Search Results (2,643)

Potato Fusarium dry rot and wilt are the most important soil- and seed-borne diseases in potatoes. They cause high economic losses during potato growth and storage across the world. Previous observations have shown that dryocrassin ABBA can induce resistance in potatoes. However, little is known about whether dryocrassin ABBA can suppress Fusarium oxysporum. In this research, we determined that exogenous dryocrassin ABBA significantly inhibited the mycelial growth, changed the cell ultrastructure, increased the MDA content, and decreased the antioxidant enzyme activity of F. oxysporum. The transcriptome analysis of F. oxysporum with or without dryocrassin ABBA indicated that 1244 differentially expressed genes (DEGs) were identified, of which 594 were upregulated and 650 were downregulated. GO term analysis showed that the DEGs were mostly related to biological processes. The KEGG pathway was mainly related to carbohydrate, amino acid, and lipid metabolism. Moreover, most of the expressions of PCWDEs, HSPs, and MFS were downregulated, decreasing the stress capacity and weakening the pathogenicity of F. oxysporum with dryocrassin ABBA treatment. These findings contribute to a new understanding of the direct functions of dryocrassin ABBA on F. oxysporum and provide a potential ecofriendly biocontrol approach for potato Fusarium dry rot and wilt. Full article

Background: Crohn’s disease (CD) is an inflammatory bowel disease marked by an abnormal immune response and excessive pro-inflammatory cytokines, leading to impaired protein processing and endoplasmic reticulum (ER) stress. This stress, caused by the accumulation of misfolded proteins, triggers the unfolded protein response (UPR) through IRE1/Xbp-1, PERK/eIF2α, and ATF6 pathways, which are linked to intestinal inflammation. This study aimed to investigate ER stress in CD patients’ intestinal mucosa and evaluate phenylbutyrate (PBA) as an ER stress inhibitor. Methods: Colon biopsies from CD patients and controls were cultured under five conditions, including 4-PBA treatments. Real-time PCR, cytokine level, and immunohistochemistry were performed. Results: Immunohistochemistry revealed that ER stress was activated in CD patients’ intestinal epithelial cells and lamina propria cells. PERK/eIF2α, but not IRE1/Xbp-1 or ATF6, was upregulated in CD patients compared to controls. UPR-related genes (STC2, CALR, HSPA5, HSP90B1) were also elevated in CD patients. PBA treatment significantly reduced ER stress and UPR markers while decreasing apoptotic markers like DDIT3. Pro-inflammatory cytokines, such as IL-1β, IL-6, IL-17, TNF- α, and sCD40L, were significantly reduced after PBA treatment. Conclusion: ER stress and UPR pathways are activated in CD colonic mucosa, and PBA reduces these markers, suggesting potential therapeutic benefits for CD-related inflammation. Full article

Heat shock proteins (HSPs), particularly HSP90, play a vital role in insect responses to environmental and biotic stresses by maintaining protein stability and supporting immune defenses. This study explores HSP90 regulation in Galleria mellonella larvae following exposure to the nematode Steinernema carpocapsae and its symbiotic bacterium Xenorhabdus nematophila. Exposure to live nematodes caused slight changes in HSP90 expression, while non-viable nematodes had no effect, suggesting that nematode secretions or symbiotic bacteria do not directly influence HSP90 levels. However, nematodes with altered surface properties significantly increased HSP90 expression. X. nematophila also moderately elevated HSP90 levels but this effect disappeared when weakly bound surface proteins were removed. Interestingly, under thermal stress, live nematodes reduced heat-induced HSP90 expression, whereas surface-treated nematodes enhanced it. These findings suggest that HSP90 modulation is influenced by biological control agents, highlighting a potential link between HSP90 and immune detection of invaders. This interaction may be crucial in adapting biological control strategies in response to climate change. Further research is needed to clarify HSP activation pathways, host immune interactions, and mechanisms of entomopathogen immune evasion, particularly under varying environmental temperatures, to enhance bioinsecticide efficacy. Full article

