RESUMEN

Astragaloside IV(AS-IV), the main active ingredient of Astragalus, has been used as a treatment for heart failure with favorable effects, but its molecular mechanism has not been fully elucidated. Network pharmacological analysis and molecular docking revealed that Heat shock transcription factor 1 (HSF1) is a potential target of AS-IV. We designed cellular and animal experiments to investigate the role and intrinsic molecular mechanisms of AS-IV in ameliorating pressure overload-induced heart failure. In cellular experiments, Myocardial microvascular endothelial cells (MMVECs) were cultured in isolation and stimulated by adding high and low concentrations of AS-IV, and a cell model with down-regulation of HSF1 expression was constructed by using siRNA technology. Changes in the expression of key molecules of HSF1/VEGF signaling pathway and differences in tube-forming ability were detected in different groups of cells using PCR, WB and tube-forming assay. In animal experiments, TAC technology was applied to establish a pressure overload-induced heart failure model in C57 mice, postoperative mice were ingested AS-IV by gavage, and adenoviral transfection technology was applied to construct a mouse model with down-regulation of HSF1 expression.Small animal ultrasound for cardiac function assessment, MASSON staining, CD31 immunohistochemistry, and Western blotting (WB) were performed on the mice. The results showed that AS-IV could promote the expression of key molecules of HSF1/VEGF signaling pathway, enhance the tube-forming ability of MMVECs, increase the density of myocardial capillaries, reduce myocardial fibrosis, and improve the cardiac function of mice with TAC.AS-IV could modulate the HSF1/VEGF signaling pathway to promote the angiogenesis and improve the pressure overload-induced heart failure.

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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.

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Non-tuberculous mycobacteria (NTM) are among the most important pathogens in wild, captive, marine, and freshwater fish species. So, it is important to consider fish as the primary source of infection for aquarium fish and humans. The present study analyzed the occurrence of NTM in aquarium fish in Ilam, west of Iran. In total, 50 samples of infected fish were collected from different aquariums. Following initial sample processing, sediment of each sample was inoculated into Lowenstein-Jensen and Herrold egg media. The positive colonies were investigated with, growth rate, pigmentation, colony morphology, niacin accumulation, nitrate reduction, catalase activity, urease activity, and arylsulfatase activity. Also, molecular identification was carried out by sequencing of heat shock protein 65 kD gene (hsp65) sequence analysis. According to our results, NTM were isolated from 13 samples (26%), comprising 6 (46.2%) rapid growing, and 7 (53.8%) slow growing mycobacteria. In addition, Mycobacterium marinum was the most common NTM isolated in ornamental fish, which is potentially dangerous for both fish and humans. In conclusion, the current study indicates that ornamental fish play a significant role as a source of NTM.

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BACKGROUND: Glioblastoma (GBM) poses a significant medical challenge due to its aggressive nature and poor prognosis. Mitochondrial unfolded protein response (UPRmt) and the heat shock factor 1 (HSF1) pathway play crucial roles in GBM pathogenesis. Post-translational modifications, such as SUMOylation, regulate the mechanism of action of HSF1 and may influence the progression of GBM. Understanding the interplay between SUMOylation-modified HSF1 and GBM pathophysiology is essential for developing targeted therapies. METHODS: We conducted a comprehensive investigation using cellular, molecular, and in vivo techniques. Cell culture experiments involved establishing stable cell lines, protein extraction, Western blotting, co-immunoprecipitation, and immunofluorescence analysis. Mass spectrometry was utilized for protein interaction studies. Computational modeling techniques were employed for protein structure analysis. Plasmid construction and lentiviral transfection facilitated the manipulation of HSF1 SUMOylation. In vivo studies employed xenograft models for tumor growth assessment. RESULTS: Our research findings indicate that HSF1 primarily undergoes SUMOylation at the lysine residue K298, enhancing its nuclear translocation, stability, and downstream heat shock protein expression, while having no effect on its trimer conformation. SUMOylated HSF1 promoted the UPRmt pathway, leading to increased GBM cell proliferation, migration, invasion, and reduced apoptosis. In vivo studies have confirmed that SUMOylation of HSF1 enhances its oncogenic effect in promoting tumor growth in GBM xenograft models. CONCLUSION: This study elucidates the significance of SUMOylation modification of HSF1 in driving GBM progression. Targeting SUMOylated HSF1 may offer a novel therapeutic approach for GBM treatment. Further investigation into the specific molecular mechanisms influenced by SUMOylated HSF1 is warranted for the development of effective targeted therapies to improve outcomes for GBM patients.

