Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”), a condition that significantly impairs the quality of life of many cancer survivors

Increasing numbers of cancer patients survive and live longer than five years after therapy, but very often side effects of cancer treatment arise at same time. One of the side effects, chemotherapy-induced cognitive impairment (CICI), also called “chemobrain” or “chemofog” by patients, brings enormous challenges to cancer survivors following successful chemotherapeutic treatment. Decreased abilities of learning, memory, attention, executive function and processing speed in cancer survivors with CICI, are some of the challenges that greatly impair survivors' quality of life. The molecular mechanisms of CICI involve very complicated processes, which have been the subject of investigation over the past decades. Many mechanistic candidates have been studied including disruption of the blood-brain barrier (BBB), DNA damage, telomere shortening, oxidative stress and associated inflammatory response, gene polymorphism of neural repair, altered neurotransmission, and hormone changes. Oxidative stress is considered as a vital mechanism, since over 50% of FDA-approved anti-cancer drugs can generate reactive oxygen species (ROS) or reactive nitrogen species (RNS), which lead to neuronal death. In this review paper, we discuss these important candidate mechanisms, in particular oxidative stress and the cytokine, TNF-alpha and their potential roles in CICI.     

Inhibition of CYP2E1 attenuates myocardial dysfunction in a murine model of insulin resistance through NLRP3-mediated regulation of mitophagy

Insulin resistance leads to myocardial contractile dysfunction and deranged autophagy although the underlying mechanism or targeted therapeutic strategy is still lacking. This study was designed to examine the impact of inhibition of the cytochrome P450 2E1 (CYP2E1) enzyme on myocardial function and mitochondrial autophagy (mitophagy) in an Akt2 knockout model of insulin resistance. Adult wild-type (WT) and Akt2^?/? mice were treated with the CYP2E1 inhibitor diallyl sulfide (100?mg/kg/d, i.p.) for 4?weeks. Cardiac geometry and function were assessed using echocardiographic and IonOptix systems. Western blot analysis was used to evaluate autophagy, mitophagy, inducible NOS (iNOS), and the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex. Akt2 deletion triggered insulin resistance, compromised cardiac contractile and intracellular Ca²⁺ property, mitochondrial ultrastructural damage, elevated O2^– production, as well as suppressed autophagy and mitophagy, accompanied with elevated levels of NLRP3 and iNOS, the effects of which were significantly attenuated or ablated by diallyl sulfide. In vitro studies revealed that the NLRP3 activator nigericin nullified diallyl sulfide-offered benefit against Akt2 knockout on cardiomyocyte mechanical function and mitophagy (using Western blot and colocalization of GFP-LC3 and MitoTracker Red). Moreover, inhibition of iNOS but not mitochondrial ROS production attenuated Akt2 deletion-induced activation of NLRP3, substantiating a role for iNOS-mediated NLRP3 in insulin resistance-induced changes in mitophagy and cardiac dysfunction. In conclusion, these data depict that insulin resistance through CYP2E1 may contribute to the pathogenesis of myopathic changes including myocardial contractile dysfunction, oxidative stress and mitochondrial injury, possibly through activation of iNOS and NLRP3 signaling.     

The influence of crop rotation on the onset of early blight (Alternaria solani)

Field experiments were carried out in 2016 and 2017 to determine the effect of crop rotation on the onset of early blight in three potato varieties in Denmark. Six and seven fields with different histories with potato (rotation‐fields) were used for the experiments in 2016 and 2017, respectively. The results showed that variety and the interaction between variety and rotation‐field had no significant effect on the onset of early blight. Rotation‐field, on the other hand, had a significant effect on the onset of early blight in both years of the study. Early blight occurred earlier in fields with <2 years between subsequent potato crops than in fields where potatoes have not been grown for at least 2 years. The onset of early blight was not different between the fields where there had not been potatoes for at least 2 years. For fields that were preceded by potatoes, early blight occurred earlier in fields in which the severity of early blight in the previous years was higher than that in the fields in which the severity of early blight in the previous years was low or moderate. In conclusion, the results of this study suggest that at least a 2‐year interval between subsequent potatoes in a rotation cycle is necessary to delay the onset of early blight. Moreover, the severity of early blight in the previous years can affect the onset of early blight.     

