The role of circadian clock genes in colorectal carcinoma: Novel insights into regulatory mechanism and implications in clinical therapy.

Colorectal cancer (CRC) is a lethal malignancy with limited treatment strategies. Accumulating evidence indicates that CRC tumorigenesis, progression and metastasis are intimately associated with circadian clock, an inherent 24-h cycle oscillation of biochemical, physiological functions in almost every eukaryote. In the present review, we summarize the altered expression level of circadian genes in CRC and the prognosis associated with gene abundance switch. We illustrate the function and potential mechanisms of circadian genes in CRC pathogenesis and progression. Moreover, circadian based-therapeutic strategies including chronotherapy, therapeutics targeting potential circadian components, and melatonin treatment in CRC are also highlighted.

Accumulation of blood chromium and cobalt in the participants with metal objects: findings from the 2015 to 2018 National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Chromium (Cr) and cobalt (Co) are the essential elements for producing metal implants, but might have potential health issues. The research on the correlation between metal implants and blood Cr and Co on a large population is still limited. METHODS: National Health and Nutrition Examination Survey (NHANES) is a program of studies designed to assess the health status of Americans began in the early 1960s. The study was based on the NHANES database from two data collection years (2015-2016 and 2017-2018). The exposure variable of this study was whether the participants had metal objects in the body or not. The outcome variables were blood concentrations of Cr and Co. Age, body mass index, sex, race/ethnicity, income to poverty ratio, tap water behavior, shellfish/fish/tuna/salmon eating habits, level of education, smoking behavior, marital status, blood hemoglobin, and data collection years were included as confounding variables. RESULTS: A total of 4412 participants, aged 40 years or older, were included in this analysis, consisting of the without metal objects group (n = 3150) and the metal objects group (n = 1262). Metal objects was positively correlated to the accumulation of blood Cr (ß = 0.072, 95% CI: 0.043-0.102, p < 0.001) and blood Co (ß = 0.079, 95% CI: 0.049-0.109, p < 0.001). However, the positive correlation of metal objects with blood Cr was only presented in women (ß = 0.112, 95% CI: 0.074-0.151, p < 0.001), but not in men. Meanwhile, the positive relationship between metal objects and blood Cr/Co was not observed in the Asian subgroup. CONCLUSIONS: Blood Cr and Co concentrations were statistically higher in people with metal objects, but with race and sex differences. LEVEL OF EVIDENCE: Level IV, cross-sectional study.

Pinellia ternata lectin induces inflammation through TLR4 receptor and mediates PI3K/Akt/mTOR axis to regulate NF-κB signaling pathway.

Pinellia ternata, a widely used traditional Chinese medicine, contains a strong mucosal irritant that is connected with Pinellia ternata lectin (PTL) in its tubers. The purpose of this study was to explore the mechanisms by which PTL induces inflammation. We found that in RAW264.7 cells, PTL activated the PI3K/Akt/mTOR and NF-κB pathways, which resulted in the release of proinflammatory cytokines. Flow cytometry and laser confocal microscopy analysis showed that FITC-labeled PTL bound to the macrophages' surface. Based on kinetic analyses and protein-protein docking simulations, PTL was shown to bind toll-like receptor 4 (TLR4).it was demonstrated that PTL binds highly to Toll-like receptor 4 (TLR4). TLR4 knock-down or knockout resulted in a decrease in both cytokine release and PI3K/Akt/mTOR and NF-κB pathway activation in PTL-stimulated macrophages or mice. RNA-seq analysis showed that genes involved in the PI3K/Akt/mTOR signaling pathway were strongly upregulated in response to PTL stimulation, confirming that the PI3K/Akt/mTOR pathway is linked to the inflammatory effect of PTL in RAW264.7 cells. These findings reveal that PTL can mediate inflammation through TLR4 and activating the PI3K/Akt/mTOR to regulate NF-κB signaling pathways.

Trends in Anterior Cruciate Ligament Repair: A Bibliometric and Visualized Analysis.

