A social theory-enhanced graph representation learning framework for multitask prediction of drug-drug interactions.

Current machine learning-based methods have achieved inspiring predictions in the scenarios of mono-type and multi-type drug-drug interactions (DDIs), but they all ignore enhancive and depressive pharmacological changes triggered by DDIs. In addition, these pharmacological changes are asymmetric since the roles of two drugs in an interaction are different. More importantly, these pharmacological changes imply significant topological patterns among DDIs. To address the above issues, we first leverage Balance theory and Status theory in social networks to reveal the topological patterns among directed pharmacological DDIs, which are modeled as a signed and directed network. Then, we design a novel graph representation learning model named SGRL-DDI (social theory-enhanced graph representation learning for DDI) to realize the multitask prediction of DDIs. SGRL-DDI model can capture the task-joint information by integrating relation graph convolutional networks with Balance and Status patterns. Moreover, we utilize task-specific deep neural networks to perform two tasks, including the prediction of enhancive/depressive DDIs and the prediction of directed DDIs. Based on DDI entries collected from DrugBank, the superiority of our model is demonstrated by the comparison with other state-of-the-art methods. Furthermore, the ablation study verifies that Balance and Status patterns help characterize directed pharmacological DDIs, and that the joint of two tasks provides better DDI representations than individual tasks. Last, we demonstrate the practical effectiveness of our model by a version-dependent test, where 88.47 and 81.38% DDI out of newly added entries provided by the latest release of DrugBank are validated in two predicting tasks respectively.

Preparation of Indolin-3-one-Containing 1,4-Naphthoquinone Derivatives via Organocatalytic Asymmetric Michael Addition Reaction.

This article explores the asymmetric Michael addition reaction of 2-hydroxy-1,4-naphthoquinone and indole-3-ones catalyzed by cinchona alkaloids. This strategy utilizes 2-hydroxy-1,4-naphthoquinone and easily prepared indole-3-one as substrates, resulting in the synthesis of 23 unprecedented indolin-3-ones bearing a 1,4-naphthoquinone unit at the C2 position of indole under simple and mild reaction conditions, with up to 88% yield, 98% ee, and >20:1 dr.

The effectiveness of various treatment approaches for laryngeal contact granulomas.

OBJECTIVES: To assess and compare the effectiveness of various treatment approaches for laryngeal contact granulomas (LCG). METHODS: A retrospective analysis was conducted on a cohort of 45 patients diagnosed with LCG at the Second Affiliated Hospital of Xi'an Jiaotong University from October 2017 to May 2023. Based on the treatment modalities administered, patients were categorized into three groups: acid suppression alone, hormone injection combined with acid suppression, and surgery combined with acid suppression. Subsequently, the study compared differences in treatment efficacy and average healing time among these three groups, using various indicators. RESULTS: The findings indicate that the granuloma size in LCG patients with hoarseness (0.126, 95% CI 0.087-0.288) was significantly greater compared to LCG patients without hoarseness (0.047, 95% CI 0.014-0.083) (P = 0.001). However, there were no significant variations in age, morphology (unlobulated/lobulated), laterality ratio (left/right), sex ratio (male/female), history of tracheal intubation (non-intubation/intubation), and RFS score (RFS > 7/RFS ≤ 7) (P > 0.05), regardless of the presence of hoarseness symptoms. At the treatment observation endpoint of 3 months, the curative ratio in the group receiving hormone injection combined with acid suppression was found to be significantly higher compared to the group receiving acid suppression alone (P = 0.018). In addition, the average healing time of patients in the hormone injection combined with acid suppression group was notably shorter than that of the acid suppression alone group (P = 0.007). CONCLUSIONS: The combination of hormonal injections and acid suppression may enhance the curative ratio and expedite the healing time of LCG.

[Effects of human umbilical cord mesenchymal stem cells (MSCs)-derived exosomes on pulmonary vascular remodeling in hypoxic pulmonary hypertension].

