JRK binds satellite III DNA and is necessary for the heat shock response.

JRK is a DNA-binding protein of the pogo superfamily of transposons, which includes the well-known centromere binding protein B (CENP-B). Jrk null mice exhibit epilepsy, and growth and reproductive disorders, consistent with its relatively high expression in the brain and reproductive tissues. Human JRK DNA variants and gene expression levels are implicated in cancers and neuropsychiatric disorders. JRK protein modulates ß-catenin-TCF activity but little is known of its cellular functions. Based on its homology to CENP-B, we determined whether JRK binds centromeric or other satellite DNAs. We show that human JRK binds satellite III DNA, which is abundant at the chromosome 9q12 juxtacentromeric region and on Yq12, both sites of nuclear stress body assembly. Human JRK-GFP overexpressed in HeLa cells strongly localises to 9q12. Using an anti-JRK antiserum we show that endogenous JRK co-localises with a subset of centromeres in non-stressed cells, and with heat shock factor 1 following heat shock. Knockdown of JRK in HeLa cells proportionately reduces heat shock protein gene expression in heat-shocked cells. A role for JRK in regulating the heat shock response is consistent with the mouse Jrk null phenotype and suggests that human JRK may act as a modifier of diseases with a cellular stress component.

Plastid HSP90C C-terminal extension region plays a regulatory role in chaperone activity and client binding.

HSP90Cs are essential molecular chaperones localized in the plastid stroma that maintain protein homeostasis and assist the import and thylakoid transport of chloroplast proteins. While HSP90C contains all conserved domains as an HSP90 family protein, it also possesses a unique feature in its variable C-terminal extension (CTE) region. This study elucidated the specific function of this HSP90C CTE region. Our phylogenetic analyses revealed that this intrinsically disordered region contains a highly conserved DPW motif in the green lineages. With biochemical assays, we showed that the CTE is required for the chaperone to effectively interact with client proteins PsbO1 and LHCB2 to regulate ATP-independent chaperone activity and to effectuate its ATP hydrolysis. The CTE truncation mutants could support plant growth and development reminiscing the wild type under normal conditions except for a minor phenotype in cotyledon when expressed at a level comparable to wild type. However, higher HSP90C expression was observed to correlate with a stronger response to specific photosystem II inhibitor DCMU, and CTE truncations dampened the response. Additionally, when treated with lincomycin to inhibit chloroplast protein translation, CTE truncation mutants showed a delayed response to PsbO1 expression repression, suggesting its role in chloroplast retrograde signaling. Our study therefore provides insights into the mechanism of HSP90C in client protein binding and the regulation of green chloroplast maturation and function, especially under stress conditions.

Discovery of indazole inhibitors for heat shock protein 90 as anti-cancer agents.

A series of indazole analogs, derived from the B,C-ring-truncated scaffold of deguelin, were designed to function as C-terminal inhibitors of heat shock protein 90 (HSP90) and investigated as novel antitumor agents against HER2-positive breast cancer. Among the synthesized compounds, compound 12d exhibited substantial inhibitory effects in trastuzumab-sensitive (BT474) and trastuzumab-resistant (JIMT-1) breast cancer cells, with IC50 values of 6.86 and 4.42 µM, respectively. Notably, compound 12d exhibited no cytotoxicity in normal cells. Compound 12d markedly downregulated the expression of the major HSP90 client proteins in both cell types, attributing its cytotoxicity to the destabilization and inactivation of HSP90 client proteins. Molecular docking studies using the homology model of an HSP90 homodimer demonstrated that inhibitor 12d fit nicely into the C-terminal domain, boasting a higher electrostatic complementary score than ATP. In vivo pharmacokinetic study indicated the high oral bioavailability of compound 12 d at F = 66.9 %, while toxicological studies indicated its negligible impact on hERG channels and CYP isozymes. Genotoxicity tests further confirmed its safety profile. The findings collectively position compound 12d as a promising candidate for further development as an antitumor agent against HER2-positive breast cancer.

The role of GmHSP23.9 in regulating soybean nodulation under elevated CO2 condition.

