LncRNA LOXL1-AS1 promotes proliferation and invasion and inhibits apoptosis in retinoblastoma by regulating the MAPK signaling pathway.

Retinoblastoma (RB) is an intraocular malignancy that is most common in children and rare in adults. Addressing novel biomarkers and therapeutic targets for RB to modulate tumor progression has become a challenge. The aim of the present study was to investigate the function of long non-coding RNAs (LncRNAs) LOXL1-AS1 in RB cell proliferation and metastasis. It was found that LOXL1-AS1 was overexpressed in RB tissues and cells. In order to evaluate cell viability and colony formation potential, the knockdown of LOXL1-AS1 has been established. Knockdown of LOXL1-AS1 was also inhibited cells migration and invasion. In addition, the proportion of cells in the G2/M phase of the sh-LOXL1-AS1 group increased significantly, and the proportion of cells in the sh-NC group decreased significantly. In the xenograft model of RB, the tumors in the sh-LOXL1-AS1 group grow slowly compared to the sh-NC group. Western blot analysis revealed that LOXL1-AS1 can regulate the progression of RB cells through MAPK signaling pathway in vitro and in vivo. These results indicated that LncRNA LOXL1-AS1 promotes proliferation, invasion and inhibits apoptosis of retinoblastoma by regulating MAPK signaling pathway, and might be expected to be a novel basis for clinical diagnosis and treatment.

Subchronic exposure to PM2.5 induced renal function damage and intestinal microflora changes in rats.

BACKGROUND: Exposure to inhalable environmental particulate matter with a diameter of 2.5 µm or smaller (PM2.5) is associated with decreased or impaired kidney function, but the underlying biological mechanisms are not fully understood. Gut microbiota is an emerging key player in the homeostasis regulation of the gut-kidney axis. Few studies have investigated its role in PM2.5 exposure-induced gut-kidney axis homeostasis abnormalities. METHODS: In this study, a versatile aerosol concentration enrichment system for medium- to long-term whole-body exposure was used to expose Sprague-Dawley rats to filtered air (FA) or concentrated ambient PM2.5 for 12 weeks. A correlation analysis of renal impairment and the intestinal microbiome was performed. RESULTS: The urine flow rate calculation and renal function analysis showed that PM2.5 exposure significantly impaired renal function and increased the urine flow rate. The fecal microbiota analysis showed that renal impairment and increased urine flow rates were consistent with the reduced estimates of the fecal bacteria Chao1, observed-species, Shannon, and Simpson (richness and diversity indices). Pearson's correlation analysis showed that the estimated bacterial richness and diversity were correlated with the urine flow rate and renal function. The linear discriminant analysis effect size (LEfSe) analysis revealed differences between animals exposed to PM2.5 and FA in 25 bacterial groups. Further correlation of a single bacterial taxon with the urine flow rate and renal function showed that the relative abundances of 30, 29, 21, and 50 distinct bacterial groups were significantly correlated with the urine flow rate, estimated glomerular filtration rate (eGFR), serum cystatin C (CysC), and beta-2 microglobulin (ß2-MG), respectively. CONCLUSION: Subchronic exposure to PM2.5 can cause intestinal ecological disorders, which may, in turn, lead to decreased kidney function or the development of impaired kidney function.

Downregulation of estrogen receptor-α36 expression attenuates metastasis of hepatocellular carcinoma cells.

This study aimed to examine the role of estrogen receptor (ER)-α36 in the metastasis of hepatocellular carcinoma (HCC) and in the epithelial-mesenchymal transition (EMT). HCC HepG2 and Huh7 cells with the knocked-down level of ER-α36 expression were established. Cell growth and migration of the HepG2 and Huh7 cell variants were studied using MTS, transwell, and wound-healing assays, and the metastatic abilities of HepG2 cell variants were examined using a tail-vein injection model in nude mice. Levels of EMT markers, Src phosphorylation in HepG2 and Huh7 cell variants, and tumors formed by HepG2 cell variants in the nude mice were examined using Western blot and immunohistochemistry. We found that the growth and metastatic abilities of HepG2 and Huh7 cells with the knocked-down level of ER-α36 expression (HepG2/Si36 and Huh7/Si36) were significantly reduced, with increased levels of cytokeratin and E-Cadherin expression, and decreased levels of Vimentin, Snail, Slug and the Src phosphorylation, compared to the HCC cells transfected with an empty vector (HepG2/Vector and Huh7/Vector). We also found ER-α36 knockdown suppressed the lung metastasis of HepG2 cells with the involvement of EMT and the Src pathway in vivo. The Src inhibitor PP2 suppressed the growth and migration of HepG2/Vector and Huh7/Vector cells with decreased Vimentin, Snail, and Slug and increased cytokeratin and E-Cadherin expressions, but failed to induce the migration and the EMT markers in HepG2/Si36 and Huh7/Si36 cells. ER-α36 is involved in the metastasis of HCC cells through the regulation of EMT and the Src signaling pathway.