Background: Bibliometrics is a methodology that measures the scientific output of an author, institution, or country. Visualized analysis is the transformation of data into visible form by software, highlighting important features, including commonalities and anomalies, allowing users to easily and quickly perceive significant aspects of their data. Purpose: To conduct a bibliometric analysis of the literature on anterior cruciate ligament (ACL) repair, with visualization of trends, in order to identify the areas of interest and the primary researchers involved in ACL repair. Study Design: Cross-sectional study. Methods: The PubMed database was queried on April 14, 2022, for publications that reported on ACL repair from 1960 onward. The initial search resulted in 1392 publications. Filter settings were applied to remove publications with weak correlation, such as those on meniscal repair and ACL reconstruction. Publication information, citations, authors, commonly used terms, and affiliated institutions and countries were analyzed by VOSviewer and Python. Results: A total of 553 articles were included for analysis. Three techniques were visualized: bridge-enhanced ACL repair, internal brace, and dynamic intraligamentary stabilization. The most published authors were Martha Murray (51 articles), Gregory Difelice (35 articles), and Braden Fleming (31 articles). The most cited article was "Collagen-Platelet Rich Plasma Hydrogel Enhances Primary Repair of the Porcine Anterior Cruciate Ligament" by Murray et al. The journals with the most publications on ACL repair were the American Journal of Sports Medicine (n = 49); Knee Surgery, Sports Traumatology, Arthroscopy (n = 49); and Arthroscopy (n = 48). The top 3 institutions by publication number were the Hospital for Special Surgery (n = 51), Boston Children's Hospital (n = 49), and Brown University (n = 31), with the most publications coming from the United States (n = 242), Germany (n = 83), and the United Kingdom (n = 47). Conclusion: The results demonstrate that the research on ACL repair comes from a small number of authors and corresponding institutions; the top sports medicine journals and the developed countries have an interest in this topic.

Arecoline Is Associated With Inhibition of Cuproptosis and Proliferation of Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma: A Potential Mechanism for Tumor Metastasis.

Background: Metastatic disease remains the primary cause of death in patients with oral squamous cell carcinoma (OSCC), especially those who use betel nut. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the TME of OSCC. However, the precise mechanisms regulating CAFs in OSCC are poorly understood. Methods: Thirteen genes related to the arecoline were analyzed to explore the significant ones involved in arecoline-related OSCC metastasis. The GSE139869 (n = 10) and The Cancer Genome Atlas (TCGA)-OSCC data (n = 361) were mined for the identification of the differentially expressed genes. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the independent prognostic signatures. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the functional enrichment of selected genes, and gene set enrichment analysis of cuproptosis-related genes was completed. Spearman's analysis and Tumor Immune Estimation Resource (TIMER) were used to visualize the correlation between the infiltration of CAFs and the gene expression. The correlation analysis of the cells and different genes, including CAF infiltration and transcripts per million expression, was assessed. The relationship between arecoline and CAFs was confirmed by cell counting kit-8 assay (CCK-8). CancerSEA was searched to identify the single-cell phenotype. Result: Arecoline-associated fibrosis-related OSCC differentially expressed genes (AFOC-DEGs), namely, PLAU, IL1A, SPP1, CCL11, TERT, and COL1A2, were screened out and selected from the Gene Expression Omnibus (GEO) database and TCGA database. AFOC-DEGs were highly expressed in OSCC, which led to poor survival of patients. Functional enrichment analysis, protein-protein interaction network construction, and Spearman's correlation analysis all suggested that AFOC-DEGs were closely associated with cuproptosis. Cellular experiments demonstrated that arecoline stimulation could significantly increase the cell viability of CAFs. Single-sample Gene Set Enrichment Analysis (ssGSEA) results showed that GLS and MTF1 were highly expressed when fibroblasts proliferated at high enrichment levels. In addition, analysis of single-cell sequencing results suggested that OSCC cells with high expression of AFOC-DEGs were associated with OSCC metastasis. Conclusion: We found a close association between arecoline, cuproptosis, and CAFs, which might play an important role in the metastasis of OSCC.

Depicting Developing Trend and Core Knowledge of Primary Open-Angle Glaucoma: A Bibliometric and Visualized Analysis.

