Question prompt list intervention for patients with advanced cancer: a systematic review and meta-analysis.

BACKGROUND: Enhanced communication in end-of-life care (EOL) improves preparation and treatment decisions for patients with advanced cancer, affecting their quality of life at the end of life. Question prompt list (QPL) has been shown to enhance physician-patient communication in patients with cancer, but there is a lack of systematic review and meta-analysis for those with advanced cancer. Enhanced communication in end-of-life care improves preparation and treatment decisions for patients with advanced cancer, affecting their quality of life at the end of life. OBJECTIVE: To review the effectiveness of QPL intervention on physician-patient communication and health outcomes during consultation in patients with advanced cancer. METHODS: CINAHL, Embase, Scopus, and PsycINFO databases were undertaken using inclusion criteria for relevant articles up to August 2021. Pooled standardized mean difference (SMD) and 95% confidence intervals (CIs) were calculated using random-effects models. We used the Cochrane risk-of-bias assessment tool and modified Jadad scale to assess the quality of the studies. RESULTS: Seven RCTs with 1059 participants were included, of which six studies were eligible for the meta-analysis. The pooled meta-analysis results indicated that QPL in patients with advanced cancer had a significant positive effect on the total number of questions asked (SMD, 0.73; 95% CI, 0.28 to 1.18; I2 = 83%) and on the patients' expectations for the future (SMD, 0.67; 95% CI, 0.08 to 1.25; I2 = 88%). There were no significant improvements in health-related outcomes such as end of life, anxiety, and quality of life. CONCLUSIONS: Using QPL in advanced cancer consultations boosts patient questions which helps communication but not health-related indicators. Optimal results depend on full reading, but timing varies. Future research should examine the relationship between communication and health outcomes, including patient/physician behavior and social context.

Improving Patient Safety Culture During the COVID-19 Pandemic in Taiwan.

Background and Aim: Patient safety culture attitude is strongly linked to patient safety outcomes. Since the onset of the COVID-19 pandemic in early 2020, pandemic prevention has become the priority of hospital staff. However, few studies have explored the changes in patient safety culture among hospital staff that have occurred during the pandemic. The present study compared the safety attitudes, emotional exhaustion (EE), and work-life balance (WLB) of hospital staff in the early (2020) and late (2021) stages of the COVID-19 pandemic and explored the effects of EE and WLB on patient safety attitudes in Taiwan. Materials and Methods: In this cross-sectional study, the Joint Commission of Taiwan Patient Safety Culture Survey, including the six-dimension Safety Attitudes Questionnaire (SAQ) and EE and WLB scales, were used for data collection. Results: This study included a total of 706 hospital employees from a district hospital in Taipei City. The respondents' scores in each SAQ sub-dimension (except for stress recognition) increased non-significantly from 2020 to 2021, whereas their EE and WLB scores improved significantly (P < 0.05 and P < 0.01, respectively). The results of hierarchical regression analysis indicated that although a respondent's WLB score could predict their scores in each SAQ sub-dimension (except for stress recognition), EE was the most important factor affecting the respondents' attitudes toward patient safety culture during the later stage of the COVID-19 pandemic. Conclusion: In the post-pandemic, employees' attitudes toward safety climate, job satisfaction, and perception of Management changed from negative to positive. Additionally, both EE and WLB are key factors influencing patient safety culture. The present study can be used as a reference for hospital managers to formulate crisis response strategies.

The Comparative Effect of Reduced Mindfulness-Based Stress on Heart Rate Variability among Patients with Breast Cancer.