Legume-rhizobia symbiosis offers a unique approach to increase leguminous crop yields. Previous studies have indicated that the number of soybean nodules are increased under elevated CO2 concentration. However, the underlying mechanism behind this phenomenon remains elusive. In this study, transcriptome analysis was applied to identify candidate genes involved in regulating soybean nodulation mediated by elevated CO2 concentration. Among the different expression genes (DEGs), we identified a gene encoding small heat shock protein (sHSP) called GmHSP23.9, which mainly expressed in soybean roots and nodules, and its expression was significantly induced by rhizobium USDA110 infection at 14 days after inoculation (DAI) under elevated CO2 conditions. We further investigated the role of GmHSP23.9 by generating transgenic composite plants carrying GmHSP23.9 overexpression (GmHSP23.9-OE), RNA interference (GmHSP23.9-RNAi), and CRISPR-Cas9 (GmHSP23.9-KO), and these modifications resulted in notable changes in nodule number and the root hairs deformation and suggesting that GmHSP23.9 function as an important positive regulator in soybean. Moreover, we found that altering the expression of GmHSP23.9 influenced the expression of genes involved in the Nod factor signaling pathway and AON signaling pathway to modulate soybean nodulation. Interestingly, we found that knocking down of GmHSP23.9 prevented the increase in the nodule number of soybean in response to elevated CO2 concentration. This research has successfully identified a crucial regulator that influences soybean nodulation under elevated CO2 level and shedding new light on the role of sHSPs in legume nodulation.

Tumor-derived Hsp70-CD14 interaction enhances the antitumor potential of cytotoxic T cells by activating tumor-associated macrophages to express CC chemokines and CD40 costimulatory molecules.

Heat shock proteins are a widely distributed group of proteins. It is constitutively expressed in almost all organisms and shows little variation throughout evolution. Previously, HSPs, particularly Hsp70, were recognized as molecular chaperones that aid in the proper three-dimensional folding of newly synthesized polypeptides in cells. Recently, researchers have focused on the potential induction of immune cells, including macrophages, antigen-specific CD8+ cytotoxic T cells, and PBMCs. It induces the expression of CC chemokines such as MIP-1α and RANTES, which are responsible for the chemotactic movement and migration of immune cells at the site of infection to neutralize foreign particles in vivo and in vitro in several cell lines but their effect on tumor-associated macrophages is still not known. These cytokines are also known to influence the movement of several immune cells, including CD8+ cytotoxic T cells, toward inflammatory sites. Therefore, the effect of tumor-derived autologous Hsp70 on the expression of MIP-lα and RANTES in tumor-associated macrophages (TAMs) was investigated. Our results indicated that Hsp70 treatment-induced MIP-lα and RANTES expression was significantly greater in TAMs than in NMOs. According to the literature, the CC chemokine shares the same receptor, CCR5, as HIV does for their action, and therefore could provide better completion to the virus for ligand binding. Furthermore, Hsp70-preactivated TAMs induced increased IL-2 and IFN-γ expression in T cells during coculture for 48 h and upregulated the antitumor immune response of the host. Therefore, the outcome of our study could be useful for developing a better approach to restricting the growth and progression of tumors.

The heat shock response in Polistes spp. brood from differing climates following heat stress.

Temperature is a crucial factor in many physiological processes, especially in small ectotherms whose body temperature is highly influenced by ambient temperature. Polistes (paper wasps) is a genus of primitively eusocial wasps found in widely varying thermal environments throughout the world. Paper wasps construct open-faced combs in which the brood is exposed to varying ambient temperatures. The Heat Shock Response is a physiological mechanism that has been shown to help cope with thermal stress. We investigated the expression of heat shock proteins in different life stages of three species of Polistes from different climates with the aim of deducing adaptive patterns. This was done by assaying heat shock protein (hsp70, hsp83, hsc70) expression during control conditions (25 °C) or a heat insult (35 or 45 °C) in individuals collected from natural populations in Alpine, Temperate, or Mediterranean climates. Basal expression of hsc70 and hsp83 was found to be high, while hsp70 and hsp83 expression was found to be highly responsive to severe heat stress. As expression levels varied based on species, geographical origin, and life stage as well as between heat shock proteins, the Heat Shock Response of Polistes was found to be complex. The results suggest that adaptive utilization of the heat shock response contributes to the ability of Polistes spp. to inhabit widely different thermal environments.

Inhibiting spinal cord-specific hsp90 isoforms reveals a novel strategy to improve the therapeutic index of opioid treatment.