Objective: The prevalence of glaucoma is rising due to an increasing aging population. Because of its insidious and irreversible nature, glaucoma has gradually become the focus of attention. We assessed primary open angle glaucoma, the most common type of glaucoma, to study its present status, global trend, and state of clinical research. Methods: Publications from 2000 to 2021 in Web of Science database were retrieved and analyzed by bibliometrics. VOSviewer and Citespace were used for analysis. Results: A total of 6,401 publications were included in this review, and we found that the number of publications increased from 139 in 2000 to 563 in 2021. American researchers have published the most papers and had the highest h-index and the most citations, while the Journal of Glaucoma has published the most papers on this topic. Some key researchers, contributing institutions, their partnerships, and scientific masterpieces were identified. The publications we reviewed fall into seven categories: publications on intraocular pressure, normal tension glaucoma, risk factors, the trabecular meshwork, optical coherence tomography, surgery, and mutation. Clear study hotspots were described, which began with epidemiology and transitioned to pathogenesis and diagnosis and then to treatment. Conclusion: Studies on primary open angle glaucoma extend well beyond ophthalmology to biochemistry molecular biology, general internal medicine, pharmacology, pharmacy, science technology, and other areas. Interest, research and publications on primary open angle glaucoma are on the rise.

Comparison of two teaching methods for stopping the bleed: a randomized controlled trial.

BACKGROUND: The "Stop the Bleed" (STB) campaign has achieved remarkable results since it was launched in 2016, but there is no report on the teaching of an STB course combined with a trauma patient simulator. This study proposes the "problem-, team-, and evidence-based learning" (PTEBL) teaching method combined with Caesar (a trauma patient simulator) based on the STB course and compares its effect to that of the traditional teaching method among outstanding doctoral candidates training in haemostasis skills. METHOD: Seventy-eight outstanding doctoral candidate program students in five and eight-year programs were selected as the research subjects and were randomly divided into a control group (traditional teaching method, n = 34) and an experimental group (PTEBL teaching method combined with Caesar, n = 44). Their confidence in their haemostasis skills and willingness to rescue injured victims were investigated before and after the course in both groups. RESULT: Students' self-confidence in their STB skills and the willingness to rescue improved after the class in both groups. Compared with the control group, students in the experimental group were more confident in compressing with bandages and compressing with a tourniquet after a class (compressing with bandages: control group 3.9 ± 0.8 vs. experimental group 4.3 ± 0.7, P = 0.014; compressing with a tourniquet: control group 3.9 ± 0.4 vs. experimental group 4.5 ± 0.8, P = 0.001) More students in the experimental group than the control group thought that the use of Caesar for scenario simulation could improve learning (control group 55.9% vs. experimental group 81.8%, P = 0.024), and using this mannequin led to higher teacher-student interaction (control group 85.3% vs. experimental group 97.7%, P = 0.042). The overall effectiveness of the teaching was better in the experimental group than in the control group (control group 85.3% vs. experimental group 97.7%, P = 0.042). There was a significant positive correlation between teacher-student interactions and the overall effectiveness of teaching (R = 1.000; 95% CI, 1.000-1.000; P < 0.001). CONCLUSION: The PTEBL teaching method combined with Caesar can effectively improve student mastery of STB skills and overcome the shortcomings of traditional teaching methods, which has some promotional value in the training of outstanding doctoral candidates in STB skills.

A Distance Increment Smoothing Method and Its Application on the Detection of NLOS in the Cooperative Positioning.

The wide use of cooperative missions using multiple unmanned platforms has made relative distance information an essential factor for cooperative positioning and formation control. Reducing the range error effectively in real time has become the main technical challenge. We present a new method to deal with ranging errors based on the distance increment (DI). The DI calculated by dead reckoning is used to smooth the DI obtained by the cooperative positioning, and the smoothed DI is then used to detect and estimate the non-line-of-sight (NLOS) error as well as to smooth the observed values containing random noise in the filtering process. Simulation and experimental results show that the relative accuracy of NLOS estimation is 8.17%, with the maximum random error reduced by 40.27%. The algorithm weakens the influence of NLOS and random errors on the measurement distance, thus improving the relative distance precision and enhancing the stability and reliability of cooperative positioning.

The Roles of Tissue-Resident Memory T Cells in Lung Diseases.

