Gaillardin exerts potent antileukemic effects on HL-60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment.

The use of all-trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard-risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high-risk subgroup more problematic, and possible side effects limit their clinical dosages. Numerous studies have proven the cytotoxic properties of Gaillardin, one of the Inula oculus-christi-derived sesquiterpene lactones. Due to the adverse effects of arsenic trioxide on the high-risk subgroup of APL patients, we aimed to assess the cytotoxic effect of Gaillardin on HL-60 cells as a single or combined-form approach. The results of the trypan blue and MTT assays outlined the potent cytotoxic properties of Gaillardin. The flow cytometric analysis and the mRNA expression levels revealed that Gaillardin attenuated the proliferative capacity of HL-60 cells through cell cycle arrest and induced apoptosis via reactive oxygen species generation. Moreover, the results of synergistic experiments indicated that this sesquiterpene lactone sensitizes HL-60 cells to the cytotoxic effects of arsenic trioxide. Taken together, the findings of the present investigation highlighted the antileukemic characteristics of Gaillardin by inducing G1 cell cycle arrest and triggering apoptosis. Gaillardin acts as an antileukemic metabolite against HL-60 cells and this study provides new insight into treating APL patients, especially in the high-risk subgroup.

Neurodegeneration of White and Gray Matter in the Hippocampus with FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that affects older premutation carriers (55-200 CGG repeats) of the fragile X gene. Despite the high prevalence of the FXTAS disorder, neuropathology studies of individuals affected by FXTAS are limited. We performed hematoxylin and eosin (H&E) staining in the hippocampus of 26 FXTAS cases and analyzed the tissue microscopically. The major neuropathological characteristics were white matter disease, intranuclear inclusions in neurons and astrocytes, and neuron loss. Astrocytes contained more and larger inclusions than neurons. There was a negative correlation between age of death and CGG repeat length in cases over the age of 60. The number of astroglial inclusions (CA3 and dentate gyrus) and the number of CA3 neuronal inclusions increased with elevated CGG repeat length. In the two cases with a CGG repeat size less than 65, FXTAS intranuclear inclusions were not present in the hippocampus, while in the two cases with less than 70 (65-70) CGG repeat expansion, neurons and astrocytes with inclusions were occasionally identified in the CA1 sub-region. These findings add hippocampus neuropathology to the previously reported changes in other areas of the brain in FXTAS patients, with implications for understanding FXTAS pathogenesis.

Investigating the multifaceted cooperation of autophagy, PI3K/AKT signaling pathways, and INPP4B gene in de novo acute myeloid leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) has been the most prevalent form of acute leukemia among adults, and it has been associated with poor survival rates over the last four decades. Understanding the processes involved in leukemogenesis, particularly autophagy and signaling pathways, can provide critical insights into their roles in disease development, risk assessment, and potential therapeutic interventions. This study investigated gene expression changes, focusing on MAP1LC3B and BECN1, related to autophagy, as well as PI3KCA and AKT1 in the PI3K-AKT pathway, and INPP4B, which regulates this signaling cascade. METHODS: We collected blood samples from 21 AML patients and 9 healthy volunteers. Gene expression was analyzed through qPCR following RNA extraction and cDNA synthesis. Statistical analysis encompassed t-tests, ANOVA, and correlation coefficients. RESULTS: AML patients exhibited significantly increased MAP1LC3B gene expression (****P < 0.0001; fold change = 11.9) and significantly reduced levels of INPP4B (****P < 0.0001; fold change = 0.026), AKT1 (*P < 0.05; fold change = 0.59), and PI3KCA (****P < 0.0001; fold change = 0.16) compared to healthy controls. However, BECN1 gene expression did not significantly differ between the two groups. Additionally, noteworthy correlations were observed between INPP4B and BECN1 (r = 0.57; P = 0.006) and BECN1 and PI3KCA (r = 0.61; P = 0.003) in AML patients. CONCLUSIONS: This study highlights variations in leukemogenesis pathways, exemplified by increased MAP1LC3B expression and diminished expression of regulatory genes in specific AML cases. These findings contribute to our comprehension of the molecular mechanisms underlying AML and may inform future diagnostic and therapeutic approaches.

