Search Results (2,467)

Bacillus thuringiensis Cry toxins are well known for their high insecticidal activity against Lepidoptera, Diptera, and Coleoptera and have been widely used in Bt transgenic crops. However, their activity against Hemipteran aphids remains relatively low. Identifying novel Cry proteins and elucidating their action mechanisms can facilitate the development of effective aphid control strategies. In this study, we found that ingestion of Cry2Ab12 did not kill Myzus persicae adults but significantly reduced their offspring number and exerted a lethal effect on M. persicae nymphs. After identifying Cry2Ab12 toxin-binding proteins in M. persicae, we further characterized the interaction with Obg-like ATPase 1 (OLA1), a conserved protein involved in growth regulation. Bio-layer interferometry (BLI), ELISA, and enzyme activity assays revealed that Cry2Ab12 and OLA1 do not interact directly. Interestingly, heat shock protein 60 (HSP60) was shown to mediate the interaction among Cry2Ab12, HSP60, and OLA1, leading to inhibition of OLA1 enzymatic activity. Based on these findings and bioinformatics simulations, we proposed a mechanistic model for Cry2Ab12 toxicity against M. persicae: upon ingestion of a sufficient amount of Cry2Ab12, the formation of the Cry2Ab12–HSP60–OLA1 complex impairs the cellular stress response, disrupts normal OLA1 expression, and ultimately restricts larval growth and development, resulting in lethality. This study provides new insights into the action of Cry toxins in aphids and offers a basis for developing enhanced aphid biocontrol strategies. Full article

Objectives: Neuroinflammation is recognized as a significant characteristic of Alzheimer’s disease (AD). Currently, there is a notable absence of effective pharmacological agents to prevent or treat neuroinflammatory processes associated with AD. Heat shock protein 70 (HSP70) is pivotal in the progression of neuroinflammation. In this study, we explored the potential of maltol, a Maillard reaction product derived from red ginseng, as a therapeutic agent for neuroinflammation. Methods: In vitro, HMC3 microglial cell models were developed to examine the regulatory effects of gradient concentrations of maltol (12.5, 25, 50 μM) on the TLR4/MyD88/NF-κB p65 signaling pathway, neuroinflammation, and pyroptosis. Analyses of the GEO database and Gene Set Enrichment Analysis (GSEA) were performed to identify the core targets of maltol, followed by HSP70 gene silencing experiments to validate the targeted regulatory mechanism. Results: Maltol significantly mitigated LPS-induced neuronal damage and cognitive deficits in mice. It effectively suppressed microglia-mediated neuroinflammation and pyroptosis, reversed oxidative stress-induced neuronal ferroptosis, and inhibited neuronal apoptosis. In vitro experiments demonstrated that maltol obstructed TLR4/MyD88 binding, thereby inhibiting NF-κB p65-mediated neuroinflammation and pyroptosis, while also alleviating excessive ROS accumulation to enhance oxidative stress and ferroptosis. Bioinformatics analysis identified HSP70 as a crucial target for the anti-inflammatory and antioxidant effects of maltol. Subsequent gene silencing experiments confirmed that maltol exerted its inhibitory effects on LPS-induced neuroinflammation and pyroptosis in an HSP70-dependent manner. Conclusions: Maltol exhibits significant protective effects against Alzheimer’s disease-related neuroinflammation, oxidative stress, pyroptosis, and ferroptosis through the targeting of HSP70. This study elucidates the molecular mechanisms by which maltol improves neuroinflammatory injury and provides a novel theoretical foundation and therapeutic strategy for the intervention of Alzheimer’s disease neuroinflammation using traditional Chinese medicine. Full article

