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During the sudden epidemic of this novel coronavirus-induced pneumonia, a number of medical staff were infected and even succumbed to coronavirus disease-19 (COVID-19). Based on the experience of medical professionals from The Hubei 672 Orthopedics Hospital of Integrated Chinese and Western Medicine on this COVID-19 pandemic, the present review summarizes the risk factors associated with the occupational exposure of front-line medical staff. Challenges encountered include insufficient understanding, lack of early protection, environmental factors and routine procedures and the lack of adequate prevention strategies. Overcoming these challenges can potentially enhance awareness of COVID-19 prevention and control among medical staff, in addition to strengthening the personal protection of front-line medical staff, rational area layout, regular disinfection, standardization of daily procedures, reasonable scheduling and early psychological intervention. The present article may serve as a referencing point for the prevention and control of this epidemic. [ABSTRACT FROM AUTHOR]

Vagus nerve activation may have important therapeutic significance for myocardial ischemia-reperfusion (IR) injury. Nitric oxide (NO) plays a vital role in the cardioprotective effects of anesthetic preconditioning (APC). Moreover, acetylcholine (ACh) prevents cardiomyocyte damage by activating AMP-activated protein kinase (AMPK) and increasing the phosphorylation of Ca2+/calmodulin-dependent protein kinase β (CaMKKβ). The aim of the present study was to determine whether APC could protect heart function by antagonizing IR damage via the cholinergic system. It was hypothesized that the NO synthase (NOS)/CaMKKβ/AMPK pathway might be involved in the cardioprotective effects induced by cholinergic receptor activation. Isolated rat hearts were subjected to ischemia for 30 min followed by 120 min of reperfusion. Volatile anesthetic sevoflurane (3.5%) was administered for 15 min before ischemia, then rinsed for 15 min. The muscarinic acetylcholine receptor (mAChR) antagonist atropine (ATR; 100 nM) and the nicotinic acetylcholine receptor (nAChR) antagonist hexamethonium (HEM; 50 μM) were administered 10 min before APC. Both mAChR and nAChR were involved in APC-induced cardioprotection. ATR and HEM treatment both abolished the protective effects of APC on IR damage in isolated hearts, demonstrating the importance of cholinergic receptors in the protection mechanism of APC. The present study thus suggests that APC plays a cardioprotective role, in part, by regulating neurohumoral pathways. In addition, there may be functional coupling between the two cholinergic receptors, and the NOS and CaMKKβ/AMPK pathways may play roles in shared pathways that mediate the cardioprotective effects of APC. These findings may provide insight into potential new mechanisms of APC-induced cardioprotection against IR injury. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has become a major cause of cancer-related mortality worldwide. Circular RNA s (circRNA s) are non-coding RNA s that serve important roles in multiple cancers. However, the role of circRNA s in HCC remains largely unknown. In the present study, a circRNA microarray dataset of HCC samples, GSE97332, was downloaded from the gene expression omnibus database. Following data preprocessing, differentially expressed circRNA s between HCC tissues and normal tissues were determined using GEO 2R. The circRNA- miRNA interactions were predicted by the miRanda database. The miRTarbase database was used to search for target genes of the miRNA s. A circRNA- miRNA- mRNA network was constructed using Cytoscape based on the obtained circRNA, miRNA and mRNA. In this network, the upregulated circRNA hsa_circRNA _100084 was found to be involved in a competing endogenous relationship of hsa_ circRNA _100084-hsa-miR- 23a-5p- insulin-like growth factor 2 (IGF2). The differential expression of hsa_circRNA _100084, hsa-miR- 23a-5p and IGF2 in HCC tissues and liver cancer cells was validated by reverse transcription-quantitative PCR. Additionally, the interactions between hsa-miR- 23a-5p with hsa_circRNA _100084 and IGF2 were validated by dual-luciferase reporter assays. Knocking down hsa_circRNA _100084 inhibited the proliferation, migration and invasion of liver cancer cells, while the simultaneous overexpression of IGF2 reversed the effects of hsa_circRNA _100084 knockdown. The results show that hsa_circRNA _100084 could promote the expression of IGF2 by acting as a sponge of hsa-miR- 23a-5p in liver cancer cells. [ABSTRACT FROM AUTHOR]

Pancreatic cancer rapidly acquires resistance to chemotherapy resulting in its being difficult to treat. Gemcitabine is the current clinical chemotherapy strategy; however, owing to gemcitabine resistance, it is only able to prolong the life of patients with pancreatic cancer for a limited number of months. Understanding the underlying molecular mechanisms of gemcitabine resistance and selecting a suitable combination of agents for the treatment of pancreatic cancer is required. Astaxanthin (ASX) is able to resensitize gemcitabine-resistant human pancreatic cancer cells (GR-HPCCs) to gemcitabine. ASX was identified to upregulate human equilibrative nucleoside transporter 1 (hENT1) and downregulate ribonucleoside diphosphate reductase (RRM) 1 and 2 to enhance gemcitabine-induced cell death in GR-HPCCs treated with gemcitabine, and also downregulates TWIST1 and ZEB1 to inhibit the gemcitabine-induced epithelial-mesenchymal transition (EMT) phenotype in GR-HPCCs and to mediate hENT1, RRM1 and RRM2. Furthermore, ASX acts through the hypoxia-inducible factor 1α/signal transducer and activator of transcription 3 signaling pathway to mediate TWIST1, ZEB1, hENT1, RRM1 and RRM2, regulating the gemcitabine-induced EMT phenotype and gemcitabine-induced cell death. Co-treatment with ASX and gemcitabine in a tumor xenograft model induced by GR-HPCCs supported the in vitro results. The results of the present study provide a novel therapeutic strategy for the treatment of gemcitabine-resistant pancreatic cancer. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the impacts of telmisartan (TEL) on hepatic fibrosis, serum leptin, leptin protein in liver tissue and its mRNA expression level in rats with non-alcoholic fatty liver disease (NAFLD). Male Sprague Dawley rats were randomly divided into the control (N), model (M), polyene phosphatidylcholine (P) and TEL (T) groups. Group M and the intervention groups were given a high-fat diet for 12 weeks to induce NAFLD, followed by 4 weeks of intragastric administration of normal saline (1.0 ml/kg/day), polyene phosphatidylcholine (PPC; 123.1 mg/kg/day) and TEL (8 mg/kg/day). The liver tissue was then assessed for the NAFLD activity score and fibrosis score (FS), and serum biochemistry and leptin levels were determined. Additionally, leptin protein expression levels were examined by western blotting and the expression of leptin mRNA was investigated by reverse transcription-polymerase chain reaction. TEL significantly improved FS in rats (P<0.01) and was more effective than PPC. TEL significantly reduced the expression of serum leptin, as well as the expression levels of leptin protein and its mRNA in liver tissue (P<0.01); however, the effects of PPC were not significant (P>0.05). TEL reduced serum leptin, leptin protein and its mRNA in the liver tissue of NAFLD rats, and improved the pathological indicators of liver fibrosis. [ABSTRACT FROM AUTHOR]

Studies have shown that the cerebrospinal fluid‑contacting nucleus (CSF‑CN) may be associated with the transduction and regulation of pain signals. However, the role of the CSF‑CN remains to be elucidated. Emerging evidence has suggested that neurokinin 1 receptor (NK1R) is important in the development of visceral pain and hyperalgesia, however, whether NK1R exists in the CSF‑CN and its exact role in visceral pain remain to be fully elucidated. In the present study, double‑labeled immunofluorescence staining and western blot analysis were performed to investigate this. It was revealed that NK1R was distributed in the CSF‑CN. Following the induction of visceral pain by formalin instillation, NK1R in the CSF‑CN was upregulated. In addition, by observing the behaviors of rats subjected to visceral pain, it was found that visceral pain was relieved by lateral intracerbroventricular injection of the NK1R antagonist, RP67580. These data provided a broader understanding of the role of NK1R in the CSF‑CN and demonstrated that the CSF‑CN was involved in acute visceral pain via the regulation of NK1R. [ABSTRACT FROM AUTHOR]