The unique environment of the lungs is protected by complex immune interactions. Human lung tissue-resident memory T cells (TRM) have been shown to position at the pathogen entry points and play an essential role in fighting against viral and bacterial pathogens at the frontline through direct mechanisms and also by orchestrating the adaptive immune system through crosstalk. Recent evidence suggests that TRM cells also play a vital part in slowing down carcinogenesis and preventing the spread of solid tumors. Less beneficially, lung TRM cells can promote pathologic inflammation, causing chronic airway inflammatory changes such as asthma and fibrosis. TRM cells from infiltrating recipient T cells may also mediate allograft immunopathology, hence lung damage in patients after lung transplantations. Several therapeutic strategies targeting TRM cells have been developed. This review will summarize recent advances in understanding the establishment and maintenance of TRM cells in the lung, describe their roles in different lung diseases, and discuss how the TRM cells may guide future immunotherapies targeting infectious diseases, cancers and pathologic immune responses.

Using Clinical-Based Discharge Criteria to Discharge Patients After Ophthalmic Ambulatory Surgery Under General Anesthesia: An Observational Study.

PURPOSE: To verify the feasibility of the clinical-based discharge (CBD) criteria and identify the reasons of long postanesthesia care unit length of stay (PACU-LOS) for ophthalmic ambulatory surgical patients under general anesthesia. DESIGN: A prospectively observational study conducted at a tertiary eye center in China. METHODS: Medical records were collected from patients admitted for strabismus ambulatory surgery under general anesthesia from September 2018 to March 2019. The patients were discharged home once met the CBD criteria based on a combination of the modified Aldrete's scoring system and Chung's Post-Anesthetic Discharge Scoring System. Postoperative complications were recorded in the PACU and within 24 hours after discharge. Multivariate logistic regression was applied to identify the factors relating to late discharges. FINDINGS: All patients (N = 400) were safely and successfully same-day discharged home as none of the patients informed severe emergency events or unanticipated readmission. Nine displayed discharge delays mainly because of mild postoperative nausea and vomiting (PONV) although met the discharge criteria. About 85.5% of patients were discharged within a PACU-LOS of 150 minutes, 379 (94.8%) were within 180 minutes, and the cutoff time in PACU-LOS was 150 minutes. Multivariable analysis indicated that sevoflurane anesthesia and the presence of PONV were related to late discharges (PACU-LOS of greater than 150 minutes, all P < .05). CONCLUSIONS: The CBD criteria can efficiently and safely guide the ophthalmic ambulatory surgical patients to discharge home on the same-surgery day, whereas sevoflurane anesthesia and the presence of PONV are associated with a relatively long PACU-LOS.

Retrospective analysis of risk factors of postoperative nausea and vomiting in patients undergoing ambulatory strabismus surgery via general anaesthesia.

BACKGROUND AND AIMS: Postoperative nausea and vomiting (PONV), one of the common complications following strabismus surgery, would delay the ambulatory discharge time. The aim of this retrospective study was to determine the risk factors of PONV in patients undergoing ambulatory strabismus surgery under general anaesthesia, with the treatments of dexamethasone and 5-HT3 antagonist combination. METHODS: We reviewed 721 consecutive patients (12-60 years old) undergoing ambulatory strabismus surgery under general anaesthesia at an academic eye centre between December 2016 and January 2019. Patients received prophylactic treatment of dexamethasone and 5-HT3 antagonist combination during anaesthesia induction, and PONV was evaluated during the early recovery period before discharge. RESULTS: The dexamethasone and 5-HT3 antagonist combination effectively reduced the incidence of PONV (3.05%, 22/721), and the patients who experienced PONV had statistically prolonged phase II recovery time as compared those who did not (P = 0.006). The sum of the extraocular muscles manipulated and the use of nalbuphine (vs flurbiprofen axetil) were the independent risk factors for PONV (P < 0.05). CONCLUSION: The sum of the extraocular muscles manipulated and the use of nalbuphine are potentially modifiable risk factors for PONV after strabismus surgery with the treatments of dexamethasone and 5-HT3 antagonist combination.

GSTP1 Inhibits LPS-Induced Inflammatory Response Through Regulating Autophagy in THP-1 Cells.

Glutathione S-transferase Pi (GSTP1) was originally identified as one of the cytosolic phase II detoxification enzymes and was also considered to function via its non-catalytic, ligand-binding activity. Autophagy is a self-protective mechanism of the cell to remove unnecessary or dysfunctional components, which plays a crucial role in balancing the beneficial and detrimental effects of immunity and inflammation. However, little is known about whether and how GSTP1 mediates autophagy via inhibiting LPS-induced inflammatory response. Here, we show that LPS-induced autophagy and autophagic flux blockade in THP-1 cells in a concentration- and time-dependent manner. Further, we found that the autophagy activation inhibited the activation of inflammatory signaling pathway and the release of inflammatory factors. However, inhibition of autophagy by 3-methyladenine or chloroquine significantly reduced the anti-inflammatory effect of GSTP1. In addition, our findings provide evidence that GSTP1 regulates autophagy through PI3K-Akt-mTOR pathway and inhibits LPS-induced inflammation. Overall, the current study provides an important reference for future applications of GSTP1 in the treatment of inflammatory diseases.

