[Knockout of Hsp70 Genes Modulates Age-Related Transcriptomic Changes in Leg Muscles and Reduces the Locomotion Speed and Lifespan of Drosophila melanogaster].

This study investigated the effect of knockout of six Hsp70 genes (orthologues of the mammalian genes Hspa1a, Hspa1b, Hspa2, and Hspa8) on age-related changes in gene expression in the legs of Drosophila melanogaster, which contain predominantly skeletal muscle bundles. For this, the leg transcriptomic profile was examined in males of the w^(1118) control strain and the Hsp70^(-) strain on the 7th, 23rd and 47th days of life. In w^(1118) flies, an age-related decrease in the locomotion (climbing) speed (a marker of functional state and endurance) was accompanied by a pronounced change in the transcriptomic profile of the leg skeletal muscles, which is conservative in nature. In Hsp70^(-) flies, the median lifespan was shorter and the locomotion speed was significantly lower compared to the control; at the same time, complex changes in the age-related dynamics of the skeletal muscle transcriptome were observed. Mass spectrometry-based quantitative proteomics showed that 47-day-old Hsp70^(-) flies, compared with w^(1118) flies, demonstrated multidirectional changes in the contents of key enzymes of glucose metabolism and fat oxidation (glycolysis, pentose phosphate pathway, Krebs cycle, beta-oxidation, and oxidative phosphorylation). Such dysregulation may be associated with a compensatory increase in the expression of other genes encoding chaperones (small Hsp, Hsp40, 60, and 70), which regulate specific sets of target proteins. Taken together, our data show that knockout of six Hsp70 genes slightly reduced the median lifespan of flies, but significantly reduced the locomotion speed, which may be associated with complex changes in the transcriptome of the leg skeletal muscles and with multidirectional changes in the contents of key enzymes of energy metabolism.

Treatment with Tau fibrils impact Huntington's disease-related phenotypes in cell and mouse models.

There is now compelling evidence for the presence of pathological forms of Tau in tissues of both patients and animal models of Huntington's disease (HD). While the root cause of this illness is a mutation within the huntingtin gene, a number of studies now suggest that HD could also be considered a secondary tauopathy. However, the contributory role of Tau in the pathogenesis and pathophysiology of this condition, as well as its implications in cellular toxicity and consequent behavioral impairments are largely unknown. We therefore performed intracerebral stereotaxic injections of recombinant human Tau monomers and fibrils into the knock-in zQ175 mouse model of HD. Tau fibrils induced cognitive and anxiety-like phenotypes predominantly in zQ175 mice and increased the number and size of insoluble mutant huntingtin (mHTT) aggregates in the brains of treated animals. To better understand the putative mechanisms through which Tau could initiate and/or contribute to pathology, we incubated StHdh striatal cells, a cellular model of HD, with the different Tau forms and evaluated the effects on cell functionality and heat shock proteins Hsp70 and Hsp90. Calcium imaging experiments showed functional impairments of HD StHdh cells following treatment with Tau fibrils, as well as significant changes to the levels of both heat shock proteins which were found trapped within mHTT aggregates. The accumulation of Hsp70 and 90 within aggregates was also present in mouse tissue which suggests that alteration of molecular chaperone-dependent protein quality control may influence aggregation, implicating proteostasis in the mHTT-Tau interplay.

Evaluation of serum levels of heat shock protein 70 in patients with psoriasis in Basra, Iraq.

Introduction: Psoriasis is a chronic, non-infectious skin disease that affects people of all ages and has no sex preference, which is caused by environmental stressors involving skin cells, immunocytes, and several biologic signaling molecules. Psoriasis has been linked to psychological, metabolic, arthritic, and cardiovascular complications. Heat shock protein 70 (HSP70) is considered the most protective member of the HSP family. HSP70 can regulate protein homeostasis, minimize stress-induced denaturation and aggregation of intracellular proteins and operate as a protective factor in tissue damage. This study aimed to investigate the serum level of HSP70 in patients with psoriasis to assess whether there is an association of HSP70 with psoriasis and to assess the effects of age, gender, body mass index (BMI), waist circumference, and disease duration on the serum level of HSP70. Material and methods: This was a case-control study which recruited 98 patients with psoriasis and 81 apparently healthy age- and sex-matched individuals as controls. Blood samples were collected via venipuncture (5 ml) to estimate the HSP70, random blood sugar, liver enzymes, lipid profile, and complete blood count. Results: The results revealed that the level of HSP70 was significantly higher in psoriasis patients compared to the control group (p-value < 0.05). The level of HSP70 showed a significant association with gender, but a non-significant positive correlation with duration of psoriasis. The level of HSP70 showed a non-significant negative correlation with age, BMI and waist circumference. Conclusions: The study suggested that HSP70 may have a potential role in the pathophysiology of psoriasis and may help to explain the mechanisms behind the development and treatment of psoriatic lesions with different severity.