Background/Objectives: Biocontrol agents (BCAs) are gaining attention as sustainable alternatives to chemical pesticides. Understanding their molecular mechanisms is crucial for improving plant protection. This study investigates the genomic features of Meyerozyma guilliermondii CECT13190, a promising BCA, to identify key genes involved in its biocontrol abilities. Methods: Whole-genome sequencing of M. guilliermondii was performed, followed by bioinformatics analysis to identify genes and pathways related to biocontrol, including gene copy number variation (CNV) analysis. Gene ontology (GO) analysis was conducted to examine gene functions, and a comparative proteomics approach assessed the presence and role of proteins in the secretome of M. guilliermondii. Results: Genomic analysis revealed key biocontrol-related pathways. CNV analysis indicated a direct correlation between gene amplification and competitive fitness, with seven genes showing gains and five genes showing losses. GO analysis identified categories such as enzymes, transcription factors, ribosomal and proteasomal complexes, transporters, membrane proteins, RNA processing, and stress-response-related proteins. Secretome analysis identified HSP70 and HSP90 as potential effectors involved in biocontrol activity. Conclusions: This study provides insights into the genomic features of M. guilliermondii and its biocontrol potential. The identification of genes involved in the stress response and the secretome highlights the multifaceted mechanisms through which M. guilliermondii antagonizes plant pathogens. Practical outcomes include the identification of candidate genes and proteins, such as HSP70 and HSP90, which can be targeted to enhance biocontrol efficiency in agricultural applications. Additionally, the observed CNVs offer a potential avenue for strain improvement programs to optimize competitiveness and efficacy in field conditions. Full article

Protein misfolding, aggregation, and aberrant aggregate accumulation play a central role in neurodegenerative disease progression. The proteotoxic factors also govern the aging process to a large extent. Molecular chaperones modulate proteostasis and thereby impact aberrant-protein-induced proteotoxicity. These chaperones have a diverse functional spectrum, including nascent protein folding, misfolded protein sequestration, refolding, or degradation. Small heat shock proteins (sHsps) possess an ATP-independent chaperone-like activity that prevents protein aggregation by keeping target proteins in a folding-competent state to be refolded by ATP-dependent chaperones. Due to their near-universal upregulation and presence in sites of proteotoxic stress like diseased brains, sHsps were considered pathological. However, gene knockdown and overexpression studies have established their protective functions. This review provides an updated overview of the sHsp role in protein aggregation amelioration and highlights evidence for sHsp modulation of neurodegenerative disease-related protein aggregation and aging. Full article

Background/Objective: Ovarian cancer (OC) is one of the most lethal gynecological cancers, having a worldwide mortality rate of 66% in 2020. The overall 5-year relative survival rate is only 21% for distant stages, due to the lack of early diagnosis. Epithelial OC, the most common high-grade serous carcinoma, carries p53 mutations in most cases. However, we found that the immediate early response 5 gene (IER5), a p53 target gene, is overexpressed in ovarian cancer cells. The molecular mechanism underlying the role of IER5 in OC has not been well studied. We previously reported that IER5 promotes the dephosphorylation and activation of heat shock factor-1 (HSF1), the master regulator of proteostasis, which induces heat shock protein (HSP) expression. Methods/Results: Here we show that Ier5 mRNA expression is higher in ovarian cancer cells (MOV, ID8G, and HM-1) compared to normal ovarian cells. We also show that OC cells floating in the ascites have higher Ier5 expression than the parental strain. Knockdown of Ier5 suppressed HSP upregulation and proliferation of OC, while overexpression of IER5 promoted HSP upregulation. Knockdown of Hsf1 showed results similar to Ier5 knockdown. Conclusions: These results indicate that the IER5-HSF1 pathway contributes to the proliferation and peritoneal dissemination of OC cells. We also found that higher expression of IER5 family genes is related to poorer prognosis of OC patients, suggesting the potential of the IER5 gene family as diagnostic markers for OC, as well as potential therapeutic targets. Full article

This study furnishes insights into how methionine mitigates heat-stress-induced impairments in hair follicle development in Rex rabbits at the cellular level. Dermal papilla cells from the dorsal skin of Rex rabbits were isolated, cultured in vitro, and divided into six groups, i.e., control (37 °C; 0 mM methionine), heat stress (45 °C; 0 mM methionine), and heat stress + methionine (45 °C; 15 mM, 30 mM, 45 mM, and 60 mM methionine), with six replicates per group. The heat stress groups were exposed to 45 °C, 5% CO₂, and 95% humidity for 30 min, followed by recovery at 37 °C, repeated three times over three days. On the third day, samples were collected post-heat stress. The results show that methionine markedly fortified HSP70, MSRA, and SOD expression (p < 0.01); augmented proliferation (p < 0.01); ameliorated cell cycle progression; and lessened apoptosis (p < 0.05). Adding Wnt signaling pathway activators and inhibitors manifested that these effects were associated with diminished β-catenin phosphorylation and aggrandized expression of the Wnt10b, β-catenin (p < 0.001), and LEF/TCF nuclear transcription factors (p < 0.01). Thus, this study demonstrates that methionine regulates the growth and development of heat-stressed hair papilla cells via the Wnt signaling pathway, remitting heat-stress trauma. Full article