Culture storage age and fungal re‐isolation from host‐tissue influence Colletotrichum spp. virulence to pepper fruits

Using resistant cultivars is the most sustainable and practical approach against plant diseases. Plant germplasm and breeding lines are selected and assayed against, usually, the most aggressive or virulent strains of a pathogen (e.g., fungus) that causes the disease. However, prolong storage of the pathogen in culture media could affect virulence that, consequently, also influence the outcome of the resistance assay. This study demonstrates that long‐term storage (at least a year) of Colletotrichum truncatum and C. scovillei, causal agents of pepper anthracnose, in potato dextrose agar (PDA) medium decreased the aggressiveness and virulence of the fungus in host‐pepper fruits. However, reintroduction of the pathogen to the host and isolation of the pathogen as the new inoculum, prior to inoculation assays, increased the virulence of the fungi. These findings suggest that re‐inoculation and re‐isolation of Colletotichum truncatum and C. scovillei that have been stored for at least 1 year in PDA medium are necessary when using fungal cultures in pathogenicity and plant resistance assays to achieve desirable, comparable and reliable results.     

Development of a bioassay to assess resistance to Fusarium oxysporum (Schlecht.) in asparagus (Asparagus officinalis L.)

Fusarium oxysporum is one of the major pathogens causing root and crown rot in asparagus. Breeding of cultivars resistant to F. oxysporum would be the most efficient strategy for pathogen control. In this study, a bioassay was developed for screening seedling resistance. The non‐destructive bioassay comprises inoculation with a highly aggressive F. oxysporum isolate, incubation in a climate chamber and quantification of disease symptoms by a digital image analysing system and a PTA‐ELISA. This bioassay is simple to implement and demonstrated high reproducibility. Subsequently, it was used to determine the resistance behaviour of 16 asparagus genotypes to F. oxysporum. The asparagus cultivars revealed different levels of susceptibility, whereas the wild relative A. densiflorus was confirmed to be resistant.     

Chitosan combined with sodium silicate treatment induces resistance against rot caused by Alternaria alternata in postharvest jujube fruit

The effect of chitosan (0.1 mol/L) combined with sodium silicate (100 mmol/L) treatment on Alternaria rot caused by Alternaria alternata in postharvest jujube fruit (Ziziphus jujuba Mill. cv. Dongzao) was studied. The results showed that chitosan combined with sodium silicate treatment significantly reduced the lesion diameter, decay incidence, red index and weight loss of jujube fruit compared with control samples. Combining treatment increased the ascorbic acid, flavonoids, total phenolic compounds and lignin content. The level of superoxide anion () and hydrogen peroxide of treated samples was also increased compared with the control samples. Meanwhile, the activities of phenylalanine ammonia lyase, polyphenol oxidase, superoxide dismutase, peroxidase, chitinase and β‐1,3‐glucanase were also accumulated in treated jujube samples, while the activity of catalase markedly decreased. These results indicated that chitosan combined with sodium silicate treatment could induce the disease resistance of postharvest jujube. Therefore, coating postharvest jujube using chitosan combined with sodium silicate could promise as a novel method for preventing the disease infection of postharvest jujube.     

Nematode ascaroside enhances resistance in a broad spectrum of plant–pathogen systems

Recognition of specific molecule signatures of microbes, including pathogens, induces innate immune responses in plants, as well as in animals. Analogously, a nematode pheromone, the ascaroside ascr#18, induces hallmark plant defences including activation of (a) mitogen‐activated protein kinases, (b) salicylic acid‐ and jasmonic acid‐mediated defence signalling pathways and (c) defence gene expression and provides protection to a broad spectrum of pathogens. Ascr#18 is a member of an evolutionarily conserved family of nematode signalling molecules and is the major ascaroside secreted by plant–parasitic nematodes. Here, we report the effects of ascr#18 on resistance in four of the major economically important crops: maize, rice, wheat and soybean to some of their associated pathogens. Treatment with low nanomolar to low micromolar concentrations of ascr#18 provided from partial to strong protection in seven of eight plant–pathogen systems tested with viruses, bacteria, fungi, oomycetes and nematodes. This research may have potential to improve agricultural sustainability by reducing use of potentially harmful agrochemicals and enhance food security worldwide.     