Effectiveness of Steroid Treatment for Sudden Sensorineural Hearing Loss: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The best way to administer steroids for sudden sensorineural hearing loss (SSHL) is still unclear. The present study was aimed at estimating the efficacy of steroids by intratympanic, systemic, and combined therapy (CT) routes. METHODS: A systematic literature search was performed from 1950 to October 2019 for randomized controlled trials comparing the use of intratympanic, systemic, and combined steroid therapy for SSHL. The outcomes of recovery rate and pure tone average (PTA) improvement were assessed by random-effects and fixed-effects meta-analysis. RESULTS: A total of 20 articles identified from 7 countries were eligible for analysis. Although no significant difference in recovery rate was observed between intratympanic steroid therapy (IST) and systemic steroid therapy (SST), IST did demonstrate better hearing improvement, as evidenced by a higher PTA than SST. Compared with SST, CT comprising IST and SST had significant recovery rate improvement. Patients treated with CT had a significantly higher PTA than those treated with SST. Through subgroup analysis based on the equivalent dose of prednisone, it was shown that CT led to a significantly higher PTA than SST only in the high-dose CT versus high-dose SST groups and moderate-dose CT versus high-dose SST groups. CONCLUSION: Moderate and high dose of CT could accelerate hearing improvement in SSHL.

Dexmedetomidine versus other sedatives for non-painful pediatric examinations: A systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: Procedural sedation for non-painful pediatric examinations outside the operating room remains a challenge, this study was designed to compare the safety and effectiveness of sedation provided by dexmedetomidine versus other sedatives including chloral hydrate, midazolam, and pentobarbital for pediatric patients to complete diagnostic examinations. DESIGN: Systematic review and meta-analysis of RCTs. SETTING: Pediatric procedural sedation. INTERVENTIONS: Comparison of sedation by dexmedetomidine and chloral hydrate, or pentobarbital, or midazolam for pediatric non-painful sedation. PATIENTS: The PubMed, Embase, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched and limited the studies to those published in English through July 30, 2018. MEASUREMENTS: Prospective randomized clinical trials (RCTs) comparing dexmedetomidine to chloral hydrate, pentobarbital, and midazolam for pediatric procedural examinations outside the operating room were included in the meta-analysis. Search terms included dexmedetomidine, precede, adrenergic alpha-2 receptor agonists, adrenergic alpha 2 agonists, adrenergic alpha-agonists, adrenergic alpha 2 receptor agonists, chloral hydrate, pentobarbital, midazolam, AND sedation. MAIN RESULTS: A total of 1486 studies were screened and nine RCTs were identified; 1076 patients were analyzed. Sedation with dexmedetomidine provided statistically higher incidences in completing examinations with fewer episodes of desaturation than the other sedatives did (OR 2.90, 95% CI: 1.39-6.07, P = 0.005, I2 = 77%; OR 0.29, 95% CI: 0.15-0.57, P = 0.0004, I2 = 0%, respectively). CONCLUSIONS: The meta-analysis shows that sedation by dexmedetomidine has lower incidence of respiratory depression and provides higher success rates in completing examinations than other traditional sedatives without compromising safety, indicating a prospective clinical use for procedural sedation.

[Study on GLI values of Polygonatum odoratum base on multi-temporal of unmanned aerial vehicle remote sensing].