Estrogen receptor-α36 is involved in diallyl sulfide-induced inhibition of malignant growth of HepG2 and Huh7 hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a highly malignant disease that currently lacks effective treatment. Epidemiological studies have suggested the preventive role of raw garlic intake in different tumors, such as HCC. Although diallyl sulfide (DAS), the main component of garlic extracts, has been reported to inhibit the growth of HCC cells, the underlying mechanism remains elusive. This study aimed to investigate the inhibitory effect of DAS on the growth of HepG2 and Huh7 hepatocellular carcinoma cells and its underlying mechanism. HepG2 and Huh7 cells were treated with DAS and nude mice were intrahepatically injected with human HCC HepG2 cells and maintained with or without DAS administration for 28 days. MTS and clonogenic assays revealed that DAS inhibited the growth and clonogenicity of HepG2 and Huh7 hepatocellular carcinoma cells. Furthermore, DAS inhibited the growth of xenograft tumors accompanied by a decreased rate of pathological karyomitosis as observed by H&E staining. The expression levels of estrogen receptor-α36 (ER-α36) and epidermal growth factor receptor (EGFR) in HepG2 and Huh7 cells and in xenograft tumors derived from HepG2 cells after DAS treatment were detected by immunohistochemistry and western blotting. We found that DAS disrupted the positive regulatory loop between ER-α36 and EGFR, and decreased the phosphorylation of AKT at Ser 473 both in vivo and in vitro. DAS also induced cell apoptosis, as evidenced by Hoechst and TUNEL staining. Western blotting revealed activation of caspase3, increased BAX and decreased Bcl-2 expression. However, the ER-α36 expression knockdown attenuated DAS-induced ERK and AKT phosphorylation in HCC cells. DAS was also able to inhibit ER-α36-mediated activation of the MAPK/ERK signaling induced by estrogen. Thus, our results indicate that ER-α36 signaling is involved in DAS-induced inhibition of HCC cell growth both in vitro and in vivo.

Luteolin inhibits the proliferation, adhesion, migration and invasion of choroidal melanoma cells in vitro.

Choroidal melanoma is a devastating disease that causes visual loss and a high mortality rate due to metastasis. Luteolin, a potential anticancer compound, is widely found in natural plants. The aim of this study was to evaluate the antiproliferative, antiadhesive, antimigratory and anti-invasive effects of luteolin on choroidal melanoma cells in vitro and to explore its potential mechanism. Cell counting kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) assays, Cell adhesion, migration, and invasion assays were performed to examine the inhibitory effects of luteolin on cell cell viability, proliferation, adhesion, migration and invasion capacities, respectively. Considering the correlation between Matrix metalloenzymes and tumor metastasis, Enzyme-linked immunosorbent assays (ELISAs) were used to assess matrix metalloproteases MMP-2 and MMP-9 secretion. Western blotting was performed to detect p-PI3K P85, Akt, and p-Akt protein expression. The cytoskeletal proteins vimentin were observed with cell immunofluorescence staining. Luteolin can inhibit OCM-1 cell proliferation, migration, invasion and adhesion and C918 cell proliferation, migration, and invasion through the PI3K/Akt signaling pathway. Therefore, Luteolin may have potential as a therapeutic medication for Choroidal melanoma.

Clinical characteristics and outcome of primary brain abscess: a retrospective analysis.

