Expression Of Heat Shock Protein Research Articles

A self‐assembled nanomedicine for glucose supply interruption‐amplified low‐temperature photothermal therapy and anti‐prometastatic inflammatory processes of triple‐negative breast cancer

AbstractThe poor prognosis of triple‐negative breast cancer (TNBC) results from its high metastasis, whereas inflammation accompanied by excessive reactive oxygen species (ROS) is prone to aggravate tumor metastasis. Although photothermal therapy (PTT) has extremely high therapeutic efficiency, the crafty tumor cells allow an increase in the expression of heat shock proteins (HSPs) to limit its effect, and PTT‐induced inflammation is also thought to be a potential trigger for tumor metastasis. Herein, myricetin, iron ions, and polyvinylpyrrolidone were utilized to develop nanomedicines by self‐assembly strategy for the treatment of metastatic TNBC. The nanomedicines with marvelous water solubility and dispersion can inhibit glucose transporter 1 and interfere with mitochondrial function to block the energy supply of tumor cells, achieving starvation therapy on TNBC cells. Nanomedicines with excellent photothermal conversion properties allow down‐regulating the expression of HSPs to enhance the effect of PTT. Interestingly, the broad spectrum of ROS scavenging ability of nanomedicines successfully attenuates PTT‐induced inflammation as well as influences hypoxia‐inducible factors‐1α/3‐phosphoinositide‐dependent protein kinase 1 related pathway through glycometabolism inhibition to reduce tumor cell metastasis. Moreover, the nanomedicines have negligible side effects and good clinical application prospects, which provides a valuable paradigm for the treatment of metastatic TNBC through glycometabolism interference, anti‐inflammation, starvation, and photothermal synergistic therapy.

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.

Enhancing Cartilage Metabolism in Rats through a Novel Thermal Stimulation Technique with Photosensitizers.

Although the moderate thermal stimulation of articular cartilage exerts chondroprotective effects, it is difficult to effectively heat deep articular cartilage with conventional methods. Photosensitizers increase the ambient temperature using near-infrared (NIR) radiation, which has high tissue permeability. We hypothesized that the intra-articular administration of photosensitizers and NIR irradiation would exert a greater heating effect on articular cartilage. We aimed to evaluate the heating effect of this method on cultured chondrocytes and rat knee cartilage. In vitro, we irradiated a photosensitizer-containing medium with NIR and measured changes in the medium temperature, cytotoxicity, and gene expression of heat shock protein (HSP) 70 and aggrecan (ACAN). In vivo, the knee joints of rats treated with photosensitizers were irradiated with NIR, and changes in intra-articular temperature and gene expression were measured, alongside histological analysis. The results showed that the medium and intra-articular temperature were raised to approximately 40 °C with no apparent disruption to articular cartilage or the immunohistochemically enhanced staining of HSP70 in chondrocytes. The gene expression of HSP70 and ACAN was increased in both cultured and articular cartilage. In summary, this method can safely heat joints and enhance cartilage metabolism by inducing HSP70 expression in articular cartilage. It presents a new hyperthermia therapy with effective cartilage protection.

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.

Are Heat Shock Proteins Important in Low-Temperature-Stressed Plants? A Minireview

Heat shock proteins (HSPs) are mainly known to play important roles in plants against high-temperature (HT) stress. Their main function is to act as molecular chaperones for other proteins. It has also been proven that HSPs have a protective effect during other environmental stresses including low temperature (LT). To the best of our knowledge, the expression and role of HSPs in plants that have been exposed to LT have not yet been sufficiently reviewed. The aims of this minireview were (1) to briefly describe the origin, classification, structure, localisation and functions of HSPs, (2) to present the current knowledge about the changes in the accumulation of HSPs in plants that have been exposed to LT, (3) to discuss some of the molecular changes that occur during LT action and that lead to the accumulation of HSPs in plants and (4) to discuss the potential role of HSPs in acquiring tolerance to cold and frost in plants including economically important crop species. Some directions of research on the role of HSPs in plants growing in LT conditions are proposed.