Background/Objectives: The genes encoding HSPA1A, HSPA1B, and HSPA1L, located in the MHC class III region at 6p21.3–22.1, a region implicated in susceptibility to schizophrenia, are critical regulators of neurodevelopmental processes and contribute to synaptic neuroprotection. This study investigated whether the HSPA1A, HSPA1B, and HSPA1L genes are associated with schizophrenia. Methods: We sequenced the coding regions of HSPA1A, HSPA1B, and HSPA1L from 100 patients with schizophrenia to identify genetic variants. Further, we conducted a genetic association analysis of three SNPs (rs9469057, rs142416335, and rs2075800) in the HSPA1L gene in 519 patients with schizophrenia and 1492 healthy controls from the Taiwan Biobank. We analyzed the function of the HSPA1L protein via immunoblotting. Results: We identified 17 coding variants, including 8 missense and 9 synonymous mutations, in 100 patients with schizophrenia. Three variants (HSPA1L^p.Ala8Pro, HSPA1L^p.Ala8Thr, and HSPA1L^p.Glu602Lys) in the HSPA1L gene did not exhibit any significant differences in allele or genotype frequencies between patients and control subjects. Notably, one ultra-rare missense mutation, HSPA1L^p.Val262Met, was not documented in the control sample in Taiwan BioBank. Immunoblotting revealed HSPA1L^p.Val262Met mutant with decreased protein expression in SH-SY5Y cells compared with the wild type. Conclusions: While common variants in the HSPA1A, HSPA1B, and HSPA1L genes do not seem to be significant genetic risk factors for schizophrenia in this cohort, the ultra-rare mutation, HSPA1L^p.Val262Met, significantly reduces protein expression. These preliminary findings suggest that a potential loss-of-function or reduced expression of the HSPA1L gene may be a predisposing factor contributing to schizophrenia vulnerability in certain individuals. However, the finding should be replicated in other independent samples. The in vitro and in vivo impacts of the associated mutation at the HSPA1L gene on the pathophysiology of schizophrenia are worthy of future investigation. Full article

The Arabidopsis thaliana Heat Shock Protein-Related (AtHSPR) gene participates in plant growth and abiotic stress tolerance, while its role in biotic stress resistance remains unclear. Here, we report that the athspr mutant is sensitive to Pseudomonas syringae pv. tomato (Pst) DC3000, whereas over-expression of AtHSPR enhances the defense of Arabidopsis against the pathogen. AtHSPR expression was induced by treatment with Pst DC3000, flg22, or salicylic acid (SA). Transcriptome analysis showed that mutation of AtHSPR changed the expression patterns of genes associated with defense response, oxidation–reduction, and SA responses, as well as transcription factors. The biochemical evidence revealed that AtHSPR interacted with Thimet Oligopeptidase 1 (TOP1), which modulated the SA-mediated immune response. Co-expression of AtHSPR and TOP1 showed that the TOP1 protein, normally located in the chloroplasts, gathered around the nucleus in response to a pathogen. After pathogen treatment, dynamic tubular projections (stromules) were present, extending from the chloroplasts toward the nucleus, and TOP1 was observed in the nucleus, together with AtHSPR. The top1athspr double mutant had lower SA levels and was more sensitive to pathogens than the top1 and athspr single mutants. Taken together, our results demonstrated that the interaction between AtHSPR and TOP1 plays a positive role in SA-mediated plant resistance against Pst DC3000. Full article

Low temperature is a major environmental factor influencing the reproductive performance of crustaceans, particularly during gonadal development. This review synthesizes current knowledge on the phenotypic, physiological, and molecular responses of crustaceans to cold stress, with a focus on its regulatory effects on gonadal development. Available evidence indicates that low temperature generally delays gonadal maturation, reduces the gonadosomatic index, impairs oocyte development and yolk deposition, and suppresses spawning. Mechanistically, cold stress induces energy limitation and triggers a growth–reproduction trade-off, in which resources are preferentially allocated to survival and somatic maintenance rather than reproductive investment. This process is closely associated with lipid metabolism remodeling, mitochondrial dysfunction, and altered ATP-dependent energy sensing. At the molecular level, several pathways and regulatory factors are involved, including PI3K–Akt–FoxO, AMPK/mTOR, heat shock proteins, vitellogenin and its receptor, cell cycle regulators, antioxidant defense systems, and neuroendocrine mediators such as MIH, MOIH, and ecdysteroids. Emerging evidence also suggests potential roles for epigenetic regulation and species- or population-specific adaptation in shaping reproductive responses to low temperatures. Overall, this review provides an integrated framework for understanding how cold stress modulates crustacean gonadal development and highlights key directions for future studies and aquaculture applications. However, a comprehensive framework integrating energy metabolism, neuroendocrine signaling, and molecular pathways to explain reproductive suppression under cold stress is currently lacking. Full article

