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Acute myelogenous leukaemia (AML) originates and is maintained by leukaemic stem cells (LSCs) that are inherently resistant to antiproliferative therapies, indicating that a critical strategy for overcoming chemoresistance in AML therapy is to eradicate LSCs. In this work, we investigated the anti‐AML activity of bortezomib (BTZ), emphasizing its anti‐LSC potential, using KG‐1a cells, an AML cell line with stem‐like properties. BTZ presented potent cytotoxicity to both solid and haematological malignancy cells and reduced the stem‐like features of KG‐1a cells, as observed by the reduction in CD34‐ and CD123‐positive cells. A reduction in NF‐κB p65 nuclear staining was observed in BTZ‐treated KG‐1a cells, in addition to upregulation of the NF‐κB inhibitor gene NFΚBIB. BTZ‐induced DNA fragmentation, nuclear condensation, cell shrinkage and loss of transmembrane mitochondrial potential along with an increase in active caspase‐3 and cleaved PARP‐(Asp 214) level in KG‐1a cells. Furthermore, BTZ‐induced cell death was partially prevented by pretreatment with the pancaspase inhibitor Z‐VAD‐(OMe)‐FMK, indicating that BTZ induces caspase‐mediated apoptosis. BTZ also increased mitochondrial superoxide levels in KG‐1a cells, and BTZ‐induced apoptosis was partially prevented by pretreatment with the antioxidant N‐acetylcysteine, indicating that BTZ induces oxidative stress‐mediated apoptosis in KG‐1a cells. At a dosage of 0.1 mg/kg every other day for 2 weeks, BTZ significantly reduced the percentage of hCD45‐positive cells in the bone marrow and peripheral blood of NSG mice engrafted with KG‐1a cells with tolerable toxicity. Taken together, these data indicate that the anti‐LSC potential of BTZ appears to be an important strategy for AML treatment.

Many alternative fuel technologies have been studied for the transport sector to increase its sustainability while reducing costs, greenhouse gases (GHG), and air pollution emissions. Nevertheless, conventional diesel is still the predominant fuel for heavy-duty trucks. Road freight transport consumes 25% of the world’s energy and is responsible for emissions with local health impacts and the global greenhouse effect. In this context, this paper reviewed items from 2015 to 2020 to analyze the technologies available for the road freight transport regarding pollutant and GHG emissions. Results are presented in two parts: first quantitatively, quantitative data was extracted from reviewed papers and statistically treated and, second, qualitatively through a comparative chart, which shows the impact on air pollutants from the use of a different type of fuels. In general, papers are mostly concerned with particulate matter (PM), carbon monoxide (CO), nitrogen oxides (NOx), and hydrocarbons (HC) emissions due to its impact on public health, with a low number of papers covering GHG emissions. The trade-off between different fuels and how this process can impact emissions, sometimes increasing or decreasing specific pollutants, is discussed. According to the analyzed papers, the main characteristics that affect the pollutant emissions are, in general, the fuel oxygen content and the combustion chamber temperature.

Obstructive sleep apnea (OSA), a common breathing disorder, is recognized as an independent risk factor for systemic hypertension. Among the alterations induced by OSA, the chronic intermittent hypoxia (CIH) is considered the main factor for the hypertension. Exposure of rodents to CIH is the gold-standard method to study the mechanisms involved in the cardiovascular alterations induced by OSA. Although it is well known that CIH produces hypertension, the underlying mechanisms are not totally elucidated. It is likely that the CIH-induced systemic oxidative stress and inflammation may elicit endothelial dysfunction and increase the arterial blood pressure. In addition, OSA patients and animals exposed to CIH show sympathetic hyperactivity and potentiated cardiorespiratory responses to acute hypoxia, suggesting that CIH enhances the peripheral hypoxic chemoreflex. Recent experimental evidences support the proposal that CIH selectively enhances carotid body (CB) chemosensory reactivity to oxygen, which in turn increases sympathetic outflow leading to neurogenic hypertension. In this review, we will discuss the supporting evidence for a critical role of the CB in the generation and maintenance of the hypertension induced by CIH, also, the contribution of oxidative stress to enhance CB chemosensory drive and the activation of sympathetic-related centers in the brain.