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

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. 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. USWD effectively improved lung structure and function, and significantly reduced IL-1β, IL-10, TGF-β1, 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. 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.

MaHsf24, a novel negative modulator, regulates cold tolerance in banana fruits by repressing the expression of HSPs and antioxidant enzyme genes.

Transcriptional regulation mechanisms underlying chilling injury (CI) development have been widely investigated in model plants and cold-sensitive fruits, such as banana (Musa acuminata). However, unlike the well-known NAC and WRKY transcription factors (TFs), the function and deciphering mechanism of heat shock factors (HSFs) involving in cold response are still fragmented. Here, we showed that hot water treatment (HWT) alleviated CI in harvested banana fruits accomplishing with reduced reactive oxygen species (ROS) accumulation and increased antioxidant enzyme activities. A cold-inducible but HWT-inhibited HSF, MaHsf24, was identified. Using DNA affinity purification sequencing (DAP-seq) combined with RNA-seq analyses, we found three heat shock protein (HSP) genes (MaHSP23.6, MaHSP70-1.1 and MaHSP70-1.2) and three antioxidant enzyme genes (MaAPX1, MaMDAR4 and MaGSTZ1) were the potential targets of MaHsf24. Subsequent electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) and dual-luciferase reporter (DLR) analyses demonstrated that MaHsf24 repressed the transcription of these six targets via directly binding to their promoters. Moreover, stably overexpressing MaHsf24 in tomatoes increased cold sensitivity by suppressing the expressions of HSPs and antioxidant enzyme genes, while HWT could recover cold tolerance, maintaining higher levels of HSPs and antioxidant enzyme genes, and activities of antioxidant enzymes. In contrast, transiently silencing MaHsf24 by virus-induced gene silencing (VIGS) in banana peels conferred cold resistance with the upregulation of MaHSPs and antioxidant enzyme genes. Collectively, our findings support the negative role of MaHsf24 in cold tolerance, and unravel a novel regulatory network controlling bananas CI occurrence, concerning MaHsf24-exerted inhibition of MaHSPs and antioxidant enzyme genes.

Effects of ultrashort wave on neuronal damage and heat shock protein 70 expression after cerebral ischemia-reperfusion injury in rats

BackgroundUltrashort wave (USW) therapy has been reported to alleviate cerebral ischemia/reperfusion (IR) injury, however the underlying mechanisms remain elusive. The aim of this study was to observe the effect of non-thermal USW therapy on neuronal damage and expression of heat shock protein 70 (HSP70) after cerebral IR in rats. MethodsFocal ischemia-reperfusion (IR) was induced in Sprague–Dawley rats by middle cerebral artery occlusion/reperfusion (MCAO/R). The Ninety-two rats (both male and female) were screened using the Zea-Longa 5 grade evaluation. Included rats were then randomly divided into blank, sham, model 1-day, model 3-day, model 7-day, USW 1-day, USW 3-day, or USW 7-day groups. All rats in the model groups received sham USW treatment, while rats in the USW groups received USW treatment, for 1, 3, or 7 days. We assessed the National Institutes of Health Stroke Scale, brain infarction volumes, ultrastructural damage scores using electron microscopy, and HSP70 expression by western blotting between the different groups. ResultsUSW treatment reduced the National Institutes of Health Stroke Scale, infarction volume, and ultrastructural neuronal damage, and increased expression of HSP70, in the hippocampal CA1 region. ConclusionsNon-thermal USW therapy may improve neurological function, decrease infarction volume, and reduce neuronal damage by increasing HSP70 expression following cerebral IR injury.