The dynamic changes of the microstructure of alveolar bone during orthodontic tooth movement in rats was explored by employing micro-computed tomography (micro-CT) system and to provide theoretical reference for clinical orthodontic treatment. Ten rats were selected randomly as control among 70 adult female Wistar rats, and the other 60 rats were divided into 25-g and 75-g groups of equal number. Orthodontic appliance with force of 25 g and 75 g was installed to perform the molar mesial movement. Microstructural parameters for trabecular bone mesial to the distobuccal root were evaluated at different time points using micro-CT system. Moreover, distance for mesial movement of the molar were measured. Microstructural parameters for trabecular bone of two groups showed no significant changes from day 0 to day 3 (P>0.05); from day 3 to day 7, bone mineral density (BMD), bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th) decreased significantly (P<0.05), whereas trabecular separation (Tb.Sp) and structure model index (SMI) increased significantly (P<0.05); from day 7 to day 14, in 25-g group, BMD, BV/TV and Tb.Th increased significantly (P<0.05), while Tb.Sp and SMI decreased significantly (P<0.05). Correspondingly, in 75-g group, changes of parameters did not carry any statistical significance (P>0.05). Furthermore, the 75-g group showed larger distance than 25-g group only at day 14 (P<0.05). In conclusion, in order to maintain the health of periodontal tissues, adequate time for repair and recovery is needed to ensure reasonable remolding of alveolar bone and healthy movement of the orthodontic tooth. [ABSTRACT FROM AUTHOR]

Extramedullary hematopoiesis (EMH) is defined as hematopoiesis occurring in organs outside of the bone marrow. The present report describes two cases of thalassemic patients with paraspinal medullary hematopoiesis and analyzes the clinical manifestations, imaging, pathology, diagnosis and treatment of EMH. In addition, a supplementary review of previously published cases is provided along with a review of the related literature. Computed tomography (CT) of the first case revealed multiple paraspinal masses, and the largest was 6.2×8.0 cm in diameter. Likewise, CT of the second patient revealed multiple paraspinal masses in the bottom of the left thoracic cavity, and the largest was measured 10.1×10.5 cm. The two cases underwent surgical biopsy and the findings were compatible with a diagnosis of EMH. In conclusion, EMH is a compatible and rare disease, and should be distinguished from other neoplasms. EMH must considered when masses with characteristic radiologic appearance are detected in patients with thalassemia intermedia. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate wound healing and scar formation in rabbit corneal lamellar wounds repaired with simple interrupted sutures (SIS) or horizontal mattress sutures (HMS). Two parallel 'I'-shaped lamellar cornea wounds were created in one eye of 40 white New Zealand rabbits, while 5 uninjured rabbits were sacrificed to serve as normal controls. One side of the wounds, in the test rabbits, was closed with SIS, while the other side was treated with HMS. Ten days later, the stitches were removed under anesthesia. The animals were sacrificed on days 14 and 21, and months 3 and 6 after the suturing surgery, and corneal samples were subjected to histological and immunofluorescent studies: α-smooth muscle actin (α-SMA) and vimentin were used to detect myofibroblasts and fibroblasts, respectively, and collagen type I and III was used to detect extracellular matrix (ECM) deposition. Relevant mRNA levels were assessed by quantitative polymerase chain reaction (qPCR) to elucidate the differences in wound healing and formation of fibrosis. Macroscopic and hematoxylin and eosin staining observations showed that the two sides of the wounds developed the most prominent fibrotic tissue on day 21. The immunofluorescence and qPCR results showed that HMS wounds produced increased α-SMA, vimentin and collagen type III compared to the SIS wounds on day 14 or 21. The collagen type I expression showed no distinctive difference in SIS and HMS wounds. In conclusion, corneal lamellar wounds treated with SIS developed less fibrotic-related proteins and related mRNA in the early stages of wound healing than wounds treated with HMS. Although differences were not distinct after 3 months, the results of the present study suggest a benefit in choosing SIS over HMS, as at least the initial fibrotic process seems more benign with SIS. Corneal wounds should be carefully sutured, ensuring the tissue is well aligned. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the inhibitory effects of angiotensin II (AngII) on angiopoietin-like protein 2 (Angptl2) in rat primary cardiomyocytes, and to investigate the potential association between angiotensin II type 1 receptor (AT1R) and these effects. Cardiomyocytes were isolated from 3-day-old Wistar rats, and were cultured and identified. Subsequently, the expression levels of Angptl2 were detected following incubation with various concentrations of AngII for various durations using western blotting, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescence. Finally, under the most appropriate conditions (100 nmol/l AngII, 24 h), the cardiomyocytes were divided into six groups: Normal, AngII, AngII + losartan, normal + losartan, AngII + PD123319 and normal + PD123319 groups, in order to investigate the possible function of AT1R in Angptl2 suppression. Losartan and PD123319 are antagonists of AT1R and angiotensin II type 2 receptor, respectively. The statistical significance of the results was analyzed using Student's t-test or one-way analysis of variance. The results demonstrated that Angptl2 expression was evidently suppressed (P<0.05) following incubation with 100 nmol/l AngII for 24 h. Conversely, the expression levels of Angptl2 were significantly increased in the AngII + losartan group compared with the AngII group (P<0.01). However, no significant difference was detected between the AngII + PD123319, normal + losartan or normal + PD123319 groups and the normal group. The present in vitro study indicated that AngII was able to suppress Angptl2 expression, whereas losartan was able to significantly reverse this decrease by inhibiting AT1R. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are endogenous transcribed RNA molecules without protein-coding potential, ranging between 200 and 100,000 nt in length. LncRNAs regulate the expression of specific genes in several ways, including guiding chromatin-remodeling, and affecting splicing, transcription or translation. The mutations and dysregulation of lncRNAs have been found to be important in various human diseases, but particularly in human cancer. Previous studies have demonstrated that changes to l ncRNAs a re c losely associated with tumorigenesis, metastasis, prognosis and diagnosis. The current review aims to present a brief overview of the associated reports of lncRNAs in malignant neoplasms, including breast cancer, prostate cancer and hematological malignancies. LncRNAs may be evaluated as novel markers in disease diagnosis, and as prospective therapeutic targets for the prevention and treatment of human diseases. [ABSTRACT FROM AUTHOR]

Cerebrovascular disease is a leading cause of morbidity and mortality worldwide, which is influenced by genetic and environmental factors. The aim of the present study was to examine the association between single-nucleotide polymorphisms (SNPs) in Notch3 exons 3-6 and lacunar infarction by comparing SNPs between control subjects and those with lacunar infarction. A single-center case-control study was conducted to investigate the association between Notch3 SNPs and risk of stroke. A total of 140 patients were included in the study, 30 of whom had no infarction (control) and 110 had lacunar infarction. Lacunar patients were divided into the 'pure lacunar' and 'lacunar + leukoarasis' groups based on brain imaging. All the patients were of Chinese Han ethnicity, and the male to female ratio was 84:56. Patient clinical histories included hypertension, diabetes mellitus (DM), hyperlipidemia, and heart disease were recorded. The Notch3 sequence was obtained from the National Centser for Biotechnology Information database. Notch3 was amplified by polymerase chain reaction from whole blood samples, and exons 3-6 were sequenced to identify SNPs. The result showed that there was no significant difference in the prevalence of hypertension, DM, hyperlipidemia, and heart disease between the control and lacunar infarction patients. Notabley, the age of the lacunar + leukoarasis patients was significantly higher than that of the control and pure lacunar patients (P<0.05). Eight SNPs were detected at low frequencies, and only rs3815388 and rs1043994 exhibited slightly higher frequencies. A χ² test indicated that Notch3 SNPs, particularly rs1043994, were associated with lacunar infarction (P<0.05). In conclusion, the result of the present study have shown that Notch3 SNPs, particularly rs1043994, are associated with lacunar infarction. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the treatment outcome of homoharringtonine, cytarabine (AraC) and aclarubicin combination therapy as induction treatment for myelodysplastic syndromes-refractory anemia with excess blasts (MDS-RAEB). A total of 24 patients with MDS-RAEB who were aged between 18 and 66 years were treated with homoharringtonine, AraC and aclarubicin (HAA regimen). The HAA regimen consisted of homoharringtonine (2 mg/m² intramuscularly twice daily, days 1-3), AraC (75 mg/m² injected subcutaneously twice daily, days 1-7) and aclarubicin (12 mg/m², days 1-7). The overall response rate was 79% with a complete remission rate of 58.3% and partial remission rate of 20.7%. There was no evidence of early mortality in this group of patients. The median overall survival (OS) was 36.2 months (95% confidence interval, 24.6-47.4 months), and the estimated three year overall survival rate was 45.8%. In conclusion, HAA combination therapy is a suitable induction regimen for patients with MDS-RAEB, which may improve the outcome for de novo higher-risk MDS patients, particularly of those with favorable and intermediate cytogenetics. [ABSTRACT FROM AUTHOR]