Acute myeloid leukaemia (AML) is a lethal bone marrow neoplasm caused by genetic alterations in blood cell progenitors. Leukaemic stem cells (LSCs) are responsible for the development of AML, drug resistance and relapse. Bithionol is an old anthelmintic drug with potential antibacterial, antiviral, antifungal, anti-Alzheimer, and antitumour properties. In this work, we focused on the anti-AML LSC properties of bithionol. This compound inhibited the viability of both solid and haematological cancer cells, suppressed AML stem-like cells, and inhibited AML growth in NSG mice at a dosage of 50 mg/kg, with tolerable systemic toxicity. Bithionol significantly reduced the levels of phospho-NF-κB p65 (Ser529) and phospho-NF-κB p65 (Ser536) and nuclear NF-κB p65 translocation in AML cells, indicating that this molecule can suppress NF-κB signalling. DNA fragmentation, nuclear condensation, cell shrinkage, phosphatidylserine externalisation, loss of transmembrane mitochondrial potential, caspase-3 activation and PARP-(Asp 214) cleavage were detected in bithionol-treated AML cells, indicating the induction of apoptosis. Furthermore, this compound increased mitochondrial superoxide levels, and bithionol-induced cell death was partially prevented by cotreatment with the selective ferroptosis inhibitor ferrostatin-1, indicating the induction of ferroptosis. In addition, bithionol synergised with venetoclax in AML cells, indicating the translational potential of bithionol to enhance the effects of venetoclax in patients with AML. Taken together, these data indicate that bithionol is a potential new anti-AML drug.

ABSTRACTObjectiveTo compare cognitive function among frail and prefrail older adults. DesignCross-sectional clinical study. ParticipantsFifty-one non-institutionalized older individuals participated in this study. MeasurementsCognitive functions were evaluated through Mini-Mental State Examination (Global Cognition), Digit Span Forward (short-term memory), Digit Span Backward (working memory), Verbal Fluency Test ( semantic memory/executive function). Data were compared using parametric and non-parametric bivariate tests. Binary logistic regression was used to test a frailty prediction model. Statistical significance was defined as p ≤ 0.01 to compare groups. In the regression model, the p value was set to be ≤0.05. ResultsStatistically significant differences were observed in global cognition, and short-term memory between frail and prefrail individuals (p ≤ 0.01). Global cognition explained 14–19% of frailty's model. ConclusionAccording to our findings, the evaluation of cognitive functions among older persons with frailty and prefrailty provides important complementary information to better manage frailty and its progression.

Xylopia laevigata (Annonaceae), known locally as “meiú” or “pindaíba”, is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (−)-roemerine, (+)-anonaine, lanuginosine, (+)-glaucine, (+)-xylopine, oxoglaucine, (+)-norglaucine, asimilobine, (−)-xylopinine, (+)-norpurpureine, (+)-N-methyllaurotetanine, (+)-norpredicentrine, (+)-discretine, (+)-calycinine, (+)-laurotetanine, (+)-reticuline, (−)-corytenchine, (+)-discretamine and (+)-flavinantine. The in vitro cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuclear cells (PBMCs) was tested using the Alamar Blue assay. Lanuginosine, (+)-xylopine and (+)-norglaucine had the highest cytotoxic activity. Additionally, the pro-apoptotic effects of lanuginosine and (+)-xylopine were investigated in HepG2 cells using light and fluorescence microscopies and flow cytometry-based assays. Cell morphology consistent with apoptosis and a marked phosphatidylserine externalization were observed in lanuginosine- and (+)-xylopine-treated cells, suggesting induction of apoptotic cell death. In addition, (+)-xylopine treatment caused G2/M cell cycle arrest in HepG2 cells. These data suggest that X. laevigata is a potential source for cytotoxic alkaloids.

Adsorption isotherms were constructed to evaluate the potential use of water lettuce ( Pistia stratiotes ) dry biomass for the biosorption of zinc and cadmium. One gram of dry biomass of this plant was treated with five increasing doses of zinc (1.8, 18, 50, 79, and 105 mg L −1 ) and four doses of cadmium (0.01, 0.1, 1, and 10 mg L −1 ), for nine collection times (1, 3, 6, 12, 24, 36, 48, 60, and 72 h). The levels of these metals were determined by atomic absorption spectrophotometry. To evaluate changes in the surface morphology of the dry biomass, scanning electron microscopy (SEM) images were taken of the samples subjected to the greatest contamination, and these were compared with the images of the samples without zinc and cadmium (control). The ISOFIT software was used to select the isotherm model that best fit the biosorption of metals by water lettuce dry biomass. The linear model was determined to be the best-fitting isotherm model, because it had the lowest corrected Akaike information criterion (AICc) value and a Akaike weight (AICw) value closest to one, which indicates the high affinity of the biosorbent for the adsorbates evaluated. The results for both metals demonstrated greater than 70% reductions in the concentrations of the metals in the contaminated solutions. The SEM images indicated changes in the morphology of the contaminated biomass, thus demonstrating the biosorption mechanisms and confirming the potential of the dry biomass of this plant for use in the remediation of solutions contaminated with zinc and cadmium.