Characterization of HSP90 expression and function following CNS injury

Spinal cord injury induces significant cellular stress responses. The Heat Shock Protein 90 (HSP90) plays a pivotal role as a molecular chaperone and is crucial for protein folding, stabilization, and cellular signaling pathways. Despite its important function in stress adaptation, the specific expression patterns and functional roles of HSP90 after nerve injury remain unclear. This study aimed to elucidate the expression dynamics and functional implications of HSP90 following central nervous system (CNS) injury. Using western blotting and immunohistochemical analyses, we observed upregulation of HSP90 expression in spinal cord tissues and within injured neurons in a spinal cord contusion injury model. Additionally, HSP90 was found to enhance neurite outgrowth in primary cortical neurons cultured in vitro. Furthermore, in a glutamate-induced neuronal injury model, the expression of HSP90 was up-regulated, and overexpression of HSP90 promoted neurite re-growth in damaged neurons. Overall, our findings highlight the critical involvement of HSP90 in the neural response to injury and offer valuable insights into potential therapeutic strategies for CNS repair.

PXL01 alters macrophage response with no effect onaxonal outgrowth or Schwann cell response after nerve repair in rats.

Background: Adjunctive pharmacological treatment may improve nerve regeneration. We investigated nerve regeneration processes of PXL01- a lactoferrin-derived peptide - after repair of the sciatic nerve in healthy Wistar rats.Materials & methods: PXL01, sodium hyaluronate (carrier) or sodium chloride was administered around the repair. After 6days axonal outgrowth, Schwann cell response, pan- (CD68) and pro-healing (CD206) macrophages in sciatic nerve, sensory neuronal response in dorsal root ganglia (DRG) and expression of heat shock protein 27 (HSP27) in sciatic nerves and DRGs were analyzed.Results: Despite a lower number of pan-macrophages, other investigated variables in sciatic nerves or DRGs did not differ between the treatment groups.Conclusion: PLX01 applied locally inhibits inflammation through pan-macrophages in repaired sciatic nerves without any impact on nerve regeneration or pro-healing macrophages.

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.

Combination of anti-inflammatory therapy and RNA interference by light-inducible hybrid nanomedicine for osteoarthritis treatment

Osteoarthritis (OA) is a type of highly prevalent heterogeneous degenerative disease that leads to joint pain, deformity, the destruction of articular cartilage, and eventual disability. The current treatment strategies for OA often suffer from systemic side effects, poor anti-inflammatory efficacy, and persistent pain. To address these issues, we develop light-inducible nanomedicine that enables the co-delivery of anti-inflammatory drug (diacerein, DIA) and small interfering RNA (siRNA) targeting nerve growth factor (NGF) for pain relief to enhance the therapeutic efficacy of OA. The nanomedicine is based on poly(β-amino-ester)-coated gold nanocages (AuNCs), which is further incorporated with the phase-change material (lauric acid/stearic acid, LA/SA). Following intra-articular (IA) injection in vivo, the nanomedicine displays high degree of drug accumulation and retention in the joint lesion of OA mouse models. The photothermal effect, induced by AuNCs, not only promotes DIA and siRNA release, but also upregulates the expression of heat shock protein 70 (HSP-70) to resist the apoptosis of chondrocytes in the inflammatory condition. The internalization of both DIA and siRNA results in strong anti-inflammatory and pain-relieving effects, which greatly contribute to the joint repair of OA mice. This study offers a promising combination strategy for OA treatment.

Impact of histone deacetylase inhibition and arimoclomol on heat shock protein expression and disease biomarkers in primary culture models of familial ALS.