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Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disorder marked by vascular remodeling, which is linked to the malignant phenotypes of pulmonary vascular cells. The prevailing therapeutic approaches for PAH tend to neglect the potential role of vascular remodeling, leading to the clinical prognosis remains poor. Previously, we first demonstrated that heat shock protein (Hsp110) was significantly activated to boost Hsp110-STAT3 interaction, which resulted in abnormal proliferation and migration of human pulmonary arterial endothelial cells (HPAECs) under hypoxia. In the present study, we initially postulated the allosteric site of Hsp110, performed a virtual screening and biological evaluation studies to discover novel Hsp110-STAT3 interaction inhibitors. Here, we identified compound 29 (AN-329/43448068) as the effective inhibitor of HPAECs proliferation and the Hsp110-STAT3 association with good druggability. In vitro, 29 significantly impeded the chaperone function of Hsp110 and the malignant phenotypes of HPAECs. In vivo, 29 remarkably attenuated pulmonary vascular remodeling and right ventricular hypertrophy in hypoxia-induced PAH rats (i.g). Altogether, our data support the conclusion that it not only provides a novel lead compound but also presents a promising approach for subsequent inhibitor development targeting Hsp110-STAT3 interaction.

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Stenothermal Antarctic notothenioid fishes are noteworthy for their history of isolation in extreme cold and their corresponding lack of the canonical heat shock response. Despite extensive transcriptomic studies, the mechanistic basis for stenothermy has not been fully elucidated. Given that the proteome better represents an organism's physiology, the possibility exists that some aspects of stenothermy arise post-transcriptionally. Here, Antarctic emerald rockcod (Trematomus bernacchii) were sampled after exposure to chronic and/or acute high temperatures, followed by thorough assessment of proteomic responses in brain, gill, and kidney. Few cellular stress response proteins were induced, and overall responses were modest in terms of numbers of differentially expressed proteins and their fold changes. Inconsistencies in protein induction across treatments and tissues are suggestive of dysregulation, rather than an adaptive response. Changes in regulation of the translational machinery in Antarctic notothenioids could explain these patterns. Some components of translational regulatory pathways are highly conserved (e.g., Ser-52 of eIF2α), but proteins comprising the cellular "integrative stress response" - specifically, the eIF2α kinases GCN2 and PERK - may have evolved along different trajectories in Antarctic fishes. Taken together, these observations suggest a novel hypothesis for stenothermy and the absence of a coordinated cellular stress response in Antarctic fishes.

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Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis. The pivotal roles of heat shock proteins in modulating the hallmarks of cancer through the activation or inhibition of various signaling pathways has been well documented. Therefore, this review provides an overview of the roles of heat shock proteins in vital biological processes from the perspective of the hallmarks of cancer and summarizes the small-molecule inhibitors that target heat shock proteins to regulate various cancer hallmarks. Moreover, we further discuss combination therapy strategies involving heat shock proteins and promising dual-target inhibitors to highlight the potential of targeting heat shock proteins for cancer treatment. In summary, this review highlights how targeting heat shock proteins could regulate the hallmarks of cancer, which will provide valuable information to better elucidate and understand the roles of heat shock proteins in oncology and the mechanisms of cancer occurrence and development and aid in the development of more efficacious and less toxic novel anticancer agents.

Asunto(s)

Proteínas de Choque Térmico , Neoplasias , Humanos , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/antagonistas & inhibidores , Proteínas de Choque Térmico/fisiología , Animales , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Transducción de Señal , Neovascularización Patológica/metabolismo , Terapia Molecular Dirigida/métodos

RESUMEN

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.