Association of TMPRSS2 Gene Polymorphisms with COVID-19 Severity and Mortality: a Case-Control Study with Computational Analyses.

Coronavirus disease 2019 (COVID-19) is a severe disease caused by a new variant of beta-coronavirus that first appeared in China. Human genetic factors, including polymorphisms, serve pivotal roles in the high transmission of SARS-CoV-2 and the stubbornly progressing sickness seen in a small but significant percentage of infected people; however, but these factors remain ill-defined. A total of 288 COVID-19 patients and 288 controls were genotyped for TMPRSS2 polymorphisms using both restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and amplification refractory mutation system (ARMS)-PCR techniques. Different genotypes of TMPRSS2 polymorphisms were compared in terms of disease susceptibility and mortality. The statistical analysis showed that minor alleles of all studied variants statistically increased the risk of COVID-19, except for the rs75603675 C > A variant. The T allele of rs12329760 conferred an increased risk of COVID-19. Moreover, the AG/AC/TT/AG combination of genotypes significantly enhanced the risk of COVID-19 in our population. Different haplotypes of rs17854725/rs75603675/rs12329760/rs4303795 polymorphisms, including GACA, GACG, GATG, GATA, AATA, ACCG, ACTG, ACTA, GCCA, and GCTG, were found to be associated with increased risk of the disease (odds ratio > 1). Regarding the clinical and paraclinical characteristics, a statistically significant difference was found between non-severe and severe forms except for gender, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and underlying diseases. In addition, case genotypes of TMPRSS2 rs17854725 A > G, rs12329760 C > T, and rs4303795 A > G were significantly different regarding severe and non-severe forms of the disease (P-value < 0.001). Specifically, death was more frequent in carriers of the AG genotype of rs17854725 A > G (P-value = 0.022). Patients who carry the minor alleles of the four studied TMPRSS2 variants were rather vulnerable to COVID-19 infection. Our findings indicated that rs17854725 A > G (AA vs. AG and AA vs. GG), rs12329760 C > T (CC vs. CT and CC vs. TT), and rs4303795 A > G (AA vs. AG) genotypes of TMPRSS2 variations are associated with a more invasive disorder pattern. More studies on larger populations are needed to confirm our results.

Association of polymorphisms in tumor necrosis factors with SARS-CoV-2 infection and mortality rate: A case-control study and in silico analyses.

The present coronavirus disease 2019 (COVID-19) is spreading rapidly and existing data has suggested a number of susceptibility factors for developing a severe course of the disease.  The current case-control experiment is aimed to study the associations of genetic polymorphisms in tumor necrosis factors (TNFs) with COVID-19 and its mortality rate. A total of 550 participants (275 subjects and 275 controls) were enrolled. The tetra-amplification refractory mutation system polymerase chain reaction technique was recruited to detect -308G>A TNFα and +252A>G TNFß polymorphisms among the Iranian subjects. We demonstrated that carriers of the G allele of TNFß-252A/G, rs909253 A>G were more frequent in COVID-19 subjects compared to the healthy group and this allele statistically increased the disease risk (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.23-1.96, p < 0.0001). At the same time, the A allele of TNFα-311A/G, rs1800629 G>A moderately decreased the risk of COVID-19 (OR = 0.68, 95% CI = 0.53-0.86, p < 0.002). Also, we analyzed the various genotypes regarding the para-clinical and disorder severity; we found that in the AA genotype of TNFß-252A/G (rs909253 A>G), the computed tomography scan pattern was different in comparison to cases carrying the AG genotype with p1 < 0.001. In addition, in the severe cases of COVID-19, leukocyte and neutrophil count and duration of intensive care unit hospitalization in the deceased patients were significantly increased (p < 0.001). Moreover, the TNFα-311A/G (rs1800629 G>A) variant is likely to change the pattern of splicing factor sites. Our findings provided deep insights into the relationship between TNFα/TNFß polymorphisms and severe acute respiratory syndrome coronavirus 2. Replicated studies may give scientific evidence for exploring molecular mechanisms of COVID-19 in other ethnicities.

Mapping the intellectual structure of the coronavirus field (2000-2020): a co-word analysis.