As the core molecular chaperones of the cellular stress response, the heat shock protein (HSP) family has gained extensive attention for its role in the occurrence, development, and target organ damage of hypertension. This review aimed to comprehensively summarize the research progress of the HSP family in the field of hypertension, and to analyze its key roles in the pathogenesis of hypertension, including its regulatory effects on key pathological processes such as endothelial dysfunction, proliferation and migration of vascular smooth muscle cells, oxidative stress, and inflammatory responses. It also summarized the potential value of HSPs as biomarkers in the early diagnosis, condition monitoring, and prognostic evaluation of hypertension. Moreover, it discussed in depth the efficacy and safety of intervention strategies targeting HSPs, including the regulation of HSPs by gene editing, the targeted effects of small-molecule inhibitors, and the modulatory effects of natural products. We need to strengthen interdisciplinary collaboration mechanisms, accelerate the transformation of basic research results into clinical applications, carry out large-scale clinical trials, and develop specific modulators in the future, so as to ultimately provide solid scientific theoretical support and a practical clinical basis for the precise prevention and treatment of hypertension. The findings of this review not only provide novel insights into the pathogenesis of hypertension but also lay a theoretical foundation for the development of HSP-based biomarkers and targeted therapeutic strategies. Full article

Background/Objectives: Tordylium trachycarpum Boiss. (Apiaceae) is traditionally used in Kurdish ethnomedicine for the management of gastrointestinal disorders; however, its pharmacological efficacy and safety profile remain insufficiently investigated. This study evaluated, for the first time, the gastroprotective activity and associated antioxidant, inflammatory, and apoptotic responses of the methanolic extract of T. trachycarpum using an ethanol-induced gastric ulcer model in Sprague–Dawley rats. Methods: Preliminary phytochemical screening revealed the presence of phenolics, flavonoids, terpenoids, tannins, coumarins, and glycosides. Acute oral toxicity testing demonstrated no signs of toxicity at doses up to 5 g/kg. Gastric ulceration was induced by absolute ethanol, and animals were pretreated with the extract (250 and 500 mg/kg) or omeprazole (20 mg/kg). Results: The extract significantly decreased the gastric lesion area from 258.50 ± 6.38 mm² in the ulcer control group to 143.70 ± 0.76 mm² and 115.50 ± 0.76 mm², corresponding to ulcer inhibition rates of 44.41% and 55.31%. Additionally, the extract increased mucus production, maintained mucosal structure, and raised stomach pH. Biochemical analysis showed a significant increase in antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] and a reduction in malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. In addition, the extract modulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10). Blood-based ELISA analysis demonstrated increased expression of heat shock protein 70 (HSP70) and reduced Bax levels, suggesting anti-apoptotic activity. Conclusions: These findings indicate that T. trachycarpum exerts significant gastroprotective activity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, supporting its traditional use and highlighting its potential as a natural therapeutic candidate for the management of gastric ulcers. Full article

Small heat shock proteins (sHSPs) serve as “first aid” stress-response proteins in both eukaryotes and prokaryotes. Their holdase activity enables binding to partially denatured proteins, maintaining them in a folding-competent state under stress. The sHSP IbpA from the mycoplasma Acholeplasma laidlawii is a unique member of its family, combining the functions of two Escherichia coli sHSPs that typically act in tandem. In this study, we demonstrate for the first time that IbpA forms distinct supramolecular structures under contrasting temperature stresses in crowded environments without any artificial truncations or mutations at the protein termini. Upon cooling, IbpA in vitro forms long fibril bundles, whereas heating induces the formation of large, rounded agglomerates. At the temperature optimal for culture growth, the protein exists as a mixture of short fibrils and small globules, with the latter predominating. IbpA’s cellular localization mirrors in vitro properties, with an increased proportion of surface-associated proteins among the sHSP partners during cold shock. We also report, for the first time, a rapid and reversible transition of IbpA to a fibrillar form in response to cold. We propose hypotheses regarding potential roles of IbpA in the mycoplasma cell. IbpA from A. laidlawii appears to act as a “molecular equilibrist,” protecting the cell against damage under opposing stresses, though the precise mechanism of its action during cold shock remains to be elucidated. Full article