Heart rate variability (HRV) is a powerful tool for observing interactions between the sympathetic and parasympathetic nervous systems. This study evaluated HRV during a mindfulness-based stress reduction (MBSR) program among women with breast cancer after receiving treatment. A quasi-experimental, nonrandomized design was used. Patients were allocated to usual care (n = 25) and MBSR (n = 25) groups. HRV was measured using recognized methods to assess the autonomic nervous system. Two-way ANOVA and t-tests were used to examine HRV changes between and within groups, respectively. A significant interaction effect of time with group was observed on heart rate (F (1, 96) = 4.92, p = 0.029, η2 = 0.049). A significant difference was also observed within the MBSR group preintervention and postintervention with regard to heart rate (t (24) = −3.80, p = 0.001), standard deviation of the RR interval (t (24) = 5.40, p < 0.001), root-mean-square difference in the RR interval (t (24) = 2.23, p = 0.035), and high-frequency power (t (24) = 7.73, p < 0.001). Large effect sizes for heart rate and SDNN of 0.94 and 0.85, respectively, were observed between the MBSR and usual care groups. This study provides preliminary evidence that an MBSR program may be clinically useful for facilitating parasympathetic activity associated with feelings of relaxation in treated breast cancer survivors.

URAT1 inhibition by ALPK1 is associated with uric acid homeostasis.

Objective: The aim of this study was to identify a protein for urate transporter 1 (URAT1) regulation. Methods: The clinical dataset consisted of 492 case-control samples of Han Chinese (104 gout and 388 controls). Three alpha kinase 1 ( ALPK1 ) and SLC22A12 loci associated with high gout risk and uric acid levels were genotyped. The overexpression of ALPK1 on URAT1 protein expression was evaluated in vivo in h ALPK1 transgenic mice. The in vitro protein levels of ALPK1 and URAT1 in ALPK1 small interfering RNA-transfected human kidney-2 cells with MSU crystal stimulation were examined. Results: ALPK1 , which is a single nucleotide polymorphism (SNP) of rs11726117 (M861T; T), reduced the risk of gout via the SLC22A12 gene SNPs rs3825016 and rs475688, as compared with the subject of ALPK1 rs11726117 (C) allele {rs11726117 [CT + TT] vs rs3825016, odds ratio [OR] 0.39 [95% confidence interval (CI) 0.23, 0.67]; rs11726117 [CT + TT] vs rs475688, OR 0.39 [95% CI 0.23, 0.67]}. ALPK1-overexpressed mice demonstrated lower levels of URAT1 protein ( P = 0.0045). Mouse endogenous ALPK1 proteins were detected in renal proximal tubule cells. MSU crystals inhibited URAT1 expressions through an upregulation of ALPK1 in human kidney-2 cells. Conclusion: Elevated ALPK1 expression decreased URAT1 expression. ALPK1 might prevent the impact of urate reuptake via SLC22A12 and appeared to be negatively associated with gout. ALPK1 is a potential repressor of URAT1 protein expression.

Pre-existent Hsp72 contributes to glutamine-induced hepatic hsp72 gene activation during heat shock recovery period in rat.

SCOPE: Functional maintenance of liver is very important at all times for personal health. Hsp induction is associated with the protection of the organ. Glutamine, a nutrient inducer of Hsps, enhances cellular survival via Hsp72 induction in several organs, but not in the liver. The present study showed a novel approach to facilitate glutamine-induced hepatic Hsp72 synthesis and its possible mechanisms were discussed. METHODS AND RESULTS: Sprague-Dawley rats were used as the experimental animals and the livers were the targets. Glutamine was administered via tail-vein injection, and its effects on hsp72 gene activation, including Hsp72 expression, heat shock factor-1 (HSF-1) phosphorylation and DNA-binding activation, were evaluated. The results showed that Hsp72 itself played a critical role in glutamine-induced hepatic Hsp72 synthesis during HS recovery period in a dose-dependent manner of preexistent Hsp72. The peak value of HSF-1 phosphorylation, HSF-1 DNA-binding activity, hsp72 mRNA accumulation, and Hsp72 synthesis was detected at 8 h after glutamine administration. CONCLUSION: Glutamine switched on alteration pathway in inducing hsp72 gene activation. The existence of Hsp72 plays a critical role in the reactivation of hsp72 gene. Glutamine sustained the induction of intracellular Hsp72, which could be beneficial in protecting the liver from various injuries.