Opioids are the gold standard for the treatment of chronic pain but are limited by adverse side effects. In our earlier work, we showed that Heat shock protein 90 (Hsp90) has a crucial role in regulating opioid signaling in spinal cord; Hsp90 inhibition in spinal cord enhances opioid anti-nociception. Building on these findings, we injected the non-selective Hsp90 inhibitor KU-32 by the intrathecal route into male and female CD-1 mice, showing that morphine anti-nociceptive potency was boosted by 1.9-3.5-fold in acute and chronic pain models. At the same time, tolerance was reduced from 21-fold to 2.9 fold and established tolerance was rescued, while the potency of constipation and reward was unchanged. These results demonstrate that spinal Hsp90 inhibition can improve the therapeutic index of morphine. However, we also found that systemic non-selective Hsp90 inhibition blocked opioid pain relief. To avoid this effect, we used selective small molecule inhibitors and CRISPR gene editing to identify 3 Hsp90 isoforms active in spinal cord (Hsp90α, Hsp90ß, and Grp94) while only Hsp90α was active in brain. We thus hypothesized that a systemically delivered selective inhibitor to Hsp90ß or Grp94 could selectively inhibit spinal cord Hsp90 activity, resulting in enhanced opioid therapy. We tested this hypothesis using intravenous delivery of KUNB106 (Hsp90ß) and KUNG65 (Grp94), showing that both drugs enhanced morphine anti-nociceptive potency while rescuing tolerance. Together, these results suggest that selective inhibition of spinal cord Hsp90 isoforms is a novel, translationally feasible strategy to improve the therapeutic index of opioids.

Sialyltransferase ST3GAL6 silencing reduces α2,3-sialylated glycans to regulate autophagy by decreasing HSPB8-BAG3 in the brain with hepatic encephalopathy. / å”¾æ¶²é ¸ç³–åŸºè½¬ç§»é ¶ST3GAL6的沉默可通过减少α2,3-å”¾æ¶²é ¸åŒ–èšç³–é™ä½ŽHSPB8-BAG3è¡¨è¾¾ä»Žè€Œè°ƒæŽ§è‚æ€§è„‘ç— å°é¼ å¤§è„‘ä¸­çš„è‡ªå™¬.

End-stage liver diseases, such as cirrhosis and liver cancer caused by hepatitis B, are often combined with hepatic encephalopathy (HE); ammonia poisoning is posited as one of its main pathogenesis mechanisms. Ammonia is closely related to autophagy, but the molecular mechanism of ammonia's regulatory effect on autophagy in HE remains unclear. Sialylation is an essential form of glycosylation. In the nervous system, abnormal sialylation affects various physiological processes, such as neural development and synapse formation. ST3 ß|-galactoside α2,|3-sialyltransferase 6 (ST3GAL6) is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures. We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction, and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3 (LC3) and Beclin-1 were upregulated in ammonia-induced astrocytes. These findings suggest that ST3GAL6 is related to autophagy in HE. Therefore, we aimed to determine the regulatory relationship between ST3GAL6 and autophagy. We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II (MAL-II) and neuraminidase can inhibit autophagy. In addition, silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein ß8 (HSPB8) and Bcl2-associated athanogene 3 (BAG3). Notably, the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression. Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.

Dexmedetomidine mitigates lipopolysaccharide-induced acute lung injury by modulating heat shock protein A12B to inhibit the toll-like receptor 4/nuclear factor-kappa B signaling pathway.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): Life-threatening medical conditions characterized by high morbidity and mortality rates, where the inflammatory process plays a crucial role in lung tissue damage, especially in models induced by lipopolysaccharide (LPS). Heat shock protein A12B (HSPA12B) has strong anti-infammatory properties However, it is unknown whether increased HSPA12B is protective against LPS-induced ALI. And Dexmedetomidine (DEX) is a potent α2-adrenergic receptor (α2-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. This study utilized bioinformatics analysis and an LPS-induced ALI model to explore how DEX alleviates lung injury by modulating HSPA12B and inhibiting the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. Results indicate that HSPA12B overexpression and DEX pre-treatment markedly mitigated LPS-induced lung injury, which was evaluated by the deterioration of histopathology, histologic scores, the W/D weight ratio, and total protein expression, tumor necrosis factor-alpha (TNF-α), and interleukin-1ß (IL-1ß) in the BALF, and the levels of NO, MDA,SOD and MPO in the lung. Moreover, HSPA12B overexpression and DEX pre-treatment significantly reduces lung injury and inflammation levels by upregulating HSPA12B and inhibiting the activation of the TLR4/NF-κB signaling pathway. On the contrary, when the expression of HSPA12B is inhibited, the protective effect of DEX pre-treatment on lung tissue is significantly weakened.In summary, our research demonstrated that the increased expression of AAV-mediated HSPA12B in the lungs of mice inhibits acute inflammation and suppresses the activation of TLR4/NF-κB pathway in a murine model of LPS-induced ALI. DEX could enhance HSPA12B and inhibit the initiation and development of inflammation through down-regulating TLR4/NF-κB pathway.These findings highlight the potential of DEX as a therapeutic agent for treating ALI and ARDS, offering new strategies for clinical intervention.