The present study aimed to investigate the effect of human umbilical cord mesenchymal stem cells (MSCs)-derived exosomes (MSCs-Exo) on mice with hypoxic pulmonary hypertension (HPH). MSCs were isolated and cultured from human umbilical cords under aseptic conditions, and exosomes were extracted from the supernatants and identified. Healthy SPF C57BL/6 mice were randomly divided into three groups: normoxic group, hypoxic group, and hypoxic+MSCs-Exo group. Mice in the hypoxic group and the hypoxic+MSCs-Exo group were maintained for 28 d at an equivalent altitude of 5 000 m in a hypobaric chamber to establish HPH mouse model. The mice in the hypoxic+MSCs-Exo group were injected with MSCs-Exo via tail vein before hypoxia and on days 1, 3, 5 and 9 of hypoxia, and the mice in the other two groups were injected with PBS. At the end of the experiment, echocardiography was performed to detect pulmonary arterial acceleration time/pulmonary arterial ejection time ratio (PAAT/PET), right ventricular free wall thickness, and right ventricular hypertrophy index RV/(LV+S). HE staining was performed to observe the lung tissue morphology. EVG staining was performed to observe elastic fiber hyperplasia. Immunohistochemistry was performed to detect α smooth muscle actin (α-SMA) expression in lung tissue. Immunofluorescence staining was used to detect macrophage infiltration in lung tissue. qPCR was performed to detect IL-1ß and IL-33 in lung tissue, and cytometric bead array was performed to detect IL-10 secretion. Western blotting was used to detect the M1 macrophage marker iNOS, M2 macrophage marker Arg-1 and IL-33/ST2 pathway proteins in lung tissues. The results showed that hypoxia increased pulmonary artery pressure and pulmonary vascular remodeling, increased macrophage infiltration, IL-1ß and IL-33 expression (P < 0.05) and upregulated the IL-33/ST2 pathway (P < 0.05). Compared with the hypoxic group, MSCs-Exo treatment increased PAAT/PET (P < 0.05), decreased right ventricular free wall thickness (P < 0.05), right ventricular hypertrophy index RV/(LV+S) (P < 0.05), α-SMA expression in small pulmonary vessels (P < 0.05), and inflammatory factors including IL-1ß and IL-33 expression in lung tissue, however increased IL-10 secretion (P < 0.05). In addition, MSCs-Exo treatment upregulated Arg-1 and downregulated iNOS and IL-33/ST2 (P < 0.05). The results suggest that MSC-Exo may alleviate HPH through their immunomodulatory effects.

Brain-derived neurotrophic factor in degenerative retinal diseases: Update and novel perspective.

Dysfunction and death of neuronal cells are cardinal features of degenerative retinal diseases that are known to arise as the disease progresses. Increasingly evidence suggests that abnormal expression of brain-derived neurotrophic factor (BDNF) may serve as an obligatory relay of the dysfunction and death of neuronal cells in degenerative retinal diseases. Although disorder of BDNF, whether depletion or augmentation, has been connected with neuronal apoptosis and neuroinflammation, the exact mechanisms underlying the effect of impaired BDNF expression on degenerative retinal diseases remain unclear. Here, we present an overview of how BDNF is linked to pathological mechanism of retinal degenerative diseases, summarize BDNF-based treatment strategies, and discuss possible research perspectives in the future.

Three New Labdane-Type Diterpenoids from the Fruits of Amomum villosum and Their Anti-Inflammatory Activities.

Three new labdane-type diterpenoids, calcaratarin E, villosumtriol, and 12-epi-villosumtriol (1-3) were isolated from the fruits of Amomum villosum, along with seven known diterpenoids (4-10). Through comprehensive analysis of chemical evidence and spectral data including UV, 1D and 2D NMR, HR-ESI-MS, IR, and X-ray crystallography, the structures of these novel compounds were successfully determined. Additionally, the inhibitory effects of compounds 2-10 on NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells were evaluated. Notably, compound 6 exhibited the most significant inhibitory effect with an IC50 value of 1.74±0.69 µM.

The subglottic involvement is an independent risk factor for recurrence of laryngeal amyloidosis.