Monoamine oxidase A variants are associated with heavy betel quid use.

Few studies have investigated whether genetic abnormalities predispose individuals to heavy betel quid (BQ) use. One of the major ingredients of BQ, arecoline, is known to affect the expression of monoamine oxidase A (MAO-A). We investigated the extent to which arecoline inhibits MAO-A expression and the role of MAO-A polymorphisms in BQ use in Taiwanese aborigines. Cytotoxicity assays, microarrays and quantitative reverse transcriptase-polymerase chain reaction were used to examine the effects of arecoline and areca nut extract (ANE) on cell viability and MAO-A expression in neuroblastoma SH-SY5Y cells. After identifying the effective concentrations of arecoline and ANE in vitro, we examined the in vivo effects of these compounds using a rat model system. Our results indicate that arecoline and ANE inhibit MAO-A expression both in vitro and in vivo. In addition, we examined the correlation between plasma MAO-A activity and cumulative exposure to BQ in humans. We recruited 1307 aborigines from a large-scale community-based survey to determine whether MAO-A variants were associated with high BQ use and a preference for use with smoking or alcohol and whether gender bias existed. MAO-A expression was significantly downregulated by arecoline and ANE at 100-200 µg/ml and in rat whole brains on days 30 and 45. MAO-A activity levels in human plasma were positively correlated with the extent of BQ exposure, and individuals with at-risk alleles exhibited lower activity, although this result did not reach statistical significance. We found two single nucleotide polymorphism (SNPs) in aboriginal males [rs2283725, odds ratio (OR) = 2.04; rs5953210, OR = 2.03] and females (rs2283725, OR = 1.54; rs5953210, OR = 1.59) that were associated with heavy BQ use. Those individuals carrying at-risk alleles who drank alcohol were twice as likely to be heavy BQ users. However, the effects of these SNPs on BQ use were significant even after controlling for alcohol use. Our results suggest that two specific loci may confer a susceptibility to BQ abuse and affect MAO-A enzymatic activity.

Lymphocyte α-kinase is a gout-susceptible gene involved in monosodium urate monohydrate-induced inflammatory responses.

The molecular functions and pathophysiologic role of the lymphocyte α-kinase gene (ALPK1) in gout are unknown. We aimed to examine ALPK1 expression in patients with gout and investigate its role in monosodium urate monohydrate (MSU)-induced inflammatory responses. Microarray data mining was performed with six datasets containing three clinical gout and three volunteer samples. Real-time quantitative polymerase chain reaction (qPCR) assay was used to profile ALPK1 mRNA expression in 62 independent samples. RNA interference for ALPK1 suppression in THP1 cells (human monocytic cell line) was used to scrutinize the functional role of ALPK1 in MSU-mediated inflammatory responses, and ALPK1 expression in MSU-treated THP1 cells was determined by qPCR and Western blot analysis. Cytokine mRNA expression in HEK293 cells after incubation with different concentrations of MSU crystals in the presence or absence of ALPK1 was also detected by qPCR, and ERK1/2, p38, and JNK expressions were investigated by Western blot analysis. ALPK1 mRNA was overexpressed in the clinical gout samples. MSU treatment promoted ALPK1 expression at the mRNA and protein levels. Furthermore, ALPK1 knockdown in THP1 cells resulted in a markedly decreased IL-1ß, TNF-α, and IL-8 mRNA expression; plasmid ALPK1 transfection and MSU stimulation synergistically increased the mRNA expression of these cytokines in a concentration-dependent manner. The synergistic effect also led to ERK1/2 activation. ALPK1 is a gout-susceptible gene involved in MSU-induced inflammatory responses. It may contribute to the development of gout by enhancing the inflammatory responses via the mitogen-activated protein kinase pathway.

CYP26B1 is a novel candidate gene for betel quid-related oral squamous cell carcinoma.