A number of previous studies have reported that sex steroid hormones, including estrogens, are involved in the regulation of the thymic function. The aim of the present study was to investigate the expression of estrogen receptor β5 (ERβ5) in thymic tumors and the correlation between ERβ5 expression and thymoma biological characteristics. The expression levels of ERβ5 in thymic epithelial tumors was evaluated in 103 patents using immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction. In addition, an indirect immunofluorescence assay was performed to evaluate the ERβ5 expression levels in the TC1889 and T1682 cell lines. The survival outcome was estimated using Kaplan-Meier plots. The results indicated that ERβ5 expression was mainly located in the thymic tumor cell cytoplasm (87.37%; 90/103 cases) and overexpression was observed in thymic tumors compared with normal thymic tissues (P=0.001). Using the Kruskal-Wallis test, a statistically significant association was observed between cytoplasmic ERβ5 (cERβ5) expression and thymic tumor subtypes (P=0.024) and stages (P=0.003 and R=-0.376). The Kaplan-Meier plots revealed that cERβ5 expression was significantly associated with improved overall and progression-free survival (P=0.008 and P=0.004, respectively). The present study suggested that overexpression of cERβ5 may indicate an improved prognosis and may be involved in the underlying mechanism through which estrogen inhibits thymoma and thymic carcinoma development. [ABSTRACT FROM AUTHOR]

Estradiol is an ovarian steroid hormone that regulates physiological functions in the central nervous system, including mood, cognition, sleep and mental state. Emerging evidence has revealed that there is an enrichment of cells that express the estrogen receptor in the lateral habenula (LHb) region, however, the precise biological functions of estradiol on neurons in the LHb remain to be elucidated. The present study aimed to determine the effects of estradiol on LHb neurons, by observing neuronal firing activity, and c-Fos mRNA and protein expression levels in the LHb using whole cell recording, reverse transcription-quantitative polymerase chain reaction and western blotting. Ovariectomized female Wistar rats were supplemented with a range of estradiol doses across five groups: Ovariectomized (no treatment); Oil (sesame oil); low estradiol; medial estradiol (ME) and high estradiol. Circulating serum estradiol levels were assessed over a 33 day period following surgery. Estradiol suppressed spontaneous firing activity in LHb neurons (P<0.05, compared with firing rates prior to estradiol treatment), which suggested a role for this hormone in regulating neuronal activity. Estradiol replacement therapy resulted in sustained serum estradiol levels for ~3 weeks after surgery. The mRNA and protein levels of c-Fos were significantly downregulated in LHb tissues from ME rats as compared with Oil animals (P<0.05). In conclusion, the present study demonstrated that estradiol suppresses neuronal activities in the LHb region, suggesting that the LHb may be a potential target for estradiol action. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy based on dendritic cells (DCs) that target survivin is a promising strategy with potential clinical applications. However, the translation of survivin-specific cytotoxic T-lymphocyte (CTL) immunotherapy into the clinical setting has numerous challenges, including the low efficiency of the treatment. The present study aimed to improve the efficiency of the treatment, and found that treatment with interleukin 4 (IL-4)/granulocyte macrophage colony-stimulating factor (GM-CSF) and a combination of proinflammatory cytokines significantly increased the antigen-presenting and -capture abilities of DCs that expressed exogenous survivin. Furthermore, lipopolysaccharide (LPS) stimulation enhanced the DC response to subsequent T-cell signals and the extent of T-cell activation. In addition, the efficiency of survivin-specific CTLs was examined, and high cytotoxicity against survivin-expressing A549 lung cancer cells was observed. However, the cytotoxicity of CTLs was significantly reduced in A549 cells with silenced survivin expression. The present study provides a novel method to optimize the generation of survivin-specific CTLs against lung cancer cells, which may advance the translation of survivin-specific CTL immunotherapy into clinical use for the treatment of cancer. [ABSTRACT FROM AUTHOR]

The Porphyromonas gingivalis bacterium is one of the most influential pathogens in oral infections. In the current study, the antimicrobial activity of α-amylase and pentamidine against Porphyromonas gingivalis was evaluated. Their in vitro inhibitory activity was investigated with the agar overlay technique, and the minimal inhibitory and bactericidal concentrations were determined. Using the bactericidal concentration, the antimicrobial actions of the inhibitors were investigated. In the present study, multiple techniques were utilized, including scanning electron microscopy (SEM), general structural analysis and differential gene expression analysis. The results obtained from SEM and bactericidal analysis indicated a notable observation; the pentamidine and α-amylase treatment destroyed the structure of the bacterial cell membranes, which led to cell death. These results were used tofurther explore these inhibitors and the mechanisms by which they act. Downregulated expression levels were observed for a number of genes coding for hemagglutinins and gingipains, and various genes involved in hemin uptake, chromosome replication and energy production. However, the expression levels of genes associated with iron storage and oxidative stress were upregulated by α-amylase and pentamidine. A greater effect was noted in response to pentamidine treatment. The results of the present study demonstrate promising therapeutic potential for α-amylases and pentamidine. These molecules have the potential to be used to develop novel drugs and broaden the availability of pharmacological tools for the attenuation of oral infections caused by Porphyromonas gingivalis. [ABSTRACT FROM AUTHOR]

DNA methylation is one of the major mechanisms via which tumor suppressor gene inactivation occurs. For example, hypermethylation of the promoter region of cadherin 11 (CDH11), a novel tumor suppressor gene, frequently occurs in human cancer. In the current study, the methylation status of CDH11 was investigated in bladder cancer tissue samples, and the correlation with clinicopathological features and patient outcome was assessed. The methylation status of CDH11 was detected in 146 bladder cancer tissues and 37 normal bladder epithelial tissues using methylation-specific polymerase chain reaction (PCR). In addition, CDH11 mRNA expression levels were examined by quantitative PCR. Subsequently, associations between CDH11 methylation and specific clinicopathological characteristics, as well as patient outcome, were analyzed. Aberrant CDH11 promoter hypermethylation was detected in 63.0% (92/146) of bladder cancer tissues, however, no CDH11 methylation was identified in the control samples; this difference was significant (P<0.05). Furthermore, CDH11 mRNA expression levels were significantly lower in the tumor samples with methylated CDH11 compared with the normal bladder epithelium and tumor samples with unmethylated CDH11 (P<0.05). When the methylation status of CDH11 was correlated with the clinicopathological features, it was identified that CDH11 methylation was significantly associated with poor differentiation (P=0.0440), an advanced disease stage (P=0.0350), a larger tumor size (P=0.0013) and multiple tumors (P=0.0390). In addition, patients with methylated CDH11 exhibited significantly poorer outcomes than patients with unmethylated CDH11 (P=0.0004). Furthermore, multivariate Cox proportional hazard analysis indicated that CDH11 methylation was independently associated with a poor outcome in the patients with bladder cancer, with a relative risk of mortality of 6.852 (P=0.0082; 95% confidence interval, 3.461-16.177). The current findings indicate that aberrant CDH11 methylation frequently occurs in bladder cancer, and correlates with malignant behavior and poor outcome. Thus, CDH11 methylation status may be used as an independent prognostic biomarker for patients with bladder cancer. [ABSTRACT FROM AUTHOR]