Genome-wide identification of the HSP70 genes in Pacific oyster Magallana gigas and their response to heat stress.

Heat shock protein 70 (HSP70), the most prominent and well-characterized stress protein in animals, plays an important role in assisting animals in responding to various adverse conditions. In the present study, a total of 113 HSP70 gene family members were identified in the updated genome of Magallana gigas (designated MgHSP70) (previously known as Crassostrea gigas). There were 75, 12, 11, and 8 HSP70s located in the cytoplasm, nucleus, mitochondria, and endoplasmic reticulum, respectively, and 7 HSP70s were located in both the nucleus and cytoplasm. Among 113 MgHSP70 genes, 107 were unevenly distributed in 8 chromosomes of M. gigas with the greatest number in chromosome 07 (61 genes, 57.01%). The MgHSP70 gene family members were mainly assigned into five clusters, among which the HSPa12 subfamily underwent lineage-specific expansion, consisting of 89 members. A total of 68 MgHSP70 genes (60.18%) were tandemly duplicated and formed 30 gene pairs, among which 14 gene pairs were under strong positive selection. In general, the expression of MgHSP70s was tissue-specific, with the highest expression in labial palp and gill and the lowest expression in adductor muscle and hemocytes. There were 35, 31, and 47 significantly upregulated genes at 6, 12, and 24 h after heat shock treatment (28 °C), respectively. The expression patterns of different tandemly duplicated genes exhibited distinct characteristics after shock treatment, indicating that these genes may have different functions. Nevertheless, genes within the same tandemly duplicated group exhibit similar expression patterns. Most of the tandemly duplicated HSP70 gene pairs showed the highest expression levels at 24 h. This study provides a comprehensive description of the MgHSP70 gene family in M. gigas and offers valuable insights into the functions of HSP70 in the mollusc adaptation of oysters to environmental stress.

The influence of HSP inducers on salinity stress in sterlet sturgeon (Acipenser ruthenus): In vitro study on HSP expression, immune responses, and antioxidant capacity.

Heat shock proteins (HSPs) play a crucial role in antioxidant systems, immune responses, and enzyme activation during stress conditions. Salinity changes can cause stress and energy expenditure in fish, resulting in mortality, especially in fingerlings. The purpose of this study was to examine the relationship between salinity and HSPs in stressed fish by assessing the effects of various HSP inducers (HSPis), including Pro-Tex® (800 mM), amygdalin (80 mM), and a novel synthetic compound derived from pirano piranazole (80 µM), on isolated cells from Sterlet Sturgeon (Acipenser ruthenus) exposed to 13 ‰ salinity (S13). After liver, kidney, and gill cells were cultured, the HSPi compounds were treated in vitro in the presence and absence of salinity. The expression patterns of HSP27, HSP70, and HSP90 were assessed by Western blotting. Biochemical enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase), cortisol levels, and immune parameters (component 3, immunoglobulin M, and lysozyme) were measured before and after treatment with HSPis and HSPi + S13. According to these findings, HSPis positively modulate HSP expression, immune responses, and antioxidant levels. Furthermore, they increased in vitro cell survival by maintaining cortisol levels and biochemical enzyme activities in A. ruthenus under saline conditions (P < 0.0001). In conclusion, HSPis can increase A. ruthenus resistance to salinity stress. However, the results also indicated that these compounds can reverse the adverse effects of salinity. The effectiveness of this approach depends on further research into the effects of these ecological factors on the health status of the species, especially in vivo and in combination with other stresses.

High-Performance NIR-II Fluorescent Type I/II Photosensitizer Enabling Augmented Mild Photothermal Therapy of Tumors by Disrupting Heat Shock Proteins.

