BACKGROUND: Acute lung injury (ALI) is a clinical syndrome characterized by pulmonary inflammation. Ultrashort wave diathermy (USWD) has been shown to be effective at in inhibiting ALI inflammation, although the underlying mechanism remains unclear. Previous studies have demonstrated that USWD generates a therapeutic thermal environment that aligns with the temperature required for heat shock protein 70 (HSP70), an endogenous protective substance. In this study, we examined the correlation between HSP70 and USWD in alleviating lung inflammation in ALI.
METHODS: Forty-eight male C57BL/6 mice were randomly divided into control, model, USWD intervention (LU) 1, 2, and 3, and USWD preintervention (UL) 1, 2, and 3 groups (n = 6 in each group). The mice were pretreated with LPS to induce ALI. The UL1, 2, and 3 groups received USWD treatment before LPS infusion, while the LU1, 2, and 3 groups received USWD treatment after LPS infusion. Lung function and structure, inflammatory factor levels and HSP70 protein expression levels were detected.
RESULTS: USWD effectively improved lung structure and function, and significantly reduced IL-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.
CONCLUSIONS: Both USWD intervention and preintervention effectively reduced the inflammatory response, alleviated lung injury symptoms, and played a protective role in LPS-pretreated ALI mice. HSP70 was potentially regulated by USWD in this process, but further studies are urgently needed to elucidate the correlation and mechanism.

Natural killer (NK) cells are central components of the innate immunity system against cancers. Since tumor cells have evolved a series of mechanisms to escape from NK cells, developing methods for increasing the NK cell antitumor activity is of utmost importance. It is previously shown that an ex vivo stimulation of patient-derived NK cells with interleukin (IL)-2 and Hsp70-derived peptide TKD (TKDNNLLGRFELSG, aa450-461) results in a significant upregulation of activating receptors including CD94 and CD69 which triggers exhausted NK cells to target and kill malignant solid tumors expressing membrane Hsp70 (mHsp70). Considering that TKD binding to an activating receptor is the initial step in the cytolytic signaling cascade of NK cells, herein this interaction is studied by molecular docking and molecular dynamics simulation computational modeling. The in silico results showed a crucial role of the heterodimeric receptor CD94/NKG2A and CD94/NKG2C in the TKD interaction with NK cells. Antibody blocking and CRISPR/Cas9-mediated knockout studies verified the key function of CD94 in the TKD stimulation and activation of NK cells which is characterized by an increased cytotoxic capacity against mHsp70 positive tumor cells via enhanced production and release of lytic granules and pro-inflammatory cytokines.

This study aimed to examine the effects of gibberellic acid (GBA) on growth, hemato-biochemical parameters related to liver functions, digestive enzymes, and immunological response in Oreochromis niloticus. Besides, the probable underlying mechanisms were explored by assessing antioxidant, apoptotic, and immune-related gene expression. Furthermore, the likelihood of restoration following alpha-lipoic acid (LIP) dietary supplementation was explored. The fish (average initial weight 30.75 ± 0.46) were equally classified into four groups: the control group, the LIP group (fed on a basal diet plus 600 mg/kg of LIP), the GBA group (exposed to 150 mg GBA/L), and the GBA + LIP group (exposed to 150 mg GBA/L and fed a diet containing LIP and GBA) for 60 days. The study findings showed that LIP supplementation significantly reduced GBA\'s harmful effects on survival rate, growth, feed intake, digestive enzymes, and antioxidant balance. Moreover, the GBA exposure significantly increased liver enzymes, stress markers, cholesterol, and triglyceride levels, all of which were effectively mitigated by the supplementation of LIP. Additionally, LIP addition to fish diets significantly minimized the histopathological alterations in the livers of GBA-treated fish, including fatty change, sharply clear cytoplasm with nuclear displacement to the cell periphery, single-cell necrosis, vascular congestion, and intralobular hemorrhages. The GBA-induced reduction in lysozyme activity, complement C3, and nitric oxide levels, together with the downregulation of antioxidant genes (cat and sod), was significantly restored by dietary LIP. Meanwhile, adding LIP to the GBA-exposed fish diets significantly corrected the aberrant expression of hsp70, caspase- 3, P53, pcna, tnf-a, and il-1β in O. niloticus liver. Conclusively, dietary LIP supplementation could mitigate the harmful effects of GBA exposure on fish growth and performance, physiological conditions, innate immunity, antioxidant capability, inflammatory response, and cell apoptosis.

