Impact of particulate matter 2.5 on the liver function of mice.

OBJECTIVE: The aim of this study was to evaluate the impact of particulate matter 2.5 (PM2.5) on liver function at the animal level and to study its impact targets. MATERIALS AND METHODS: 60 male and female BALB/c mice of SPF grade, aged 6-8 weeks, were randomly divided into four groups, with 15 mice in each, including the normal saline control group, the PM2.5 low dose group [2 µg/(100 g/d)], the PM2.5 medium dose group [8 µg/(100 g/d)] and the PM2.5 high dose group [16 µg/(100 g/d)]. Each day, 0.9% saline or PM2.5 particles were administered through the nasal route, and samples were taken after 3 weeks of continuous exposure. Hematoxylin-eosin staining (HE) was used to observe the liver damage caused by PM2.5. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected by using an automatic biochemical analyzer to detect the content of liver glycogen and blood glucose. Multiple indicators were observed, including plasma tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) levels, oxidative stress response indicators reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) detection, RT-PCR and Western blot detection of glycogen synthase (GS), glucokinase (GK), nuclear factor erythroid 2-related factor 2 (Nrf2) expression and phosphorylation level of phospho-c-Jun N-terminal kinases (p-JNK). RESULTS: PM2.5 can cause damage to the liver by increasing PM2.5 concentrations, raising the metabolic rate of liver cells, resulting in a substantial amount of inflammatory infiltration and vacuolar degeneration of cells, and increasing the liver/body weight. TNF-α and IL-6 inflammatory factor expression increased (p<0.05). An increase in the serum ALT and AST levels were also observed. The blood glucose of mice increased, whereas the content of liver glycogen declined (p<0.05). ROS, MDA, and SOD levels all increased considerably. PM2.5 can drastically lower the expression of GS and GK, increase the expression of Nrf2, and raise the phosphorylation level of p-JNK (p<0.05). CONCLUSIONS: PM2.5 can induce oxidative stress in mouse liver through the Nrf2/JNK pathway, induce liver inflammation in mice, and inhibit glycogen synthesis.

Risk factors of hepatocellular carcinoma in non-alcoholic fatty liver disease: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to systematically review and quantitatively synthesize the existing evidence to better identify the high-risk population of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: We searched databases including MEDLINE, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov up to February 2023. The meta-analysis was performed using RevMan5.3 software, and we calculated the estimated combined effect using inverse variance weighting of OR. I2 statistics were used to quantify the inter-study heterogeneity. Funnel plots and Egger test were used to assess publication bias, and sensitivity analysis was carried out through the transformation effect model or the removal of literature one by one. RESULTS: Finally, 29 articles were included in the study, which involved a total of 726,656 patients with NAFLD. A total of 15 major risk factors were evaluated. Statistically significant risk factors were: advanced liver fibrosis (OR=6.40), diabetes (OR=2.38), obesity (OR=1.46), hypertension (OR=1.75), older age (OR=3.57), male (OR=2.45), alcohol intake (OR=2.98), smoking (OR=1.44), PNPLA3 genotype variation (OR=1.76), elevated liver enzymes (OR=2.92), low platelet counts (OR=4.61), and low albumin levels (OR=2.11). CONCLUSIONS: Our results showed that advanced liver fibrosis, diabetes, obesity, hypertension, older age, male, alcohol intake, smoking, PNPLA3 genotype variation, elevated liver enzymes, low platelet counts, and low albumin levels were all significant risk factors for HCC in NAFLD. However, dyslipidemia was not found to be a risk factor. Further exploration is needed to confirm whether Hispanic ethnicity and high ferritin levels are also risk factors.

Association between the Lymphocyte-to-C-Reactive Protein Ratio and Survival Outcomes in Cancer Patients with GLIM-Defined Malnutrition: A Multicenter Study.