Differences in transcriptomic responses upon Phytophthora palmivora infection among cultivars reveal potential underlying resistant mechanisms in durian.

BACKGROUND: Phytophthora palmivora is a devastating oomycete pathogen in durian, one of the most economically important crops in Southeast Asia. The use of fungicides in Phytophthora management may not be a long-term solution because of emerging chemical resistance issues. It is crucial to develop Phytophthora-resistant durian cultivars, and information regarding the underlying resistance mechanisms is valuable for smart breeding programs. RESULTS: In this study, we conducted RNA sequencing (RNA-seq) to investigate early gene expression responses (at 8, 24, and 48 h) after the P. palmivora infection in three durian cultivars, which included one resistant cultivar (Puangmanee; PM) and two susceptible cultivars (Monthong; MT and Kradumthong; KD). We performed co-expression and differential gene expression analyses to capture gene expression patterns and identify the differentially expressed genes. The results showed that genes encoding heat shock proteins (HSPs) were upregulated in all infected durians. The expression levels of genes encoding HSPs, such as ERdj3B, were high only in infected PM. A higher level of P. palmivora resistance in PM appeared to be associated with higher expression levels of various genes encoding defense and chitin response proteins, such as lysM domain receptor-like kinases. MT had a lower resistance level than PM, although it possessed more upregulated genes during P. palmivora infection. Many photosynthetic and defense genes were upregulated in the infected MT, although their expression levels were lower than those in the infected PM. KD, the least resistant cultivar, showed downregulation of genes involved in cell wall organization or biogenesis during P. palmivora infection. CONCLUSIONS: Our results showed that the three durian cultivars exhibited significantly different gene expression patterns in response to P. palmivora infection. The upregulation of genes encoding HSPs was common in all studied durians. The high expression of genes encoding chitin response proteins likely contributed to P. palmivora resistance in durians. Durian susceptibility was associated with low basal expression of defense genes and downregulation of several cell wall-related genes. These findings enhance our understanding of durian resistance to Phytophthora infection and could be useful for the development of elite durian cultivars.

The molecular impact of sonoporation: A transcriptomic analysis of gene regulation profile.

Sonoporation has long been known to disrupt intracellular signaling, yet the involved molecules and pathways have not been identified with clarity. In this study, we employed whole transcriptome shotgun sequencing (RNA-seq) to profile sonoporation-induced gene responses after membrane resealing has taken place. Sonoporation was achieved by microbubble-mediated ultrasound (MB-US) exposure in the form of 1 MHz ultrasound pulsing (0.50 MPa peak negative pressure, 10 % duty cycle, 30 s exposure period) in the presence of microbubbles (1:1 cell-to-bubble ratio). Using propidium iodide (PI) and calcein respectively as cell viability and cytoplasmic uptake labels, post-exposure flow cytometry was performed to identify three viable cell populations: 1) unsonoporated cells, 2) sonoporated cells with low uptake, and 3) sonoporated cells with high uptake. Fluorescence-activated cell sorting was then conducted to separate the different groups followed by RNA-seq analysis of the gene expressions in each group of cells. We found that sonoporated cells with low or high calcein uptake showed high similarity in the gene responses, including the activation of multiple heat shock protein (HSP) genes and immediate early response genes mediating apoptosis and transcriptional regulation. In contrast, unsonoporated cells exhibited a more extensive gene expression alteration that included the activation of more HSP genes and the upregulation of diverse apoptotic mediators. Four oxidative stress-related and three immune-related genes were also differentially expressed in unsonoporated cells. Our results provided new information for understanding the intracellular mobilization in response to sonoporation at the molecular level, including the identification of new molecules in the sonoporation-induced apoptosis regulatory network. Our data also shed light on the innovative therapeutic strategy which could potentially leverage the responses of viable unsonoporated cells as a synergistic effector in the microenvironment to favor tumor treatment.