NIR-II fluorescent photosensitizers as phototheranostic agents hold considerable promise in the application of mild photothermal therapy (MPTT) for tumors, as the reactive oxygen species generated during photodynamic therapy can effectively disrupt heat shock proteins. Nevertheless, the exclusive utilization of these photosensitizers to significantly augment the MPTT efficacy has rarely been substantiated, primarily due to their insufficient photodynamic performance. Herein, we present the utilization of high-performance NIR-II fluorescent type I/II photosensitizer (AS21:4) as a simple but effective nanoplatform derived from molecule AS2 to enhance the MPTT efficacy of tumors without any additional therapeutic components. By taking advantage of heavy atom effect, AS21:4 as a type I/II photosensitizer demonstrates superior efficacy in producing 1O2 (ΦΔ = 12.4%) and O2 •- among currently available NIR-II fluorescent photosensitizers with absorption exceeding 800 nm. In vitro and in vivo findings demonstrate that the 1O2 and O2 •- generated from AS21:4 induce a substantial reduction in the expression of HSP90, thereby improving the MPTT efficacy. The remarkable phototheranostic performance, substantial tumor accumulation, and prolonged tumor retention of AS21:4, establish it as a simple but superior phototheranostic agent for NIR-II fluorescence imaging-guided MPTT of tumors. This article is protected by copyright. All rights reserved.

Effects of ferroptosis-related gene HSPB1 on acute myeloid leukemia.

INTRODUCTION: The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML). METHODS: The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection. RESULTS: A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress. CONCLUSION: Ferroptosis-related gene HSPB1 is highly expressed in patients with AML. In addition, HSPB1 may be involved in the occurrence and development of AML by regulating oxidative stress and ferroptosis-related pathways. This study provides new clues for further understanding of AML molecular mechanisms. Also, HSPB1 is expected to be a potential therapeutic target for AML in the future.

All-Trans Retinoic Acid-Induced Cell Surface Heat Shock Protein 90 Mediates Tau Protein Internalization and Degradation in Human Microglia.

This study investigates the role of all-trans retinoic acid (ATRA) in modulating the expression of heat shock protein 90 (Hsp90) and its influence on the uptake and degradation of tau proteins in immortalized human microglia cells. We demonstrate that ATRA significantly upregulates Hsp90 expression in a concentration-dependent manner, enhancing both extracellular and intracellular Hsp90 levels. Our results show that ATRA-treated cells exhibit increased tau protein uptake via caveolae/raft-dependent endocytosis pathways. This uptake is mediated by surface Hsp90, as evidenced by the inhibition of tau internalization using an extracellular Hsp90-selective inhibitor. Further, we establish that the exogenously added full-sized monomeric tau proteins bind to Hsp90. The study also reveals that ATRA-enhanced tau uptake is followed by effective degradation through both lysosomal and proteasomal pathways. We observed a significant reduction in intracellular tau levels in ATRA-treated cells, which was reversed by lysosome or proteasome inhibitors, suggesting the involvement of both degradation pathways. Our findings highlight the potential therapeutic role of ATRA in Alzheimer's disease and related tauopathies. By enhancing Hsp90 expression and facilitating tau degradation, ATRA could contribute to the clearance of pathological tau proteins, offering a promising strategy for mitigating neurodegeneration. This research underscores the need for further exploration into the molecular mechanisms of tau protein internalization and degradation, which could provide valuable insights into the treatment of neurodegenerative diseases.

Heat shock protein HvHSP16.9 from wild barley enhances tolerance to salt stress.

Heat shock proteins (HSPs) are known to play a crucial role in the response of plants to environmental stress, particularly heat stress. Nevertheless, the function of HSPs in salt stress tolerance in plants, especially in barley, remains largely unexplored. Here, we aimed to investigate and compare the salt tolerance mechanisms between wild barley EC_S1 and cultivated barley RGT Planet through a comprehensive analysis of physiological parameters and transcriptomic profiles. Results demonstrated that the number of differentially expressed genes (DEGs) in EC_S1 was significantly higher than in RGT Planet, indicating that wild barley gene regulation is more adaptive to salt stress. KEGG enrichment analysis revealed that DEGs were mainly enriched in the processes of photosynthesis, plant hormone signal transduction, and reactive oxygen species metabolism. Furthermore, the application of weighted gene correlation network analysis (WGCNA) enabled the identification of a set of key genes, including small heat shock protein (sHSP), Calmodulin-like proteins (CML), and protein phosphatases 2C (PP2C). Subsequently, a novel sHSP gene, HvHSP16.9 encoding a protein of 16.9 kDa, was cloned from wild barley, and its role in plant response to salt stress was elucidated. In Arabidopsis, overexpression of HvHSP16.9 increased the salt tolerance. Meanwhile, barley stripe mosaic virus-induced gene silencing (BSMV-VIGS) of HvHSP16.9 significantly reduced the salt tolerance in wild barley. Overall, this study offers a new theoretical framework for comprehending the tolerance and adaptation mechanisms of wild barley under salt stress. It provides valuable insights into the salt tolerance function of HSP, and identifies new candidate genes for enhancing cultivated barley varieties. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01455-4.