BACKGROUND: Patients with primary brain abscess often present with atypical symptoms, and the outcome varies. We investigated the demographic, laboratory, and neuroimaging features of patients with brain abscess at our hospital and identified factors associated with their outcomes. METHODS: We retrospectively collected the data of patients diagnosed with primary brain abscess at our hospital between January 2011 and December 2020. Their clinical characteristics, predisposing factors, laboratory and neuroimaging findings, treatment, and outcome were analyzed. RESULTS: Of the 57 patients diagnosed with primary abscess, 51 (89.47%) were older than 40 years, and 42 (73.68%) were male. Only eight patients (14.04%) showed the classical triad of headache, fever, and focal neurological deficit. Fifteen patients (26.31%) had comorbidities, of which diabetes mellitus was the most common. Positive intracranial purulent material cultures were obtained in 46.15% of the patients, and gram-negative enteric bacteria were found in 33.33% of them, with Klebsiella pneumoniae being the most frequently observed. Surgical treatment, most commonly in the form of stereotactic drainage, was received by 54.39% of the patients. Good outcomes were achieved in 75.44% of the patients. Multivariate logistic regression analysis showed that patients with headaches were more likely to have a poor outcome (odds ratio 6.010, 95% confidence interval 1.114-32.407, p = 0.037). CONCLUSIONS: Male patients and those older than 40 years were more susceptible to brain abscess than female patients and those younger than 40 years, respectively. Only a few patients showed the classical triad of clinical symptoms. Diabetes mellitus was the most common comorbidity. Positive intracranial specimens' culture results were uncommon, with gram-negative enteric bacteria, especially Klebsiella pneumoniae, being the main organisms found. Most patients had a good outcome, and the presence of headache may influence the outcome.

The circular RNA circ_GRHPR promotes NSCLC cell proliferation and invasion via interactions with the RNA-binding protein PCBP2.

As the most common malignancy, lung cancer is characterised by high rates of occurrence and mortality. Although circular RNAs (circRNAs) are known to act as important regulators in cancer, their role in lung cancer remains poorly understood. In this study, circ_GRHPR expression was found to be significantly upregulated in the serum of five patients with non-small cell lung cancer (NSCLC), compared to that in healthy controls. It is expressed at high levels in NSCLC cell lines, as revealed by qRT-PCR analysis. Functionally, we demonstrated that circ_GRHPR promotes NSCLC proliferation and invasion in vitro and in vivo by cell proliferation, transwell, cell cycle, and tumour-forming assays. Mechanistically, RNA pull-down and RNA immunoprecipitation assays showed that circ_GRHPR interacts with the RNA-binding protein poly(rC)-binding protein 2 (PCBP2) and regulates its subcellular localisation by forming the circ_GRHPR/PCBP2 complex, localizing PCBP2 mainly in the cytoplasm and reducing the proportion found in the nucleus. Furthermore, we demonstrated that four-and-a-half LIM-only protein 3 (FHL3) is a tumour-stimulating factor in NSCLC that interacts with and is influenced by PCBP2. Circ_GRHPR increased FHL3 expression in the nucleus of NSCLC cells by decreasing PCBP2 expression therein and promoting the proliferation and invasion of NSCLC cells. Therefore, our study identified that circ_GRHPR promotes NSCLC proliferation and invasion, providing a possible explanation for its mechanism of action.

Antitumoral Potential of the Histone Demethylase Inhibitor GSK-J4 in Retinoblastoma.

Purpose: The purpose of this study was to investigate the antitumor effects of GSK-J4 on retinoblastoma, as well as its related biological functions and molecular mechanisms. Methods: The antitumor effect of GSK-J4 on retinoblastoma was evaluated by in vitro and in vivo assays. CCK-8, EdU incorporation, and soft agar colony formation assays were performed to examine the effect of GSK-J4 on cell proliferation. Flow cytometry was used to evaluate the effect of GSK-J4 on the cell cycle and apoptosis. RNA-seq and Western blotting were conducted to explore the molecular mechanisms of GSK-J4. An orthotopic xenograft model was established to determine the effect of GSK-J4 on tumor growth. Results: GSK-J4 significantly inhibited retinoblastoma cell proliferation both in vitro and in vivo, arrested the cell cycle at G2/M phase, and induced apoptosis. Mechanistically, GSK-J4 may suppress retinoblastoma cell growth by regulating the PI3K/AKT/NF-κB signaling pathway. Conclusions: The antitumor effects of GSK-J4 were noticeable in retinoblastoma and were at least partially mediated by PI3K/AKT/NF-κB pathway suppression. Our study provides a novel strategy for the treatment of retinoblastoma.

Association of body mass index with clinical outcome of primary WHO grade 4 glioma.