OBJECTIVE: To analyze the risk factors for recurrence of laryngeal amyloidosis (LA). METHODS: The clinical data of patients with LA admitted in the Otolaryngology Head and Neck Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University from August 2009 to June 2022 were analyzed retrospectively; then, the risk factors for recurrence and their impacts on the recurrence time were also analyzed. RESULTS: Of the 44 patients with LA, the majority (38 cases, 86.4%) only involved one anatomical region and the others (6 cases, 13.6%) involved two laryngeal regions concurrently. Overall, the glottic region was the most commonly affected area (28 cases, 63.6%), followed by the supraglottic region (16 cases, 36.4%) and subglottic region (6 cases, 13.6%). In addition, all the lesions were categorized as isolated nodule (31.8%), submucosal localized deposition (52.3%), and submucosal diffuse deposition (15.9%) according to their morphologies under electronic laryngoscope. Finally, six patients (13.6%) had recurrence after operation with a median recurrence time of 24.5 months, and subglottic involvement was confirmed to be an independent risk factor for recurrence of LA by univariate and multivariate logistic regression analyses (P < 0.05). Meanwhile, the patients with subglottic involvement presented as submucosal diffuse deposition had a considerable shorter recurrence time (t = 5.759, P = 0.005). CONCLUSION: The subglottic involvement is an independent risk factor for recurrence of LA.

deepMDDI: A deep graph convolutional network framework for multi-label prediction of drug-drug interactions.

It is crucial to identify DDIs and explore their underlying mechanism (e.g., DDIs types) for polypharmacy safety. However, the detection of DDIs in assays is still time-consuming and costly, due to the need for experimental search over a large space of drug combinations. Thus, many computational methods have been developed to predict DDIs, most of them focusing on whether a drug interacts with another or not. And a few deep learning-based methods address a more realistic screening task for identifying various DDI types, but they assume a DDI only triggers one pharmacological effect, while a DDI can trigger more types of pharmacological effects. Thus, here we proposed a novel end-to-end deep learning-based method (called deepMDDI) for the Multi-label prediction of Drug-Drug Interactions. deepMDDI contains an encoder derived from relational graph convolutional networks and a tensor-like decoder to uniformly model interactions. deepMDDI is not only efficient for DDI transductive prediction, but also inductive prediction. The experimental results show that our model is superior to other state-of-the-art deep learning-based methods. We also validated the power of deepMDDI in the DDIs multi-label prediction and found several new valid DDIs in the case study. In conclusion, deepMDDI is beneficial to uncover the mechanism and regularity of DDIs.

The effects of Helicobacter pylori eradication therapy on salivary pepsin concentration in patients with laryngopharyngeal reflux.

OBJECTIVE: To investigate the effect of Helicobacter pylori (HP) eradication therapy on salivary pepsin concentration in laryngopharyngeal reflux (LPR) patients with HP infection. MATERIALS AND METHODS: A total of 477 patients with suspected LPR were enrolled from June 2020 to September 2021. Reflux symptom index, reflux finding score, the positive rates and disintegrations per minute values of HP infection detected by 14C urea breath test and salivary pepsin concentrations analyzed using enzyme-linked immunosorbent assay were compared in LPR patients and non-LPR patients with or without HP infection. HP-positive patients were treated with HP eradication therapy while HP-negative patients with PPI therapy. RESULTS: The scores of nagging cough (0.88 vs. 0.50, P = 0.035), erythema or hyperemia (1.93 vs. 1.78, P = 0.035) and vocal fold edema (1.04 vs. 0.85, P = 0.025) were higher in the LPR (+) Hp (+) subgroup than in LPR (+) Hp (-) subgroup. The concentrations of salivary pepsin in the Hp (+) subgroup were higher than in the Hp (-) subgroup either in LPR patients (75.24 ng/ml vs. 61.39 ng/ml, P = 0.005) or the non-LPR patients (78.42 ng/ml vs. 48.96 ng/ml, P = 0.024). Compared to baseline (before treatment), scores of nagging cough (0.35 vs. 0.84, P = 0.019) and erythema or hyperemia (1.50 vs. 1.83, P = 0.039) and the concentrations of salivary pepsin (44.35 ng/ml vs. 74.15 ng/ml, P = 0.017) in LPR patients with HP infection decreased after HP treatment; yet, this was not observed for the LPR patients without HP infection treated with PPI only (P > 0.05). CONCLUSION: HP infection may aggravate the symptoms and signs of LPR patients, partly by increasing their salivary pepsin concentration.