Substantial epidemiological data suggest a role for environmental factors (for example, the use of alcohol, betel quid (BQ), and cigarettes) in the occurrence of oral squamous cell carcinoma (OSCC), but the evidence for the genes involved has been inconsistent. This study was to investigate the role of CYP26B1, together with the use of alcohol, BQ, and cigarettes, on BQ-related OSCC. The association study (247 OSCC cases and 338 controls) was conducted to examine the possible interplay between CYP26B1 polymorphisms and alcohol, BQ, and cigarettes use. Additional gene expression was evaluated between OSCC tissue and adjacent normal tissue. The genetic polymorphism AA of CYP26B1 appeared to correlate with the risk of OSCC (OR=2.26; 95% CI, 1.35-3.80). Chewing BQ multiplicatively interacted with CYP26B1 AA to increase the OSCC risk (aOR=70.04; 95% CI, 13.62-360.11). The independent risk of OSCC was observed among BQ chewers with CYP26B1 AA, and compared with chewers with the CYP26B1 CC genotype (stratified aOR=2.88; 95% CI, 1.07-7.74). Increased expression of CYP26B1 was observed in tumor tissue compared with adjacent normal tissue. The CYP26B1 gene plays a novel role in the BQ dependent pathogenesis of OSCC.

Associations of a non-synonymous variant in SLC2A9 with gouty arthritis and uric acid levels in Han Chinese subjects and Solomon Islanders.

OBJECTIVE: To study the associations of gout, tophi and uric acid levels with the gout-related SLC2A9 (solute carrier family 2, member 9) single nucleotide polymorphisms (SNPs) between two different racial groups. METHODS: Eight SLC2A9 SNPs were genotyped in 109 subjects with gout and 191 control subjects from Han Chinese men in Taiwan and 69 subjects with gout and 168 control subjects from the Solomon Islands. RESULTS: Non-synonymous SLC2A9 rs3733591 Arg265His was associated with risk for gout and tophaceous gout in Han Chinese subjects (p=0.0012 and p=0.0044). The genetic effect of this SNP on tophaceous gout was replicated in Solomon Islanders (p=0.0184). Patients with SLC2A9 Arg265His risk C-allele consistently had a higher risk for tophi (OR 2.05-2.15) than non-tophi (OR 0.91-1.62). SNP rs3733591 described 3.68% and 5.98% of the total variability in uric acid levels for Chinese and Solomon Island subjects, respectively. CONCLUSION: Non-synonymous SNP rs3733591 variant within the SLC2A9 gene from two geographically diverse populations served as an important genetic checkpoint for tophaceous gout and increased uric acid levels.

Monoamine oxidase A gene polymorphisms and enzyme activity associated with risk of gout in Taiwan aborigines.

Taiwanese aborigines have a high prevalence of hyperuricemia and gout. Uric acid levels and urate excretion have correlated with dopamine-induced glomerular filtration response. MAOs represent one of the major renal dopamine metabolic pathways. We aimed to identify the monoamine oxidase A (MAOA, Xp11.3) gene variants and MAO-A enzyme activity associated with gout risk. This study was to investigate the association between gout and the MAOA single-nucleotide polymorphisms (SNPs) rs5953210, rs2283725, and rs1137070 as well as between gout and the COMT SNPs rs4680 Val158Met for 374 gout cases and 604 controls. MAO-A activity was also measured. All three MAOA SNPs were significantly associated with gout. A synonymous MAOA SNP, rs1137070 Asp470Asp, located in exon 14, was associated with the risk of having gout (P = 4.0 x 10(-5), adjusted odds ratio 1.46, 95% confidence intervals [CI]: 1.11-1.91). We also showed that, when compared to individuals with the MAOA GAT haplotype, carriers of the AGC haplotype had a 1.67-fold (95% CI: 1.28-2.17) higher risk of gout. Moreover, we found that MAOA enzyme activity correlated positively with hyperuricemia and gout (P for trend = 2.00 x 10(-3) vs. normal control). We also found that MAOA enzyme activity by rs1137070 allele was associated with hyperuricemia and gout (P for trend = 1.53 x 10(-6) vs. wild-type allele). Thus, our results show that some MAOA alleles, which have a higher enzyme activity, predispose to the development of gout.