BACKGROUND: Oral cancer is a common cause of death worldwide. The search for novel biomarkers for oral cancer is an ongoing struggle. Prognostic biomarkers are of great importance in diagnosis, and prediction of the cancer outcome. There are several disagreements in oral cancer studies over the role of heat shock proteins as prognostic markers. The current study investigated HSP70 expression in diverse tissues ranging from normal oral mucosa to dysplastic oral epithelium and oral squamous cell carcinoma to determine its role in oral carcinogenesis. Moreover, HSP70 was evaluated concerning different prognostic parameters to determine its capability in predicting cancer progression. Recurrence of tumor was recorded, and patients` disease-free survival was calculated and analyzed considering HSP70 expression to determine the potential utility of HSP70 immuno-expression in predicting recurrence.
METHODS: A retrospective study was accomplished on 50 cases of OSCC. Biopsies from the cancerous tissue, the free surgical margin, and the normal oral mucosa were used. The grading of dysplastic epithelium and OSCCs followed the criteria of WHO classification (2017). The clinicopathological and follow-up records for each patient were retrieved. Pearson\'s Chi-square test, one-way ANOVA, and post hoc tests were used to analyze the variance of HSP70 immuno-expression concerning different parameters. The Kaplan-Meier method was used to compute and visualize disease-free survival, and the log-rank test was used to analyze the data. With Cox regression, univariate and multivariate survival analyses were run. A P-value of 0.05 or less was regarded as statistically significant.
RESULTS: A significant increased expression of HSP70 was observed as the tissue progressed from normal to dysplastic epithelium, and carcinoma (P = 0.000). HSP70 revealed a significant increased expression by progression from mild to severe dysplasia (P = 0.023), and also from well to moderately and poorly differentiated carcinoma (P = 0.000). High HSP70 immuno-expression was significantly associated with progression of OSCC; large-sized tumors (P = 0.002), advanced TNM clinical stages (P = 0.001), positive nodal involvement (P = 0.001), presence of recurrence (P = .008), and reduced DFS (P = 0.014).
CONCLUSIONS: HSP70 has a crucial contribution to oral carcinogenesis, and its immune-expression could potentially be used as predictor of progression and recurrence of OSCC patients.
BACKGROUND: Retrospectively registered.

Hyperthermia-induced overexpression of heat shock protein 70 (HSP70) leads to the thermoresistance of cancer cells and reduces the efficiency of photothermal therapy (PTT). In contrast, cancer cell-specific membrane-associated HSP70 has been proven to activate antitumor immune responses. The dual effect of HSP70 on cancer cells inspires us that in-depth research of membrane HSP70 (mHSP70) during PTT treatment is essential. In this work, a PTT treatment platform for human breast cancer cells (MCF-7 cells) based on a mPEG-NH2-modified polydopamine (PDA)-coated gold nanorod core-shell structure (GNR@PDA-PEG) is developed. Using the force-distance curve-based atomic force microscopy (FD-based AFM), we gain insight into the PTT-induced changes in the morphology, mechanical properties, and mHSP70 expression and distribution of individual MCF-7 cells with high-resolution at the single-cell level. PTT treatment causes pseudopod contraction of MCF-7 cells and generates a high level of intracellular reactive oxygen species, which severely disrupt the cytoskeleton, leading to a decrease in cellular mechanical properties. The adhesion maps, which are recorded by aptamer A8 functional probes using FD-based AFM, reveal that PTT treatment causes a significant upregulation of mHSP70 expression and it starts to exhibit a partial aggregation distribution on the MCF-7 cell surface. This work not only exemplifies that AFM can be a powerful tool for detecting changes in cancer cells during PTT treatment but also provides a better view for targeting mHSP70 for cancer therapy.