[Salidroside inhibits phenotypic transformation of rat pulmonary artery smooth muscle cells induced by hypoxia].

This study investigated the effect of salidroside on phenotypic transformation of rat pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia. Rat pulmonary arteries were isolated by tissue digestion and PASMCs were cultured. The OD values of cells treated with salidroside at different concentrations for 48 hours were measured by cell counting kit-8(CCK-8) to determine the appropriate concentration range of salidroside. The cells were divided into a normal(normoxia) group, a model(hypoxia) group, and three hypoxia + salidroside groups(40, 60, and 80 µg·mL~(-1)). Quantitative real-time PCR(qRT-PCR) was used to detect the mRNA expression of cell contractile markers in each group, such as α-smooth muscle actin(α-SMA), smooth muscle 22(SM22), and calcium-binding protein(calponin), and synthetic marker vimentin. The expression levels of cell phenotypic markers and proliferating cell nuclear antigen(PCNA) were detected by Western blot. The proliferation of cells in each group was detected by the 5-ethynyl-2'-deoxyuridine(EdU) assay. Cell migration was measured by Transwell assay. As revealed by results, compared with the normal group, the model group showed decreased mRNA and protein expression of contractile phenotypic markers of PASMCs and increased mRNA and protein expression of synthetic markers. Compared with the conditions in the model group, salidroside could down-regulate the mRNA and protein expression of synthetic markers in PASMCs and up-regulated the mRNA and protein expression of contractile phenotypic markers. Compared with the normal group, the model group showed potentiated proliferation and migration. Compared with the model group, the hypoxia + salidroside groups showed blunted proliferation and migration of cells after phenotypic transformation. The results suggest that salidroside can inhibit the expression of synthetic markers in PASMCs and promote the expression of contractile markers to inhibit the hypoxia-induced phenotypic transformation of PASMCs. The mechanism of salidroside in inhibiting the proliferation and migration of PASMCs is related to the inhibition of the phenotypic transformation of PASMCs.

Hydrogen sulfide rescues high glucose-induced migration dysfunction in HUVECs by upregulating miR-126-3p.

Diabetes (especially Type II) is one of the primary threats to cardiovascular health. Wound healing defects and vascular dysfunction are common in diabetic patients, and the primary cause of deterioration is sustained high plasma glucose. microRNA, a noncoding RNA, has regulatory functions that are critical to maintaining homeostasis. MicroRNA (miR)-126-3p is a potential diabetes biomarker and a proangiogenic factor, and its plasma level decreases in diabetic patients. Previous studies have revealed the proangiogenic character of the gasotransmitter hydrogen sulfide (H2S). However, little is known about the relationship between H2S and miR-126-3p when the extracellular glucose level is high, let alone their influences on deteriorated endothelial cell migration, a key component of angiogenesis, which is crucial for wound healing. Human umbilical vein endothelial cells (HUVECs) were treated with high glucose (33.3 mmol/L) or normal glucose (5.5 mmol/L) for 48 h. Affymetrix miRNA profiling and real-time PCR were used to validate the miRNA expression. An H2S probe (HSip-1) was used to detect endogenous H2S. Scratch wound-healing assays were used to evaluate HUVEC migration. The protein levels were quantified by Western blot. Both exogenous and endogenous H2S could upregulate the miR-126-3p levels in HUVECs or muscle tissue. High glucose decreased the H2S level and the protein expression of the H2S-producing enzyme cystathionine γ-lyase (CSE) in HUVECs; however, the DNA methyltransferase 1 (DNMT1) protein level was upregulated. CSE overexpression not only increased the miR-126-3p level by decreasing the DNMT1 protein level but also rescued the deteriorated cell migration in HUVECs treated with high glucose. DNMT1 overexpression decreased the miR-126-3p level and inhibited the migration of HUVECs, whereas silencing DNMT1 improved cell migration. High glucose decreased the endogenous H2S and miR-126-3p levels and increased the DNMT1 expression, thus inducing the migration dysfunction of HUVECs. Treatment with exogenous H2S or the overexpression of the endogenously produced enzyme CSE would rescue this migration dysfunction through H2S-DNMT1-miR-126-3p.