The ganglioside GM3 exerts its different effects via various growth factor receptors. The present study investigated and comparatively analyzed the opposing effects exerted by GM3 on the migration of mouse hepatocellular carcinoma Hepa1-6 cells via epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR/cMet). The results demonstrated that GM3 inhibited EGF-stimulated motility, but promoted HGF-stimulated motility of the Hepa1-6 cells via phosphatidylinositol 3-kinase/Akt-mediated migration signaling. It is well established that the main cytokines modulating cell proliferation, invasion and metastasis are different in different types of tumor. This difference may, at least in part, explain why GM3 exerted its actions in a tumor-type specific manner. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the prognostic value of serum α-fetoprotein (AFP) levels in patients with ovarian yolk sac tumor (OYST). We performed a systematic review and meta-analysis to assess the associations between serum AFP level and prognosis in OYST. A total of 12 quantitative studies met the inclusion criteria. Preoperative AFP was not found to be associated with overall survival (OS) [odds ratio (OR)=0.84, 95% confidence interval (CI): 0.43-1.62] in OYST. However, a high postoperative AFP level was associated with worse OS (OR=0.16, 95% CI: 0.05-0.48) and relapse-free survival (RFS) (OR=0.18, 95% CI: 0.08-0.43) compared to a low postoperative AFP level in patients with OYST. In addition, a postoperative AFP level of >1,000 ng/ml was associated with a decrease in OS (OR=0.16, 95% CI: 0.05-0.50) and RFS (OR=0.21, 95% CI: 0.08-0.57). In conclusion, the postoperative, but not the preoperative, AFP level was found to be a prognostic factor in patients with OYST. In particular, a postoperative AFP level of >1,000 ng/ml was an indicator of poor prognosis in patients with OYST. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the function of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and cyclooxygenase-2 (COX-2) in angiogenesis and their association with the prognosis of non-small cell lung cancer (NSCLC). Using immunohistochemical staining, the expression of 15-PGDH and COX-2, and the microvessel density (MVD) levels were evaluated in 35 NSCLC specimens. Paracancerous normal lung tissue was collected as control samples from six patients. The correlation of 15-PGDH with COX-2, clinicopathological characteristics, MVD and overall survival (OS) was studied. NSCLC tissues showed a significantly lower expression level of 15-PGDH (P=0.009) and a significantly higher expression level of COX-2 (P=0.004) compared with normal lung tissue. The expression level of 15-PGDH was negatively correlated with MVD (P<0.001) and COX-2 expression (P=0.032). A low expression level of 15-PGDH, a high expression level of COX-2 and high levels of MVD were significantly correlated with a shorter OS time (15-PGDH, P<0.0001; COX-2, P=0.038; MVD, P<0.0001). This study provided clinical evidence that a low expression level of 15-PGDH is associated with a poor prognosis in NSCLC. Furthermore, it was shown that 15-PGDH and COX-2 reciprocally regulate cancer angiogenesis, which may affect the prognosis of patients with NSCLC. [ABSTRACT FROM AUTHOR]

Yolk sac tumor (YST), also known as an endodermal sinus tumor, is a rare malignant germ cell tumor. Primary retroperitoneal YST (PRYST) is extremely rare and, to the best of our knowledge, has only been described in case reports. The histogenesis of PRYST and the appropriate treatment strategy remain unclear due to the rarity of this type of tumor. The present study reports a case of YST in the retroperitoneum. A 19-year-old female presented with abdominal distension and edema of the lower limbs. A computed tomography scan revealed a large, solid mass located in the retroperitoneum. The tumor size was 20x25x30 cm and widespread metastasis was identified during the exploratory laparotomy. The postoperative histopathology report showed a malignant retroperitoneal tumor (although a YST was initially considered). The patient underwent three surgical procedures and 17 cycles of five different chemotherapy regimens. The patient succumbed to cachexia, which was due to tumor recurrence, and liver and spleen metastases 21 months after diagnosis. PRYST may relapse following surgical treatment; however, surgical resection is currently the optimal treatment method. In this case, bleomycin, etoposide and cisplatin; bleomycin, vincristine and cisplatin; and vincristine and cisplatin chemotherapy regimens were effective for the patient with PRYST, although the tumor was not completely resected. a-fetoprotein (AFP) is an important tumor marker for monitoring PRYST recurrence and observation of elevated serum AFP levels during chemotherapy indicates a poor prognosis. [ABSTRACT FROM AUTHOR]

The role of resveratrol (Res) in inflammation induced by ischemia/reperfusion is not well understood. The aim of the present study was to investigate whether Res modulates neutrophil accumulation and tumor necrosis factor-α (TNF-α) induction in an ischemia/reperfusion-injured rat heart model. The rats were randomly exposed to sham surgery, myocardial ischemia/reperfusion (MI/R) alone, MI/R + Res, MI/R + Res + L-NG-nitroarginine methyl ester (L-NAME) and MI/R + Res + methylene blue (MB). The results demonstrated that compared with MI/R, Res reduced the myocardial infarct area, myocardial myeloperoxidase levels, serum creatinine kinase and lactate dehydrogenase levels, and serum and myocardial TNF-α production. All the effects of Res demonstrated were inhibited by L-NAME (a nitric oxide (NO) synthase inhibitor) and MB [a cyclic guano-sine monophosphate (cGMP) inhibitor]. Thus, Res produces cardioprotective and anti-inflammatory effects. These effects may be associated with an increase in NO production, the inhibition of neutrophil accumulation, TNF-α induction and cGMP signaling pathways in myocardium subjected to MI/R. [ABSTRACT FROM AUTHOR]

It is important to accurately determine the resectability of thoracic esophageal squamous cell carcinoma (ESCC) for treatment decision-making. Previous studies have revealed that the CT-derived gross tumor volume (GTV) is associated with the staging of ESCC. The present study aimed to explore whether the anatomical distribution-based GTV of non-distant metastatic thoracic ESCC measured using multidetector computed tomography (MDCT) could quantitatively determine the resectability. For this purpose, 473 consecutive patients with biopsy-confirmed non-distant metastatic thoracic ESCC who underwent contrast-enhanced CT were randomly divided into a training cohort (TC; 376 patients) and validation cohort (VC; 97 patients). GTV was retrospectively measured using MDCT. Univariate and multivariate analyses were performed to identify the determinants of the resectability of ESCC in the TC. Receiver operating characteristic (ROC) analysis was performed to clarify whether anatomical distribution-based GTV could help quantitatively determinate resectability. Unweighted Cohen's Kappa tests in VC were used to assess the performance of the previous models. Univariate analysis demonstrated that sex, anatomic distribution, cT stage, cN stage and GTV were related to the resectability of ESCC in the TC (all P<0.05). Multivariate analysis revealed that GTV [P<0.001; odds ratio (OR) 1.158] and anatomic distribution (P=0.027; OR, 1.924) were independent determinants of resectability. ROC analysis revealed that the GTV cut-offs for the determination of the resectability of the upper, middle and lower thoracic portions were 23.57, 22.89 and 22.58 cm3, respectively, with areas under the ROC curves of >0.9. Unweighted Cohen's Kappa tests revealed an excellent performance of the ROC models in the upper, middle and lower thoracic portions with Cohen k-values of 0.913, 0.879 and 0.871, respectively. On the whole, the present study demonstrated that GTV and the anatomic distribution of non-distant metastatic thoracic ESCC may be independent determinants of resectability, and anatomical distribution-based GTV can effectively be used to quantitatively determine resectability. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the association between anemia and the risks and outcomes of diabetic foot (DF) in patients with type 2 diabetes mellitus (T2DM). A total of 145 patients with T2DM were recruited between January and December 2021 and divided into the DF and non-DF groups according to whether they were diagnosed with DF. Individual patient data were extracted and blood samples were evaluated in a biochemical center for routine biochemical and blood-related indicators. The patients' survival rates were followed up until December 2022. An independent-samples t-test and ?2 test were used to compare the differences between the two groups. The association between the various clinical indicators for the DF and non-DF groups was evaluated using single-factor binary logistic regression analysis. Multi-factor binary logistic regression analysis was used to analyze the association between hemoglobin (Hb) and the risk for DF. A Kaplan-Meier survival curve was used to analyze the impact of anemia and DF on the 1-year survival rate. The diabetes duration, number of patients who smoked and consumed alcohol, and serum creatinine and C-reactive protein levels in the DF group were significantly higher than those in the non-DF group (P<0.05). By contrast, the estimated glomerular filtration rate (eGFR) and Hb, albumin (Alb) and total cholesterol levels, were lower in the DF group when compared with those in the non-DF group (P<0.05). All of the study participants were divided into two groups, according to their baseline eGFR [eGFR =90 or <90 ml/(min x 1.73 m²)]. It was found that, independently of renal function, lower Hb and Alb levels were associated with a higher incidence of DF. The 1-year survival rate for DF with anemia was significantly lower when compared with that in patients with DF without anemia (P<0.05). In conclusion, the Hb level in patients with T2DM is a protective factor against DF and anemia is an independent risk factor for DF. The present study suggested that anemia is associated with a decrease in the survival rate of patients with DF. This finding provided a theoretical basis for the clinical correction of anemia and improvement of DF prognosis (clinical trial no. 20220003). [ABSTRACT FROM AUTHOR]