Heat shock responsive genes in Brassicaceae: genome-wide identification, phylogeny, and evolutionary associations within and between genera.

Heat stress affects the growth and development of Brassicaceae crops. Plant breeders aim to mitigate the effects of heat stress by selecting for heat stress tolerance, but the genes responsible for heat stress in Brassicaceae remain largely unknown. During heat stress, heat shock proteins (HSPs) function as molecular chaperones to aid in protein folding, and heat shock transcription factors (HSFs) serve as transcriptional regulators of HSP expression. We identified 5002 heat shock related genes, including HSPs and HSFs, across 32 genomes in Brassicaceae. Among these, 3347 genes were duplicated, with segmented duplication primarily contributing to their expansion. We identified 466 physical gene clusters, including 240 homogenous clusters and 226 heterogeneous clusters, shedding light on the organization of heat shock related genes. Notably, 37 genes were co-located with published thermotolerance quantitative trait loci, which supports their functional role in conferring heat stress tolerance. This study provides a comprehensive resource for the identification of functional Brassicaceae heat shock related genes, elucidates their clustering and duplication patterns and establishes the genomic foundation for future heat tolerance research. We hypothesise that genetic variants in HSP and HSF genes in certain species have potential for improving heat stress tolerance in Brassicaceae crops.

Precision Photothermal Therapy at Mild Temperature: NIR-II Imaging-Guided, H2O2-Responsive Stealth Nanobomb.

The therapeutic efficacy of photothermal therapy (PTT) under mild temperatures (<45 °C) is hindered as cancer cells can activate heat shock proteins (HSPs) to mend fever-type cellular damage swiftly. The previous attempt fabricated first-generation nanobombs (nanobomb1G) by self-assembly of polymeric NIR-II AIEgens and carbon monoxide (CO) carrier polymer mPEG(CO) to inhibit the expression of HSPs after intratumor injection. A new generation nanobomb (Stealth NanoBomb (SNB)) is developed by self-assembling small molecular NIR-II AIEgens with CO carrier polymer PLGA(CO) coated by PEG-lipid. This design allows for intravenous administration, enabling the SNB to circulate safely in the bloodstream and selectively target cancer cells. Upon accumulation in tumors, the SNB releases CO to effectively suppress HSP expression, enhancing the therapeutic efficacy of mild-temperature PTT. Compared to the previous generation, the SNB offers a safer, more stable, and more efficient CO gas/drug co-delivery system for cancer treatment. This work represents a significant advancement in PTT, providing a promising strategy for enhanced antitumor therapy with reduced systemic toxicity.

The role of heat shock proteins in HIV-1 pathogenesis: a systematic review investigating HSPs-HIV-1 correlations and interactions.

Background: The human immunodeficiency virus (HIV) pandemic is a global health emergency. Studies suggest a connection between heat shock proteins (HSPs) and HIV-1 infection pathogenesis. This systematic review aims to summarize HSPs' role in HIV-1 infection pathogenesis. Materials and Methods: A systematic literature search was undertaken across the National Library of Medicine (MEDLINE-PubMed), Science Direct, Web of Science, Scopus, SpringerLink, Sage, ProQuest, and Google Scholar databases, using related keywords to synthesize the HSPs' role in HIV-1 infection pathogenesis. This literature review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the protocol was registered in the Open Science Framework (OSF) database under DOI 10.17605/OSF.IO/VK3DJ. Results: A database search revealed 3,332 articles, with 14 in vitro studies analysing the interaction between HSPs and HIV-1 across different cell types. HSPs are involved in HIV-1 infection through direct interactions and indirect responses to cellular stress, including HSP40, HSP70, HSPBP1, and HSP90. The study explores HSP interactions at various stages of the viral life cycle, including entry, uncoating, replication, transmission, and latency reactivation. Conclusion: HSPs are crucial for the HIV lifecycle and immune response, offering the potential for new therapeutic strategies. Further research is needed to understand the clinical significance and target potential.

