HOXC10 and mitochondrial fission regulator 2 (MTFR2) have been reported to be abnormally expressed in multiple types of cancer tissues. However, the effects of HOXC10 and MTFR2 on colorectal cancer (CRC) remain poorly understood. Therefore, the present study aimed to investigate the expression of HOXC10 and MTFR2 in CRC tissues and cells, and analyze their effects on CRC cell proliferation, invasion and migration. Reverse transcription‑quantitative PCR and western blotting were used to detect the expression levels of MTFR2 and HOXC10 in tissues and cells. To investigate the association between MTFR2 and HOXC10, short hairpin RNA‑MTFR2 and overexpression vector‑HOXC10 were transfected into the cells, respectively. Furthermore, western blotting was performed to detect the expression levels of invasion‑associated proteins. The proliferation, clone formation, invasion and migration of colorectal cancer cells were in turn analyzed by the Cell Counting Kit‑8, clone formation, wound healing and Transwell assays. Japan Automotive Software Platform and Architecture software predicted the binding sites between HOXC10 and MTFR2, which was confirmed by the dual‑luciferase reporter assay and chromatin immunoprecipitation. The present study demonstrated that HOXC10 and MTFR2 mRNA and protein expression levels were significantly upregulated in CRC tissues and cells. MTFR2 knockdown significantly inhibited CRC cell proliferation, clone formation, invasion and migration. Furthermore, HOXC10 was shown to interact with MTFR2. HOXC10 overexpression was able to significantly reverse the inhibitory effects of MTFR2 knockdown on CRC cells. In conclusion, HOXC10 overexpression activated MTFR2 expression to enhance the proliferation, clone formation, invasion and migration of CRC cells.

CD83 is a widely recognized surface marker for mature dendritic cells, which are essential for priming naïve CD4+ T cells into effector cells. However, CD83 is also expressed on activated CD4+ T cells, which remains an enigma in T‑cell mediated immunity. Therefore, the identification of the biological features and regulation of the expression of CD83 on activated CD4+ T cells is important in understanding the function of CD83 in the adaptive immune response. The present study revealed a time‑dependent manner of the expression of CD83 on anti‑CD3/CD28‑stimulated human CD4+ T cells, which is characterized by the maximum expression at day 2 and a significant decrease at day 3. The reduced expression is not a result of a reduced rate of cell proliferation. The activation of interleukin‑2 and secretion of interferon‑γ accumulated progressively from day 1 to 3. Of note, sustained expression of CD83 was observed when CD4+ T cells were induced by transforming growth factor-β to differentiate into CD4+CD25+ forkhead box P3+ regulatory T (iTreg) cells. Confocal immunofluorescence microscopy analysis demonstrated that CD83 was highly co‑localized with CD25 on activated CD4+ T cells. In conclusion, the findings of the present study suggested that the continuous expression of CD83 on activated human CD4+ T cells is correlated with their differentiation into iTreg cells.

Behcet's disease is a multi‑system inflammatory disorder, and ocular Behcet's disease (OBD) is one of the most common causes of uveitis in China. A number of studies have indicated that Th17 cells, a subset of interleukin-17 (IL-17)-producing CD4+ T‑helper cells, serve important roles in the pathogenesis of OBD. Berberine (BBR) is an isoquinoline derivative alkaloid isolated from Chinese herbs, and has been used traditionally for the treatment of gastrointestinal disorders. The aim of the present study was to investigate the effect of BBR on Th17 cell proliferation and cytokine secretion, and the expression and activation of the signal transducer and activator of transcription 3 (STAT3) transcription factor in OBD in vitro. Blood samples were obtained from healthy controls and patients with active ocular Behcet's disease. Peripheral blood mononuclear cells (PBMCs) or CD4+ T cells were cultured for three days with or without BBR and in the presence of anti‑CD3 and anti‑CD28 antibodies. IL‑17 expression in cell sample supernatants was determined by enzyme‑linked immunosorbent assay, and cell viability was measured using the Cell Counting kit‑8 assay. The number of CD4+IL‑17+ cells and the expression level of phosphorylated (p)‑STAT3 in CD4+ T cells was determined using flow cytometry analysis. The expression of IL‑17 was increased in patients with active OBD following the activation of PBMCs and CD4+ T cells with anti‑CD3 and anti‑CD28 antibodies when compared with healthy controls. However, no significant difference in cell viability following exposure to BBR was observed in PBMCs derived from healthy controls or patients with OBD. Following incubation with BBR, the expression of IL‑17 was reduced and the number of CD4+IL‑17+ cells was decreased in patients with active OBD and healthy controls. Furthermore, the expression of p-STAT3 was significantly decreased in the presence of BBR in healthy controls. In conclusion, the results of the present study demonstrate that BBR may suppress the Th17 response in patients with OBD by reducing STAT3 phosphorylation. BBR may be a potential therapeutic agent for the treatment of OBD.