Protein Phosphatase 5 (PP5) is an evolutionarily conserved serine/threonine phosphatase with a unique tetratricopeptide domain. It has been implicated in a wide range of cellular processes in mammals, but its function in plants is unknown. Here, we uncovered that Arabidopsis PP5 is required for immunity mediated by the nucleotide-binding leucine-rich repeat immune receptor protein SUMM2. Loss-of-function mutations in PP5 suppress the autoimmune phenotypes caused by the activation of SUMM2 due to the disruption of the MEKK1-MKK1/MKK2-MPK4 kinase cascade. Further biochemical analysis revealed that SUMM2 interacts with Heat Shock Protein 90 (HSP90) and PP5, and SUMM2 level is reduced in pp5 knockout mutant plants, suggesting that PP5 promotes the accumulation of SUMM2, likely through its association with the HSP90 chaperone complex. Full article

Nuclear factor erythroid 2-related factor 2 (NRF2) has traditionally been framed as a Kelch-like ECH-associated protein 1 (KEAP1)-regulated stress-response transcription factor, but three observations now require a broader framework: NRF2 turnover is controlled by parallel E3 ligase systems; transcriptional output can be limited by coactivator assembly despite unchanged NRF2 abundance; and NRF2 activation can be beneficial or harmful depending on disease context, as illustrated by lung cancer models in which NRF2 paradoxically promotes metastasis through BTB and CNC homology 1 (BACH1) stabilization. We synthesize these observations into an NRF2 partner-code framework in which NRF2 acts as a context-dependent transcriptional platform assembled through four partly independent modules: a degradation module (KEAP1; β-transducin repeat-containing protein, β-TrCP; HMG-CoA reductase degradation protein 1/synoviolin 1, Hrd1/SYVN1; WD repeat-containing protein 23/DDB1- and CUL4-associated factor 11, WDR23/DCAF11); a cytoplasmic scaffold module (p62/sequestosome 1, p62/SQSTM1; IQ motif-containing GTPase-activating protein 1, IQGAP1; type I phosphatidylinositol 4-phosphate 5-kinase γ/heat shock protein 27, PIPKIγ–HSP27; peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, PIN1; peptidyl-prolyl isomerase A/cyclophilin A, PPIA); a nuclear coactivator module at Neh4/5 (CREB-binding protein/p300, CBP/p300; receptor-associated coactivator 3/steroid receptor coactivator 3, RAC3/SRC-3; protein arginine methyltransferase 1/coactivator-associated arginine methyltransferase 1, PRMT1/CARM1; Mediator complex subunit 16, MED16); and a DNA/chromatin module at Neh1 (small musculoaponeurotic fibrosarcoma [Maf] proteins, BACH1, and chromodomain helicase DNA-binding protein 6, CHD6). Mapping 22 partners onto the Neh-domain architecture identifies approximately 25 pharmacologically addressable interfaces, stratified into four translational tiers. The framework reframes NRF2 pharmacology around one principle: the most actionable target is often a partner rather than NRF2 itself, with disease context dictating the direction of modulation. We close with five testable hypotheses and a partner-code decision matrix linking disease, biomarker, and candidate target. Full article