Unmanned aerial vehicle(UAV) remote sensing and vegetation index have great potential in the field of Chinese herbal medicine planting. In this study, the visible light image of Polygonatum odoratum planting area in Changyi district of Jilin province were acquired by UAV, and the real-time monitoring of P. odoratum planting area was realized. The green leaf index(GLI) was established, and GLI values of P. odoratum were collected used the spatial sampling points. To compare the GLI values in different periods, it was found that the GLI values of P. odoratum have three stages changing rule of rising-gentle-falling related to the germination, vigorous growth and withered of P. odoratum growth. Meanwhile, the GLI values were compared with four biomass data of P. odoratum, including plant height, leaf area, chlorophyll a and chlorophyll b content in leaves, and it was found that the GLI value was related to the growth potential of P. odoratum. The GLI value with a rapid increase in rising stage or at a high level in the gentle stage means the P. odoratum was in a better growth potential. GLI value has a same change trend with plant height, and has certain correlation with plant height and leaf area. However, there is no obvious relationship between chlorophyll a and chlorophyll b contents in leaves and GLI value. The study clarified the change rule of GLI value of P. odoratum, explained the reason for the change of GLI value, and expanded the application range of GLI. The research shows that UAV and vegetation index can be applied to monitoring the Chinese herbal medicines planting, and provides a new idea for exploring more effective information extraction methods of Chinese herbal medicines.

Phosphorylated Heat Shock Protein 27 Inhibits Lipopolysaccharide-Induced Inflammation in Thp1 Cells by Promoting TLR4 Endocytosis, Ubiquitination, and Degradation.

The aims of this study were to investigate the effect of Hsp27 on LPS-induced inflammation and identify the precise mechanisms about how Hsp27 regulates LPS-induced TLR4 signaling in Thp1 cells. Thp1 cells were transfected with Flag-Hsp27 or pcDNA3.1, and then treated with LPS for indicated time. TNF-α, IL-1ß, and IL-6 were determined by ELISA. The protein levels of Hsp27, p-Hsp27 (Ser15, Ser78, and Ser82), and TLR4 were measured by Western blotting. In vitro study showed that over-expression of Hsp27 downregulated the release of TNF-α, IL-1ß, and IL-6 and suppressed the activation of TLR4 signals after stimulated by LPS. The location of TLR4 and RAB5 was detected by confocal microscopy. Immunoprecipitation was used to determine the ubiquitination and degradation of TLR4 and interaction between Hsp27 and TLR4. Results showed that Hsp27 could promote TLR4 endocytosis and ubiquitination and degradation. Further research revealed that Hsp27 was phosphorylated after LPS, only phosphorylated Hsp27 can interact with TLR4 and inhibit the activation of TLR4 signaling, which was demonstrated by inhibition of Hsp27 phosphorylation with inhibitors or transfection of Hsp27 mutants into Thp1 cells. Phosphorylated Hsp27 reduced the release of TNF-α, IL-1ß, and IL-6, and suppressed the activation of TLR4 signaling by promoting TLR4 endocytosis, ubiquitination, and degradation.

Heat shock protein 27 inhibits HMGB1 translocation by regulating CBP acetyltransferase activity and ubiquitination.

Heat-shock protein 27 (Hsp27) is a member of the small heat shock protein family that has been reported to protect cells against pro-inflammatory stresses. High mobility group box 1 (HMGB1) is a proinflammatory cytokine associated with death from sepsis and other inflammatory diseases. After being acetylated by CREB-binding protein (CBP), the transcriptional adaptor and acetyltransferase, HMGB1 translocates from the nucleus to the cytoplasm. In the present study, we investigated the effects of Hsp27 on HMGB1 translocation from the nucleus to the cytoplasm in THP-1 cells. We found that Hsp27 phosphorylation decreased LPS-induced HMGB1 acetylation and translocation from the nucleus to the cytoplasm, as well as its release from THP-1 cells. The study further showed that cytosolic non-phosphorylated Hsp27 enhanced CBP ubiquitination and degradation in LPS-unstimulated cells, which suggested that Hsp27 maintained suitable CBP levels under normal physiological conditions. After LPS stimulation, Hsp27 was phosphorylated at serine residues 15/78 and translocated from the cytoplasm into the nucleus. Consequently, LPS stimulation increased CBP levels and promoted its translocation into the nucleus. In the nucleus, Hsp27 bound to CBP and suppressed CBP acetyltransferase activity and the subsequent CBP-dependent acetylation of HMGB1. Taken together, our data demonstrated that cytosolic non-phosphorylated Hsp27 enhanced the ubiquitin-mediated degradation of CBP, while phosphorylated Hsp27 inhibited CBP acetyltransferase activity in the nucleus. By regulating CBP, Hsp27 maintained cell homeostasis and inhibited excessive inflammatory response.