Natriuretic peptides, which are produced by the heart, bind to natriuretic peptide receptor A (NPR1 encoded by natriuretic peptide receptor 1 gene) and cause vasodilation and natriuresis. Thus, they serve an important role in regulating blood pressure. In the present study, microinjection of CRISPR associated protein 9/single guide RNA into fertilized C57BL/6N mouse eggs was performed to generate filial generation zero (F0) Npr1 knockout homozygous mice (Npr1-/-). F0 mice mated with wild-type (WT) mice to obtain F1 Npr1 knockout heterozygous mice with stable heredity (Npr1+/-). F1 self-hybridization was used to expand the population of heterozygous mice (Npr1+/-). The present study performed echocardiography to investigate the impact of NPR1 gene knockdown on cardiac function. Compared with those in the WT group (C57BL/6N male mice), the left ventricular ejection fraction, myocardial contractility and renal sodium and potassium excretion and creatinine-clearance rates were decreased, indicating that Npr1 knockdown induced cardiac and renal dysfunction. In addition, expression of serum glucocorticoid-regulated kinase 1 (SGK1) increased significantly compared with that in WT mice. However, glucocorticoids (dexamethasone) upregulated NPR1 and inhibited SGK1 and alleviated cardiac and renal dysfunction caused by Npr1 gene heterozygosity. SGK1 inhibitor GSK650394 ameliorate cardiorenal syndrome by suppressing SGK1. Briefly, glucocorticoids inhibited SGK1 by upregulating NPR1, thereby ameliorating cardiorenal impairment caused by Npr1 gene heterozygosity. The present findings provided novel insight into the understanding of cardiorenal syndrome and suggested that glucocorticoids targeting the NPR1/SGK1 pathway may be a potential therapeutic target to treat cardiorenal syndrome. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate protein kinase C ζ type (PKCζ), matrix metalloproteinase (MMP)-2 and MMP-9 expression in lung adenocarcinoma and to define their association with in vitro invasion and metastatic capacity. PKCζ, MMP-2 and MMP-9 expression was assessed by immunohistochemistry in 110 cases of lung adenocarcinoma. PKCζ small interfering (si)RNA was transfected into A549 cells, and western blotting was used to confirm PKCζ-knockdown in transfected cells and to measure MMP-2 and MMP-9 levels. A Transwell invasion assay was used to detect in vitro invasive capacity. The rates of positive PKCζ, MMP-2 and MMP-9 staining in lung adenocarcinoma tissues were 52.73, 55.45 and 61.82%, respectively. PKCζ expression was increased in malignant tissues compared with adjacent normal lung tissues and was associated with lymph node metastasis (P<0.05), although it was not associated with any other clinicopathological parameters, including sex, age, tumor size, smoking status or distant metastases (all P>0.05). PKCζ, MMP-2 and MMP-9 expression was markedly decreased in siPKCζ-treated A549 cells, which exhibited a significantly decreased invasive capacity in the Transwell invasion assay (P<0.05). In conclusion, PKCζ promoted lung adenocarcinoma invasion and metastasis, and its expression was associated with MMP-2 and MMP-9 expression. PKCζ may be a potential target for gene therapy in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Homocysteine (Hcy) and glutathione (GSH) are crucial reduction-oxidation mediators. The underlying mechanisms governing the effects of Hcy on GSH generation in the progression of alcoholic liver disease has so far received little attention. The present study hypothesized that the antioxidant transcriptional factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) may participate in Hcy-mediated regulation of GSH production in HepG2 human liver cancer cells. MTT assay was used to study the cytotoxicity of homocysteine, western blot analysis and immunofluorescence staining were used to determine the effect of Hcy on Nrf2 expression. Our data demonstrated that HepG2 cells exposed to exogenous levels of Hcy (0-100 μM) exhibited elevated GSH levels in a concentration-dependent manner. Furthermore, 4-hydroxynonenal (4-HNE)-induced cell injury was attenuated by Hcy; however, this protective effect was blocked by the GSH-production inhibitor buthionine sulfoximine. Hcy treatment was able to induce Nrf2 protein expression in HepG2 cells. Treatment with the Nrf2 activator tert-butylhydroquinone (0-100 μM) increased GSH expression in a concentration-dependent manner; however, Nrf2-siRNA abolished the Hcy-induced increase in GSH expression and cellular protection in 4-HNE-stressed HepG2 cells. In conclusion, the antioxidant transcriptional factor Nrf2 was demonstrated to mediate the Hcy-induced increase in GSH expression levels and cellular protection in HepG2 cells. [ABSTRACT FROM AUTHOR]

Interleukin-35 (IL-35) has been proposed as a novel immune-suppressing cytokine. However, the function of IL-35 in malignant diseases is yet to be elucidated. The present study investigated IL-35 expression levels in laryngeal squamous cell carcinoma (LSCC) tissues and the peripheral blood of patients to explore the potential involvement of IL-35 in LSCC progression. In the present study, IL-35 expression levels in tissues and peripheral blood were analyzed by reverse transcription-quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The association between IL-35 expression levels and clinical characteristics was also evaluated. The present results demonstrated that IL-35 expression in tumor tissues was significantly higher than in adjacent normal tissues, and a significant association between IL-35 expression levels in tissues and the tumor site was detected. Furthermore, the expression of IL-35 in the peripheral blood of patients was significantly decreased subsequent to tumor resection. No correlation between peripheral blood IL-35 expression and clinical characteristics was detected. In conclusion, the present study demonstrated that IL-35 is highly expressed in LSCC tissues and in the peripheral blood of patients with LSCC. There was a notable, significant reduction of peripheral blood IL-35 expression following surgical resection of tumors. These results may be useful for diagnostic or therapeutic purposes in patients with LSCC. [ABSTRACT FROM AUTHOR]

Human laryngeal papilloma (LP) is a human papillomavirus-induced hyperplastic tumor of the respiratory tract, which is characterized by rapid growth and apoptosis resistance. Isoflurane (ISO) inhibits proliferation and elicits apoptosis in cancer cells. The results of the present study found that the mRNA and protein levels of cyclooxygenase-2 (COX2) were higher in LP tissues than in normal laryngeal samples, and prostaglandin E2 (PGE2) production was increased in LP cells, as determined by quantitative polymerase chain reaction, western blot and radioimmunoassay analyses. Notably, the increase in COX2 and PGE2 levels was significantly abrogated in the ISO-treated LP cells. The inhibitory effects of ISO on COX2 expression and activity depended on the inactivation of p38 mitogen-activated protein kinase (MAPK) in LP cells. By inhibiting the COX2 activity of LP cells, ISO treatment markedly suppressed cell viability and proliferation, as determined using Cell Counting Kit-8, flow cytometry and 5-ethynyl-20-deoxyuridine incorporation assays. Furthermore, ISO treatment promoted cell apoptosis, as demonstrated by flow cytometry, nucleosomal fragmentation and caspase-3 activity assays. Collectively, the present results suggest that COX2 is critical in the progression of LP, and ISO is a potential agent for LP therapy by impeding p38 MAPK/COX2 signaling. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a widespread health concern, and there is currently insufficient understanding regarding its pathogenesis and treatment. The present study aimed to explore the effects of Artemisia capillaris formula (ACF) on high-fat diet-induced hepatic steatosis and fatty acid-induced intracellular lipid accumulation, by micro (mi)RNA regulation. A total of 72 Sprague-Dawley rats were divided into six groups (n=12/group). One group was designated as the control group and fed a normal diet, and the remaining five groups were allowed ad libitum access to a high-fat diet for eight weeks, in order to establish an NAFLD rat model. The rats were subsequently administered polyene phosphatidylcholine (PP; 0.076 g/kg body weight/day), low dose of ACF (0.462 g/kg body weight/day), middle dose of ACF (0.924 g/kg body weight/day) or high dose of ACF (1.848 g/kg body weight/day) intragastrically for four weeks. HepG2 human hepatocellular carcinoma cells were treated with oleic acid and palm acid, followed by treatment with various concentrations of ACF. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and steatotic HepG2 human liver carcinoma cell TC and TG levels were measured. ACF and PP treatments attenuated high-fat diet-induced hepatic steatosis and fatty acid-induced intracellular lipid accumulation. A modified high-fat diet significantly increased ALT, AST, TG, TC, LDL-C levels and decreased HDL-C levels. Treatment with ACF and PP abrogated the increase in liver enzymes and TG, TC and LDL-C levels, but did not influence HDL-C levels in a high-fat diet induced rat model of steotosis. Steatotic HepG2 cells exhibited significantly increased levels of both TG and TC. Treatment with ACF significantly decreased TC and TG levels in vivo, and ACF and PP treatment decreased the expression levels of fatty acid synthase (FASN) and increased miR-122 in vivo and in vitro. In conclusion, these results suggested that ACF may inhibit hepatic steatosis via miR-122-induced downregulation of FASN in vivo and in vitro. [ABSTRACT FROM AUTHOR]