Mitochondrial dysfunction in colonic smooth muscle cells (SMCs) is closely associated with impaired gut motility in functional constipation (FC), but the underlying molecular mechanisms remain incompletely understood. The mitochondrial unfolded protein response (UPR^mt) is a critical pathway for maintaining mitochondrial proteostasis, and heat shock factor 1 (HSF1) acts as an important upstream regulator of this response. In the present study, we employed a loperamide-induced FC mouse model, combined with single-cell transcriptomic, molecular, and functional analyses to characterize the HSF1-UPR^mt pathway in colonic SMCs and to investigate its role in FC. Single-cell transcriptomic analysis of colon tissue from FC mice revealed marked downregulation of UPR^mt-associated genes in colonic SMCs. Immunofluorescence, Western blotting, and RT-qPCR analyses of colonic tissue confirmed that HSF1 expression was reduced in colonic SMCs, along with the downregulation of the UPR^mt components, including HSP60, mtHSP70, and LONP1. These molecular changes were accompanied by mitochondrial structural damage, seen by transmission electron microscopy, and by functional impairments, including reduced mitochondrial membrane potential, elevated mtROS production, decreased ATP levels, and diminished activities of respiratory chain complexes I–V. AAV9-mediated overexpression of HSF1 reactivated the UPR^mt pathway, improved mitochondrial function, and ameliorated constipation, whereas shRNA-mediated knockdown of HSF1 further suppressed UPR^mt activity and aggravated mitochondrial damage, indicating that HSF1 bidirectionally regulates this pathway. Complementary experiments in primary colonic SMCs confirmed that this regulatory mechanism operates in a cell-autonomous manner, as modulation of HSF1 expression produced corresponding changes in the UPR^mt pathway, in the expression of mitochondrial respiratory chain complex subunits (ATP5A, NDUFA9, COX1, SDHA, UQCRC1), and in ATP production, mirroring the in vivo findings. Collectively, these results demonstrate that HSF1 plays a pivotal role in maintaining mitochondrial homeostasis in colonic SMCs through regulation of the UPR^mt pathway and that HSF1 dysfunction is closely associated with slowed gut motility in FC. These findings offer a new mechanistic perspective on FC and point to the HSF1–UPR^mt axis as a potential therapeutic target. Full article

Heat shock protein 90 (HSP90) is a molecular chaperone essential for maintaining the stability of many oncogenic client proteins. Although several HSP90 inhibitors (HSP90i) have entered clinical trials, their use has been limited by toxicity and resistance, underscoring the need for improved therapeutic strategies. In this study, we assessed the therapeutic potential of a new HSP90i, SP11, in T-cell acute lymphoblastic leukemia (T-ALL) in vitro and in the DLA mouse model in vivo, using single-cell transcriptomic profiling. Single-cell RNA sequencing showed that SP11 treatment reduces key oncogenic drivers, including MYC, BCL2, and stemness-related genes, consistent with impaired leukemic survival programs. In the DLA mouse model, SP11-mediated HSP90 inhibition was associated with alterations in the tumor microenvironment, including increased immune cell representation and enrichment of cytokine- and antigen-presentation-related transcriptional pathways. Despite these antitumor effects, a distinct subpopulation of cells continued to express or re-express MYC and BCL2, suggesting the development of early adaptive resistance. Consistent with these findings, an SP11-resistant MOLT4 cell line maintained high levels of MYC and BCL2 at both the transcript and protein levels, maintained CD44 expression, and exhibited altered inflammatory cytokine signaling. Functional studies confirmed that pharmacological inhibition of BCL2 notably increased SP11 sensitivity, supporting a rational combination strategy. Collectively, our results show that SP11 may exert both tumor-intrinsic and immune-modulating effects and reveal transcriptionally defined adaptive cellular states linked to resistance. This study provides mechanistic in sights into responses to HSP90 inhibition and supports combination approaches for improving therapeutic outcomes in T-ALL. Full article