Protein misfolding and mislocalization are common themes in neurodegenerative disorders, including motor neuron disease, and amyotrophic lateral sclerosis (ALS). Maintaining proteostasis is a crosscutting therapeutic target, including the upregulation of heat shock proteins (HSP) to increase chaperoning capacity. Motor neurons have a high threshold for upregulating stress-inducible HSPA1A, but constitutively express high levels of HSPA8. This study compared the expression of these HSPs in cultured motor neurons expressing three variants linked to familial ALS: TAR DNA binding protein 43kDa (TDP-43)G348C, fused in sarcoma (FUS)R521G, or superoxide dismutase I (SOD1)G93A. All variants were poor inducers of Hspa1a, and reduced levels of Hspa8 mRNA and protein, indicating multiple compromises in chaperoning capacity. To promote HSP expression, cultures were treated with the putative HSP coinducer, arimoclomol, andclass I histone deacetylase inhibitors, to promote active chromatin for transcription, and with the combination. Treatments had variable, often different effects on the expression of Hspa1a and Hspa8, depending on the ALS variant expressed, mRNA distribution (somata and dendrites), and biomarker of toxicity measured (histone acetylation, maintaining nuclear TDP-43 and the neuronal Brm/Brg-associated factor chromatin remodeling complex component Brg1, mitochondrial transport, FUS aggregation). Overall, histone deacetylase inhibition alone was effective on more measures than arimoclomol. As in the FUS model, arimoclomol failed to induce HSPA1A or preserve Hspa8 mRNA in the TDP-43 model, despite preserving nuclear TDP-43 and Brg1, indicating neuroprotective properties other than HSP induction. The data speak to the complexity of drug mechanisms against multiple biomarkers of ALS pathogenesis, as well as to the importance of HSPA8 for neuronal proteostasis in both somata and dendrites.

Mutational landscape of HSP family on human breast cancer

Breast cancer (BRCA) is a prevalent malignancy with the highest incidence among females. BRCA can be categorized into five intrinsic molecular subtypes (LumA, LumB, HER2, Basal, and Normal), each characterized by varying molecular and clinical features determined by the expression of intrinsic genes (PAM50). The Heat Shock Protein (HSP) family is composed of 95 genes evolutionary conservated, they have critical roles in proteostasis in both normal and cancerous processes. Many studies have linked HSP to the development and spread of cancer. They modulate the activity of multiple proteins expressed by oncogenes and anti-oncogenes through a range of interactions. In this study, we evaluate the mutational changes that HSP undergoes in BRCA mainly from the TCGA database. We observe that Copy Number Variations (CNV) are the more frequent events analyzed surpassing the occurrence of point mutations, indels, and translation start site mutations. The Basal subtype showcased the highest count of amplified CNV, including subtype-specific changes, whereas the Luminals tumors accumulated the greatest number of deletion CNV. Meanwhile, the HER2 subtype exhibited a comparatively lower frequency of CNV alterations when compared to the other subtypes. This study integrates CNV and expression data, finding associations between these two variables and the influence of CNV on the deregulation of HSP expression. To enhance the role of HSP as a risk predictor in BRCA, we succeeded in identifying CNV profiles as a prognostic marker. We included Artificial Intelligence to improve the clustering of patients, and we achieved a molecular CNV signature as a significant risk factor independent of known classic markers, including molecular subtypes PAM50. This research enhances the comprehension of HSP DNA alterations in BRCA and its relation with predicting the risk of affected individuals providing insights to develop guide personalized treatment strategies.

VARIATIONS IN HEAT SHOCK PROTEINS BETWEEN DIFFERENT HONEY BEES AND BEE TAXA UTILIZING BIOINFORMATICS

The changes in climate and exposure to heat stress are major concerns for agricultural communities as it affects pollinators like bees. Bees from different taxa play a crucial role in plant pollination, and their exposure to heat stress induces the expression of heat shock proteins (HSPs) to protect their cells. Several studies have analyzed the variations in HSPs expression levels and amino acid sequences. Databases for sequences of HSPs with different molecular weights are currently available. Variations in HSPs expression levels have been noted among individuals belonging to the same or different bee taxa exposed to heat stress. The properties of HSPs could help in understanding these variations. This study utilized bioinformatics and protein analysis tools to investigate the variations in sequences of heat shock proteins 60 (HSP60) and 83 (HSP83) in 18 bee taxa (15 from Family Apidae, 2 from Family Halictidae, and one from Megachilidae). The analysis showed some identical values to bees from genus Apis and Bombus. For HSP60, all bee taxa had high G content (587-602), followed by A (438-444), then C (389-404), and finally T (282-291). For HSP83, all bee taxa had high A content (730-759), followed by G (572-592), then C (406-419), and finally T (415-429). The conserved domains were highly identical in case of HSP60 versus HSP83. The motifs were from one or more protein families with variation among taxa. All proteins showed hydrophilic properties with variable isoelectric points. The study suggested an identical 3-D structure for proteins in all bee taxa. The role of the detected variations in affecting the response of HSPs to stress was discussed. This study paves the way for more investigations on HSPs and encourages the use of bioinformatics and protein analysis tools to explain any observable variations.