Asunto(s)

Glucosa Oxidasa , Estructuras Metalorgánicas , Fotoquimioterapia , Terapia Fototérmica , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Humanos , Animales , Ratones , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/síntesis química , Concentración de Iones de Hidrógeno , Indoles/química , Indoles/farmacología , Línea Celular Tumoral , Nanopartículas/química , Ratones Endogámicos BALB C , Especies Reactivas de Oxígeno/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/patología , Ratones Desnudos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Imidazoles

RESUMEN

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.

Asunto(s)

Cobre , Melanoma , Óxido Nítrico , Terapia Fototérmica , Animales , Óxido Nítrico/metabolismo , Cobre/química , Cobre/farmacología , Ratones , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/metabolismo , Melanoma/terapia , Agujas , Línea Celular Tumoral , Albúmina Sérica Bovina/química , S-Nitroso-N-Acetilpenicilamina/química , S-Nitroso-N-Acetilpenicilamina/farmacología , Humanos , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Nuclear transport is the basis for the biological reaction of eukaryotic cells, as it is essential to coordinate nuclear and cytoplasmic events separated by nuclear envelope. Although we currently understand the basic molecular mechanisms of nuclear transport in detail, many unexplored areas remain. For example, it is believed that the regulations and biological functions of the nuclear transport receptors (NTRs) highlights the significance of the transport pathways in physiological contexts. However, physiological significance of multiple parallel transport pathways consisting of more than 20 NTRs is still poorly understood, because our knowledge of each pathway, regarding their substrate information or how they are differently regulated, is still limited. In this report, we describe studies showing how nuclear transport systems in general are affected by temperature rises, namely, thermal stress or heat stress. We will then focus on Importin α family members and unique transport factor Hikeshi, because these two NTRs are affected in heat stress. Our present review will provide an additional view to point out the importance of diversity of the nuclear transport pathways in eukaryotic cells.

Asunto(s)

Transporte Activo de Núcleo Celular , Respuesta al Choque Térmico , Humanos , Respuesta al Choque Térmico/fisiología , Animales , Núcleo Celular/metabolismo , alfa Carioferinas/metabolismo , alfa Carioferinas/genética

RESUMEN

Almost all types of cellular stress induce post-translational O-GlcNAc modifications of proteins, and this increase promotes cell survival. We previously demonstrated that O-GlcNAc on certain small heat shock proteins (sHSPs), including HSP27, directly increases their chaperone activity as one potential protective mechanism. Here, we furthered our use of synthetic proteins to prepare biotinylated sHSPs and show that O-GlcNAc modification of HSP27 also changes how it interacts within the sHSP system and the broader HSP network. Specifically, we show that O-GlcNAc modified HSP27 binds more strongly to the co-chaperone protein BAG3, which then promotes refolding of a model substrate by HSP70. We use proteomics to identify other potential HSP27 interactions that are changed by O-GlcNAc, including one that we confirm with another sHSP, αB-crystallin. These findings add additional evidence for O-GlcNAc as a switch for regulating protein-protein interactions and for modifications of chaperones as one mechanism by which O-GlcNAc protects against protein aggregation.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales , Proteínas Reguladoras de la Apoptosis , Chaperonas Moleculares , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/química , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/química , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/química , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP27/química , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/química , Acetilglucosamina/metabolismo , Acetilglucosamina/química , Replegamiento Proteico , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/química , Unión Proteica , Cadena B de alfa-Cristalina/química , Cadena B de alfa-Cristalina/metabolismo , Procesamiento Proteico-Postraduccional

RESUMEN

Escherichia coli small heat-shock protein IbpB (MW: 16 KDa) has holding chaperone activity and is present in cells at 30 °C as two large oligomers of MW 2.0-3.0 MDa and 600-700 KDa. We report here about the presence of two additional oligomers of MW around 400 and 130 KDa in cells under heat-stress at 50 °C. These two smaller oligomers possess the most chaperone activity, as observed from the extent of inhibition of inactivation and aggregation separately, of L-Lactate dehydrogenase in the presence of the individual oligomers at 52 and 60 °C, respectively. It is suggested here that the two larger oligomers act as poorly active storage forms, which under heat stress dissociate partially into smaller oligomers with high holdase activity.