Acute myeloid leukemia (AML) is a fatal malignancy of the blood and bone marrow. Leukemic stem cells (LSCs) are a rare subset of leukemic cells that promote the development and progression of AML, and eradication of LSCs is critical for effective control of this disease. Emetine is an FDA-approved antiparasitic drug with antitumor properties; however, little is known about its potential against LSCs. Herein, we explored the antileukemic potential of emetine, focusing on its effects on AML stem/progenitor cells. Emetine exhibited potent cytotoxic activity both in hematologic and solid cancer cells and induced AML cell differentiation. Emetine also inhibited AML stem/progenitor cells, as evidenced by decreased expression of CD34, CD97, CD99, and CD123 in KG-1a cells, indicating anti-AML stem/progenitor cell activities. The administration of emetine at a dosage of 10 mg/kg for two weeks showed no significant toxicity and significantly reduced xenograft leukemic growth in vivo. NF-κB activation was reduced in emetine-treated KG-1a cells, as shown by reduced phospho-NF-κB p65 (S529) and nuclear NF-κB p65. DNA fragmentation, YO-PRO-1 staining, mitochondrial depolarization and increased levels of active caspase-3 and cleaved PARP (Asp214) were detected in emetine-treated KG-1a cells. Moreover, treatment with the pancaspase inhibitor Z-VAD(OMe)-FMK partially prevented the apoptotic cell death induced by emetine. Emetine treatment also increased cellular and mitochondrial reactive oxygen species, and emetine-induced apoptosis in KG-1a cells was partially prevented by the antioxidant N -acetylcysteine, indicating that emetine induces apoptosis, at least in part, by inducing oxidative stress. Overall, these studies indicate that emetine is a novel potential anti-AML agent with promising activity against stem/progenitor cells, encouraging the development of further studies aimed at its clinical application.

The market demand for grafted mango seedlings is increasing because they provide uniformity and precocity for orchards and gain in productive performance. However, studies on suitable rootstocks for mango seedling production of the main mango cultivars of economic interest in the Sao Francisco Valley, Brazil, are incipient. In this context, the objective of the present study was to evaluate growth, gas exchange, and carbohydrate accumulation in the 'Palmer', 'Tommy Atkins', 'Kent', and 'Keitt' mango scions grafted onto polyembryonic rootstocks ('Capucho', 'Coquinho', and 'Espada'). The experiment was carried out under nursery conditions, with 50% shading. A randomized block experimental design was used, in a 3 × 4 factorial arrangement, consisting of three mango rootstocks ('Espada', 'Capucho', and 'Coquinho') and four mango scion cultivars ('Palmer', 'Keitt', 'Kent', and 'Tommy Atkins'), with five replications and five plants per plot. Graft success was evaluated 28 days after grafting (DAG) to determine the effects of the rootstocks on each scion. Growth, photosynthetic parameters, and total soluble carbohydrate (TSC) and starch content were evaluated 227 DAG. The rootstocks used affected the growth, photosynthetic pigments, contents of TSC and starch, and gas exchange of the mango scions. The higher graft success percentages were found for the cultivars 'Keitt', 'Palmer', and 'Kent' grafted on 'Espada' rootstocks. The cultivar 'Tommy Atkins' showed the highest graft success percentages when grafted on 'Espada' and 'Capucho' rootstocks. 'Capucho' rootstocks showed higher performance for most of the analysed variables, mainly when using 'Palmer' and 'Tommy Atkins' cultivars as scions.

Acute myeloid leukaemia (AML) is a haematological malignancy characterised by the accumulation of transformed myeloid progenitors in the bone marrow. Piplartine (PL), also known as piperlongumine, is a pro-oxidant small molecule extracted from peppers that has demonstrated antineoplastic potential in solid tumours and other haematological malignancies. In this work, we explored the potential of PL to treat AML through the use of a combination of cellular and molecular analyses of primary and cultured leukaemia cells in vitro and in vivo. We showed that PL exhibits in vitro cytotoxicity against AML cells, including CD34 + leukaemia-propagating cells, but not healthy haematopoietic progenitors, suggesting anti-leukaemia selectivity. Mechanistically, PL treatment increased reactive oxygen species (ROS) levels and induced ROS-mediated apoptosis in AML cells, which could be prevented by treatment with the antioxidant scavenger N -acetyl-cysteine and the pancaspase inhibitor Z-VAD(OMe)-FMK. PL treatment reduced NFKB1 gene transcription and the level of NF-κB p65 (pS536), which was depleted from the nucleus of AML cells, indicating suppression of NF-κB p65 signalling. Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.