Over the two last decades, coronaviruses have affected human life in different ways, especially in terms of health and economy. Due to the profound effects of novel coronaviruses, growing tides of research are emerging in various research fields. This paper employs a co-word analysis approach to map the intellectual structure of the coronavirus literature for a better understanding of how coronavirus research and the disease itself have developed during the target timeframe. A strategic diagram has been drawn to depict the coronavirus domain's structure and development. A detailed picture of coronavirus literature has been extracted from a huge number of papers to provide a quick overview of the coronavirus literature. The main themes of past coronavirus-related publications are (a) "Antibody-Virus Interactions," (b) "Emerging Infectious Diseases," (c) "Protein Structure-based Drug Design and Antiviral Drug Discovery," (d) "Coronavirus Detection Methods," (e) "Viral Pathogenesis and Immunity," and (f) "Animal Coronaviruses." The emerging infectious diseases are mostly related to fatal diseases (such as Middle East respiratory syndrome, severe acute respiratory syndrome, and COVID-19) and animal coronaviruses (including porcine, turkey, feline, canine, equine, and bovine coronaviruses and infectious bronchitis virus), which are capable of placing animal-dependent industries such as the swine and poultry industries under strong economic pressure. Although considerable research into coronavirus has been done, this unique field has not yet matured sufficiently. Therefore, "Antibody-virus Interactions," "Emerging Infectious Diseases," and "Coronavirus Detection Methods" hold interesting, promising research gaps to be both explored and filled in the future.

Chandelier Cartridge Density Is Reduced in the Prefrontal Cortex in Autism.

An alteration in the balance of excitation-inhibition has been proposed as a common characteristic of the cerebral cortex in autism, which may be due to an alteration in the number and/or function of the excitatory and/or inhibitory cells that form the cortical circuitry. We previously found a decreased number of the parvalbumin (PV)+ interneuron known as Chandelier (Ch) cell in the prefrontal cortex in autism. This decrease could result from a decreased number of Ch cells, but also from decreased PV protein expression by Ch cells. To further determine if Ch cell number is altered in autism, we quantified the number of Ch cells following a different approach and different patient cohort than in our previous studies. We quantified the number of Ch cell cartridges-rather than Ch cell somata-that expressed GAT1-rather than PV. Specifically, we quantified GAT1+ cartridges in prefrontal areas BA9, BA46, and BA47 of 11 cases with autism and 11 control cases. We found that the density of GAT1+ cartridges was decreased in autism in all areas and layers. Whether this alteration is cause or effect remains unclear but could result from alterations that take place during cortical prenatal and/or postnatal development.

A new chromogenic and fluorescent chemosensor based on a naphthol-bisthiazolopyridine hybrid: a fast response and selective detection of multiple targets, silver, cyanide, sulfide, and hydrogen sulfide ions and gaseous H2S.

A novel chemosensor 1 based on a naphthol-bisthiazolopyridine hybrid was synthesized and characterized. Among the various screened cations and anions, chemosensor 1 selectively recognized Ag+ and CN- ions by relying on the color change and distinct absorption and emission changes. Moreover, the probe 1·Ag+ was well operable for the selective monitoring of S2-, HS- and H2S as evidenced by the different color and optical changes. The selective detection of all the anions was simply based on the breakage of the intramolecular hydrogen bonding of 1, followed by the protonation or deprotonation mechanism. In general, chemosensor 1 is a promising indicator in terms of its ease-of-use, selectivity, sensitivity, and rapid response (<1 s). Moreover, the visual detection and concentration determination of these analytes by solution or solid kits are the advantages for the practical applications of this sensor.

A Successful implementation of an idea to a nationally approved plan: Analyzing Iran's National Health Roadmap using the Kingdon model of policymaking.