GGsTOP is a novel and selective inhibitor of gamma-glutamyl transferase (GGT), a cell-surface enzyme that has a key role in glutathione homeostasis and the maintenance of cellular reactive oxygen species (ROS). ROS are essential for wound healing. However, little is known about the molecular mechanisms underlying the inhibition of GGT by GGsTOP in human periodontal ligament cells (hPLCs). The present study assessed GGT expression in mouse periodontal ligament tissues, GGT activity in hPLCs, and the potential physiological effect of GGsTOP on hPLC migration. Immunohistochemical analysis confirmed that GGT was widely expressed in mouse periodontal ligament tissue. Treatment with GGsTOP was associated with greater proliferation and migration of hPLCs, and higher levels of cellular ROS compared with untreated hPLCs. However, the increase in intracellular ROS was attenuated in hPLCs co-cultured with the anti-oxidant N-acetylcysteine (NAC), a precursor of glutathione. The higher ROS levels associated with GGsTOP treatment were in parallel with increases in the levels of type I collagen and alpha smooth muscle actin, which was inhibited in hPLCs co-cultured with NAC. Thus, GGsTOP may promote hPLC migration and participate in the maintenance of the periodontal ligament apparatus via the ROS pathway. [ABSTRACT FROM AUTHOR]

Membranous obstruction of the inferior vena cava (MOVC) is a common type of Budd-Chiari syndrome. However, the pathogenesis of MOVC has not been fully elucidated. Recent studies demonstrated that microRNAs (miRNAs or miRs) are involved in multiple diseases. To the best of our knowledge, specific changes in the expression of miRNAs in MOVC patients have not been previously assessed. The present study used a microarray analysis, followed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation, with the aim to access the miRNA expression levels in the plasma of 34 MOVC patients, compared with those in healthy controls. The results revealed a total of 16 differentially expressed miRNAs in MOVC patients. Subsequently, RT-qPCR analysis verified the statistically consistent expression of 5 selected miRNAs (miR-125a-5p, miR-133b, miR-423-5p, miR-1228-5p and miR-1266), in line with the results of the microarray analysis. These 5 miRNAs, which were described as crucial regulators in numerous biological processes and vascular diseases, may play an important role in the pathogenesis of MOVC. Bioinformatics analysis of target genes of the differentially expressed miRNAs revealed that these predicted targets were significantly enriched and involved in several key signaling pathways important for MOVC, including the ErbB, Wnt, MAPK and VEGF signaling pathway. In conclusion, miRNAs may involve in multiple signaling pathways contributing to the pathological processes of MOVC. The present study offers an intriguing new perspective on the involvement of miRNAs in MOVC; however, the precise underlying mechanisms require further validation. [ABSTRACT FROM AUTHOR]

The significance of promoter mutations of microRNAs (miRNAs) in lung cancer is poorly understood. Recent evidence demonstrated that miRNA-7 (miR-7), a unique member of the miRNA family, exhibited decreased expression and has emerged as an important regulator in lung tumorigenesis. However, the mechanism underlying the down-regulation of miR-7 in lung cancer remains largely unknown. In this study, we investigated the sites of mutation of the miR-7 promoter in lung cancer tissues using DNA sequencing. We identified a G^C change at the -617 site (25/39, 64.1%) and an A-^G change at the -604 site (20/39, 51.3%) in the miR-7 promoter region in lung cancer tissues. Moreover, the expression of miR-7 in cancer tissue with promoter site mutations was lower compared with that in cancer tissue without mutations (P<0.05). Furthermore, we demonstrated that mutations at these sites may decrease the activity of the miR-7 promoter and alter the expression of miR-7. Notably, mutations at these sites of the miR-7 promoter were found to be closely associated with poor prognosis of lung cancer patients (P=0.037). These data may provide novel insight on the altered expression of speciic miRNA molecules in lung cancer and ultimately prove to be helpful in the development of prognostic and thera- peutic strategies against lung cancer. [ABSTRACT FROM AUTHOR]

There have been conflicting reports regarding the catalytic role of cytochrome P450 (CYP)3A5, which range from deeming it irrelevant to suggesting it is equally as important as CYP3A4, the most potent and abundant catalytic cytochrome enzyme in the human liver. This was partially attributed to the fact that CYP3A5 is highly polymorphic. However the importance of other underlying mechanisms remain unclear. The aim of the present study was to investigate the interaction between these enzymes. A human HepG2 hepatocellular line stably overexpressing CYP3A5 was constructed. The results suggested that CYP3A5 does not affect CYP3A4 expression directly. However, overexpression of CYP3A5 attenuated the inducibility of CYP3A4 in response to dexamethasone. A luciferase reporter assay indicated that this attenuation was due to a decrease in CYP3A4 promoter activity. Furthermore, a pharmacokinetic assay using quinidine and amlodipine showed that CYP3A4 enzyme activity per mg of microsomal protein was also decreased in the group overexpressing CYP3A5 compared with the dexamethasone-induced control group. In conclusion, the current study demonstrated that CYP3A5 may affect CYP3A4 at the transcriptional level and may thus modify CYP3A4 expression and activity in the presence of substrates and inducers. The results indicate that CYPs may interact with each other under certain conditions and that this interaction may be a novel mechanism by which drug-drug interactions are mediated. [ABSTRACT FROM AUTHOR]

The aim of the present study was to observe the effects of sorafenib on the proliferation, apoptosis and invasion of A549/DDP cisplatin-resistant lung adenocarcinoma cells cultured in vitro. The A549/DDP cisplatin-resistant lung adenocarcinoma cell strain was cultured in vitro, the cell culture group incubated in culture medium only was set as the control group (Group S0) and the four concentration gradients of sorafenib were added to the culture groups as the experimental groups: S1, 2 μmol/l; S2, 4 μmol/l; S3, 8 μmol/l; and S4, 16 μmol/l. The MTT assay was used to determine the growth inhibition rate of the cells, which were respectively subjected to sorafenib treatment for 24, 48 and 72 h. Flow cytometry was used to determine the rate of apoptosis of cells in each group following sorafenib treatment for 72 h. Furthermore, the Transwell invasion experiment was used to determine the effect on A549/DDP cell invasion following sorafenib treatment for 24 h. Based on the MTT assay, it was found that the inhibition rates of A549/DDP cisplatin-resistant lung adenocarcinoma cells in groups S1-4 following sorafenib treatment for 24 h were 4.58±2.82, 14.93±2.62, 37.58±7.13 and 58.39±8.15%, respectively. For 48 h, inhibition rates in S1-4 were 14.98±2.93, 26.28±7.31, 63.00±3.05 and 78.84±3.96%, respectively, and for 72 h, inhibition rates were 18.80±2.82, 32.71±2.55, 75.51±4.73 and 87.50±3.36%, respectively. The difference in the inhibition rates of cells among the experimental groups for the same incubation time showed statistical significance (P<0.05). Flow cytometric analysis indicated that the rate of apoptosis in the control group was 8.88±0.81% following sorafenib treatment for 72 h, and the rates of apoptosis in groups S1-4 were, 12.84±0.24, 17.27±0.78, 21.98±0.75 and 49.67±1.38%, respectively. The rate of apoptosis in each experimental group was higher compared with that in the control group (P<0.05). The difference in the rate of apoptosis among the experimental groups was statistically significant (P<0.05). The Transwell assay showed that the number of cells permeating the septum in the control group was 82.7±2.3/high power lens (HP), while the average number of cells permeating septum in groups S1-4 following treatment with sorafenib for 24 h was 58.2±2.5, 41.3±1.3, 22.6±2.1 and 14.7±1.1/HP, which was significantly lower compared with the control group. The number of cells permeating the septum in each experimental group decreased with the enhancement of the concentration gradient. The differences were statistically significant (P<0.05). In conclusion, sorafenib inhibits the proliferation of A549/DDP cisplatin-resistant lung adenocarcinoma cells in a time- and concentration-dependent manner. In addition, sorafenib induces apoptosis in A549/DDP cisplatin-resistant lung adenocarcinoma cells, thus reducing their invasiveness. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of lactuside B (LB) on aquaporin-4 (AQP4) and caspase-3 mRNA expression in the hippocampus and the striatum following cerebral ischaemia-reperfusion (I/R) injury in rats. Cerebral I/R injury was established in Sprague-Dawley rats by occluding the middle cerebral artery for 2 h and then inducing reperfusion. Rats in the I/R + LB groups were treated with various doses of LB following reperfusion. Neurological deficit scores and brain water content were obtained to determine the pharmacodynamics of LB. Reverse transcription polymerase chain reaction was performed to determine the expression levels of AQP4 and caspase-3 mRNA in the hippocampus and the striatum. The results of the present study indicate that LB decreased the neurological deficit scores and the brain water content. In the hippocampus, AQP4 and caspase-3 mRNA expression levels were significantly downregulated in the I/R + LB groups at 24 and 72 h following drug administration, compared with those in the I/R group (P<0.05). In the striatum, LB was also shown to significantly reduce AQP4 and caspase3 mRNA expression levels at 24 and 72 h following drug administration, compared with those in the I/R group (P<0.05). The effects became stronger as the LB dose was increased. The most significant reductions in AQP4 and caspase-3 mRNA expression were noted in the I/R + LB 25 mg/kg and I/R + LB 50 mg/kg groups at 72 h following drug administration. The results of the present study show that LB is capable of significantly downregulating AQP4 and caspase-3 mRNA expression in the hippocampus and striatum following cerebral I/R injury in rats. The mechanism by which LB improved ischaemic brain injury may be associated with changes in AQP4 and caspase-3 mRNA expression in the hippocampus and the striatum. [ABSTRACT FROM AUTHOR]