Background: The prognostic value of body mass index (BMI) in primary WHO grade 4 gliomas is not widely acknowledged. This study aims to assess the survival outcomes of patients with different BMIs. Methods: Real-world data of patients diagnosed with primary WHO grade 4 (2021 version) glioma was assessed. All 127 patients admitted in this study were administered with standard-of-care from September 2018 to September 2021. The outcomes of overall survival and progression-free survival were analyzed. Results: The baseline characteristics of clinical features, molecular features, and secondary treatment in BMI subsets showed no significant difference. The survival analyses showed a significantly superior overall survival (OS) in the overweight group compared to the normal weight group. A trend of better OS in the overweight group compared to the obesity group was observed. The univariate Cox regression demonstrated patients of round-BMI 25 and 26 had superior OS outcomes. Conclusion: In this real-world setting, patients with a BMI between 24 and 28 have superior overall survival. Patients in the proper BMI range may acquire survival benefits undergoing standard-of-care of primary WHO grade 4 gliomas. The prospective studies on a larger scale on these subsets of patients are necessary to solve the paradox of BMI in glioma.

Identification of MGMT promoter methylation as a specific lipid metabolism biomarker, reveals the feasibility of atorvastatin application in glioblastoma.

BACKGROUND: Glioblastoma is one of the deadliest tumors, and limited improvement in managing glioblastoma has been achieved in the past decades. The unmethylated promoter area of 6-O-Methylguanine-DNA Methyltransferase (MGMT) is a significant biomarker for recognizing a subset of glioblastoma that is resistant to chemotherapy. Here we identified MGMT methylation can also work as a specific biomarker to classify the lipid metabolism patterns between methylated and unmethylated glioblastoma and verify the potential novel therapeutic strategy for unmethylated MGMT glioblastoma. METHODS: Liquid Chromatograph Mass Spectrometer has been applied for non-targeted metabolome and targeted lipidomic profiling to explore the metabolism pattern correlated with MGMT promoter methylation. Transcriptome has been performed to explore the biological differences and the potential mechanism of lipid metabolism in glioblastoma samples. In vivo and ex vivo assays were performed to verify the anti-tumor activity of atorvastatin in the administration of glioblastoma. RESULTS: Multi-omics assay has described a significant difference in lipid metabolism between MGMT methylated and unmethylated glioblastoma. Longer and unsaturated fatty acyls were found enriched in MGMT-UM tumors. Lipid droplets have been revealed remarkably decreased in MGMT unmethylated glioblastoma. In vivo and ex vivo assays revealed that atorvastatin and also together with temozolomide showed significant anti-tumor activity, and atorvastatin alone was able to achieve better survival and living conditions for tumor-hosting mice. CONCLUSIONS: MGMT promoter methylation status might be a well-performed biomarker of lipid metabolism in glioblastoma. The current study can be the basis of further mechanism studies and implementation of clinical trials, and the results provide preclinical evidence of atorvastatin administration in glioblastoma, especially for MGMT unmethylated tumors.

Simultaneous Detection and Survey of Three Rice Viruses in China.

Rice black-streaked dwarf virus, Rice stripe virus, and Southern rice black-streaked dwarf virus (SRBSDV) have been epidemic in large areas of China where rice is grown, causing significant losses of rice yield in recent years. These viral diseases sometimes occur in the same regions, and even in the same fields, making it difficult to detect and diagnose the viral pathogens. A set of primers specific to the genes encoding the capsid proteins of the three viruses were designed, and a multiple one-step reverse-transcription polymerase chain reaction protocol was developed. The method proved to be simple, rapid, and sensitive. It was used to detect the viruses in samples of rice, maize, small brown planthoppers, and white-backed planthoppers collected from different regions of China, showing that it is suitable for routine diagnosis. A simultaneous survey of the three viruses was further conducted by this method throughout Zhejiang Province, Eastern China. The results showed that both RBSDV and RSV had continued to spread and that the newly emerging virus, SRBSDV, was present in at least 27 counties or cities, suggesting that more effort is needed to monitor and control the threat from these three viral diseases.

Post-operative cognitive dysfunction in patients following gastrointestinal endoscopic treatment.