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Gametogenesis involves active protein synthesis and is proposed to rely on proteostasis. Our previous work in C. elegans indicates that germline development requires coordinated activities of insulin/IGF-1 signaling (IIS) and HSF-1, the central regulator of the heat shock response. However, the downstream mechanisms were not identified. Here, we show that depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, reduced fecundity and gamete quality. Conversely, reduced IIS confers germ cell resilience to HSF-1 depletion-induced protein folding defects and various proteotoxic stresses. Surprisingly, this effect was not mediated by an enhanced stress response, which underlies longevity in low IIS conditions, but by reduced ribosome biogenesis and translation rate. We found that IIS activates the expression of intestinal peptide transporter PEPT-1 by alleviating its repression by FOXO/DAF-16, allowing dietary proteins to be efficiently incorporated into an amino acid pool that fuels germline protein synthesis. Our data suggest this non-cell-autonomous pathway is critical for proteostasis regulation during gametogenesis.

RESUMEN

The heat shock response (HSR) is a universal mechanism of cellular adaptation to elevated temperatures and is regulated by heat shock transcription factor 1 (HSF1) or HSF3 in vertebrate endotherms, such as humans, mice, and chickens. We here showed that HSF1 and HSF3 from egg-laying mammals (monotremes), with a low homeothermic capacity, equally possess a potential to maximally induce the HSR, whereas either HSF1 or HSF3 from birds have this potential. Therefore, we focused on cellular adaptation to daily temperature fluctuations and found that HSF1 was required for the proliferation and survival of human cells under daily temperature fluctuations. The ectopic expression of vertebrate HSF1 proteins, but not HSF3 proteins, restored the resistance in HSF1-null cells, regardless of the induction of heat shock proteins. This function was associated with the up-regulation of specific HSF1-target genes. These results indicate the distinct role of HSF1 in adaptation to thermally fluctuating environments and suggest association of homeothermic capacity with functional diversification of vertebrate HSF genes.

Asunto(s)

Adaptación Fisiológica , Factores de Transcripción del Choque Térmico , Respuesta al Choque Térmico , Factores de Transcripción del Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico/genética , Animales , Humanos , Respuesta al Choque Térmico/genética , Respuesta al Choque Térmico/fisiología , Adaptación Fisiológica/genética , Temperatura , Ratones , Proliferación Celular , Pollos/genética , Supervivencia Celular/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética

RESUMEN

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.

RESUMEN

Prostaglandin E2 (PGE2) interacts with four specific G protein-coupled receptors, namely EP1, EP2, EP3, and EP4, playing a pivotal role in determining the fate of cells. Our previous findings highlighted that stimulating the EP4 receptor with its agonist, CAY10598, triggers apoptosis in colon cancer HCT116 cells via the production of reactive oxygen species (ROS). This process also reduces the phosphorylation of the oncogenic protein JAK2 and leads to its degradation in these cells. In this study, our goal was to explore the pathways through which CAY10598 leads to JAK2 degradation. We focused on Hsp90, a heat shock protein family member known for its role as a molecular chaperone maintaining the stability of several key proteins including EGFR, MET, Akt, and JAK2. Our results show that CAY10598 decreases the levels of client proteins of Hsp90 in HCT116 cells, an effect reversible by pretreatment with the ROS scavenger N-acetyl cysteine (NAC) or the proteasome inhibitor MG132, indicating that the degradation is likely driven by ROS. Furthermore, we observed that CAY10598 cleaves both α and ß isoforms of Hsp90, the process inhibited by NAC. Inhibition of EP4 with the antagonist GW627368x not only prevented the degradation of Hsp90 client proteins but also the cleavage of Hsp90 itself in CAY10598-treated HCT116 cells. Additionally, CAY10598 suppressed the growth of HCT116 cells implanted in mice. Our findings reveal that CAY10598 induces apoptosis in cancer cells by a novel mechanism involving the ROS-dependent cleavage of Hsp90, thereby inhibiting the function of crucial Hsp90 client proteins.