Nuclear factor (NF)-κB expression occurs during sciatic injury. In addition, 7,8-dihydroxycoumarin exhibits a neurotrophic effect on peripheral nerve regeneration. To investigate the effects of 7,8-dihydroxycoumarin on the expression levels of NF-κB in L4-6 spinal cord segments of the injured sciatic nerve in mice and on the functional recovery and regeneration following nerve injury, a total of 160 healthy adult male BALB/c mice underwent unilateral sciatic nerve interruption and anastomosis. The mice were separated into groups and subsequently treated with physiological saline (control) or high, medium or low doses of 7,8-dihydroxycoumarin. NF-κB levels were detected by western blot analysis and quantitative polymerase chain reaction (qPCR), and the sciatic functional index (SFI) was measured. Neuronal apoptosis was detected by terminal-deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) staining. The results revealed that NF-κB was activated in the L4-6 spinal cord connected to the injured sciatic nerve. qPCR and western-blot analysis results showed that the expression levels of NF-κB in the high- and medium-dose groups were significantly lower compared with the low-dose and control groups at 12 h, one day, three days, five days and one week (P<0.05 for each). SFI and TUNEL results demonstrated that the high- and medium-dose groups exhibited improved functional nerve regeneration and reduced apoptosis compared with the low-dose and control groups. In conclusion, 7,8-dihydroxycoumarin is capable of suppressing the immune activation of NF-κB in the neurons of the L4-6 spinal cord connected with the injured sciatic nerve, thereby reducing the focal filtration of inflammatory cells, producing the optimum environment for nerve regeneration. [ABSTRACT FROM AUTHOR]

Hypoxia regulates a number of cell biological processes, including cell survival, development and differentiation. Deferoxamine (DFO), an oral chelator for blood transfusion patients, has been demonstrated to induce hypoxia and is frequently used as a hypoxia-mimicking agent. The purpose of the present study was to investigate the influence of DFO on the proliferation, migration and osteogenic differentiation of human periodontal ligament cells (hPDLCs). The effects of DFO on hPDLC viability and migration were measured using an MTT and wound healing assay. To characterize the hypoxia microenvironment, the expression of hypoxia-inducible factor-1α (HIF-1α) in hPDLCs treated with DFO was quantified using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the osteogenic differentiation potential of DFO was determined by RT-qPCR of the mRNA of osteogenic markers (runt-related transcription factor 2 [Runx-2], osteopontin [OPN] and collagen type I [Col-1]). The alkaline phosphatase activity and mineral deposition were analyzed using alizarin red S staining. The MTT and wound healing assays demonstrated that low-concentrations of DFO had little impact on hPDLC viability and migration 48 h into the treatment. DFO upregulated the expression of hPDLC genes specific for osteogenic differentiation: HIF-1α, Runx-2, OPN and Col-1. Furthermore, formation of mineralized nodules was enhanced by DFO. The present study suggests that DFO provided favorable culture conditions to promote the osteogenic differentiation and mineralization of hPDLCs. The mechanism underlying these alterations remains to be elucidated. [ABSTRACT FROM AUTHOR]

Placenta previa is often associated with preterm delivery, reduced birth weight, a higher frequency of placental accreta and postpartum haemorrhage, and increased likelihood of blood transfusion. The present study aimed to examine the expression of high mobility group box protein 1 (HMGB1) in the placenta of women with or without placenta previa. The study group consisted of placental tissues obtained from women with or without placenta previa. The expression levels of HMGB1 and vascular endothelial growth factor (VEGF) were evaluated in the placental tissues using reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The mRNA expression levels of HMGB1 and VEGF were significantly increased in the placenta previa group compared with in the normal group. In addition, the placenta previa group exhibited increased HMGB1 and VEGF staining in vascular endothelial cells and trophoblasts. There were no significant differences in the expression of HMGB1 or VEGF between groups with or without placenta accreta or postpartum haemorrhage. The present study hypothesised that the increased expression of HMGB1 in the placenta may be associated with the pathogenesis of placenta previa by regulating the expression of the proangiogenic factor VEGF. [ABSTRACT FROM AUTHOR]

2‑[(2E)‑3,7‑dimethyl‑2,6‑octadienyl]‑6‑methy l‑2,5‑cyclohexadiene‑1,4‑dione (DMD) is a compound isolated from Atractylodes macrocephala; however, its antitumor activity has not yet been investigated. Therefore, the present study aimed to investigate the antitumor activity of DMD in the H22 mouse hepatocellular carcinoma (HCC) cell line in vitro and in vivo. In the present study, the antiproliferative effects of DMD against H22 cells were evaluated using the MTT assay in vitro. Furthermore, xenograft nude mice were established to evaluate the antitumor effects of DMD on H22 cells in vivo. In addition, apoptosis of H22 cells was determined by flow cytometry with Annexin V‑fluorescein isothiocyanate/propidium iodide staining, and western blotting was subsequently performed to examine the expression levels of proteins associated with apoptosis, and c‑Jun N‑terminal kinase (JNK), p38 and extracellular signal‑regulated kinase (ERK)1/2 mitogen‑activated protein kinases (MAPKs). The results demonstrated that DMD exerts an antitumor effect against H22 cells in vitro and in vivo, and the underlying mechanism may be associated with mitochondria‑mediated apoptosis through upregulation of cytochrome c, cleaved (c)‑caspase‑3, c‑caspase‑9, c‑caspase‑7 and B‑cell lymphoma 2 (Bcl‑2)‑associated X protein, and downregulation of Bcl‑2. In addition, the antitumor effects of DMD against H22 cells may be also associated with the MAPK signaling pathway via increased p‑JNK and reduced p‑ERK1/2 expression. In conclusion, the present study demonstrated the DMD exerts antitumor effects against HCC in mice and provides a scientific basis for the clinical use of DMD for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Cancer cell-derived immunoglobulin G (cancer-IgG) has been implicated in the pathogenesis and progression of various types of cancer. However, its role in salivary adenoid cystic carcinoma (SACC) remains unclear. The present study aimed to investigate the effects of cancer-IgG on metastasis and prognosis in 96 patients with SACC. Immunohistochemical staining showed that cancer-IgG expression was present in all 96 individual SACC tissues. Additionally, high cancer-IgG expression was significantly correlated with metastasis, nerve invasion and recurrence in SACC (P<0.05). Moreover, cancer-IgG expression was significantly correlated with the survival duration of patients with SACC (P<0.05). Proliferation, cell motility and invasion all decreased significantly following knockdown of cancer-IgG in SACC cells (P<0.05) through population-doubling time, wound healing and transwell invasion assays. Additionally, cancer-IgG-knockdown in SACC cells induced the increased expression of E-cadherin and matrix metalloproteinase 9, and promoted the epithelial-mesenchymal transition, but decreased the expression of F-actin filaments. Taken together, these results showed that the high expression of cancer-IgG was strongly associated with metastasis, recurrence and invasion in SACC, suggesting that cancer-IgG expression could serve as a useful biomarker to predict the prognosis of the disease. [ABSTRACT FROM AUTHOR]