We aimed to explore the changes in post-operative cognitive dysfunction (POCD) after gastrointestinal endoscopic treatment using detailed neuropsychological assessments. Patients hospitalized for gastrointestinal endoscopic polypectomy were recruited for neuropsychological evaluations, which included the Chinese version of the Mini-Mental State Examination (MMSE), Auditory-Verbal Learning Test, Digit Span Test (DST), Trail Making Task (TMT), Verbal Fluency Test, Clock Drawing Test, and Stroop test. Cognitive assessments were performed twice: one day before and 24 h after treatment. Healthy control subjects participated in the neuropsychological assessment during the same intervals. Detailed cognitive assessments were performed for 40 patients and 60 control subjects. Based on the Z scores, the incidence of POCD 24 h after gastrointestinal endoscopic treatment was 20%. Patients with POCD had significant impairment in the post-operative MMSE, forward DST, TMT, and Stroop interference effect correct count tests (all p < 0.05). Our preliminary results showed that patients were not fully recovered, and 20% had impairment in multiple cognitive assessments 24 h after a gastrointestinal endoscopy. As attention was affected, safety while discharging those patients should be a concern.

Asthma and Other Respiratory Diseases of Children in Relation to Personal Behavior, Household, Parental and Environmental Factors in West China.

Asthma and other respiratory diseases, which are of great concern in public health, are paid less attention in areas that are less economically developed. This research aimed to study the prevalence of critical respiratory diseases of children living in West China and figure out the potential influencing factors. A total of 575 children under the age of 14 were recruited from Xinjiang, China, to participate in the study in 2022. Information on activity patterns, socioeconomic and parental factors, and household and surrounding environment situations was obtained using a questionnaire survey. Logistic regression models were applied to estimate the odds ratios of respiratory disease prevalence in relation to behavior patterns, household, parental and environmental factors, respectively. The prevalence of ever doctor-diagnosed asthma, doctor-diagnosed bronchitis and current bronchitis were 4.7%, 19.0% and 14.4%, respectively. The prevalence of doctor-diagnosed pneumonia was 8.2%, which was two times higher in urban than rural areas. Longer annual heating duration was significantly associated with higher risks in children's asthma and bronchitis, with an odds ratio (OR) and 95% confidence interval (95% CI) of 3.363 (95% CI: 1.215-9.298) and 1.267 (95% CI: 1.002-1.601), respectively. Opening the window longer in autumn would lead to higher risks of bronchitis, with ORs of 1.165 and 1.133, respectively, for doctor-diagnosed bronchitis and current bronchitis. Residential air pollution and having a residence close to waste incineration plant or garbage station were, respectively, significantly associated with higher risks of doctor-diagnosed bronchitis and asthma. Parental disease history was associated with a higher prevalence of children's asthma and respiratory diseases, whereas breastfeeding and doing physical exercise were, respectively, significantly associated with a lower risk of asthma. A high prevalence of respiratory diseases in children in West China may be partly attributed to longer annual heating time, opening windows longer in autumn, surrounding environmental pollution, as well as parental disease history, whereas promoting physical activity and breastfeeding could be an effective measure to reduce the risk of childhood asthma in West China.

Effect of CPAP on cognitive function in stroke patients with obstructive sleep apnoea: a meta-analysis of randomised controlled trials.

OBJECTIVE: To investigate the effect of continuous positive airway pressure (CPAP) treatment on cognitive function in stroke patients with obstructive sleep apnoea (OSA) by exploring randomised controlled trials (RCTs). METHODS: Published RCTs that assessed the therapeutic effects of CPAP on cognition in stroke patients with OSA, compared with controls or sham CPAP, were included. Electronic databases, including MEDLINE, Embase and Cochrane library, were searched in October 2020 and October 2021. Risk of bias was assessed using the Cochrane collaboration tools. A random effects or fixed effects model was used according to heterogeneity. The outcomes were global cognitive gain, improvement in cognitive domain and subjective sleepiness. RESULTS: 7 RCTs, including 327 participants, comparing CPAP with control or sham CPAP treatment were included. 6 RCTs with 270 participants reported results related to global cognition, and CPAP treatment had no significant effects on global cognitive gain in stroke patients with OSA (standardised mean difference (SMD), 0.18; 95% CI, -0.07 to 0.42; p=0.153). A subgroup analysis showed that an early start to (<2 weeks post stroke) CPAP treatment after stroke significantly improved global cognition (SMD, 0.66; 95% CI, 0.18 to 1.14; p=0.007), which was not found in the case of a delayed start to CPAP treatment. However, CPAP did not significantly help with memory, language, attention or executive function. Moreover, CPAP therapy significantly alleviated subjective sleepiness (SMD, -0.73; 95% CI, -1.15 to -0.32; p≤0.001). CONCLUSIONS: Early initiation of CPAP treatment might contribute to improvement in global cognition in stroke patients with OSA. This study had the following limitations: the sample size in each included study was relatively small; the scales related to cognitive assessment or subjective sleepiness were inconsistent; and the methodological quality was not high. Future trials should focus on including a greater number of stroke patients with OSA undergoing CPAP treatment. PROSPERO REGISTRATION NUMBER: CRD42020214709.