Previous heat shock facilitates the glutamine-induced expression of heat-shock protein 72 in septic liver.

OBJECTIVES: This study investigated the effects of glutamine administration on the expression of the heat-shock protein 72 (Hsp72) in the liver during sepsis. The role of heat-shock factor 1 (HSF-1) was analyzed for possible mechanisms to the phenomenon. METHODS: Male Sprague-Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). Heat-shock treatment was applied to the rats' whole body using an electric heating pad 24 h before CLP. Glutamine or saline was administered 1 h after initiation of sepsis by tail vein injection. The Hsp72 and HSF-1 expressions were detected using western blot analysis, and Hsp72 mRNA expression was measured using reverse transcription-polymerase chain reaction. RESULTS: The Hsp72 content noticeably increased in the livers of preheated rats supplied by glutamine 1 h after sepsis. However, no further synthesis of Hsp72 was found in septic livers or sham glutamine-treated livers. Hsp72, which was induced by preheating, decreased with time, whereas a large amount of Hsp72 could be detected by glutamine administration. Reverse transcription-polymerase chain reaction data indicated that Hsp72 mRNA could be detected only in the group treated with preheating and glutamine administration. The translocation of HSF-1 occurred significantly during sepsis in preheated and non-preheated rats. However, only the preheated group showed the phosphorylation in HSF-1. With the administration of glutamine, the nuclear accumulation of phosphorylated HSF-1 was observed to decline significantly 9 and 18 h after CLP when the Hsp72 mRNA became detectable. CONCLUSIONS: These results demonstrated that Hsp72 could be induced by glutamine in septic liver only if the liver was preconditioned by heat-shock response. The selective facilitating effect might depend on the accumulation of intranuclear phosphorylated HSF-1 caused by previous heat-shock treatment.

Suppression of mitochondrial ATPase inhibitor protein (IF1) in the liver of late septic rats.

Sepsis and ensuing multiple organ failure continue to be the most leading cause of death in critically ill patients. Despite hepatocyte-related dysfunctions such as necrosis, apoptosis as well as mitochondrial damage are observed in the process of sepsis, the molecular mechanism of pathogenesis remains uncertain. We recently identified one of the differentially expressed genes, mitochondrial ATPase inhibitor protein (IF1) which is down-regulated in late septic liver. Hence, we further hypothesized that the variation of IF1 protein may be one of the causal events of the hepatic dysfunction during late sepsis. The results showed that the elevated mitochondrial F0F1-ATPase activity is concomitant with the decline of intramitochondrial ATP concentration in late septic liver. In addition, the key finding of this study showed that the mRNA and the mitochondrial content of IF1 were decreased in late sepsis while no detectable IF1 was found in cytoplasm. When analyzed by immunoprecipitation, it seems reasonable to imply that the association capability of IF1 with F1-ATPase beta-subunit is not affected. These results confirm the first evidence showing that the suppression of IF1 expression and subsequent elevated mitochondrial F0F1-ATPase activity might contribute to the bioenergetic failure in the liver during late sepsis.

In vivo heat shock protein assembles with septic liver NF-kappaB/I-kappaB complex regulating NF-kappaB activity.

This study elucidates the mechanism through which heat shock treatment influences the outcome of sepsis. Post-heat shock sepsis was induced in rats by CLP 24 h after whole-body hyperthermia. Liver cytosolic and nuclear fractions were collected and analyzed in early and late sepsis rats (sacrificed 9 and 18 h after CLP, respectively). During sepsis, levels of I-kappaB and nuclear factor-kappaB (NF-kappaB) declined in the cytosol of liver, whereas NF-kappaB increased in nucleus. NF-kappaB activity was significantly enhanced during sepsis, and the products of NF-kappaB target genes, such as TNF-alpha and inducible nitric oxide synthase (iNOS), were overexpressed. Heat shock treatment, inducing heat shock protein synthesis, prevented down-regulation of cytosolic I-kappaB and decreased translocation of NF-kappaB into the nucleus. Therefore, the sepsis-induced acceleration of NF-kappaB activation was inhibited. Expression of TNF-alpha and iNOS mRNA was also down-regulated. Coimmunoprecipitation with anti-NF-kappaB (p65) and anti-IkappaB antibodies verified an assembling phenomenon of heat shock protein (HSP) 72 with NF-kappaB and I-kappaB. We suggest that the mechanism preventing septic activation of NF-kappaB is that oversynthesized HSP72 forms a complex with NF-kappaB/I-kappaB, thus inhibiting nuclear translocation of NF-kappaB. HSP72 appears to play a crucial protective role in modulating the gene expression controlled by NF-kappaB in sepsis.