The present study aimed to investigate the serum metabolomic profiles in genetically modified cows carrying and expressing human lactalbumin α (LALBA) and non‑LALBA cows, and identify altered metabolic characteristics following the genetic modification. Serum biochemistry indexes were measured according to protocols recommended by International Federation of Clinical Chemistry. The metabolomic profiles were determined using the serum samples collected from LALBA (n=6) and non‑LALBA cows (n=6). Welch's two‑sample t‑test was used to identify the metabolites that significantly differed between the LALBA and non‑LALBA groups (fold‑change ≠ 1 and P<0.05), followed by random forest and pathway analysis. The serum biochemistry indexes of LALBA and non‑LALBA cows were within the normal ranges of healthy cows. A total of 273 metabolites were detected, among which 79 metabolites, including 46 increased and 33 decreased metabolites, differed significantly between the LALBA and non‑LALBA groups. Random forest analysis identified 30 potential key metabolites, including 14 elevated and 16 reduced metabolites. These metabolites were primarily involved in pathways concerning the metabolism of leucine, isoleucine, valine, tryptophan and lipids, such as myristate and eicosapentaenoate. However, the serum in LALBA cow had unique metabolomic signature compared with non‑LALBA cows. The accumulation of polyunsaturated fatty acids and amino acids, and the reduced levels of long chain saturated fatty acids in serum may benefit LALBA cows. However, further investigations are required to validate these benefits and the corresponding mechanisms.

The growth of biomedical research over the previous decades has been accompanied by an increase in the number, complexity and diversity of experimental animals developed as research tools, and inbred mice are some of the most widely used. However, thus far, no inbred mice have exhibited strong radioresistance for use in radiation‑damage research. To develop a radioresistant mouse model, a female Japanese outbreeding strain ICR/JCL mouse was mated with a male Chinese inbred strain 615 mouse. From the F1 generation, the mouse line was maintained by brother‑to‑sister mating. A novel mouse strain was established over >20 continuous generations and designated the Institute of Radiation Medicine-2 (IRM-2) mouse. The biological characteristics, genetic characteristics and susceptibility to radiation of these mice were determined. The IRM‑2 mice inherited traits from the parents, including strong reproductive capacity, stable physiological and biochemical indices and few differences among individuals. According to the genetic results, the IRM‑2 mice exhibited homozygosity, isogenicity and consistency, in agreement with international standards for inbred strains. Radiosensitivity studies have previously suggested that the lethal dose (LD)50 values for IRM‑2 mice were 7.17 Gy (male) and 7.5 Gy (female), resulting in a dose reduction factor value of 1.39 (male) and 1.37 (female). The mortality of IRM‑2 mice irradiated with 8 Gy total body irradiation was 15% at day 9 and 90% at day 15 after radiation. The number of nucleated cells in bone marrow, DNA content and colony‑forming unit‑spleen counts in IRM‑2 mice after exposure to γ‑ray irradiation were markedly higher than the corresponding values for the parental strains, suggesting that the IRM‑2 mice exhibit high resistance to ionizing radiation. Thus, it is suggested that this novel inbred mouse strain may be developed as an animal model of radioresistance for future use in radiation research.