The Hsp20 protein family, essential in heat stress responses across all organisms, is part of the heat shock protein (Hsp) superfamily, recognized for its conserved alpha-crystallin domain (ACD). Hsp20s are the smallest proteins in the superfamily and primarily assist in protein refolding during stress and developmental processes. We present an in silico characterization of the Hsp20 gene family in Chenopodium quinoa (2n = 4x = 36) using an integrative approach. Quinoa is well known for its global contributions to food production and tolerance to various abiotic stresses. We identified 69 CqHsp20 genes that exhibit a well-conserved evolutionary pattern, characterized by a balanced copy number distributed symmetrically across 19 homeologous pairs in both subgenomes (A and B), with localized expansions driven by tandem duplications on eight chromosomes. High sequence identity in contiguous gene pairs and Ka/Ks ratios consistently below 1 (0.14–0.84) mathematically demonstrate that strict purifying selection has maintained the structural and sequence integrity of these genes since the ancestral polyploidization event. The phylogenetic analysis grouped CqHsp20 into two main clusters, splitted into four sub-clusters based on peptides’ cellular localization, consistent with a characteristic gene structure and conserved motif analysis, which may reflect the evolutionary trajectory and functional specialization of the Hsp20 family in plants. The integration of transcriptomic data from published experiments enabled us to detect a cluster of putatively ubiquitously expressed CqHsp20, as well as other groups that showed differential responses across abiotic stress conditions. The pattern shows that more genes exhibit higher transcription abundance under drought and salinity than under heat, key adaptive traits underlying quinoa’s known ecological versatility. Some of these genes, which are undetectable or have low abundance under heat stress, encode organelle-targeting peptides, a phenomenon not reported in other model plant studies. Differential expression analysis revealed a highly transcribed sub-cluster where six out of seven of nuclear CqHsp20 genes were active in aerial tissue during initial heat stress, with a specific cohort of four genes (CQ025082, CQ031384, CQ041158, and CQ055373) maintaining significant upregulation ($|{log}_2\mathrm{Fold}\mathrm{Change}|\ge 1.0$, $\mathrm{padj}<0.05$) under prolonged and simultaneous shoot/root exposure. Varying expression within CqHsp20 homologous and paralogs supports the idea that gene duplication creates genomic diversity, facilitating adaptation to variable extreme environments. However, while theoretical and in silico analysis provide valuable insight into quinoa Hsp20 response, empirical data are essential to unequivocally understand how these gene expression variations affect quinoa response to abiotic stressors. Full article

This study reports, for the first time, changes in the microbiome community associated with anhydrobiosis in two tardigrade species of the genus Paramacrobiotus. To identify bacteria linked to the anhydrobiosis phenomenon and to track microbiome changes under anhydrobiotic stress, next-generation sequencing of bacterial 16S rRNA genes was conducted. Microbiome profiling was performed across various developmental and physiological stages of tardigrades, including: eggs; active adult specimens (both before and after 7, and 120 days of anhydrobiosis, referred to as short- and long-term anhydrobiosis, respectively); specimens in the desiccated tun stage; dead specimens following long-term anhydrobiosis (no dead specimens were observed after short-term anhydrobiosis); and the culture medium. It was shown that the microbiome community varied among stages, with high stage-specificity. Several bacterial genera were identified that may assist the host during anhydrobiosis, potentially through biofilm formation and by supporting stress-protective mechanisms such as heat shock protein expression and trehalose synthesis in eggs and tuns. These findings reveal that microbiota may contribute to anhydrobiotic survival in tardigrades, providing novel insights into host–microbe interactions under extreme environmental stress. Full article

Sungaya inexpectata is a tropical stick insect endemic to the Philippines, providing a useful system for investigating cold responses in tropical ectotherms. In this study, we exposed individuals to low temperature (8 °C) and normal temperature (25 °C) and characterized their transcriptomic responses. A total of 1656 differentially expressed genes were identified, including those involved in energy metabolism, cuticular proteins (CPs), and heat shock proteins. Since CP-related genes were notably enriched, we focused on this family. qPCR assessment provided preliminary expression profiles for selected candidate CP genes. Using comparative transcriptomics with eight New Zealand alpine stick insect species, we reconstructed the phylogeny of major CP families and annotated their conserved domains. Clade analysis revealed significant positive selection in the CPAP3-3 gene. In summary, this study reveals the transcriptional response of cuticular protein genes in S. inexpectata under cold exposure at 8 °C. These findings provide preliminary transcriptional data for understanding how this species responds to low temperature. Full article