Facile Synthesis of Fe-Based Metal-Quinone Networks for Mutually Enhanced Mild Photothermal Therapy and Ferroptosis.

Mild photothermal therapy (MPTT) has emerged as a promising therapeutic modality for attenuating thermal damage to the normal tissues surrounding tumors, while the heat-induced upregulation of heat shock proteins (HSPs) greatly compromises the curative efficacy of MPTT by increasing cellular thermo-tolerance. Ferroptosis has been identified to suppress the overexpression of HSPs by the accumulation of lipid peroxides and reactive oxygen species (ROS), but is greatly restricted by overexpressed glutathione (GSH) in tumor microenvironment and undesirable ROS generation efficiency. Herein, a synergistic strategy based on the mutual enhancement of MPTT and ferroptosis is proposed for cleaving HSPs to recover tumor cell sensitivity. A facile method for fabricating a series of Fe-based metal-quinone networks (MQNs) by coordinated assembly is proposed and the representative FTP MQNs possess high photothermal conversion efficiency (69.3%). Upon 808 nm laser irradiation, FTP MQNs not only trigger effective MPTT to induce apoptosis but more significantly, potentiate Fenton reaction and marked GSH consumption to boost ferroptosis, and the reinforced ferroptosis effect in turn can alleviate the thermal resistance by declining the HSP70 defense and reducing ATP levels. This study provides a valuable rationale for constructing a large library of MQNs for achieving mutual enhancement of MPTT and ferroptosis.

Hormetic and transcriptomic responses of the toxic alga Prymnesium parvum to glyphosate.

Growth of the toxic alga Prymnesium parvum is hormetically stimulated with environmentally relevant concentrations of glyphosate. The mechanisms of glyphosate hormesis in this species, however, are unknown. We evaluated the transcriptomic response of P. parvum to glyphosate at concentrations that stimulate maximum growth and where growth is not different from control values, the zero-equivalent point (ZEP). Maximum growth occurred at 0.1 mg l-1 and the ZEP was 2 mg l-1. At 0.1 mg l-1, upregulated transcripts outnumbered downregulated transcripts by one order of magnitude. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that the upregulated transcriptome is primarily associated with metabolism and biosynthesis. Transcripts encoding heat shock proteins and co-chaperones were among the most strongly upregulated, and several others were associated with translation, Redox homeostasis, cell replication, and photosynthesis. Although most of the same transcripts were also upregulated at concentrations ≥ZEP, the proportion of downregulated transcripts greatly increased as glyphosate concentrations increased. At the ZEP, downregulated transcripts were associated with photosynthesis, cell replication, and anion transport, indicating that specific interference with these processes is responsible for the nullification of hormetic growth. Transcripts encoding the herbicidal target of glyphosate, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), were upregulated at concentrations ≥ZEP but not at 0.1 mg l-1, indicating that disruption of EPSPS activity occurred at high concentrations and that nullification of hormetic growth involves the direct interaction of glyphosate with this enzyme. Results of this study may contribute to a better understanding of glyphosate hormesis and of anthropogenic factors that influence P. parvum biogeography and bloom formation.

LrHSP17.2 Plays an Important Role in Abiotic Stress Responses by Regulating ROS Scavenging and Stress-Related Genes in Lilium regale.

As an important part of heat shock response module, heat shock proteins (HSP) play an important role in plant defense response against heat stress; however, the involvement of the majority of the HSP family members against other abiotic stresses remains poorly understood. In the present study, LrHSP17.2 was identified and its function against abiotic stress was analyzed. The expression level of LrHSP17.2 was significantly induced by heat. Heterologous transgenes of LrHSP17.2 showed that LrHSP17.2 can increase the activity of catalase, peroxidase, superoxide dismutase to removes excess reactive oxygen species (ROS), maintain the stability of the membrane structure, and regulate genes related to antioxidant enzymes and defense under abiotic stress. In addition, LrHSP17.2 could be regulated by exogenous abscisic acid and melatonin, and the related hormone synthesis genes of transgenic plants were significantly up-regulated under heat stress. Taken together, our results revealed that LrHSP17.2 is involved in regulating abiotic stress responses by regulating ROS scavenging and stress-related genes in Lilium regale.

One-Pot Synthesis of a pH-Sensitive MOF Integrated with Glucose Oxidase for Amplified Tumor Photodynamic/Photothermal Therapy.