First-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR‑TKIs) have markedly improved the treatment of non-small cell lung cancer (non‑SCLC) with EGFR‑sensitive mutations. However, acquired resistance to these drugs was inevitable. The transformation of lung adenocarcinoma to SCLC following treatment with EGFR‑TKIs is a rare phenomenon that contributes to resistance to EGFR‑TKIs. The present case concerns a 74‑year‑old man previously diagnosed with and treated for pneumonia; however, this was later pathologically confirmed as lung adenocarcinoma by transbronchial lung biopsy. Deletion of exon 19 of EGFR was identified by next‑generation sequencing technology. The patient improved markedly when treated with gefitinib, but relapsed after 1 year, with markedly increased serum levels of neuron-specific enolase (NSE). Transformation to SCLC was detected by endobronchial ultrasound transbronchial needle aspiration (EBUS‑TBNA) re‑biopsy, which was negative for the deletion of exon 19 of EGFR. The patient was positive for vimentin expression and refractory to etoposide and cisplatin chemotherapy, and succumbed to the disease 18 months after diagnosis. Transformation of the disease from adenocarcinoma to SCLC may have been due to cancer heterogeneity. Re‑biopsy is therefore important in EGFR‑TKI‑resistant patients for genetic and histological re‑evaluation. NSE serum levels may also be useful for detecting early SCLC transformation. [ABSTRACT FROM AUTHOR]

The present study was designed to test the hypothesis that butylphthalide protects the brain of Alzheimer's disease (AD) model rats by inhibiting apoptosis. Ninety Sprague-Dawley rats were randomly divided into drug, control and blank groups of 30 rats in each. The rats in the drug and control groups were treated to induce AD. Then, the rats in the drug group were administered with butylphthalide daily, the rats in the AD control group were given normal saline, and the rats in the healthy group were fed routinely. All rats were sacrificed after 30 days; the brain tissues were used for testing for apoptosis by the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling (TUNEL) staining method, for determining mitogen-activated protein kinase (MAPK), ERK and P21 protein by western blot analysis, and their cognate mRNA levels by RT-PCR. The results of the TUNEL staining indicated that apoptosis of the brain tissues of rats in the drug group was significantly less than that in the control group and blank group. The protein expression levels of MAPK in the drug group were significantly lower than that in the control group, but higher than that in the normal healthy group (P<0.05). The mRNA expression levels of MAPK in the drug group were significantly lower than those in the control group, but higher than those in the normal healthy group (P<0.05). Based on these results, butylphthalide showed a protective apoptosis-inhibition effect on the brain tissues of the AD rats and this seems to be a consequence of its inhibition of the expressions of MAPK mRNA and MAPK protein in the brain of the rat. [ABSTRACT FROM AUTHOR]

The β1-adrenergic receptor (AR) is the primary β-AR subtype in the heart and is the target of metoprolol (Met), which is commonly used to treat angina and hypertension. Previous studies have revealed a positive correlation between the methylation levels of the adrenoreceptor β1 gene (Adrb1) promoter in the myocardium with the antihypertensive activity of Met in spontaneously hypertensive rats (SHR), which affects β1-AR expression in H9C2 cells. The aim of the present study was to investigate the effects of myocardial β1-AR downregulation using short-hairpin RNA (shRNA) against Adrb1 on the antihypertensive activity of Met in SHR. Recombinant adeno-associated virus type 9 (rAAV9) vectors carrying Adrb1 shRNA (rAAV9-Adrb1) or a negative control sequence (rAAV9-NC) were generated and used to infect rat hearts via the pericardial cavity. The results of reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blotting analyses demonstrated that cardiac β1-AR expression in the rAAV9-Adrb1 group was significantly downregulated when compared with the rAAV9-NC group (P<0.001, P<0.001 and P=0.032, respectively). In addition, a greater reduction in systolic blood pressure (SBP) was observed in the rAAV9-NC group compared with the rAAV9-Adrb1 group following Met treatment (P=0.035). Furthermore, downregulation of myocardial β1-AR was associated with a significant decrease in SBP (P<0.001). In conclusion, these data suggest that suppression of β1-AR expression in the myocardium reduces SBP and sensitivity to Met in SHR. [ABSTRACT FROM AUTHOR]

Aberrant promoter methylation of multiple genes is associated with various diseases, including Alzheimer's disease (AD). The goal of the present study was to determine whether dopamine receptor D4 (DRD4) promoter methylation is associated with AD. In the current study, the methylation levels of the DRD4 promoter were measured in 46 AD patients and 61 controls using bisulfite pyrosequencing technology. The results of the present study demonstrated that DRD4 promoter methylation was significantly higher in AD patients than in controls. A further breakdown analysis by gender revealed that there was a significant association of DRD4 promoter methylation with AD in males (23 patients and 45 controls). In conclusion, the results of the present study demonstrated that elevated DRD4 promoter methylation was associated with AD risk in males. [ABSTRACT FROM AUTHOR]

The aim of the present study was to provide reliable experimental evidence for the application of autologous skin fibroblasts (asFbs) in the repair of depressed scars. In the experiments, depressed trauma was induced in male Wistar rats, and fibroblasts were separated from the removed skin tissues to culture in medium. In vitro cultured asFbs were injected into the depressed scar sites of rats, and the repair function of asFbs in the depressed scars was then examined at the cellular and whole-animal levels. The expression levels of type I and type III collagen in the dermal layer of the skin injected with asFb cells were significantly higher, as compared with those of the control, and type I collagen expression was significantly higher compared with Type III. Re-injection of asFbs into the dermal layer of depressed scars can markedly improve their repair. These results may prove useful for skin repair in clinical settings. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC), caused by various mutations in a spectrum of cancer driver genes, may have distinct pathological characteristics and drug responses. Extensive genetic screening and pathological characterization is required for the design of customized therapies to improve patient outcomes. Notably, NSCLC in never-smokers exhibits distinctive clinicopathological features, which are frequently associated with tumorigenic mutations, and thus may be treated as a unique disease entity. However, to the best of our knowledge, these mutations have not been extensively and accurately characterized in an NSCLC study with a large sample size. Therefore, the present study enrolled a large cohort of NSCLC patients, which consisted of 358 never-smokers, for the screening of genetic alterations in the epidermal growth factor receptor (EGFR), ret proto-oncogene (RET), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene serine/threonine kinase (BRAF) tumorigenic genes. It was identified that the mutation rate was 47.8, 7.5, 3.6, 1.4 and 0.3% for EGFR, ALK, KRAS, RET and BRAF, respectively. In addition, clinicopathological features associated with these mutations were characterized. EGFR mutations were more frequently observed in female and older patients. By contrast, KRAS mutations were more frequently detected in male patients, and ALK and RET translocations in younger patients. The cancer cells were frequently well-differentiated in carcinoma cases exhibiting EGFR mutations, however, were less differentiated in those with ALK translocations. In conclusion, the present study determined the frequency of oncogenic alterations and associated clinicopathological features in NSCLC exhibited by never-smokers using a large sample size. The results of the present study may enrich our knowledge of NSCLC in never-smokers and provide useful insights for improvement of the outcome of molecularly targeted therapies for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Human adipose-derived stem cells (hADSCs), widely present in the adult human body, are an emerging and attractive tool for the establishment of stem cell-based therapies for the treatment of liver disease. However, the mechanism underlying hADSCs hepatic differentiation remains to be elucidated. Caveolin-1 (Cav-1), a 21-24 kDa membrane structural protein, is important in liver regeneration and development. In the present study, fluorescence immunocytochemistry and western blotting were used to analyze the expression levels of Cav-1 and evaluate its effects on the hepatic differentiation of hADSCs. The results revealed that primary hADSCs preserved the ability to proliferate and differentiate into hepatocyte-like cells. As demonstrated by semiquantitative reverse transcription-polymerase chain reaction, hepatocyte-inducing factors significantly increased the expression of Cav-1 in a time-dependent manner, as indicated by increased expression levels of the albumin (ALB) and a-fetoprotein (AFP) markers. In addition the expression levels of ALB and HNF1A significantly decreased following small interfering RNA-mediated knockdown of Cav-1. The mitogen-activated protein kinase (MAPK) signaling pathway was activated during hepatic differentiation and inhibited following Cav-1 knockdown. These results suggested that Cav-1 may regulate the hepatocyte-like differentiation of hADSCs by modulating mitogen-activated protein kinase kinase/MAPK signaling. The results of the present study will provide experimental and theoretical basis for further clinical studies on stem cell transplantation in the treatment of liver disease. [ABSTRACT FROM AUTHOR]