RESUMEN

Organisms respond to proteotoxic-stress by activating the heat-shock response, a cellular defense mechanism regulated by a family of heat-shock factors (HSFs); among six human HSFs, HSF1 acts as a proteostasis guardian regulating severe stress-driven transcriptional responses. Herein we show that human coronaviruses (HCoV), both low-pathogenic seasonal-HCoVs and highly-pathogenic SARS-CoV-2 variants, are potent inducers of HSF1, promoting HSF1 serine-326 phosphorylation and triggering a powerful and distinct HSF1-driven transcriptional-translational response in infected cells. Despite the coronavirus-mediated shut-down of the host translational machinery, selected HSF1-target gene products, including HSP70, HSPA6 and AIRAP, are highly expressed in HCoV-infected cells. Using silencing experiments and a direct HSF1 small-molecule inhibitor we show that, intriguingly, HCoV-mediated activation of the HSF1-pathway, rather than representing a host defense response to infection, is hijacked by the pathogen and is essential for efficient progeny particles production. The results open new scenarios for the search of innovative antiviral strategies against coronavirus infections.

Asunto(s)

Factores de Transcripción del Choque Térmico , SARS-CoV-2 , Replicación Viral , Humanos , Factores de Transcripción del Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico/genética , SARS-CoV-2/fisiología , SARS-CoV-2/metabolismo , Fosforilación , Interacciones Huésped-Patógeno/genética , COVID-19/virología , COVID-19/metabolismo , Animales , Coronavirus/fisiología , Coronavirus/metabolismo , Chlorocebus aethiops , Células HEK293 , Coronavirus Humano OC43/fisiología , Coronavirus Humano OC43/genética

RESUMEN

Tardigrades are known for their ability to survive extreme conditions. Reports indicate that tardigrade thermal tolerance is enhanced in the desiccated state, however these reports have almost always used a single tardigrade species and drying/heating methods vary between studies. Using six different species of tardigrades we confirm that desiccation enhances thermal tolerance in tardigrades. Furthermore, we show that differences in thermal tolerance exist between tardigrade species both when hydrated and desiccated. While Viridiscus viridianus survives the highest temperatures in the hydrated state of any species tested here, under hydrated conditions, the thermal tolerance of V. viridianus is restricted to an acute transient stress. Furthermore, unlike other stresses, such as desiccation, where mild initial exposure preconditions some species to survive subsequent harsher treatment, for V. viridianus exposure to mild thermal stress in the hydrated state does not confer protection to harsher heating. Our results suggest that while tardigrades have the capacity to tolerate mild thermal stress while hydrated, survival of high temperatures in a desiccated state is a by-product of tardigrades' ability to survive desiccation.

RESUMEN

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.

RESUMEN

Cutibacterium acnes, common resident of the human skin, can establish both commensal and pathogenic relations with the human host; however, long-term consequences of C. acnes-induced inflammation remained un(der)explored. To infer the capacity of triggering autoimmunity in humans via molecular mimicry, a comprehensive immunoinformatics analysis of the experimentally characterized C. acnes proteome was performed. The protocol included homology screening between the C. acnes and the human proteome, and validation of shared specificity regions against the collection of experimentally characterized T-cell epitopes, related to autoimmunity. To obtain highly reliable predictions, the results were subjected to additional cross-validation by a dedicated MHC-restriction analysis, including a docking study of C. acnes mimotopes and human counterparts with the highest degree of sequence similarity to MHCII molecules representing the highest risk for detected autoimmune pathologies. Due to mimicking of highly immunogenic, but also evolutionary conserved autoantigens from the Heat Shock protein family, association between C. acnes and the pathogenesis of highly incident autoimmune diseases: Type 1 Diabetes, Rheumatoid Arthritis, and Juvenile Idiopathic Arthritis, was found. To the best of our knowledge, this study is the first one to provide preliminary information and a mechanistic link on the putative involvement of C. acnes in the pathogenesis of autoimmunity in humans.