Heat shock proteins, thermotolerance, and insecticide resistance in mosquitoes.

Mosquitoes transmit pathogens that pose a threat to millions of people globally. Unfortunately, widespread insecticide resistance makes it difficult to control these public health pests. General mechanisms of resistance, such as target site mutations or increased metabolic activity, are well established. However, many questions regarding the dynamics of these adaptations in the context of developmental and environmental conditions require additional exploration. One aspect of resistance that deserves further study is the role of heat shock proteins (HSPs) in insecticide tolerance. Studies show that mosquitoes experiencing heat stress before insecticide exposure demonstrate decreased mortality. This is similar to the observed reciprocal reduction in mortality in mosquitoes exposed to insecticide prior to heat stress. The environmental shifts associated with climate change will result in mosquitoes occupying environments with higher ambient temperatures, which could enhance existing insecticide resistance phenotypes. This physiological relationship adds a new dimension to the problem of insecticide resistance and further complicates the challenges that vector control and public health personnel face. This article reviews studies illustrating the relationship between insecticide resistance and HSPs or hsp genes as well as the intersection of thermotolerance and insecticide resistance. Further study of HSPs and insecticide resistance could lead to a deeper understanding of how environmental factors modulate the physiology of these important disease vectors to prepare for changing climatic conditions and the development of novel strategies to prevent vector-borne disease transmission.

Emerging role of natural products in cancer immunotherapy.

Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.

Thermotolerance and plasticity of camel somatic cells exposed to acute and chronic heat stress.

The Arabian camel is the largest known mammal that can survive in severe hot climatic conditions. We provide the molecular explanation for the thermotolerance of camel granulosa somatic cells after exposure to 45 °C for 2 (acute heat shock) or 20 h (chronic heat shock). The common features of the cellular responses to acute heat stress were the increase of heat shock proteins and DNA repair enzymes expression. Actin polymerization and Rho signaling were critically activated as a cellular defense against heat shock. Cells exposed to chronic heat shock showed altered cell architecture with a decrease in total detected proteins, metabolic enzymes, and cytoskeletal protein expression. Treatment with transforming growth factor beta (TGFß) pathway inhibitor SB-431542 suppressed the morphological alterations of cells exposed to chronic heat shock. Moreover, during the recovery stage at 38 °C for 24 h, proteomic changes were partially restored with an exponential increase in HSP70 expression, and the cells restored their normal cellular morphology on the 9th day of recovery. Full proteomics data are available via ProteomeXchange with identifier PXD012159. The strategies of cellular defense and tolerance to both thermal conditions reflect the flexible adaptability of camel somatic cells to conserve life under extremely hot conditions.

Exosomal Chaperones and miRNAs in Gliomagenesis: State-of-Art and Theranostics Perspectives.

Gliomas have poor prognosis no matter the treatment applied, remaining an unmet clinical need. As background for a substantial change in this situation, this review will focus on the following points: (i) the steady progress in establishing the role of molecular chaperones in carcinogenesis; (ii) the recent advances in the knowledge of miRNAs in regulating gene expression, including genes involved in carcinogenesis and genes encoding chaperones; and (iii) the findings about exosomes and their cargo released by tumor cells. We would like to trigger a discussion about the involvement of exosomal chaperones and miRNAs in gliomagenesis. Chaperones may be either targets for therapy, due to their tumor-promoting activity, or therapeutic agents, due to their antitumor growth activity. Thus, chaperones may well represent a Janus-faced approach against tumors. This review focuses on extracellular chaperones as part of exosomes' cargo, because of their potential as a new tool for the diagnosis and management of gliomas. Moreover, since exosomes transport chaperones and miRNAs (the latter possibly related to chaperone gene expression in the recipient cell), and probably deliver their cargo in the recipient cells, a new area of investigation is now open, which is bound to generate significant advances in the understanding and treatment of gliomas.

Shifting the Balance: Heat Stress Challenges the Symbiotic Interactions of the Asian Citrus Psyllid, Diaphorina citri (Hemiptera, Liviidae).

Global warming may impact biodiversity by disrupting biological interactions, including long-term insect-microbe mutualistic associations. Symbiont-mediated insect tolerance to high temperatures is an ecologically important trait that significantly influences an insect's life history. Disruption of microbial symbionts that are required by insects would substantially impact their pest status. Diaphorina citri, a worldwide citrus pest, is associated with the mutualistic symbionts Candidatus Carsonella ruddii and Candidatus Profftella armatura. Wolbachia is also associated with D. citri, but its contribution to the host is unknown. Symbiont density is dependent on a range of factors, including the thermosensitivity of the host and/or symbiont to heat stress. Here, we predicted that short-term heat stress of D. citri would disrupt the host-symbiont phenological synchrony and differentially affect the growth and density of symbionts. We investigated the effects of exposing D. citri eggs to different temperatures for different periods of time on the growth dynamics of symbionts during the nymphal development of D. citri (first instar to fifth instar) by real-time polymerase chain reaction. Symbiont densities were assessed as the number of gene copies, using specific molecular markers: 16S rRNA for Carsonella and Profftella and ftsZ for Wolbachia. Statistical modeling of the copy numbers of symbionts revealed differences in their growth patterns, particularly in the early instars of heat-shocked insects. Wolbachia was the only symbiont to benefit from heat-shock treatment. Although the symbionts responded differently to heat stress, the lack of differences in symbiont densities between treated and control late nymphs suggests the existence of an adaptive genetic process to restore phenological synchrony during the development of immatures in preparation for adult life. Our findings contribute to the understanding of the potential deleterious effects of high temperatures on host-symbiont interactions. Our data also suggest that the effects of host exposure to high temperatures in symbiont growth are highly variable and dependent on the interactions among members of the community of symbionts harbored by a host. Such dependence points to unpredictable consequences for agroecosystems worldwide due to climate change-related effects on the ecological traits of symbiont-dependent insect pests.