Photothermal therapy (PTT) and photodynamic therapy (PDT) provide targeted approaches to cancer treatment, but each therapy has inherent limitations such as insufficient tissue penetration, uneven heat distribution, extreme hypoxia, and overexpressed HSP90 in tumor cells. To address these issues, herein, by encapsulating the IR780 dye and glucose oxidase (GOx) enzyme within ZIF-8 nanoparticles, we created a versatile system capable of combining photodynamic and enhanced photothermal therapy. The integration of the IR780 dye facilitated the generation of reactive oxygen species and hyperthermia upon light activation, enabling dual-mode cancer cell ablation. Moreover, GOx catalyzes the decomposition of glucose into gluconic acid and hydrogen peroxide, leading to the inhibition of ATP production and downregulation of heat shock protein 90 (HSP90) expression, sensitizing cancer cells to heat-induced cytotoxicity. This synergistic combination resulted in significantly improved therapeutic outcomes. Both in vitro and in vivo results validated that the nanoplatform demonstrated superior specificity and favorable therapeutic responses. Our innovative approach represents a promising strategy for overcoming current limitations in cancer treatments and offers the potential for clinical translation in the future.

Partitioned Microneedle Patch Based on NO Release and HSP Inhibition for mPTT/GT Combination Treatment of Melanoma.

Photothermal therapy (PTT) shows promise in cancer treatments due to its good spatiotemporal selectivity and minimal invasiveness. However, PTT has some problems such as excessive heat damage to normal tissues, tumor thermo-resistance caused by heat shock proteins (HSPs), and limited efficacy of monotherapy. Here, we construct a patch named "partitioned microneedles" (PMN-SNAP/CuS), which separates the "catalyst" bovine serum albumin-based copper sulfide nanoparticles (CuS@BSA NPs) and the "reactant" S-nitroso-N-acetylpenicillamine (SNAP) into different regions of microneedles, for enhancing mild PTT (mPTT) of melanoma. PMN-SNAP/CuS showed an excellent photothermal effect, Fenton-like catalytic activity, and nitric oxide (NO) generation ability. The combination of NO and reactive oxygen species (ROS) produced by PMN-SNAP/CuS effectively blocked the synthesis of HSPs at the source and enhanced the efficacy of mPTT. Both in vitro and in vivo results proved that PMN-SNAP/CuS significantly enhanced the inhibition of melanoma under 808 nm laser irradiation. In conclusion, our partitioned microneedle strategy based on the combination of enhanced mPTT and gas therapy (GT) provides a promising approach to enhance the therapeutic effect on melanoma.

Progressive Thickening of Retinal Nerve Fiber and Ganglion Cell Complex Layers Following SDM Laser Vision Protection Therapy in Open-Angle Glaucoma.

INTRODUCTION: This work aims to determine the effect on nerve fiber layer (NFL) and ganglion cell complex (GCC) thickness trends in eyes with open-angle glaucoma (OAG) treated with Vision Protection Therapy™ (VPT). METHODS: A retrospective analysis of spectral-domain optical coherence tomography (OCT) measured NFL and GCC thickness trends was performed, excluding eyes with poor-quality scans and principal diagnoses other than OAG. This study compares eyes with OAG managed conventionally with IOP control alone (controls) to eyes managed with the addition of VPT (VPT eyes). The direction (+ or -) and magnitude (microns/year) of the OCT trends were the study endpoints. RESULTS: Seventy-eight control eyes of 40 patients and 61 VPT-treated eyes of 39 patients were included in the study. Positive NFL trends were noted in 5% of control eyes vs. 71% of VPT eyes (p < 0.0001). Positive GCC trends were noted in 8% of control eyes vs. 43% of VPT eyes (p < 0.0001). Mean NFL trends (µm/year) were - 0.692 for controls vs. 0.347 for VPT (p < 0.0001). Mean GCC trends (µm/year) were - 0.554 for controls vs. - 0.148 for VPT (p = 0.0175). CONCLUSIONS: The addition of VPT to the conventional management of OAG resulted in highly significant improvements in NFL and GCC trends, indicating a reversal of key indicators of glaucoma severity and progression.