H63D CG genotype of HFE is associated with increased risk of sporadic amyotrophic lateral sclerosis in a single population.

This paper describes the genetic etiology of sporadic amyotrophic lateral sclerosis in a single population. Polymerase chain reaction-restriction fragment length polymorphism and DNA sample sequencing of 3 common HFE gene variants (C282Y and H63D and S65C) were performed on 10 randomly selected samples of H63D gene variant (124 patients with sporadic amyotrophic lateral sclerosis) and 10 wild types of H63D samples (210 controls). The C282Y and S65C gene variant were absent. There were 24 cases (7.18%) with H63D heterozygous variants, including 16 cases (13%) in the sporadic amyotrophic lateral sclerosis group and 8 cases (4%) in the healthy control group. The polymorphism frequency of the H63D gene variant in the sporadic amyotrophic lateral sclerosis group was significantly different than that in the control group (p < 0.05), and the difference at allele level, which is still more significant (p < 0.05). H63D gene variant could be a risk factor for sporadic amyotrophic lateral sclerosis in a single population. The results showed HFE gene variants play a role in the occurrence of sporadic amyotrophic lateral sclerosis, but its effect should be carefully estimated.

[Clinical effect of sirolimus in treatment of blue rubber bleb nevus syndrome in children: a report of 2 cases and literature review].

To study the clinical effect of oral sirolimus in the treatment of children with blue rubber bleb nevus syndrome (BRBNS) in the gastrointestinal tract, a retrospective analysis was performed on the clinical data and follow-up results of two children with BRBNS treated by sirolimus. The two children with BRBNS had gastrointestinal bleeding and anemia and were treated with sirolimus at a dose of 1 mg/day as part of treatment. The plasma concentration of the drug was maintained between 2.5-12.0 ng/mL. The children showed disappearance of gastrointestinal bleeding and improvements in anemia and coagulation function, and blood transfusion could be stopped during treatment, with no obvious adverse drug reactions. PubMed, Wanfang Data, and CNKI were searched for related articles on sirolimus in the treatment of BRBNS. A total of 26 cases of children with BRBNS, aged 0-18 years, were obtained. With the addition of the 2 cases in this study, sirolimus treatment achieved a satisfactory clinical effect in all 28 cases. Sirolimus may be effective and safe in the treatment of children with BRBNS, and further prospective studies are needed to evaluate the long-term efficacy of this drug.

Molecular diversity of phenothiazines: design and synthesis of phenothiazine-dithiocarbamate hybrids as potential cell cycle blockers.

Novel phenothiazine-dithiocarbamate analogues were designed by molecular hybridization strategy and synthesized and evaluated for their anticancer activity in vitro against three selected cancer cell lines (EC-109, MGC-803, and PC-3). The preliminary structure-activity relationship (SAR) for this phenothiazine-dithiocarbamate hybrids is explored. Among all analogues, 2-oxo-2-(10H-phenothiazin-10-yl)ethyl 4-ethylpiperazine-1-carbodithioate (8a) showed the most potent inhibitory activity with an [Formula: see text] value of [Formula: see text] against PC-3 cells. In addition, compound 8a could arrest the cell cycle at the G1 phase and regulate the expression of G1 checkpoint-related proteins, suggesting that phenothiazine-dithiocarbamate hybrids might be useful as cell cycle blockers.

[Rapid analysis on phenolic compounds in Rheum palmatum based on UPLC-Q-TOF/MSE combined with diagnostic ions filter].

Diagnostic ions filter method was used to rapidly detect and identify the phenolic compounds in Rheum palmatum based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). The representative authentic standards of phenolic compounds, including gallic acid, (+)-catechin, (－)-epicatechin, (－)-epicatechin-3-O-gallate and procyanidin B2, were subjected to analysis by UPLC-Q-TOF/MSE system with negative ion mode. Fragmentation patterns of each standard were summarized based on assigned fragment ions. The prominent product ions were selected as diagnostic ions. Subsequently, diagnostic ions filter was employed to rapidly recognize analogous skeletons. Combined with retention time, accurate mass, characteristic fragments and previous literature data, the structures of the filtered compounds were identified or tentatively characterized. A total 63 phenolic compounds (36 phenolic acid derivatives, 8 flavonoid derivatives and 19 tennis derivatives) in R. palmatum were identified, including 6 potential new compounds. The method of diagnostic ions filter could rapidly detect and identify phenolic compounds in R. palmatum This study provides a method for rapid detection of phenolic compounds in R. palmatum and is expected to complete the material basis of rhubarb.