BACKGROUND: The aim of this study was to determine the effect of low-level light therapy (LLLT) on orthodontic tooth movement (OTM) rate, heat shock protein 70 (HSP-70) expression, and matrix metalloproteinase 8 (MMP-8) expression.
METHODS: In this experimental study twenty-four male guinea pigs were randomly divided into three groups (n = 8): control group (K) without orthodontic force and LLLT; treatment group 1 (T1) with orthodontic force, and treatment group 2 (T2) with orthodontic force and LLLT. The labial surfaces of both maxillary central incisors in treatments groups were installed with single-wing bracket before being inserted with close coil spring to give 10 g/cm2 orthodontic force. For the T2 group, 4 J/cm2 of LLLT was administered in the mesial-distal and labial-palatal regions for 3 min every day. On day 14, the gap between teeth was measured and immunohistochemistry staining was done to determine HSP-70 and MMP-8 expression. Data were analyzed using (IBM, New York, (ANOVA), followed by Turkey\'s HSD test to determine the differences between groups. Nonnormal distributed data would be analyzed using Kruskal-Wallis test, followed by Mann-Whitney test with P < 0.05 being performed.
RESULTS: The gap between teeth in the T2 group was greater compared to T1 group (P = 0.00). However, there was a significant decrease of HSP-70 and MMP-8 expression in T2 group compared to T1 group in the tensile and compressive sides.
CONCLUSIONS: LLLT intervention during orthodontic treatment could accelerate OTM rate and decreased HSP-70 and MMP-8 expression both in tension and in compressive side. Thus, LLLT interventions can be used as adjuvant therapy to shorten orthodontic treatment duration.

The objective of this study was to evaluate the effects of zearalenone (ZEA) and estradiol benzoate (EB) on stress injury and uterine development in post-weaning gilts. Thirty healthy post-weaning female gilts (Duroc × Landrace × Large White) aged 28-32 days were randomly allocated to three treatments as follows: (a) basal diet (Control), (b) basal diet plus 1.0 mg/kg purified ZEA (ZEA) and (c) basal diet plus 0.75 ml (1.5 mg) EB per pig at 3-days intervals by intramuscular injection (EB). The serum estradiol (E2 ), the final and the increased vulvar area, uterine index, thickness of the myometrium and endometrium, and protein expression of heat shock protein 70 (HSP70) in ZEA group were higher than those in the control group (p < .05), but lower than those in the EB group (p < .05). The serum luteinizing hormone in ZEA group was lower than that of the control group (p < .05), but higher than that in the EB group (p < .05). Higher serum follicle-stimulating hormone and progesterone were observed in the ZEA and control groups than those in the EB group (p < .05). The serum glutathione peroxidase activity in the ZEA group was lower than that in the control and EB groups (p < .001), and the malondialdehyde in the ZEA group was higher than that in the control and EB groups (p < .001). Moreover, the relative mRNA and protein expression of growth hormone receptor (GHR) and relative mRNA expression of HSP70 in the ZEA and EB groups were higher than those in the control group (p < .05). In conclusion, both ZEA (1.0 mg/kg) and EB (1.5 mg at 3 days intervals by intramuscular injection) stimulated vulvar swelling and uterine hypertrophy by disordering serum hormones and up-regulating GHR expression, and induced stress by different mechanisms in this study. Furthermore, the observed up-regulating HSP70 expression challenged by ZEA or EB may be part of the mechanism to resist stress injury.