HSP70-mediated mitochondrial dynamics and autophagy represent a novel vulnerability in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is one of the deadliest forms of cancer with limited therapy options. Overexpression of the heat shock protein 70 (HSP70) is a hallmark of cancer that is strongly associated with aggressive disease and worse clinical outcomes. However, the underlying mechanisms by which HSP70 allows tumor cells to thrive under conditions of continuous stress have not been fully described. Here, we report that PDAC has the highest expression of HSP70 relative to normal tissue across all cancers analyzed. Furthermore, HSP70 expression is associated with tumor grade and is further enhanced in metastatic PDAC. We show that genetic or therapeutic ablation of HSP70 alters mitochondrial subcellular localization, impairs mitochondrial dynamics, and promotes mitochondrial swelling to induce apoptosis. Mechanistically, we find that targeting HSP70 suppresses the PTEN-induced kinase 1 (PINK1) mediated phosphorylation of dynamin-related protein 1 (DRP1). Treatment with the HSP70 inhibitor AP-4-139B was efficacious as a single agent in primary and metastatic mouse models of PDAC. In addition, we demonstrate that HSP70 inhibition promotes the AMP-activated protein kinase (AMPK) mediated phosphorylation of Beclin-1, a key regulator of autophagic flux. Accordingly, we find that the autophagy inhibitor hydroxychloroquine (HCQ) enhances the ability of AP-4-139B to mediate anti-tumor activity in vivo. Collectively, our results suggest that HSP70 is a multi-functional driver of tumorigenesis that orchestrates mitochondrial dynamics and autophagy. Moreover, these findings support the rationale for concurrent inhibition of HSP70 and autophagy as a novel therapeutic approach for HSP70-driven PDAC.

HSP70 protects against acute pancreatitis-elicited intestinal barrier damage in rats

Acute pancreatitis (AP) is a frequent but severe abdominal emergency in general surgery with intestinal barrier dysfunction. Heat shock protein 70 (HSP70) is a ubiquitous molecular chaperone that has been proposed to exert favorable effects on AP. Nonetheless, the detailed impacts of HSP70 on the intestinal barrier function in AP are unknown, which will be investigated here. After the injection of sodium taurocholate into the biliopancreatic duct, the rat models of AP were established. After modeling, HSP70 expression was up-regulated through lentivirus infection. Western blot was used to detect HSP70 expression. H&E staining was used to examine the histological changes in the pancreatic and intestinal tissues. The levels of pancreatic biochemical markers and oxidative stress markers were detected using corresponding assay kits. ELISA was used to detect the levels of inflammatory cytokines and gastrointestinal function indicators. Immunofluorescence staining and Western blot were used to detect the expression of tight junction proteins. DCFH-DA probe and MitoSOX Red probe were used to detect total reactive oxygen species (ROS) and mitochondrial ROS (mtROS), respectively. TUNEL assay and Western blot were used to detect apoptosis. During the model construction, severe pancreatic and abnormal intestinal tissue abnormalities were observed, inflammatory response was activated and the intestinal barrier was disrupted. HSP70 expression was down-regulated in the intestinal tissues AP rat models. HSP70 ameliorated the morphological damage of pancreatic and intestinal tissues of AP rats. In addition, HSP70 significantly reduced intestinal barrier damage, inflammatory response, oxidative stress and apoptosis in the intestinal tissues of AP rat models. Collectively, HSP70 might attenuate AP through exerting anti-inflammatory, anti-oxidant, anti-apoptotic effects and inhibiting intestinal barrier disruption.