BACKGROUND AND AIMS: This study assessed the prognostic value of LCR in patients with cancer-associated malnutrition (CAM). Systemic inflammatory markers, particularly the lymphocyte-to-C-reactive protein ratio (LCR), are related to the survival of patients with CAM. The present retrospective analysis based on a prospective multicenter cohort study, which involved 1,437 hospitalized patients with CAM. METHODS: The area under the receiver operating characteristic curve (AUC) of ten inflammatory indicators-LCR, advanced lung cancer inflammation index, neutrophil-to-lymphocyte ratio, prognostic nutritional index, modified Glasgow prognostic score, systemic immune-inflammation index, albumin-to-globulin ratio, LCR score, glucose-to-lymphocyte ratio, and platelet-to-lymphocyte ratio-were constructed. Nutritional status, blood markers, and quality of life (QoL) were evaluated within 48 h of admission. The overall survival (OS) was evaluated from September 1 to December 29, 2021. RESULTS: A total of 1,431 cancer patients diagnosed with malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Male patients were 62.8% of all, and the mean age was 60.66 years old. The AUC of LCR was higher than that of other inflammatory markers. The restricted cubic spline (RCS) of the Hazard ratios (HRs) showed an inverse L-shaped relationship with LCR. In addition, patients with low LCR had significantly poorer OS than those with high LCR. The addition of LCR to the model increased the predictive ability of 1-year mortality (AUC increase of 0.036), 3-year mortality (AUC increase of 0.038), and 5-year mortality (AUC increase of 0.031). CONCLUSIONS: Assessing the LCR can help the medical staff identify cancer patients with nutritional deficiency at high risk of oncological outcomes and develop individualized therapeutic strategies.

Impact of Spectators on a Two-Qubit Gate in a Tunable Coupling Superconducting Circuit.

Cross-resonance (CR) gates have emerged as a promising scheme for fault-tolerant quantum computation with fixed-frequency qubits. We experimentally implement an entangling CR gate by using a microwave-only control in a tunable coupling superconducting circuit, where the tunable coupler provides extra degrees of freedom to verify optimal conditions for constructing a CR gate. By developing a three-qubit Hamiltonian tomography protocol, we systematically investigate the dependency of gate fidelities on spurious qubit interactions and present the first experimental approach to the evaluation of the perturbation impact arising from spectator qubits. Our results reveal that the spectator qubits lead to reductions in CR gate fidelity dependent on ZZ interactions and particular frequency detunings between spectator and gate qubits. The target spectator demonstrates a more serious impact than the control spectator under a standard echo pulse scheme, whereas the degradation of gate fidelity is observed up to 22.5% as both the spectators are present with a modest ZZ coupling to the computational qubits. Our experiments uncover an optimal CR operation regime, and the method we develop here can readily be applied to improving other kinds of two-qubit gates in large-scale quantum circuits.

Long noncoding RNA XIST enhances cerebral ischemia-reperfusion injury by regulating miR-486-5p and GAB2.

OBJECTIVE: LncRNA XIST has been reported to act as diverse function in different human diseases. Our study is designed to detect the role of lncRNA XIST and the regulatory mechanisms of XIST/miR-486-5p/GAB2 in cerebral I/R injury. MATERIALS AND METHODS: In our article, SH-SY5Y cells were treated with oxygen-glucose deprivation reperfusion (OGDR) to mimic I/R injury. RT-qPCR assay was performed to detect the mRNA expression of XIST, GAB2 and miR-486-5p. The correlation between XIST and miR-486-5p, miR-486-5p and GAB2 were verified by RT-qPCR assay and Dual-Luciferase reporter assay. MTT assay was used to detect cell viability of SH-SY5Y cells treated with I/R. The protein expression of GAB2, apoptosis-related proteins (Bax/Bcl-2) were explored by Western blot assay. RESULTS: XIST and GAB2 were significantly highly expressed, while miR-486-5p was low expressed in SH-SY5Y cells under I/R. XIST exacerbated the oxidative damage of I/R cells. Moreover, XIST was found to restrain cell viability and induce cell apoptosis. For our experiment, miR-486-5p was a target of XIST, and GAB2 was a downstream gene of miR-486-5p. Furthermore, miR-486-5p mimic promoted cell proliferation and inhibited cell apoptosis, while XIST co-transfection reversed the effect of miR-486-5p. In addition, XIST was found to impair the inhibitory effect of miR-486-5p on expression of GAB2 in I/R cells. CONCLUSIONS: Our results indicated that XIST promoted cerebral I/R injury via modulating miR-486-5p and GAB2.

Suppression of microRNA-101 attenuates hypoxia-induced myocardial H9c2 cell injury by targeting DIMT1-Sp1/survivin pathway.

The article "Suppression of microRNA-101 attenuates hypoxia-induced myocardial H9c2 cell injury by targeting DIMT1-Sp1/survivin pathway, by Z.-X. Guo, F.-Z. Zhou, W. Song, L.-L. Yu, W.-J. Yan, L.-H. Yin, H. Sang, H.-Y. Zhang, published in Eur Rev Med Pharmacol Sci 2018; 22 (20): 6965-6976-DOI: 10.26355/eurrev_201810_16167-PMID: 30402863" has been withdrawn from the authors due to some inaccuracies. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16167.