Ab initio studies on the spin-forbidden cooling transitions of the LiRb molecule.

The spin-forbidden cooling of the LiRb molecule is investigated based on ab initio quantum chemistry calculations. The multireference configuration interaction method is used to generate the potential energy curves (PECs) of the ground state X(1)Σ(+) and the low-lying excited states a(3)Σ(+), B(1)Π, and b(3)Π. The spin-orbit coupling effects for the PECs and the transition dipole moments (TDMs) between the X(1)Σ(+), b(3)Π and a(3)Σ(+) states are also calculated. The analytical functions for the PECs are deduced. The rovibrational energy levels, the spectroscopic parameters and the Franck-Condon factors (FCF) are determined by solving the Schrödinger equation of nuclear movement with the obtained analytical functions. The b(3)Π0 ↔ X(1)Σ(+) and b(3)Π1 ↔ X(1)Σ(+) transitions have highly diagonal distributed FCFs and non-zero TDMs, demonstrating that the LiRb molecule could be a very promising candidate for laser cooling. Therefore, a three-cycle laser cooling scheme for the molecule has been proposed based on these two spin-forbidden transitions. Using the radiative lifetime and linewidth calculated from the obtained TDM functions, we present further analysis of the cooling of LiRb and the corresponding KRb molecule. The transition b(3)Π0 ↔ X(1)Σ(+) is found to be a practical transition to cool the LiRb molecule, and a sub-microkelvin cool temperature could be reached for the KRb molecule using a similar laser cooling scheme.

Stat3 signaling activation crosslinking of TGF-ß1 in hepatic stellate cell exacerbates liver injury and fibrosis.

BACKGROUND/AIMS: The role of signal transducer and activator of transcription 3 (Stat3) in liver fibrosis is still controversial. Since hepatic stellate cells (HSCs) and transforming growth factor-ß1 (TGF-ß1) are central to the fibrogenesis, our goal was to clarify the mechanism of Stat3 crosslinking of TGF-ß1 signaling. METHODS: Stat3, TGF-ß1 mRNA and protein expressions were examined in liver tissues of chronic hepatitis B (CHB) patients and diethylinitrosamine (DEN)-induced rat fibrosis model. The effect of Stat3 activation or suppression on TGF-ß1 signaling in HSCs was tested in vitro and in vivo. RESULTS: Stat3 expression as well as TGF-ß1 was increased in CHB patients and DEN-induced fibrosis rat model. This was strongly correlated with increase in fibrosis staging. TGF-ß1, a mediator of fibrosis, was enhanced by Stat3, but suppressed by siRNA-mediated RNA knockdown of Stat3 (siStat3) or Janus kinase 2 inhibitor (AG490) both in vivo and in vitro. Stat3 crosslinking TGF-ß1 signaling plays an important role in HSC activation and increasing fibrosis related products. TGF-ß1 could not achieve profibrogenic cytokine and anti-apoptosis characteristics without Stat3 activation in HSCs. CONCLUSION: We provide a novel role of Stat3 cooperating TGF-ß1 in activation and anti-apoptotic effect of HSCs. Stat3 worsens liver fibrosis through the up-regulation of TGF-ß1 and fibrotic product expression.