The common octopus (Octopus vulgaris), among coleoid cephalopods, has evolved the most complex nervous system and sophisticated behaviors. Historically, O. vulgaris was a key animal model for neurophysiology research, and today, it is studied for its genomic innovations. However, unlike other models, there is no octopus farming for research, so specimens must be collected from the wild. This study assessed the impact of fishing on octopuses used in research, considering those caught using artisanal pots in the ‘Regno di Nettuno’ Marine Protected Area, Ischia (NA). To evaluate fishing stress, we identified morphological stress indicators such as chromatophore pattern and posture, and three potential molecular markers, estrogen receptor (ER), catalase (CAT), and heat shock protein (HSP70). We measured the percentage of stress signals shown by fished specimens and analyzed their differential gene expression. The transcriptional levels of octopuses caught using traps were compared to control specimens acclimated in captivity. Results indicated fluctuations in gene expression due to fishing stress. These findings suggest that an acclimation period after the stress event of fishing is crucial for ensuring the welfare of octopuses used in research, thus enhancing the quality of physiological and ethological studies. Full article

In this study, we were dedicated to investigating the effect caused by heat stress on wheat flag leaves. Metabolome and transcriptome analysis were introduced to identify some key biological processes. As a result, 182 and 214 metabolites were significantly changed at the anthesis and post-anthesis stages, respectively; most of them were lipids, amino acids and derivatives, phenolic acids, and alkaloids. Aminoacyl-tRNA biosynthesis was the most significantly enriched pathway by metabolites at both two stages, each of which included 13 types of amino acid, and 12 of them were shared and up-regulated. Therefore, we further measured 22 kinds of amino acid content in ten different wheat genotypes at the post-anthesis stage. Based on the average content of each amino acid, 17 kinds of them were significantly increased after heat stress, and 4 types were significantly decreased. Both the metabolism analysis and the transcriptome analysis had a higher number of significantly changed metabolites or differential expressed genes at the post-anthesis stage, which indicated that the post-anthesis stage is more sensitive to heat stress, with 21,361 and 17,130 differential expressed genes, respectively. Two pathways, protein processing in endoplasmic reticulum and ABC transporters, were significantly enriched at two stages. The differential expressed genes in processing in endoplasmic reticulum pathway mainly encoded various types of molecular chaperones; among them, the HSP20 family was the most predominant and intensively up-regulated. The ABC transporter gene family is another pathway that is deeply involved in heat-stress response, which could be classified into five subfamilies; among them, subfamilies B and G were the most active. In summary, this study revealed the heat response pattern of amino acids, HSPs, and ABC transporter which may play a vital role during the wheat reproductive stage. Full article

Background: The rising rates of gallstones and cholecystectomy in pediatric populations underscore the increasing concern regarding chronic cholecystitis. However, the morphopathogenesis of pediatric calculous cholecystitis is still not well understood. This study aimed to determine the expression and distribution of immunomodulatory factors interleukin-12 (IL-12), interleukin-13 (IL-13), interleukin-1β (IL-1β), sonic hedgehog protein (SHH), nuclear factor NF-kappa-B p65 subunit (NFkBp65), and heat shock protein 60 (HSP60) in the gallbladder walls of pediatric patients with chronic calculous cholecystitis. Methods: In total, 11 gallbladder samples were collected from pediatric patients with calculous cholecystitis during cholecystectomy, while 5 healthy gallbladder samples served as controls. IL-12, IL-13, IL-1β, SHH, NFkBp65, and HSP60 were detected by immunohistochemistry. The number of positive structures in gallbladder wall epithelium, vasculature, and inflammatory infiltrate was assessed semi-quantitatively by microscopy. A Mann–Whitney U test and Spearman’s rank-order correlation coefficient were calculated. Results: Statistically significant differences were observed between patient and control samples in the expression of IL-1β, SHH, and NFkBp65 in the epithelium, as well as in the expression of IL-12, SHH, and HSP60 in the blood vessels. The expression of IL-1β was stronger in the epithelium of controls, while other markers were more prominent in patient samples. Conclusions: An increased number of NFkBp65, IL-12, and HSP60 positive cells in patient gallbladder tissue suggests a significant role of these tissue factors in driving immune modulation and sustaining the inflammation in pediatric chronic calculous cholecystitis. The noticeable expression of SHH in patient gallbladder tissue indicates its part in tissue regeneration and repair processes, as well as in modulating inflammation and vascular responses in calculous cholecystitis. The significant positive correlations between the factors studied highlight the importance of their coordinated interaction and intricate crosstalk in the morphopathogenesis of calculous cholecystitis. Full article