The neurological disorders and neural pathology brought about by chronic alcoholism are difficult to be reversed. Increasing evidence highlights the protective roles of erythropoietin (EPO) in neurodegenerative diseases and injuries of the central nervous system. In the present study, we investigated the therapeutic effects of EPO on the neurological function deficits and neural pathology caused by chronic alcoholism and the regulatory mechanisms. Using the canonical mouse model of chronic alcohol exposure designed to mimic the repeated cycles of heavy abuse typical of chronic alcoholism, it was found that EPO delivered via intranasal route effectively restored the alcohol‑impaired motor cooperation in rotarod and beam walk tests, reversed alcoholic cognitive and emotional alterations in the novel location recognition task and open‑filed test, and rescued alcohol‑disrupted nervous conduction in the somatosensory‑evoked potential (SSEP) test. Consistently, the intranasally administered EPO promoted the remyelination and synapse formation in chronic alcohol‑affected neocortex and hippocampus as evidenced by immunofluorescence staining and transmission electron microscopy. Additionally, we discovered that the exogenous rhEPO, which entered the cerebrum through intranasal route, activated the erythropoietin receptor (EPOR) and the downstream ERKs and PI3K/AKT signaling, and suppressed autophagy‑related degradation of nuclear factor, erythroid 2‑like 2 (Nrf2). Furthermore, the intranasal EPO‑exerted neuroprotection was almost abolished when the specific Nrf2 antagonist ATRA was administered intraperitoneally prior to intranasal EPO treatment. Collectively, our data demonstrated the repairing potential of EPO for the neurological disorders and neural pathology caused by chronic alcoholism, and identified the Nrf2 activity as the key mechanism mediating the protective effects of EPO.

The present study aimed to investigate the effects of sufentanil on sepsis-induced acute lung injury (ALI), and identify the potential molecular mechanisms underlying its effect. In order to achieve this, a rat sepsis model was established. Following treatment with sufentanil, the lung wet/dry (W/D) weight ratio was calculated. Histopathological analysis was performed via hematoxylin and eosin staining. Levels of inflammatory factors in bronchoalveolar lavage fluid were determined via ELISA. Furthermore, malondialdehyde (MDA) content and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in tissue homogenates were assessed using commercial kits. Western blot analysis was performed to determine kininogen-1 (KNG1) protein expression. In addition, alveolar epithelial type II cells (AEC II) were stimulated with lipopolysaccharide (LPS) to mimic ALI. The levels of inflammation and oxidative stress were evaluated following overexpression of KNG1. Protein expression levels of nuclear factor-κB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling were determined via western blot analysis. The results of the present study demonstrated that sufentanil alleviated histopathological injury and the W/D ratio in lung tissue. Following treatment with sufentanil, levels of inflammatory factors also decreased, accompanied by decreased concentrations of MDA, and increased activities of SOD, CAT and GSH-Px. Notably, KNG1 was decreased in lung tissues following treatment with sufentanil. Furthermore, overexpression of KNG1 attenuated the inhibitory effects of sufentanil on LPS-induced inflammation and oxidative stress in AEC II. Sufentanil markedly downregulated NF-κB expression, while upregulating Nrf2 and HO-1 expression levels, which was reversed following overexpression of KNG1. Taken together, the results of the present study suggested that sufentanil may alleviate inflammation and oxidative stress in sepsis-induced ALI by downregulating KNG1 expression.

Endothelial dysfunction is a key pathophysiological step in early stage diabetes mellitus (DM) macrovascular complications and is also crucial in the inflammatory mechanisms of macrovascular complications. However, there is currently no effective intervention to improve endothelial dysfunction associated with DM macrovascular complications. Astragaloside IV (AS‑IV), which can be extracted from the traditional Chinese medicine Astragalus membranaceus, has potential therapeutic effects on DM and its complications. The present study evaluated the effect of AS‑IV on high glucose‑induced human umbilical vein endothelial cell (HUVEC) injury and its possible mechanism. The result indicated that AS‑IV has a significant protective effect on high glucose‑induced HUVEC injury. AS‑IV could significantly promote cell proliferation, reduce apoptosis and decrease the protein and mRNA expression levels of tumor necrosis factor‑α and interleukin‑1β in HUVECs. Furthermore, AS‑IV could decrease the expression of phosphorylated c‑Jun NH2‑terminal kinase (JNK) phosphorylated apoptosis signal‑regulating kinase 1, cytochrome c, cleaved‑caspase‑9, cleaved‑caspase‑3 and the relative ratio of B‑cell lymphoma‑2 associated X protein/B‑cell lymphoma‑2 in HUVECs. In conclusion, the present study demonstrated that AS‑IV could suppress apoptosis and inflammatory reactions promoted by high glucose conditions in HUVECs by inhibiting the JNK signaling pathway. These findings suggest that AS‑IV could inhibit the process of endothelial dysfunction in diabetic macrovascular complications.