Electrical stimulation to improve meat quality: Factors at interplay, underlying biochemical mechanisms and a second look into the molecular pathways using proteomics.

Ensuring consistent beef eating quality is paramount for meeting consumer demands and sustaining the meat industry. Electrical stimulation (ES) is a post-slaughter intervention used to accelerate post-mortem glycolysis, to avoid cold shortening, to control the tenderization rate of meat through sophisticated physical, chemical and biochemical mechanisms including proteolysis, to improve beef tenderness and to achieve normal pHu that might lead to positive impact on color. This review comprehensively examines the multifaceted effects of ES on beef quality, encompassing factors and settings influencing its efficacy and the underlying biochemical mechanisms revealed using traditional biochemistry methods. It then delves into the molecular pathways modulated by ES, as unveiled by muscle proteomics, aiming to provide a second look and an unprecedented understanding of the underlying biochemical mechanisms through an integrative proteomics analysis of low-voltage ES (LVES) proteomics studies. The proteins changing as a result of ES were gathered in a compendium of 67 proteins, from which 14 were commonly identified across studies. In-depth bioinformatics of this compendium allowed a comprehensive overview of the molecular signatures and interacting biochemical pathways behind electrically stimulated beef muscles. The proteins belong to interconnected molecular pathways including the ATP metabolic process and glycolysis, muscle structure and contraction, heat shock proteins, oxidative stress, proteolysis and apoptosis. Understanding the intricate interplay of molecular pathways behind ES could improve the efficiency of beef production, ensuring consistent meat quality and meeting consumer expectations. The integrative analysis approach performed in this study holds promise for the meat industry's sustainability and competitiveness.

Expression of Heat Shock Protein 90 in Testicular Cancer: A Retrospective Cohort Study.

BACKGROUND: The HSP90 marker is believed to play a constructive role in facilitating neoplastic transformation mainly via interaction with multiple pro-survival proteins. Welldesigned studies are needed to elucidate the role of HSP90 as a diagnostic marker and therapeutic target in testicular tumors. OBJECTIVE: The current study aimed to investigate the expression of HSP90 in various types of testicular cancer and highlight its expression in embryonal testicular cancer. MATERIAL AND METHODS: Immunohistochemical staining for HSP90 in 84 male patients, with nonmetastatic testicular cancer, who underwent orchiectomy from 2000 to 2023, was retrospectively performed at the Laboratory Department of General Hospital of Nikaia in Greece. RESULTS: A total of 84 males, with a mean age of 36.2 years, who have undergone high-cord radical orchiectomy, were included in this study. Out of the included males, 28.57% had embryonal carcinoma, 23.81% had seminoma, 19.05% had yolk sac tumor, 11.9% had mature teratoma, 9.52% had immature teratoma, and 7.14% had choriocarcinoma. HSP90b was positive in all embryonal carcinoma, seminoma, and choriocarcinoma cases, while it was positive in 75% of the yolk sac tumor, 75% of mature teratoma, and 75% of immature teratoma specimens. HSP90 was found negative in all choriocarcinoma, mature teratoma, and immature teratoma specimens, while it was positive in 25% of yolk sac tumor, 8.33% of embryonal carcinoma, and 10% of seminoma cases. Concerning the expression of HSP90b, a statistically significant relationship was found between excised tumor specimens and normal parenchyma specimens, especially in sac cases (p <0.001). Regarding HSP90a expression, a statistically significant relationship (OR=21.5, p =0.021) was found between excised tumor specimens and normal parenchyma specimens, especially in embryonal carcinoma cases (p <0.001). CONCLUSION: HSP90b is highly expressed in the majority of the types of testicular tumors, both in tumor and normal parenchyma specimens, while HSP90a staining is negative in resected specimens. Further well-designed studies are needed to elucidate the role of HSP90 as a diagnostic marker and therapeutic target in testicular tumors.

Vanadium Toxicity Is Altered by Global Warming Conditions in Sea Urchin Embryos: Metal Bioaccumulation, Cell Stress Response and Apoptosis.