Susceptibility of Cypriot Tuta absoluta populations to four targeted insecticides and control failure likelihood

Tuta absoluta, known as the South American tomato pinworm, is one of the most disastrous pests of tomato cultivations, presently menacing tomato cultivations worldwide. In 2006, T. absoluta invaded Spain from South America. Since then, it was rapidly spread to most European, African and Asian countries. Such alien invasive species can minimize crop production, whereas the increasing use of insecticides raises various environmental concerns as well as on control costs, control failure and the toxicity to non‐target organisms. The S. American tomato pinworm is mostly controlled by chemical insecticides, and failure to control it is not a rare phenomenon. Resistance to numerous insecticides has been reported and is mainly due to the fact that farmers do not follow a sustainable resistance management scheme. Several examples have been reported from several countries where the tomato pinworm is present. In order to develop a successful insecticide resistance management (IRM) strategy for any major pest, one needs to identify the baseline toxicity to insecticides and then monitor susceptibility levels . In Cyprus, the current status of susceptibility levels to the main insecticides that are used to control T. absoluta has never been studied before. Herein, nine Cypriot populations of the pest were subjected to laboratory bioassays between 2016 and 2018 using the main insecticides applied against it. We found that the insecticides chlorantraniliprole and indoxacarb could not control the Cypriot T. absoluta populations anymore, with a resistance ratio (RR) >28 and 3–23, respectively. Furthermore, mortality achieved by those two insecticides was 20.6%–72% for chlorantraniliprole and 27.5%–78% for indoxacarb. However, the insecticides emamectin benzoate and spinosad are very effective, since mortality to both of them ranged between 99.5% and 100%.     

Induction of systemic resistance in tomato against broomrape (Phelipanche aegyptiaca)

Rhizosphere dwelling bacteria can increase plant resistance to biotic and abiotic stresses, and they promote plant growth through various mechanisms. In this study, three bioassays were conducted including the following: (a) screening for effective bacterial isolates in the suppression of broomrape, (b) evaluating induced systemic resistance against broomrape and (c) comparing the selected bacterium isolate with plant chemical inducers. Fifteen plant growth‐promoting rhizobacteria (PGPR) were examined to assess their biocontrol potential against Egyptian broomrape (Phelipanche aegyptiaca). Ten isolates significantly reduced the broomrape biomass compared to the control. The Lysinibacillus boronitolerans B124 reduced the dry weight of broomrape plants from 2.15 g in control to 0.45 g. Bacillus megaterium B6 was the best isolate in reducing the number of broomrape tubercles. In addition, the activity of three selected bacterial isolates was investigated in induced systemic resistance to broomrape by split‐root method. The Bacillus pumilus INR7 reduced the number of visible broomrape tubercles by 90%, and B. megaterium B71 and L. boronitolerans B124 were the next two in rank. Compared with the control, L. boronitolerans B124 reduced the dry weight of broomrape from 1.49 g in control to 0.39 g. In a subsequent experiment, L. boronitolerans B124 was evaluated along with some resistance‐inducing volatile compounds. Lysinibacillus boronitolerans B124 decreased the number of broomrapes by 87% on average, while the lowest dry weight of broomrape was observed in methyl jasmonate treatment. In conclusion, PGPR have considerable potential to be used in the integrated management of broomrape. It is also possible to use a mixture of rhizobacteria and defence inducers, such as biogenic volatiles as a promising approach in the management of this noxious parasitic weed.     

Mapping quantitative trait loci associated with southern leaf blight resistance in maize (Zea mays L.)

Southern leaf blight (SLB) caused by the fungus Cochliobolus heterostrophus (Drechs.) Drechs. is a major foliar disease of maize worldwide. Our objectives were to identify quantitative trait loci (QTL) for resistance to SLB and flowering traits in recombinant inbred line (RIL) population derived from the cross of inbred lines LM5 (resistant) and CM140 (susceptible). A set of 207 RILs were phenotyped for resistance to SLB at three time intervals for two consecutive years. Four putative QTL for SLB resistance were detected on chromosomes 3, 8 and 9 that accounted for 54% of the total phenotypic variation. Days to silking and anthesis–silking interval (ASI) QTL were located on chromosomes 6, 7 and 9. A comparison of the obtained results with the published SLB resistance QTL studies suggested that the detected bins 9.03/02 and 8.03/8.02 are the hot spots for SLB resistance whereas novel QTL were identified in bins 3.08 and 8.01/8.04. The linked markers are being utilized for marker‐assisted mobilization of QTL conferring resistance to SLB in elite maize backgrounds. Fine mapping of identified QTL will facilitate identification of candidate genes underlying SLB resistance.