The effect of recombinant lentiviral vector encoding miR-145 on human esophageal cancer cells.

miR-145, a newly identified microRNA molecule, is hypothesized to function as a tumor suppressor, but this activity has not been investigated in esophageal l carcinoma (EC). The aim of this study was to investigate the effect of miR-145 on the biological features of EC cells. miR-145 was obtained using PCR technology and cloned into the lentiviral vector, pLVX-IRES-ZsGreen1, to construct the resulting vector, pLVX-IZ-miR-145. The vector was packaged, the viral titer was tested, and ECA109 cells were infected with the optimal viral titer. Cells that were stably transfected with miR-145 were screened. Flow cytometry was used to analyze enhanced green fluorescence protein gene expression, and to measure cell apoptosis and cell cycle. miR-145 expression was detected by real-time fluorescent quantitative PCR. Furthermore, cell proliferation was assayed using CCK-8 assay. The pLVX-IZ-miR-145 vector was successfully constructed, and the viral titer achieved up to 5.0 × 10(8) TU/mL. The transfection efficiency was 90 %. Compared to the control group, the expression level of miR-145 in the transfected group was significantly higher (185-fold, P < 0.05). miR-145 overexpression significantly inhibited esophageal cancer cell proliferation (P < 0.05). Moreover, the number of cells at the G2/M stage, as well as the cell apoptotic rate, in the miR-145-transfected group was significantly increased (P < 0.05). Our study reveals that overexpression of miR-145 inhibits cell proliferation, increases apoptosis, and influences the cell cycle progression of EC cell.

Cathepsin L suppression increases the radiosensitivity of human glioma U251 cells via G2/M cell cycle arrest and DNA damage.

AIM: Cathepsin L is a lysosomal cysteine protease that plays important roles in cancer tumorigenesis, proliferation and chemotherapy resistance. The aim of this study was to determine how cathepsin L regulated the radiosensitivity of human glioma cells in vitro. METHODS: Human glioma U251 cells (harboring the mutant type p53 gene) and U87 cells (harboring the wide type p53 gene) were irradiated with X-rays. The expression of cathepsin L was analyzed using Western blot and immunofluorescence assays. Cell survival and DNA damage were evaluated using clonogenic and comet assays, respectively. Flow cytometry was used to detect the cell cycle distribution. Apoptotic cells were observed using Hoechst 33258 staining and fluorescence microscopy. RESULTS: Irradiation significantly increased the cytoplasmic and nuclear levels of cathepsin L in U251 cells but not in U87 cells. Treatment with the specific cathepsin L inhibitor Z-FY-CHO (10 µmol/L) or transfection with cathepsin L shRNA significantly increased the radiosensitivity of U251 cells. Both suppression and knockdown of cathepsin L in U251 cells increased irradiation-induced DNA damage and G2/M phase cell cycle arrest. Both suppression and knockdown of cathepsin L in U251 cells also increased irradiation-induced apoptosis, as shown by the increased levels of Bax and decreased levels of Bcl-2. CONCLUSION: Cathepsin L is involved in modulation of radiosensitivity in human glioma U251 cells (harboring the mutant type p53 gene) in vitro.

Association of 25-hydroxyvitamin D, lipoprotein-associated phospholipase A2 and asymptomatic coronary artery disease in patients with type 2 diabetes mellitus.

AIM: To evaluate the relationship of 25-hydroxyvitamin D (25(OH)D), lipoprotein-associated phospholipase A2 (Lp-PLA2), and coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients with no history or symptoms of cardiovascular disease. METHODS: The study identified 66 pairs of T2DM patients with and without CAD using propensity score matching. All subjects performed coronary computed tomography angiography (CCTA). Data on 25(OH)D, Lp-PLA2, and metabolic indexes were collected and analyzed. RESULTS: Compared to the patients without CAD, the patients with CAD had lower 25(OH)D levels and the rate of vitamin D sufficiency, but higher Lp-PLA2 levels. Meanwhile, subjects in the vitamin D sufficiency group had a lower prevalence of CAD and Lp-PLA2 levels. Furthermore, 25(OH)D was inversely correlated with Lp-PLA2, Gensini score, Leiden score, segment involvement score, and segment stenosis score (P < 0.05). After adjusting for age, gender, blood lipids and blood pressure, 25(OH)D was associated with a decreased risk of CAD (aOR 0.933, 95 %CI 0.887-0.983, P = 0.009), while Lp-PLA2 was associated with an increased risk of CAD (aOR 1.014, 95 %CI 1.005-1.022, P = 0.002). CONCLUSIONS: Decreased 25(OH)D and increased Lp-PLA2 could identify patients with a high risk of CAD and are associated with the severity of coronary artery stenosis in T2DM.