Cytochrome c oxidase as the target of the heat shock protective effect in septic liver.

Liver function failure is one of the characteristics of critically ill, septic patients and is associated with worse outcome. Our previous studies have demonstrated that heat-shock response protects cells and tissue from subsequent insults and improves survival during sepsis. In this study, we have shown that mitochondrial cytochrome c oxidase (CCO) is one of the major sources of that protective effect. Experimental sepsis was induced by the cecal ligation and puncture (CLP) method. Heat-shock treatment was induced in rats by hyperthermia 24 h before CLP operation. The results showed that ATP content of the liver declined significantly, and the enzymatic activity of mitochondrial CCO was apparently suppressed during the late stages of sepsis. The mitochondrial ultrastructure of septic liver showed the deformity, mild swelling and inner membrane budding. Heat-shock treatment led to heat-shock protein 72 overexpression and prevented the downregulation of Grp75 during sepsis. On the contrary, the expression of the enzyme complex and its activity were preserved, associated with the minimization of ultrastructural deformities. In conclusion, the maintenance of mitochondrial function, especially the CCO, may be an important strategy in therapeutic interventions of a septic liver.

Fall risk factors assessment tool: enhancing effectiveness in falls screening.

A quasi-experimental study was conducted to explore the effectiveness of fall prevention among hospital patients based on the modified fall risk factors assessment tool. We investigated the frequency of falls among hospital patients at a medical center in Taiwan. The experimental group of falls victims was selected from patients (n = 39) hospitalized in 2002 after falls. The control group of patients falls was selected by means of a retrospective incident report review which identified patients (n = 43) hospitalized one year earlier. The results showed that there was no significant difference in the incidence of falls between the two groups. Nevertheless, there were significant differences in age, indications of falls, use of sedatives, walking ability and evaluated grade of fall risk factors. In addition, the average level of satisfaction under recently modified fall risk factors evaluation guideline was 2.68 points (upper limit = 4 points) based upon investigation derived from nursing staff ' s opinions. Moreover, nursing staff from GYN/OBS and orthopedics departments acknowledged the enhanced effectiveness of these new guidelines. The screening rate for high-risk orthopedic patients was increased from 20.7 % to 41.9 %. Furthermore, the screening rate among the experimental group (74.4 % ) was also higher than that among the control group (60.5 % ) ( p <.01). In line with our effective tool to screen high-risk patients, we also added the concept of continuous quality improvement in nursing care to implement a fall prevention program to reduce unnecessary injury. This strategy may assist nursing personnel in providing immediate and individualized care as well as health education for high-risk patients. It may also cause the incidence of patient falls in hospitals to continue to decline.

The essential role of PKCalpha in the protective effect of heat-shock pretreatment on TNFalpha-induced apoptosis in hepatic epithelial cell line.