Hollow magnetic vortex nanorings loaded with quercetin encapsulated in polydopamine: A high-performance, intelligent nanotheranostic platform for enhanced tumor imaging and dual thermal treatment.

Nanoparticle-mediated thermotherapeutic research strives innovative, multifunctional, efficient, and safe treatments. Our study introduces a novel nanoplatform: the hollow magnetic vortex nanorings within a polydopamine layer (HMVNp), which exhibit dual functionality as magnetic and photothermal agents. Utilizing a "Dual-mode" approach, combining an alternating magnetic field (AMF) with near-infrared (NIR) laser irradiation, HMVNp demonstrated a significant enhancement in heating efficacy (58 ± 8 %, SAR = 1441 vs 1032 W/g) over traditional solid magnetite nanoparticles coated with polydopamine (SMNp). The unique geometry larger surface area to volume ratio facilitates efficient magnetic vortex dynamics and enhanced heat transfer. Addressing the challenge of heat resistant heat shock protein (Hsp) expression, encapsulated quercetin (Q) within HMVNp leverages tumor acidity and dual-mode thermal therapy to enhance release, showing a 28.8 ± 6.81 % increase in Q loading capacity compared to traditional SMNp. Moreover, HMVNp significantly improves contrast for both magnetic resonance imaging (MRI) and photoacoustic imaging (PAI), with an approximately 62 % transverse relaxation (R2 = 81.5 vs 31.6 mM-1s-1 [Fe]). In vivo studies showed that while single treatments slowed tumor growth, dual-mode therapy with quercetin significantly reduced tumors and effectively prevented metastases. Our study highlights the potential of HMVNp/Q as a versatile agent in thermotherapeutic interventions, offering improved diagnostic imaging capabilities.

Marine algae-derived oligosaccharide via protein crotonylation of key targeting for management of type 2 diabetes mellitus in the elderly.

Global aging is a tendency of the world, as is the increasing prevalence of diabetes, and the two are closely linked. In our early research, Enteromorpha prolifera oligosaccharide (EPO) possesses the excellent ability of anti-oxidative, anti-inflammatory, and anti-diabetic. We aim to further explore the deeper mechanism of how EPO delays aging and regulates glycometabolism. EPO effectively impacts crotonylation procession to enhance glucose metabolism and reduce cell senescence in aging diabetic rats. Crotonylation modification of XPO1 influences the expression of critical genes, including p53, CDK1, and CCNB1, which affect cell cycle regulation and aging. Additionally, EPO improves glucose metabolism by inhibiting the crotonylation modification of HSPA8-K126 and activating the AKT pathway. EPO promotes crotonylation of histones in intestinal cells, influencing the aging process by increasing the butyric acid-producing bacteria Ruminococcaceae. The observed enhancement in pyrimidine metabolism underscores EPO's potential role in regulating intestinal health, presenting a promising avenue for delaying aging. In summary, our findings affirm EPO as a naturally bioactive ingredient with significant potential for anti-aging and antidiabetic interventions.

Ultrashort wave diathermy inhibits pulmonary inflammation in mice with acute lung injury in a HSP70 independent way: a pilot study.

