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The present study aimed to investigate vascular endothelial apoptosis, and the regulatory molecules involved in the condition of heatstroke caused by direct hyperthermia due to high core temperature and gut‑derived endotoxemia. Human umbilical vascular endothelial cells (HUVECs) were isolated and treated with heat stress (43˚C for 1 h), lipopolysaccharide (LPS; 1 µg/ml), or a combination of heat stress pretreatment followed by LPS. Caspase‑3 activity, DNA fragmentation, and cell viability, determined using a 3‑(4, 5‑dimethyl thiazol‑2‑yl)‑2,5‑diphenyl tetrazolium bromide assay, were measured to examine cellular apoptosis. Changes in the expression levels of heat shock protein (HSP) 27, HSP90 and B‑cell lymphoma 2 (Bcl‑2), and the phosphorylation of p38 were detected using Western blot assays. The specific inhibitor of p38, SB203580, was also used. LPS induced endothelial apoptosis, as indicated by increased caspase‑3 activity, a high level of DNA fragmentation and low cell viability. LPS also increased p38 phosphorylation and decreased the expression levels of HSP27, HSP90 and Bcl‑2. Heat stress pretreatment inhibited LPS‑induced cellular apoptosis, increased the phosphorylation of p38, and increased the expression levels of HSP27, HSP90 and Bcl‑2. Pretreatment with SB203580 had effects similar to those of heat stress in the amelioration of LPS‑induced effects. These findings demonstrated that heat stress pretreatment decreased LPS‑induced Bcl‑2‑associated apoptosis in HUVECs by attenuating p38 activation, thereby increasing the expression levels of HSP27 and HSP90.

Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced inhibition of the transcription of the H+, K+‑ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+‑ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+‑ATPase promoter and in the expression of the gastric H+,K+‑ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+‑ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+‑ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.

Previous studies have demonstrated that traumatic brain injury (TBI) may cause neurological deficits and neuronal cell apoptosis. Quercetin, one of the most widely distributed flavonoids, possesses anti‑inflammatory, anti‑blood coagulation, anti‑ischemic and anti‑cancer activities, and neuroprotective effects in the context of brain injury. The purpose of the present study was to investigate the neuroprotective effects of quercetin in TBI. A total of 75 rats were randomly arranged into 3 groups as follows: Sham group (Sham); TBI group (TBI); and TBI + quercetin group (Que). Brain edema was evaluated by analysis of brain water content. The neurobehavioral status of the rats was evaluated by Neurological Severity Scoring. Immunohistochemical and western blot analyses were used to measure the expression of certain proteins. The results of the present study demonstrated that post‑TBI administration of quercetin may attenuate brain edema, in addition to improving motor function in rats. Additionally, quercetin caused a marked inhibition of extracellular signal‑regulated kinase 1/2 phosphorylation and activated Akt serine/threonine protein kinase phosphorylation, which may result in attenuation of neuronal apoptosis. The present study provided novel insights into the mechanism through which quercetin may exert its neuroprotective activity in a rat model of TBI.

Heat stress may induce intestinal epithelial cell apoptosis; however, the molecular mechanisms have not yet been identified. The present study used IEC‑6 rat small intestinal epithelial cells to investigate heat stress‑induced production of reactive oxygen species (ROS), which may be involved in nuclear factor (NF)‑κB activation during heat stress. IEC‑6 cells were transfected with NF‑κB p65‑specific small interfering RNA (siRNA), and observed a significant increase in cell apoptosis and caspase‑3 cleavage; however, in cells transfected with adenovirus that constitutively overexpressed p65, the opposite results were obtained. Furthermore, p65 knockdown increased the heat stress‑induced expression and activity of heat shock transcription factor 1 (HSF1); conversely, p65 overexpression slightly decreased HSF1 activity. The levels of heat stress‑induced c‑Jun phosphorylation were also examined: Knockdown of p65 resulted in a reduction of c‑Jun phosphorylation, whereas p65 overexpression resulted in increased phosphorylation. Furthermore, siRNA‑mediated knockdown of HSF1 in IEC‑6 cells significantly increased heat stress‑induced apoptosis. Cells pretreated with c‑Jun peptide, an inhibitor of c‑Jun activation, exhibited a significant reduction in apoptosis. These findings indicated that heat stress stimulation in IEC‑6 cells induced the pro‑apoptotic role of NF‑κB by regulating HSF1 and c‑Jun activation.

Trichohepatoenteric syndrome (THES) is a rare autosomal, recessively inherited disorder. Mutations in the tetratricopeptide repeat domain 37 (TTC37) gene and the superkiller viralicidic activity 2‑like (SKIV2L) gene have been identified to cause THES. The present study reported a case of a Chinese boy, who presented clinically with intrauterine growth retardation, intractable diarrhea, facial dysmorphism, abnormal scalp hair shafts, immune disorders and liver involvement. Targeted next‑generation sequencing and Sanger DNA sequencing showed compound heterozygous mutations of the SKIV2L gene. The present study was the first, to the best of our knowledge, to report a case of a boy with THES resulting from compound heterozygous mutations of the SKIV2L gene in China. Target sequence capture combined with high‑throughput next‑generation sequencing technologies have shown to be effective methods for the molecular genetic assessment of rare inherited disorders.

Gut-derived endotoxin and pathogenic bacteria have been proposed to be important causative factors of morbidity and mortality due to heat stroke. However, the molecular mechanisms underlying the small intestinal lesions caused by heat stroke have yet to be well characterized. In order to verify the possible inflammatory pathogenesis of intestinal tissue injury, a mouse heat stroke model was established. Cooling treatment was applied, mimicking the clinical therapy. Morphologic changes in intestinal tissue and 10 cytokines and chemokines produced from ileum tissue were detected, and their correlation was analyzed. As a result, intestinal lesions in mice worsened with the increase in rectal core temperature (Tc) during heat stress. When heat stress was halted at a Tc of no more than 41°C followed by cooling treatment, pathological recovery from the injury of heat stress was observed. However, when cooling treatment was applied after the Tc reached 42°C, the lesions continuously deteriorated until the animals succumbed. The levels of pro-inflammatory (IL-1β, IL-2, IL-6 and TNF-α) and anti-inflammatory (IL-10, IL-12p40) cytokines showed significant changes at different time points during the heat stress and cooling treatment, but no changes in GM-CSF, MCP-1, MIP-1α and IL-4 were observed. Levels of IL-1β, IL-10 and IL-12p40 were moreover significantly correlated with intestinal injury scores. A significant inverse linear correlation was observed between intestinal injury and IL-12p40 levels. In conclusion, this study provided insight into the inflammatory pathogenesis of intestinal tissue injury after heat stress and cooling treatment in a mouse model, and presented a potential biomarker for the evaluation of intestinal injury during heat stroke.