During sepsis, hepatic apoptosis occurred, which is associated with inactivation of PKCalpha and elevation of tumor necrosis factor-alpha (TNFalpha), an apoptosis trigger. Heat shock, accompanied by the increase of heat-shock protein (Hsp72), has been shown to exhibit a protective role on cell survival. However, Hsp72 was unable to express during sepsis when the apoptosis was markedly increased. We hypothesized that hepatic apoptosis during sepsis may be due to the failure to induce expression of Hsp72, which is activated by PKC-phosphorylated HSF. This study was designed to examine the role of PKCalpha in Hsp72 expression and the anti-apoptotic effect of Hsp72 on hepatic epithelial cells by analyzing a TNFalpha-induced apoptosis system. The following results were observed: (1) Hsp72 was highly expressed at 8 h after heat-shock treatment in a clone 9 hepatic epithelial cell line; (2) the protein expression of PKCalpha in membrane-associated fraction was decreased by TNFalpha treatment; (3) the TNFalpha-induced cell death, especially apoptosis, was diminished by heat-shock pretreatment; (4) in the presence of PKCalpha antisense, which blocks the PKCalpha resynthesis, no protective effect of heat-shock pretreatment was observed, and the protein expression of Hsp72 was significantly suppressed. These results suggest that PKCalpha plays a critical role in the expression of Hsp72, which subsequently protects against TNFalpha-induced hepatic apoptosis.

Heat shock treatment protects osmotic stress-induced dysfunction of the blood-brain barrier through preservation of tight junction proteins.

The blood-brain barrier (BBB) is a specialized structure in the central nervous system (CNS), which participates in maintenance of a state of cerebrospinal fluid homeostasis. The endothelial cells of the cerebral capillaries and the tight junctions between them form the basis of the BBB. Research has shown that destruction of the BBB is associated with diseases of the CNS. However, there is little research on how the BBB might be protected. In this study, we used a high osmotic solution (1.6 M D-mannitol) to open the BBB of rats and Evans blue dye as a macromolecular marker. The effect of heat shock treatment was evaluated. The results show that increased synthesis of heat shock protein 72 (Hsp72) was induced in the heated group only. BBB permeability was significantly less in the heat shock-treated group after hyperosmotic shock. The major tight junction proteins, occludin and zonula occludens (ZO)-1, were significantly decreased after D-mannitol treatment in the nonheated group, whereas they were preserved in the heated group. The coimmunoprecipitation studies demonstrated that Hsp72 could be detected in the precipitates of brain extract interacting with anti-ZO-1 antibodies as well as those interacting with anti-occludin antibodies in the heated group. We conclude that the integrity of tight junctions could be maintained by previous heat shock treatment, which might be associated with the increased production of Hsp72.

Heat shock pretreatment prevents cardiac mitochondrial dysfunction during sepsis.

The present study was designed to investigate the effect of previous heat shock treatment on the mitochondria function of the heart during a cecal ligation and puncture (CLP)-induced sepsis model. Rats of the heated group were heated by whole-body hyperthermia 24 h before the CLP operation. Cardiac mitochondria were freshly collected 9 and 18 h after CLP, indicating early and late sepsis, respectively. The expressions of heat shock protein 72 (Hsp72), glucose-regulated protein 75 (Grp75), and mitochondrial complexes I, II, III, and IV were evaluated by Western blot and immunochemical analysis. Enzyme activities of NADH cytochrome c reductase (NCCR), succinate cytochrome c reductase (SCCR), and cytochrome c oxidase (CCO) were measured after the reduction or oxidation of cytochrome c using a spectrophotometer. The results showed that the ATP content in the heart significantly declined during late sepsis, whereas heat shock treatment reversed this declination. The enzyme activities of NCCR, SCCR, and CCO were apparently suppressed during late stage of sepsis. The protein expressions of mitochondrial complex II and complex IV and Grp75 were also down-regulated during sepsis. Previously treated by heat shock, late-sepsis rats emerged with a high preservation of mitochondrial respiratory chain enzymes, both the protein amount and enzyme activity. Aspects of morphology were observed by electron microscopy, while heat shock treatment revealed the attenuation of cardiac mitochondrial damage induced by sepsis. In conclusion, structural deformity and the decrease of respiratory chain enzyme activity in mitochondria and its leading to a decline of ATP content are highly correlated with the deterioration of cardiac function during sepsis, and heat shock can reverse adverse effects, thus achieving a protective goal.