BACKGROUND: Acute lung injury (ALI) is a clinical syndrome characterized by pulmonary inflammation. Ultrashort wave diathermy (USWD) has been shown to be effective at in inhibiting ALI inflammation, although the underlying mechanism remains unclear. Previous studies have demonstrated that USWD generates a therapeutic thermal environment that aligns with the temperature required for heat shock protein 70 (HSP70), an endogenous protective substance. In this study, we examined the correlation between HSP70 and USWD in alleviating lung inflammation in ALI. METHODS: Forty-eight male C57BL/6 mice were randomly divided into control, model, USWD intervention (LU) 1, 2, and 3, and USWD preintervention (UL) 1, 2, and 3 groups (n = 6 in each group). The mice were pretreated with LPS to induce ALI. The UL1, 2, and 3 groups received USWD treatment before LPS infusion, while the LU1, 2, and 3 groups received USWD treatment after LPS infusion. Lung function and structure, inflammatory factor levels and HSP70 protein expression levels were detected. RESULTS: USWD effectively improved lung structure and function, and significantly reduced IL-1ß, IL-10, TGF-ß1, and TNF-α levels in both the USWD preintervention and intervention groups. However, HSP70 expression did not significantly differ across the experimental groups although the expression of TLR4 was significantly decreased, suggesting that USWD may have anti-inflammatory effects through multiple signaling pathways or that the experimental conditions should be restricted. CONCLUSIONS: Both USWD intervention and preintervention effectively reduced the inflammatory response, alleviated lung injury symptoms, and played a protective role in LPS-pretreated ALI mice. HSP70 was potentially regulated by USWD in this process, but further studies are urgently needed to elucidate the correlation and mechanism.

Celastrol Regulates the Hsp90-NLRP3 Interaction to Alleviate Rheumatoid Arthritis.

Previous studies have verified that celastrol (Cel) protects against rheumatoid arthritis (RA) by inhibiting the NLRP3 inflammasome signaling pathway, but the molecular mechanism by which Cel regulates NLRP3 has not been clarified. This study explored the specific mechanisms of Cel in vitro and in vivo. A type II collagen-induced arthritis (CIA) mouse model was used to study the antiarthritic activity of Cel; analysis of paw swelling, determination of the arthritis score, and pathological examinations were performed. The antiproliferative and antimigratory effects of Cel on TNF-α induced fibroblast-like synoviocytes (FLSs) were tested. Proinflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB/NLRP3 pathway components was determined by western blotting and immunofluorescence staining in vitro and in vivo. The putative binding sites between Cel and Hsp90 were predicted through molecular docking, and the binding interactions were determined using the Octet RED96 system and coimmunoprecipitation. Cel decreased arthritis severity and reduced TNF-α-induced FLSs migration and proliferation. Additionally, Cel inhibited NF-κB/NLRP3 signaling pathway activation, reactive oxygen species (ROS) production, and proinflammatory cytokine secretion. Furthermore, Cel interacted directly with Hsp90 and blocked the interaction between Hsp90 and NLRP3 in FLSs. Our findings revealed that Cel regulates NLRP3 inflammasome signaling pathways both in vivo and in vitro. These effects are induced through FLSs inhibition of the proliferation and migration by blocking the interaction between Hsp90 and NLRP3.

Litopenaeus vannamei heat shock protein 90 (LvHSP90) interacts with white spot syndrome virus protein, WSSV322, to modulate hemocyte apoptosis during viral infection.

As cellular chaperones, heat shock protein can facilitate viral infection in different steps of infection process. Previously, we have shown that the suppression of Litopenaeus vannamei (Lv)HSP90 not only results in a decline of white spot syndrome virus (WSSV) infection but also induces apoptosis in shrimp hemocyte cells. However, the mechanism underlying how LvHSP90 involved in WSSV infection remains largely unknown. In this study, a yeast two-hybrid assay and co-immunoprecipitation revealed that LvHSP90 interacts with the viral protein WSSV322 which function as an anti-apoptosis protein. Recombinant protein (r) LvHSP90 and rWSSV322 inhibited cycloheximide-induced hemocyte cell apoptosis in vitro. Co-silencing of LvHSP90 and WSSV322 in WSSV-infected shrimp led to a decrease in expression level of viral replication marker genes (VP28, ie-1) and WSSV copy number, while caspase 3/7 activity was noticeably induced. The number of apoptotic cells, confirmed by Hoechst 33342 staining assay and annexin V/PI staining, was significantly higher in LvHSP90 and WSSV322 co-silenced-shrimp than the control groups. Moreover, the co-silencing of LvHSP90 and WSSV322 triggered apoptosis by the mitochondrial pathway, resulting in the upregulation of pro-apoptotic protein expression (bax) and the downregulation of anti-apoptotic protein expression (bcl, Akt). This process also involved the release of cytochrome c (CytC) from the mitochondria and a decrease in mitochondrial membrane potential (MMP). These findings suggest that LvHSP90 interacts with WSSV322 to facilitate viral replication by inhibiting host apoptosis during WSSV infection.