Human, vector and parasite Hsp90 proteins: A comparative bioinformatics analysis.

The treatment of protozoan parasitic diseases is challenging, and thus identification and analysis of new drug targets is important. Parasites survive within host organisms, and some need intermediate hosts to complete their life cycle. Changing host environment puts stress on parasites, and often adaptation is accompanied by the expression of large amounts of heat shock proteins (Hsps). Among Hsps, Hsp90 proteins play an important role in stress environments. Yet, there has been little computational research on Hsp90 proteins to analyze them comparatively as potential parasitic drug targets. Here, an attempt was made to gain detailed insights into the differences between host, vector and parasitic Hsp90 proteins by large-scale bioinformatics analysis. A total of 104 Hsp90 sequences were divided into three groups based on their cellular localizations; namely cytosolic, mitochondrial and endoplasmic reticulum (ER). Further, the parasitic proteins were divided according to the type of parasite (protozoa, helminth and ectoparasite). Primary sequence analysis, phylogenetic tree calculations, motif analysis and physicochemical properties of Hsp90 proteins suggested that despite the overall structural conservation of these proteins, parasitic Hsp90 proteins have unique features which differentiate them from human ones, thus encouraging the idea that protozoan Hsp90 proteins should be further analyzed as potential drug targets.

Biochemical analysis of 'kerosene tree' Hymenaea courbaril L. under heat stress.

Hymenaea courbaril or jatoba is a tropical tree known for its medically important secondary metabolites production. Considering climate change, the goal of this study was to investigate differential expression of proteins and lipids produced by this tree under heat stress conditions. Total lipid was extracted from heat stressed plant leaves and various sesquiterpenes produced by the tree under heat stress were identified. Gas chromatographic and mass spectrometric analysis were used to study lipid and volatile compounds produced by the plant. Several volatiles, isoprene, 2-methyl butanenitrile, ß ocimene and a numbers of sesquiterpenes differentially produced by the plant under heat stress were identified. We propose these compounds were produced by the tree to cope up with heat stress. A protein gel electrophoresis (2-D DIGE) was performed to study differential expression of proteins in heat stressed plants. Several proteins were found to be expressed many folds different in heat stressed plants compared to the control. These proteins included heat shock proteins, histone proteins, oxygen evolving complex, and photosynthetic proteins, which, we believe, played key roles in imparting thermotolerance in Hymenaea tree. To the best of our knowledge, this is the first report of extensive molecular physiological study of Hymenaea trees under heat stress. This work will open avenues of further research on effects of heat stress in Hymenaea and the findings can be applied to understand how global warming can affect physiology of other plants.

Subtractive hybridization-mediated analysis of genes and in silico prediction of associated microRNAs under waterlogged conditions in sugarcane (Saccharum spp.).

Sugarcane is an important tropical cash crop meeting 75% of world sugar demand and it is fast becoming an energy crop for the production of bio-fuel ethanol. A considerable area under sugarcane is prone to waterlogging which adversely affects both cane productivity and quality. In an effort to elucidate the genes underlying plant responses to waterlogging, a subtractive cDNA library was prepared from leaf tissue. cDNA clones were sequenced and annotated for their putative functions. Major groups of ESTs were related to stress (15%), catalytic activity (13%), cell growth (10%) and transport related proteins (6%). A few stress-related genes were identified, including senescence-associated protein, dehydration-responsive family protein, and heat shock cognate 70 kDa protein. A bioinformatics search was carried out to discover novel microRNAs (miRNAs) that can be regulated in sugarcane plants subjected to waterlogging stress. Taking advantage of the presence of miRNA precursors in the related sorghum genome, seven candidate mature miRNAs were identified in sugarcane. The application of subtraction technology allowed the identification of differentially expressed sequences and novel miRNAs in sugarcane under waterlogging stress. The comparative global transcript profiling in sugarcane plants undertaken in this study suggests that proteins associated with stress response, signal transduction, metabolic activity and ion transport play important role in conferring waterlogging tolerance in sugarcane.

Tumor cell lysates as immunogenic sources for cancer vaccine design.

Autologous dendritic cells (DCs) loaded with tumor-associated antigens (TAAs) are a promising immunological tool for cancer therapy. These stimulate the antitumor response and immunological memory generation. Nevertheless, many patients remain refractory to DC approaches. Antigen (Ag) delivery to DCs is relevant to vaccine success, and antigen peptides, tumor-associated proteins, tumor cells, autologous tumor lysates, and tumor-derived mRNA have been tested as Ag sources. Recently, DCs loaded with allogeneic tumor cell lysates were used to induce a potent immunological response. This strategy provides a reproducible pool of almost all potential Ags suitable for patient use, independent of MHC haplotypes or autologous tumor tissue availability. However, optimizing autologous tumor cell lysate preparation is crucial to enhancing efficacy. This review considers the role of cancer cell-derived lysates as a relevant source of antigens and as an activating factor for ex vivo therapeutic DCs capable of responding to neoplastic cells. These promising therapies are associated with the prolonged survival of advanced cancer patients.