Leptin promotes proliferation and inhibits apoptosis of prostate cancer cells by regulating ERK1/2 signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effect of leptin (Lep) on the proliferation, invasion and apoptosis of prostate cancer cells through the extracellular regulated protein kinase 1/2 (ERK1/2) signaling pathway. MATERIALS AND METHODS: Prostate cancer DU145 cells in the logarithmic growth phase were randomly divided into Lep (10, 20, 40, 80, 160 and 320 ng/mL) groups and blank control (Con) group. After culture, the cells were treated for 6 h, 12 h and 24 h, respectively. The effects of Lep on the proliferation and invasion of DU145 cells were detected via methyl thiazolyl tetrazolium (MTT) assay and transwell chamber assay, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to examine the messenger ribonucleic acid (mRNA) expressions of ERK1/2, b-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in DU145 cells after Lep treatment for 24 h. Thereafter, immunofluorescence assay was performed to detect the localization of ERK1/2 protein in prostate cancer DU145 cells. In addition, the expressions of phosphorylated (p)-ERK, ERK1/2 and apoptosis-related proteins, Bcl-2, Bax and cleaved cysteinyl aspartate specific proteinase (c-Caspase 3) in prostate cancer DU145 cells after treatment with different concentrations of Lep for 24 h were examined by Western blotting. RESULTS: MTT assay results showed that the proliferation rate of DU145 cells increased significantly at 6 h, 12 h and 24 h after 5-320 ng/mL of Lep treatment (p<0.05). Transwell assay manifested that the number of invasive cells was significantly raised after Lep treatment for 24 h (p<0.05). Meanwhile, the invasion ability of cells increased gradually with the elevation of Lep concentration. Subsequent qRT-PCR results demonstrated that after treatment with different concentrations of Lep, the mRNA expressions of ERK1/2 and Bcl-2 rose markedly (p<0.05). However, the mRNA expression of Bax was remarkably down-regulated (p<0.05) with the increase of Lep concentration in a concentration-dependent manner. According to the detection using a laser scanning confocal microscope, ERK1/2 red fluorescence showed punctiform aggregation, which was gradually raised with the increase of Lep concentration for 24 h. Moreover, Western blotting results denoted that with the increase of Lep concentration, the protein expressions of p-ERK, ERK1/2 and Bcl-2 were notably elevated (p<0.05), while those of Bax and c-Caspase 3 were distinctly reduced (p<0.05). CONCLUSIONS: Lep activation induces the proliferation, promotes the invasion and inhibits the apoptosis of prostate cancer cells through the ERK1/2 signaling pathway.

Hsa-miR-337 inhibits non-small cell lung cancer cell invasion and migration by targeting TCF7.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Hsa-miR-337 inhibits non-small cell lung cancer cell invasion and migration by targeting TCF7, by J. Zhang, W.-H. Gong, Y. Li, H.-Y. Zhang, C.-X. Zhang, published in Eur Rev Med Pharmacol Sci 2019; 23 (15): 6548-6553-DOI: 10.26355/eurrev_201908_18540-PMID: 31378895" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18540.

PKMYT1 aggravates the progression of ovarian cancer by targeting SIRT3.

OBJECTIVE: This experiment aims to elucidate the role of PKMYT1 in the malignant progression of ovarian cancer (OC) and its underlying mechanism. PATIENTS AND METHODS: Expression pattern of PKMYT1 in 43 paired OC tissues and adjacent normal ones was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The potential relationship between PKMYT1 level and clinical data of OC patients was analyzed. PKMYT1 level in OC patients either with distant metastasis or not was examined. Through Cell Counting Kit (CCK-8) and transwell assay, influences of PKMYT1 on proliferative and metastatic abilities in 3AO and CAOV3 cells were assessed. At last, the role of PKMYT1/SIRT3 regulatory loop in the progression of OC was identified. RESULTS: PKMYT1 was upregulated in OC tissues relative to controls. OC patients accompanied with distant metastasis had higher abundance of PKMYT1. High level of PKMYT1 predicted worse prognosis in OC patients. Knockdown of PKMYT1 attenuated proliferative, migratory, and invasive abilities in OC cells. Moreover, SIRT3 was downregulated in OC tissues, which was negatively correlated to PKMYT1. Silencing of SIRT3 could abolish the regulatory effect of PKMYT1 on proliferative and metastatic abilities in OC. CONCLUSIONS: Upregulated PKMYT1 in OC is closely linked to distant metastasis and poor prognosis. PKMYT1 accelerates the malignant progression of OC via negatively regulating SIRT3.