In crude oil production, large volumes of produced water are generated as a highly polluting waste byproduct. On average, at least two barrels of produced water are generated for every barrel of oil. This water contains oil traces in stable and complex emulsions. To purify it, a method is proposed based on breaking these emulsions using solvents that induce the coalescence of oil droplets, facilitating their separation from the water. The method has two main objectives: (1) To identify the characteristics a solvent must have to effectively break oil emulsions according to the Hansen solubility parameter (HSP) model. (2) To select, from 40 solvents of different chemical families, the most suitable ones based on efficiency, low toxicity, industrial availability, and cost. The experimental procedure included the following steps: (1) Contacting the solvent with produced water containing 150 ppm of oil under agitation. (2) Allowing the mixture to rest until a layer of recovered oil formed. (3) Spectrophotometric analysis of the residual oil. Three distinct HSP solubility spheres were identified, within which the most effective solvents were xylene (99.4% recovery), cyclohexane (99.5% recovery), and tetrahydrofuran (100% recovery). Their high efficiency not only facilitated oil separation but also made the recovered oil suitable for commercialization. Full article

The study objectives were to investigate the heat resistance using peripheral blood mononuclear cells (PBMCs) and hair follicles in beef and dairy calves based on heat shock protein (HSP) 70 genetic polymorphisms. The hair follicle samples from sixty calves (6 months old; 30 Korean native beef calves and 30 Holstein dairy calves) were collected for DNA extraction. The HSP70 single nucleotide polymorphism (SNP) was genotyped using a 5′-exonuclease activity (TaqMan) assay. In Study 1, PBMCs were isolated from 20 calves categorized by their HSP70 genotypes during a thermoneutral period: 10 Korean native beef calves (B-CC and B-C/-type) and 10 Holstein dairy calves (D-CC, D-C/-type). The PBMCs were then exposed to heat stress at 37 °C (control, CON) and 42 °C (heat stress, HS) for 3 h. Following this, the cells were returned to the 37 °C incubator at 0, 1, 3, 6, and 12 h for further recovery analysis. In Study 2, hair follicles were collected from 20 calves (six times every 30 days; threshold, mild, and moderate stress levels) and HSP70 gene expression was measured. Data were analyzed via two-way analysis of variance (ANOVA) and Tukey’s honestly significant difference (HSD) test. The cell proliferation in the D-C/-group was significantly higher (p < 0.05) than in the D-CC and B-C/-groups at 0 and 1 h after HS for 3 h. The mRNA gene expression of HSP70 was greater (p < 0.01) in all HS groups compared to the CON groups after heat exposure. The expression of the HSP70 gene in the D-C/-group was significantly higher (p < 0.05) compared to the B-CC and B-C/-groups immediately (0 h) following 3 h of HS. The expression in the D-CC group also higher (p < 0.05) than in the B-C/-group. The gene expression of HSP70 in hair follicles increased more at the moderate HS level than that at the threshold level. In addition, overexpression of HSP70 was noted (p < 0.05) in the D-CC and D-C/-groups compared to the B-CC and B-C/-groups. In conclusion, our results indicate that breeds and HSP70 genetic polymorphisms exhibit a distinctive pattern of immune cell proliferation and HSP70 expression profiles. Additionally, the HSP70 gene expression in hair follicles may serve as an indicator of heat resistance across different breeds, making it a potential novel barometer for HS. Full article