Effects of probiotic supplementary bioflocs (Rhodospirillum rubrum, Bacillus subtilis, Providencia rettgeri) on growth, immunity, and water quality in cultures of Pacific white shrimp (Litopenaeus vannamei)

Biofloc technology is a promising strategy for the super-intensive cultivation of Pacific white shrimp (Litopenaeus vannamei). However, conventional bioflocs originating from pre-existing systems have shown to be inferior to bioflocs with constant probiotic supplementation regarding the stability in yield. Hence we compared bioflocs supplemented with Rhodospirillum rubrum (RR), Bacillus subtilis (BS), and Providencia rettgeri (PR) to the clear water system (CT), in terms of growth performances, immune status, nitrogen substances, and Vibrio populations in cultures of L. vannamei together with microbial profiles in both the midgut and bioflocs. Our findings exhibited increased average daily gain (ADG) and protein efficiency ratio (PER) among shrimp reared in BS and PR while BS also reduced feed conversion ratio (FCR). Gene expression analyses of growth-related markers revealed an upregulation of amylase and peptide transporter 1 in shrimp of PR treatment, whilst the changes did not outperform the BS supplement in growth promotion. Furthermore, PR treatment was found to enhance the expression of immune-related genes toll-like receptor, prophenoloxidase (proPO), and heat shock protein 70 (hsp70). All biofloc treatments effectively reduced NO2-N level and mitigated Vibrio parahaemolyticus proliferation, particularly in the BS and PR groups. The redundant analysis illustrated shrimp growth closely associated with improved water quality instead of the expression of genes participating in digestion, absorption, or immunity. Moreover, microflora sequencing exhibited the supplemental probiotics altered microbial communities in bioflocs and gut, whereas they did not dominate in either environment. In spite of the discrepancies in microbial composition between bioflocs and midgut of shrimp, BS and PR treatments enriched Rhodobacteraceae populations in both environments. In summary, B. subtilis and P. rettgeri supplementary bioflocs promote L. vannamei growth through nutritional supplementation and water environment optimization. Supplementation of P. rettgeri will simultaneously enhance immune responses and stress resistance of L. vannamei via activating proPO cascade and upregulating hsp70. Given the apparent benefits of heterotrophic probiotic supplementary bioflocs, it is imperative to investigate more microbial species or their combinations that can stimulate bioflocs to produce more nutrients.

Photoacoustic Imaging-Guided Self-Adaptive Hyperthermia Supramolecular Cascade Nano-Reactor for Diabetic Periodontal Bone Regeneration.

Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real-time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self-adaptive hyperthermia supramolecular cascade nano-reactor ACFDG is constructed via one-step supramolecular self-assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS-inflammatory cascade through catalytic cascade reactions, up-regulate the expression of heat shock proteins (HSPs) under near-infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real-time non-invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano-reactor combined with PA imaging for real-time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

Modulation of heat shock protein expression and cytokine levels in MCF-7 cells through photodynamic therapy.

In this study, we assess the impact of photodynamic therapy (PDT) using aluminum phthalocyanine tetrasulfonate (AlPcS4) on the viability and cellular stress responses of MCF-7 breast cancer cells. Specifically, we investigate changes in cell viability, cytokine production, and the expression of stress-related genes. Experimental groups included control cells, those treated with AlPcS4 only, light-emitting diode (LED) only, and combined PDT. To evaluate these effects on cell viability, cytokine production, and the expression of stress-related genes, techniques such as 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, enzyme-linked immunosorbent assays (ELISA), and real-time quantitative PCR (RT‒qPCR) were employed. Our findings reveal how PDT with AlPcS4 modulates mitochondrial activity and cytokine responses, shedding light on the cellular pathways essential for cell survival and stress adaptation. This work enhances our understanding of PDT's therapeutic potential and mechanisms in treating breast cancer.