Introduction: Hospital beds, human resources, and medical equipment are the costliest elements in the health system and play an essential role at the time of treatment. In this paper, different phases of the NEDA 2026 project and its methodological approach were presented and its formulation process was analysed using the Kingdon model of policymaking. Methods: Iran Health Roadmap (NEDA 2026) project started in March 2016 and ended in March 2017. The main components of this project were hospital beds, clinical human resources, specialist personnel, capital medical equipment, laboratory facilities, emergency services, and service delivery model. Kingdon model of policymaking was used to evaluate NEDA 2026 development and implementation. In this study, all activities to accomplish each step in the Kingdon model was described. Results: The followings were done to accomplish the goals of each step: collecting experts' viewpoint (problem identification and definition), systematic review of the literature, analysis of previous experiences, stakeholder analysis, economic analysis, and feasibility study (solution appropriateness analysis), three-round Delphi survey (policy survey and scrutinization), and intersectoral and interasectoral agreement (policy legislation). Conclusion: In the provision of an efficient health service, various components affect each other and the desired outcome, so they need to be considered as parts of an integrated system in developing a roadmap for the health system. Thus, this study demonstrated the cooperation process at different levels of Iran's health system to formulate a roadmap to provide the necessary resources for the health sector for the next 10 years and to ensure its feasibility using the Kingdon policy framework.

Bioavailability of Sodium and Trace Metals under Direct and Indirect Effects of Compost in Urban Soils.

The contamination of urban soil with sodium (Na) and trace metals can be one of the major concerns for groundwater contamination and street tree health. The bioavailability of Na, copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) in urban soil amended with 0, 5, and 10% w/w compost was evaluated at none, medium, and high contamination levels of soil mixtures. The relationship between soil properties, compost addition, contamination level and metal uptake by barley ( L.) was determined using multivariate linear regression and path analysis. The results indicated the direct negative effect of compost on metal absorption possibly through specific complexation for Cu, Zn, Cd, and Pb. Compost can also affect the absorption of Na and Cd indirectly by means of cation exchange capacity (CEC) and pH. The degree of soil contamination with metals can affect the competition of cations for the complexing sites of the soil mixtures and, therefore, can induce changes in metal availability for plants. Compost addition to the soil also increased nutrient availability, except for ammonium (NH) and nitrate (NO). We concluded that in the short term, the addition of compost significantly reduced metal bioavailability and improved nutrient availability. However, more studies are required to monitor the long-term ability of the compost to reduce Na and trace metal bioavailability in urban soil.

The effect of Citrus Aurantifolia (Lemon) peels on cardiometabolic risk factors and markers of endothelial function in adolescents with excess weight: A triple-masked randomized controlled trial.

Background: Childhood obesity is becoming a global problem and its incidence is increasing. The role of dietary intervention with fruits containing vitamin C and flavonoid to control obesity consequences in childhood has not been yet defined. Lemon (Citrus aurantifolia) peels contain flavonoid, pectin and vitamin C. We aimed to compare the effects of lemon peels and placebo on cardiometabolic risk factors and markers of endothelial function among adolescents with overweight and obesity. Methods: In this triple-masked, randomized controlled trial, 60 overweight/obese adolescents were enrolled in a 4-week trial. Eligible participants were randomly assigned into two groups of equal number receiving daily oral capsules containing lemon powder or placebo. Fasting blood sugar, lipid profile, ICAM-1 and VCAM-1, as well as systolic and diastolic blood pressure were compared between the two groups before and after administration of medication and placebo. Results: Of the total 60 enrolled patients, 30 and 29 patients in the lemon and control groups completed the study, respectively. The results of within-group analysis demonstrated a slight reduction in body mass index, LDL-C and systolic blood pressure in the lemon group, but no between group differences existed in the studied variables. Conclusion: This study revealed that consumption of lemon peel extract has some beneficial effects for childhood obesity; however, no considerable effect was documented on anthropometric measures and biochemical factors. Future studies with longer follow up are highly recommended.

Trace metal contamination influenced by land use, soil age, and organic matter in montreal tree pit soil.