Pulmonary arterial hypertension (PAH) is characterized by increased lung vascular stiffness and impaired vessel relaxation, primarily due to reduced nitric oxide (NO) production in endothelial cells. Recent studies indicate that chloroquine, an autophagy inhibitor, may help lower pulmonary arterial pressure and enhance lung vascular function. This study investigates the mechanisms underlying the chloroquine-mediated restoration of NO bioavailability in endothelial cells derived from aortopulmonary shunt lambs, a relevant model for congenital heart defect (CHD)-associated PAH. We found that NO production was significantly reduced in shunt pulmonary artery endothelial cells (PAECs), attributable to decreased levels of tetrahydrobiopterin (BH₄) and diminished expression of GTP cyclohydrolase 1 (GCH1), despite a slight increase in endothelial nitric oxide synthase (eNOS) levels. Chloroquine robustly restored endothelial NO production, which correlated with increased BH₄ levels and restored GCH1 expression. The mechanistically upregulated carboxyl terminus of Hsp70-interacting protein (CHIP) in shunt PAECs is responsible for heightened GCH1 degradation, and chloroquine disrupted the assembly of the GCH1-HSP70-CHIP complex to preserve cellular GCH1. Similarly, another autophagy inhibitor, bafilomycin A1, demonstrated comparable effects. These findings suggest that autophagy inhibition can effectively enhance NO synthesis in endothelial cells experiencing depleted NO bioavailability, presenting a potential therapeutic strategy for managing PAH. Full article

Using NHANES data from 2003 to 2008, 2011 to 2012, and 2015 to 2020, we examined the relationship between urinary organophosphate pesticide (OPP) metabolites and the triglyceride glucose (TyG) index. The TyG index evaluates insulin resistance, a crucial factor in metabolic diseases. Linear regression analyzed urinary metabolites in relation to the TyG index and OPPs. An RCS (restricted cubic spline) model explored the nonlinear relationship of a single OPP metabolite to TyG. A weighted quantile regression and quantile-based g-computation assessed the impact of combined OPP exposure on the TyG index. XGBoost, Random Forest, Support Vector Machines, logistic regression, and SHapley Additive exPlanations models investigated the impact of OPPs on the TyG index and cardiovascular disease. Network toxicology identified CVD targets associated with OPPs. This study included 4429 participants based on specific criteria. Linear regression analysis indicated that diethyl thiophosphate was positively correlated with the TyG index. The positive correlation between OPP metabolites and the TyG index at low to moderate concentrations was confirmed by WQS and QGC analyses. The machine learning results aligned with traditional statistical findings. Network toxicology identified PTGS3, PPARG, HSP40AA1, and CXCL8 as targets influenced by OPPs. OPP exposure influences IR and cardiometabolic health, highlighting the importance of public health prevention. Full article

Background: A hallmark of cancer is the presence of an immunosuppressive tumor microenvironment (TME). Immunosuppressive M2 macrophages (MΦs) in the TME facilitate escape from immune surveillance and promote tumor growth; therefore, TME-induced immunosuppression is a potent immunotherapeutic approach to treating cancer. Methods: Cancer cell-secreted proteins were detected by using liquid chromatography–mass spectrometry (LC-MS). Neutralizing antibodies (nAbs) were used to assess which proteins were involved in MΦs polarization and differentiation. The protein–protein interaction was characterized using co-immunoprecipitation and immunofluorescence assays. Cancer-secreted heat shock protein 70 (Hsp70) protein was quantified using an enzyme-linked immunosorbent assay (ELISA). MΦ polarization and tumor growth were assessed in vivo with subcutaneous LLC-GFP tumor models and toll-like receptor 2 (TLR2) knockout mice; in vitro assessments were conducted using TLR2 knockout and both LLC-GFP and LN227 lentiviral-mediated knockdown (KD) cells. Results: Cancer cells released a secreted form of Hsp70 that acted on MΦ TLR2 to upregulate Mer receptor tyrosine kinase (MerTK) and induce MΦ M2 polarization. Hsp70 nAbs led to a reduction in CD14 expression by 75% in THP-1 cells in response to Gli36 EMD-CM. In addition, neutralizing TLR2 nAbs resulted in a 30% and 50% reduction in CD14 expression on THP-1 cells in response to MiaPaCa-2 and Gli36 exosome/microparticle-depleted conditioned media (EMD-CMs), respectively. Hsp70, TLR2, and MerTK formed a protein complex. Tumor growth and intra-tumor M2 MΦs were significantly reduced upon cancer cell Hsp70 knockdown and in TLR2 knockout mice. Conclusions: Cancer-secreted Hsp70 interacts with TLR2, upregulates MerTK on MΦs, and induces immunosuppressive MΦ M2 polarization. This previously unreported action of secreted Hsp70 suggests that disrupting the Hsp70-TLR2-MerTK interaction could serve as a promising immunotherapeutic approach to mitigate TME immunosuppression in solid cancers. Full article