validity and reliability were confirmed. The data were analyzed using SPSS24 by K-Score test for qualitative and variance for quantitative variables. Results: The discharge rate by personal satisfaction was 7.01%, the average age was 42 years, and the average length of stay was 4 days. Further, 57.1% of patients were female, 63.7% were married, and 21% were babies. A total of 22.77% of the patients were discharged with the father's consent, of which 13.2% were re-admitted. The most common reasons for the discharge were feeling of recovery (47.2%), the hospital being educational (30%), and dissatisfaction with the services of doctors (51.6%). Discharge with personal satisfaction had a significant relationship with the length of hospitalization (p < 0.001) and type of hospital (p = 0.04). Conclusion: The feeling of recovery, the educational nature of the hospital, and dissatisfaction with the services of doctors were the most common reasons for discharge with personal satisfaction. Therefore, monitoring the provision of services, establishing proper patient-doctor communication, and increasing the awareness of patients and parents could reduce this type of discharge and its consequences.

Potential Anti-Inflammatory and Growth Inhibitory Effect of Cyrtopodion scabrum Extract on Colon Cancer; An in vivo Study.

BACKGROUND: The use of complementary and/or alternative medicine to increase the efficacy and decrease the side effects of current cancer treatment is highly required. In this in-vivo study, we aimed to investigate the anti-tumor activity and probable side effects of a natural treatment, Cyrtopodion scabrum extract (CsE), in a model of tumor bearing mice. METHODS: We established 28 female CT26-tumor bearing balb/c-mice model. We divided them randomly into four groups (n=7): Negative control received distilled water (DW) and the three treatment groups were administered with 5-FU and two different doses (300 and 600 mg/kg) of the gecko aqueous extract, respectively. The changes in the tumor volumes and weights during and after treatment, along with the blood cell counts; spleen and thymus indices were assessed in the treatment groups. We have also measured the serum TNF-α, VEGF, AST, ALT and GSH, as well as the physical activities of the experimental mice. RESULTS: We found that the means of tumor weights and volumes in both CsE and 5-FU treated groups were significantly lower than the untreated group (p<0.05). Serum TNF-α and VEGF levels in both CsE treated groups were remarkably lower than 5-FU and untreated groups (p<0.05). The 5-FU treatment caused a remarkably decrease in serum GSH, RBC count, WBC count, thymus index, and spleen index , while CsE treatment maintained these quantities, with no significant changes, compared to the control group. AST and ALT were not significantly changed in none of the treated groups compared to control. CONCLUSION: Altogether, data suggest C. scabrum, as an effective and safe anti-cancer natural source, which could be used as an alternative/complementary medicine for the treatment of patients who suffer from colon cancer.

Bioinformatics evaluation of anticancer properties of GP63 protein-derived peptides on MMP2 protein of melanoma cancer.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Recent advances in gene therapy-based cancer monotherapy and synergistic bimodal therapy using upconversion nanoparticles: Structural and biological aspects.

In accordance with human genetics and genomics advances over the past years, it can be found that cancer is created through a somatic aberration in the host genome. Accordingly, researchers use therapeutic methods in genetic manipulation to discover the possible cure for the disease. In combination with traditional cancer treatments, gene therapy (GT) is essential in future cancer therapy. The development of powerful nanocarriers for targeted, controlled, and efficient intracellular delivery of therapeutic biomolecules that increase pharmacokinetics indicates that the development of GT is highly dependent on nanotechnology. Among nanocarriers, upconversion nanoparticles (UCNPs) have become the focus of great attention in the realm of inorganic nanomedicines following the strategy of "diagnosis for treatment" due to their outstanding features including safety, deep penetration of near-infrared (NIR) light into tissue, and reduction of unfavorable side effects of NIR-triggered therapies. Moreover, various individual therapies can be intelligently combined into a single nanotranostic system based on a UCNP platform for multimodal synergistic treatment. Given that the preparation of multifunctional nanomaterials is a prerequisite for the realization of cancer treatment, especially synergistic therapies, the recognition of the main components of advanced nanoparticles can help researchers in choosing the proper platform for cancer treatment. In view of this, the main goal of this review is to highlight the latest advances in the construction and application of upconversion nanoparticles as carriers for gene delivery and gene editing in cancer monotherapy and bimodal synergistic therapy, with an emphasis on the structural and biological aspects of these studies.

Fifty years of struggle to control cutaneous leishmaniasis in the highest endemic county in Iran: A longitudinal observation inferred with interrupted time series model.

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.

Antiproliferative properties of Turmerone on Leishmania major: Modes of action confirmed by antioxidative and immunomodulatory roles.

Treatment of leishmaniasis by conventional synthetic compounds has faced a serious challenge worldwide. This study was performed to evaluate the effect and modes of action of aromatic Turmerone on the Leishmania major intra-macrophage amastigotes, the causative agent of zoonotic cutaneous leishmaniasis in the Old World. In the findings, the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Turmerone plus meglumine antimoniate (Glucantime®; MA) than MA alone, especially at 50 µg/mL. In addition, Turmerone demonstrated no cytotoxicity as the selectivity index (SI) was 21.1; while it induced significant apoptosis in a dose-dependent manner on L. major promastigotes. In silico molecular docking analyses indicated an affinity of Turmerone to IL-12, with the MolDock score of - 96.8 kcal/mol; which may explain the increased levels of Th1 cytokines and decreased level of IL-10. The main mechanism of action is more likely associated with stimulating a powerful antioxidant and promoting the immunomodulatory roles in the killing of the target organism.