BACKGROUND: Heat shock protein 70 (HSP70) exhibits protective effects against ultraviolet (UV)-induced premature skin aging. A standardized extract of Asparagus officinalis stem (EAS) is produced as a novel and unique functional food that induces HSP70 cellular expression. To elucidate the anti-photoaging potencies of EAS, we examined its effects on HSP70 expression levels in UV-B-irradiated normal human dermal fibroblasts (NHDFs).
METHODS: NHDFs were treated with 1 mg/mL of EAS or dextrin (vehicle control) prior to UV-B irradiation (20 mJ/cm2). After culturing NHDFs for different time periods, HSP70 mRNA and protein levels were analyzed using real-time polymerase chain reaction and western blotting, respectively.
RESULTS: UV-B-irradiated NHDFs showed reduced HSP70 mRNA levels after 1-6 h of culture, which were recovered after 24 h of culture. Treatment with EAS alone for 24 h increased HSP70 mRNA levels in the NHDFs, but the increase was not reflected in its protein levels. On the other hand, pretreatment with EAS abolished the UV-B irradiation-induced reduction in HSP70 expression at both mRNA and protein levels. These results suggest that EAS is capable to preserve HSP70 quantity in UV-B-irradiated NHDFs.
CONCLUSIONS: EAS exhibits anti-photoaging potencies by preventing the reduction in HSP70 expression in UV-irradiated dermal fibroblasts.

The present study aimed to investigate the effect of HSF1 proteins on cell proliferation, apoptosis and invasion of breast cancer. The Michigan Cancer Foundation-7 (MCF-7) HSF1-knocked down stable cell line (experimental group) and control cell line (control group) were obtained using a lentivirus assay, and the effects of HSF1 knockdown on the proliferation, tumor formation, apoptosis and invasion ability were analyzed, respectively. The effects of HSF1 on downstream signals were analyzed using western blotting. Western blotting results showed that lentivirus successfully established a HSF1 knockdown stable cell line of MCF-7. Compared with the control group, the growth rate of MCF-7 cells in the experimental group was significantly decreased (P<0.05). Flow cytometry showed that the proportion of apoptosis in the control group was significantly lower than that of the experimental group (P<0.05). Notably, the invasion ability of cells in the control group was significantly higher than that in the experimental group (P<0.05). Compared with cells in the control group, the levels of heat shock protein (HSP)70, HSP90, anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and macrophage migration inhibitory factor (MIF) in the experimental group were significantly downregulated, whereas the level of Bax was significantly increased (P<0.05). In conclusion, HSF1 protein, as a transcription factor, regulates the expression levels of HSP70, HSP90, MIF, Bcl-2 and Bax, thus controlling the proliferation, apoptosis and invasion of cells. These findings suggest HSF1 protein as a potential target for the treatment of breast cancer.

The present study aimed to investigate the effect of HSF1 proteins on cell proliferation, apoptosis and invasion of breast cancer. The Michigan Cancer Foundation-7 (MCF-7) HSF1-knocked down stable cell line (experimental group) and control cell line (control group) were obtained using a lentivirus assay, and the effects of HSF1 knockdown on the proliferation, tumor formation, apoptosis and invasion ability were analyzed, respectively. The effects of HSF1 on downstream signals were analyzed using western blotting. Western blotting results showed that lentivirus successfully established a HSF1 knockdown stable cell line of MCF-7. Compared with the control group, the growth rate of MCF-7 cells in the experimental group was significantly decreased (P<0.05). Flow cytometry showed that the proportion of apoptosis in the control group was significantly lower than that of the experimental group (P<0.05). Notably, the invasion ability of cells in the control group was significantly higher than that in the experimental group (P<0.05). Compared with cells in the control group, the levels of heat shock protein (HSP)70, HSP90, anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and macrophage migration inhibitory factor (MIF) in the experimental group were significantly downregulated, whereas the level of Bax was significantly increased (P<0.05). In conclusion, HSF1 protein, as a transcription factor, regulates the expression levels of HSP70, HSP90, MIF, Bcl-2 and Bax, thus controlling the proliferation, apoptosis and invasion of cells. These findings suggest HSF1 protein as a potential target for the treatment of breast cancer.