Biological activity of a vascular endothelial cell-hydroxyapatite orbital implant complex: An experimental study.

The reduction in postoperative complications is a considerable concern after orbital reparation and reconstruction. Selecting the appropriate scaffold materials to improve the survival rates of the seeded cells is a challenge in tissue engineering. The aim of the present study was to evaluate the biological activity of a vascular endothelial cell-hydroxyapatite orbital complex, which was constructed with tissue engineering and used as an implant after enucleation of the eyeNew Zealand white rabbits were randomly divided into two groups that underwent hydroxyapatite orbital implant surgery in the right eye. The primary orbital microvascular endothelial cells were collected from the microvascular tissue and subsequently cultured. Then, hydroxyapatite ocular implants were cultured with vascular endothelial cells in the endothelial cell (EC) group, and implants were cultured without vascular endothelial cells in the blank group. Characterization of the cells was performed with immunofluorescence staining and a Transwell migration and cell tube formation assay. The levels of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) in the rabbit conjunctiva were measured with an ELISA. The results showed that the levels of IL-8 were decreased in the EC group and increased in the blank group. The levels of VEGF were increased in the EC group when compared to the blank group with statistical significance. The average depth of the fibrovascular tissue was obviously thicker in the EC group compared with that found in the blank group. These findings suggest that the vascular endothelial cell-hydroxyapatite orbital implant complex may be an effective strategy with which to accelerate vascularization and reduce complications of infection with satisfactory biological activity.

A three-dimensional LUR framework for PM2.5 exposure assessment based on mobile unmanned aerial vehicle monitoring.

Land use regression (LUR) models have been widely used in epidemiological studies and risk assessments related to air pollution. Although efforts have been made to improve the performance of LUR models so that they capture the spatial heterogeneity of fine particulate matter (PM2.5) in high-density cities, few studies have revealed the vertical differences in PM2.5 exposure. This study proposes a three-dimensional LUR (3-D LUR) assessment framework for PM2.5 exposure that combines a high-resolution LUR model with a vertical PM2.5 variation model to investigate the results of horizontal and vertical mobile PM2.5 monitoring campaigns. High-resolution LUR models that were developed independently for daytime and nighttime were found to explain 51% and 60% of the PM2.5 variation, respectively. Vertical measurements of PM2.5 from three regions were first parameterized to produce a coefficient of variation for the concentration (CVC) to define the rate at which PM2.5 changes at a certain height relative to the ground. The vertical variation model for PM2.5 was developed based on a spline smoothing function in a generalized additive model (GAM) framework with an adjusted R2 of 0.91 and explained 92.8% of the variance. PM2.5 exposure levels for the population in the study area were estimated based on both the LUR models and the 3-D LUR framework. The 3-D LUR framework was found to improve the accuracy of exposure estimation in the vertical direction by avoiding exposure estimation errors of up to 5%. Although the 3-D LUR-based assessment did not indicate significant variation in estimates of premature mortality that could be attributed to PM2.5, exposure to this pollutant was found to differ in the vertical direction. The 3-D LUR framework has the potential to provide accurate exposure estimates for use in future epidemiological studies and health risk assessments.

SP2509, a Selective Inhibitor of LSD1, Suppresses Retinoblastoma Growth by Downregulating ß-catenin Signaling.