The short life span of many street trees in the Montreal downtown area may be due in part to higher than standard concentrations of trace metals in the tree pit soils. The effects of land use, soil organic matter, and time since tree planting in a given tree pit (soil age) were studied with respect to the total concentration of trace metals (Cr, Ni, Cu, Zn, Cd, and Pb) in soil collected from tree pits on commercial and residential streets. Contingency table analysis and multiple linear regression were applied to study how these variables were related to the total concentrations of trace metals in soil. Other variables, such as pH, street width, distance of the tree pit from the curb, and tree pit volume, were also used as input to statistical analysis to increase the analysis' explanatory power. Significantly higher concentrations of Cu, Cd, Zn, and Pb were observed in soils from commercial streets, possibly as a result of heavier traffic as compared with residential streets. Soil organic matter was positively correlated with the concentrations of Cu and Pb, probably due to the ability of organic matter to retain these trace metals. Nickel, Cu, Zn, Cd, and Pb were positively correlated with the soil age presumably because trace metals accumulate in the tree pit soil over time. This knowledge can be helpful in providing soil quality standards aimed at improving the longevity of downtown street trees.

Investigation into the potential ability of Pickering emulsions (food-grade particles) to enhance the oxidative stability of oil-in-water emulsions.

In this study the potential ability of food-grade particles (at the droplet interface) to enhance the oxidative stability was investigated. Sunflower oil-in-water emulsions (20%), stabilised solely by food-grade particles (Microcrystalline cellulose (MCC) and modified starch (MS)), were produced under different processing conditions and their physicochemical properties were studied over time. Data on droplet size, surface charge, creaming index and oxidative stability were obtained. Increasing the food-grade particle concentration from 0.1% to 2.5% was found to decrease droplet size, enhance the physical stability of emulsions and reduce the lipid oxidation rate due to the formation of a thicker interfacial layer around the oil droplets. It was further shown that, MCC particles were able to reduce the lipid oxidation rate more effectively than MS particles. This was attributed to their ability to scavenge free radicals, through their negative charge, and form thicker interfacial layers around oil droplets due to the particles size differences. The present study demonstrates that the manipulation of emulsions' interfacial microstructure, based on the formation of a thick interface around the oil droplets by food-grade particles (Pickering emulsions), is an effective approach to slow down lipid oxidation.

Statistical source identification of major and trace elements in groundwater downward the tailings dam of Miduk Copper Complex, Kerman, Iran.

Identifying the possible sources of potential harmful metals in groundwater systems plays a crucial role in evaluating the potential risks to residents and local plant cover. An attempt was made to define the origin of Al, Cd, Cu, Fe, Mo, Ni, and Pb in groundwater using multivariate statistic approaches [principal component analysis (PCA), hierarchical cluster analysis], and tailings sequential extraction by the method of Tessier et al. The concentrations of studied elements were measured in 42 samples collected from 15 stations surrounding and downward the tailings dam of Miduk Copper Complex, central province of Kerman, Iran. According to the PCA results, confirmed by cluster dendrogram and metal content measurement of tailings sequential extracts, two components accounting for nearly 73% of the total variance, controlled the heavy metal variability and classified the possible source of groundwater contamination into two categories: (1) upper seepage which controls the variability of Cd, Cu, Fe, Ni, and Pb and (2) toe seepage of tailings dump affecting on Mo and Al concentration in downstream groundwater.

The effect of interfacial microstructure on the lipid oxidation stability of oil-in-water emulsions.

A novel approach to reduce lipid oxidation in oil-in-water emulsions has been taken and involves the manipulation of the emulsions' interfacial microstructure. Oil-in-water emulsions stabilised by sodium caseinate (CAS), Tween 20 and silica particles were prepared and their lipid oxidation stability was assessed over a week. Lipid oxidation was monitored by measuring the concentration of primary lipid oxidation product, using the peroxide value method and secondary lipid oxidation products formation were evaluated with the p-anisidine technique. Oil-phase volume fraction and emulsifier type both play key roles in influencing the rate of lipid oxidation. Decreasing the oil fraction from 30% to 5% was found to promote lipid oxidation as a result of an increase in the amount of pro-oxidant iron per gram of oil. It was further shown that, CAS in the continuous phase reduces lipid oxidation at pH 7 due to its metal chelating ability. In addition, the results show that, emulsions stabilised with silica particles (at pH 2) inhibit lipid oxidation to a greater extent than emulsions stabilised with surfactants alone. The present study demonstrates that emulsions' physical properties such as oil-phase volume fraction, droplet size and droplet interfacial microstructure are all formulation parameters that can be used to significantly reduce the rate of lipid oxidation.