Anti-leishmanial activity of Avicennia marina (Avicenniaceae family) leaves hydroalcoholic extract and its possible cellular mechanisms.

Natural products are the main source of potent antioxidants and anti-leishmanial agents. This study was aimed to evaluate Avicennia marina (Avicenniaceae family) extract inhibitory effect against Leishmania tropica by accessing apoptotic markers and arginase activity. The A. marina were extracted and phytochemical analysis conducted. The inhibitory effect of A. marina was evaluated on L. tropica promastigote and amastigote forms, compared to meglumine antimoniate (Glucantime, MA) as standard drug. The level of apoptosis, Reactive Oxygen Species (ROS) production and arginase activity was assessed in A. marina-treated cells compared to control group. Phytochemical screening of A. marina extract showed strong presence of tannins and saponins. We demonstrated the inhibitory effect of A. marina on promastigote stages in a dose dependent manner. Also, lower 50% inhibitory concentration (IC50) value of amastigotes was indicated in A. marina group compared with the standard group of Glucantime (60.57 ± 1.46 vs. 73.19 ± 10.12 µg/mL, respectively, P < 0.05). Besides, A. marina represented no cytotoxicity as the selectivity index (SI) was 10.7. Also, it showed the potential to induce early apoptosis of 46.5% in promastigotes at 125 µg/mL concentration. Significant reduction of arginase level was observed in both A. marina-treated cells and promastigotes. The promising results indicated higher effectiveness of A. marina in decreasing parasite growth, inducing apoptosis in promastigotes, increasing ROS production and decreasing arginase level. So, A. marina can be a native plant candidate for anti-leishmanial drug in tropical regions with cutaneous leishmaniasis due to L. tropica.

In vitro and in vivo therapeutic potentials of 6-gingerol in combination with amphotericin B for treatment of Leishmania major infection: Powerful synergistic and multifunctional effects.

The ongoing conventional drugs for leishmaniasis treatment are insufficient. The present study aimed to assess 6-gingerol alone and in combination with amphotericin B on Leishmania major stages using experimental and in vivo murine models. Here, arrays of experimental approaches were designed to monitor and evaluate the 6-gingerol potential therapeutic outcomes. The binding affinity of 6-gingerol and IFN-γ was the basis for docking conformations. 6-Gingerol combined with amphotericin B represented a safe mixture, extremely leishmanicidal, a potent antioxidant, induced a remarkable apoptotic index, significantly increased the expression of the Th1-related cytokines (IL-12p40, IFN-γ, and TNF- α), iNOS, and transcription factors (STAT1, c-Fos, and Elk-1). In contrast, the expression of the Th2-related cytokines was significantly downregulated (p < 0.001). This combination was also potent when the lesion appearance was evaluated following three weeks of treatment. The histopathological and immunohistochemical patterns of the murine model represented clusters of CD4+ and CD8+ T lymphocytes which compressed and deteriorated the macrophages harboring Leishman bodies. The primary mode of action of 6-gingerol and amphotericin B involved broad mechanistic insights providing a coherent basis for further clinical study as a potential drug candidate for CL. In conclusion, 6-gingerol with amphotericin B synergistically exerted anti-leishmanial activity in vitro and in vivo and potentiated macrophages' leishmanicidal activity, modulated Th1- and Th2-related phenotypes improved the histopathological changes in the BALB/c mice infected with L. major. They elevated the leukocyte infiltration into the lesions. Therefore, this combination should be considered for treating volunteer patients with CL in clinical studies.

High occurrence of Acanthamoeba spp. in the water samples of public swimming pools from Kerman Province, Iran.

Acanthamoeba spp. is a free-living amoeba that can cause major infections in humans, including keratitis and granulomatous encephalitis. Thus, water resources play an important role in transmitting Acanthamoeba spp. infection to humans. The purpose of this study was to investigate the presence of Acanthamoeba spp. in public swimming pools from three cities of Kerman Province, southeastern Iran. Eighty water samples of 20 public indoor swimming pools were taken from Kerman, Jiroft, and Kahnauj cities. Water temperature (°C), pH, and free chlorine concentration (ppm) were measured. Filtration and cultivation were applied on non-nutrient agar medium. The polymerase chain reaction was applied by using the genus-specific primers (JDP1 and JDP2) on positive samples; these primers can amplify the 423-551 bp fragment. Eighteen of the 20 swimming pools (including 32/80; 40% samples) were contaminated with Acanthamoeba spp. All swimming pools of Jiroft and Kahnauj and 88.2% of swimming pools in Kerman were contaminated. As such, all 32 Acanthamoeba isolates were amplified using the JDP primer pairs. Two genotypes, T3 and T4, were also identified. The present research is the first to report Acanthamoeba spp. in public swimming pools from Kerman Province. Due to high occurrence of this protozoan, it is recommended to use warning signs around swimming pools to create awareness of this infection.