Purpose: To study the role of lysine-specific demethylase 1 (LSD1) in retinoblastoma (RB) growth and to determine whether the LSD1 inhibitor SP2509 can inhibit RB progression. Methods: We detected the levels of LSD1 in 12 RB tissue samples, two RB cell lines (Y79 and Weri-RB1), and a retinal pigment epithelium cell line (ARPE-19). Overexpression or knockdown of LSD1 was performed to examine the role of LSD1 in RB cancer cell survival. In vitro and in vivo experiments were conducted to detect the antitumor effect of SP2509, and the antitumor mechanism of SP2509 was examined by RNA sequencing and Western blot. Results: LSD1 is overexpressed in RB tissues and cells and increases RB cancer cell viability and colony formation ability. The LSD1 inhibitor SP2509 inhibits RB cell proliferation in vitro and in vivo. Treatment with SP2509 increases the levels of dimethylated histone 3 lysine 4 (H3K4me2) and inhibits the expression of ß-catenin signaling pathway-related proteins in RB cells. Conclusions: We demonstrated that LSD1 is overexpressed in RB cells and promotes RB cell survival. The LSD1 inhibitor SP2509 exerted strong growth inhibition in vitro and in vivo, which was at least partially mediated by suppression of the ß-catenin pathway.

Circular RNA circ_0008934 promotes hepatocellular carcinoma growth and metastasis through modulating miR-1305/TMTC3 axis.

Circular RNAs (circRNAs) play important roles in the progression of hepatocellular carcinoma (HCC). However, the exact function of circ_0008934 in HCC is unknown. Our study aimed to investigate the expression characteristics of circ_0008934 in HCC and its effects on the proliferation and metastasis of HCC, and to explore the potential mechanism. In this study, circ_0008934 expression was found to be significantly upregulated in HCC tissues and cell lines by qRT-PCR. High level of circ_0008934 is closely associated with higher serum AFP (P < 0.001), larger tumor diameter (P = 0.012), microvascular invasion (P = 0.008) and poorer prognosis (P = 0.007) of HCC patients. Functionally, knockdown of circ_0008934 inhibited HCC cell proliferation, invasion and migration in vitro and vivo. Mechanically, circ_0008934 was a sponge of miR-1305 to facilitate the TMTC3 expression, and the TMTC3 expression in HCC tissues was negatively associated with the survival of HCC patients. Furthermore, rescued assays revealed that the circ_0008934 facilitated HCC proliferation, invasion and migration by regulating miR-1305/ TMTC3 signaling pathways. Overall, these results demonstrate that downregulation of circ_0008934 repress HCC growth and metastasis by upregulating miR-1305 to inhibit TMTC3, suggesting circ_0008934/ miR-1305/ TMTC3 regulatory axis may be a possible novel therapeutic target for HCC.

Bufalin enhances the killing efficacy of NK cells against hepatocellular carcinoma by inhibiting MICA shedding.

Bufalin, as a Chinese traditional anti-tumor agent, has been studied about inhibiting proliferation and promoting apoptosis of liver cancer, however, there are few reports on immune modulating function. We used the human liver cancer cell lines along with 91 pathologically-verified postoperative hepatocellular carcinoma (HCC) specimens to assess immune modulating function of bufalin. We found that bufalin directly balances stimulatory and inhibitory receptors on the surface of NK cells and indirectly activates natural killer (NK) cells by inhibiting MICA shedding, which prevented immune escape and indirectly enhanced NKG2D-dependent immune surveillance. This study showed that bufalin can directly or indirectly regulate the immune response, which provides a new theoretical basis for the clinical application of "Huachansu injection".

Neuroendocrine carcinoma of the nasal cavity with epiphora as the first symptom: A case report.

RATIONALE: Neuroendocrine carcinomas (NECs) are rare malignancies that originate from the hormone-producing cells of the neuroendocrine system. They can grow in most organs of the body but are commonly found in the gastrointestinal and respiratory tracts. The nasal cavity is a rare site for NECs. PATIENT CONCERNS: We report a case of NECs in a 45-year-old woman who presented with epiphora in the right eye for a year owing to an unknown reason. DIAGNOSES: The diagnosis was initially confirmed via histological and immunohistochemical assays. Postoperatively, computed tomography of the neck revealed C4 vertebral bone metastasis. INTERVENTIONS: The tumor was endoscopically removed from the right eye. The patient received a full course of adjuvant polychemotherapy. OUTCOMES: Six months after diagnosis, the patient died due to bone metastasis. LESSONS: Diagnosing nasal neuroendocrine carcinoma is clinically challenging. It must be distinguished from other orbital masses, such as chronic dacryocystitis or nasal polyps. The treatment should be further investigated for this rare malignancy in near future.