In recent decades, the global vanadium (V) industry has been steadily growing, together with interest in the potential use of V compounds as therapeutics, leading to V release in the marine environment and making it an emerging pollutant. Since climate change can amplify the sensitivity of marine organisms already facing chemical contamination in coastal areas, here, for the first time, we investigated the combined impact of V and global warming conditions on the development of Paracentrotus lividus sea urchin embryos. Embryo-larval bioassays were carried out in embryos exposed for 24 and 48 h to sodium orthovanadate (Na3VO4) under conditions of near-future ocean warming projections (+3 °C, 21 °C) and of extreme warming at present-day marine heatwave conditions (+6 °C, 24 °C), compared to the control temperature (18 °C). We found that the concomitant exposure to V and higher temperature caused an increased percentage of malformations, impaired skeleton growth, the induction of heat shock protein (HSP)-mediated cell stress response and the activation of apoptosis. We also found a time- and temperature-dependent increase in V bioaccumulation, with a concomitant reduction in intracellular calcium ions (Ca2+). This work demonstrates that embryos' sensitivity to V pollution is increased under global warming conditions, highlighting the need for studies on multiple stressors.

Catchers of folding gone awry: a tale of small heat shock proteins.

Small heat shock proteins (sHsps) are an important part of the cellular system maintaining protein homeostasis under physiological and stress conditions. As molecular chaperones, they form complexes with different non-native proteins in an ATP-independent manner. Many sHsps populate ensembles of energetically similar but different-sized oligomers. Regulation of chaperone activity occurs by changing the equilibrium of these ensembles. This makes sHsps a versatile and adaptive system for trapping non-native proteins in complexes, allowing recycling with the help of ATP-dependent chaperones. In this review, we discuss progress in our understanding of the structural principles of sHsp oligomers and their functional principles, as well as their roles in aging and eye lens transparency.

Multi-responsive cascade enzyme-like catalytic nanoassembly for ferroptosis amplification and nanozyme-assisted mild photothermal therapy.

Ferroptosis is greatly restricted by low reactive oxygen species (ROS) generation efficiency, and the inherent self-protection mechanism originating in heat shock proteins (HSPs) seriously impedes the efficiency of photothermal therapy (PTT). Herein, we designed an intelligent strategy utilizing cascade catalytic nanoassemblies (Au@COF@MnO2) with triple-enzyme activity for amplifying ferroptosis therapy and improving the efficiency of PTT in tumor. Gold nanozyme was encapsulated within a hollow manganese dioxide (MnO2) shell with the help of covalent organic frameworks (COFs). The nanoassemblies possess the ability of photothermal conversion. Mechanism studies suggested that glutathione (GSH) depletion by Au@COF@MnO2 leads to the inactivation of glutathione peroxidase 4 (GPX4). This effect synergized with Mn2+-mediated reactive oxygen species (ROS) generation to enhance the accumulation of lipid peroxide (LPO), thereby inducing high-efficiency ferroptosis. Notably, gold nanozyme facilitated the conversion of glucose into gluconic acid and hydrogen peroxide (H2O2). This process augmented the endogenous H2O2 levels necessary for Fenton chemistry, which could effectively promote the generation of ROS. Simultaneously, glucose depletion downregulated the expression of HSPs induced by hyperthermia, consequently reducing cellular heat resistance for enhancing PTT. Therefore, the cascade catalytic nanoassembly not only exhibits high tumor inhibition and admirable biosafety, but also possesses trimodal imaging performance for imaging-guided tumor therapy in vivo, holding great potential for clinical application. STATEMENT OF SIGNIFICANCE: This study engineered multi-responsive cascade catalytic nanoassembly (Au@COF@MnO2) with triple enzymatic functions for amplifying ferroptosis therapy and improving the efficiency of PTT in tumor. The nanoassembly exhibited multi-responsive release and great photothermal conversion performance. Glucose consumption-evoked starvation downregulated the hyperthermia-induced expression of HSPs in tumor cells, thereby improving the efficacy of PTT. Mechanism studies suggested that GSH depletion by Au@COF@MnO2 lead to the inactivation of GPX4, which synergized with Mn2+-mediated ROS generation to bolster the accumulation of LPO, thereby inducing high-efficiency ferroptosis. Moreover, the nanoassembly demonstrated trimodal (PT, PA, and MR) imaging in vivo, enabling the visualization of the tumor treatment with nanoassembly. Such nanoassembly exhibited high tumor inhibition and admirable biosafety in tumor therapy in vivo, holding a great potential for clinical application.