Circular RNA TTBK2 regulates cell proliferation, invasion and ferroptosis via miR-761/ITGB8 axis in glioma.

OBJECTIVE: Glioma is a primary intracranial tumor with an unfavorable prognosis. Evolving evidence indicates that circular RNA Tau tubulin kinase 2 (circ-TTBK2) is a cancer-associated gene. Therefore, this study was to explore the potential role of circ-TTBK2. MATERIALS AND METHODS: Levels of circ-TTBK2, microRNA (miR)-761, and integrin subunit beta 8 (ITGB8) were determined by adopting quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to detect cell viability, and the invaded cells were distinguished utilizing transwell assay. Iron and lipid reactive oxygen species (ROS) assays were implemented to examine the iron (total iron and ferrous iron) and lipid-based ROS in glioma cells, respectively. Besides, dual-luciferase reporter assay was administrated to illustrate the interaction between miR-761 and circ-TTBK2 or ITGB8. The role of circ-TTBK2 was identified via xenograft tumor model. RESULTS: Levels of circ-TTBK2 and ITGB8 were upregulated, whereas miR-761 level was low-expressed in glioma tissues and cells. Circ-TTBK2 was a sponge of miR-761 to modulate ITGB8. Additionally, circ-TTBK2 knockdown or miR-761 increase could retard cell proliferation, invasion, and promote ferroptosis in glioma cells. Interestingly, miR-761 inhibitor could abolish the repressive impact of circ-TTBK2 silencing on cell growth in vitro. Also, the influence of miR-761 mimic on cell phenotypes was regained after ITGB8 upregulation. Meanwhile, circ-TTBK2 deficiency caused the decrease of tumor growth. CONCLUSIONS: Circ-TTBK2 regulated cell proliferation, invasion and ferroptosis via targeting ITGB8 by sponging miR-761 in glioma, providing a promising biomarker for the clinical therapy of human glioma.

Higher liver stiffness scores are associated with early kidney dysfunction in patients with histologically proven non-cirrhotic NAFLD.

AIM: The association between Liver fibrosis (LF), as assessed by either histology or Liver stiffness measurement (LSM), and the presence of Early kidney dysfunction (EKD) was investigated in this study, as was also the diagnostic performance of LSM for identifying the presence of EKD in patients with Non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: A total of 214 adults with non-cirrhotic biopsy-proven NAFLD were recruited from two independent medical centres. Their histological stage of LF was quantified using Brunt's criteria. Vibration-controlled Transient elastography (TE), using M-probe (FibroScan®) ultrasound, was performed in 154 patients and defined as significant when LSM was≥8.0kPa. EKD was defined as the presence of microalbuminuria with an estimated glomerular filtration rate≥60mL/min/1.73 m2. Logistic regression modelling was used to estimate the likelihood of having EKD with NAFLD (LSM-EKD model). RESULTS: The prevalence of EKD was higher in patients with vs without LF on histology (22.14% vs 4.82%, respectively; P<0.001) and, similarly, EKD prevalence was higher in patients with LSM≥8.0kPa vs LSM<8.0kPa (23.81% vs 6.59%, respectively; P<0.05). The area under the ROC curve of the LSM-EKD model for identifying EKD was 0.80 (95% CI: 0.72-0.89). LF detected by either method was associated with EKD independently of established renal risk factors and potential confounders. CONCLUSION: LF was independently associated with EKD in patients with biopsy-proven NAFLD. Thus, TE-measured LSM, a widely used technique for quantifying LF, can accurately identify those patients with NAFLD who are at risk of having EKD.

LncRNA PCAT6 promotes occurrence and development of ovarian cancer by inhibiting PTEN.

OBJECTIVE: The purpose of this study was to explore the expression and function of long non-coding RNA (lncRNA) PCAT6 in ovarian cancer. PATIENTS AND METHODS: Quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA PCAT6 in 42 pairs of ovarian cancer tissues and adjacent normal tissues. Then, the relationship between PCAT6 expression and pathological indicators of ovarian cancer was analyzed. Subsequently, the transfection efficiency of PCAT6 in ovarian cancer cells was verified, and the PCAT6 knockdown model was constructed using lentiviruses in SKOV3 and CAOV3 ovarian cancer cell lines. In addition, Cell Counting Kit-8 (CCK-8) test, wound healing assay and transwell invasion and migration experiments were performed to estimate the effect of PCAT6 on the biological function of ovarian cancer cells, to further explore the possible potential mechanisms. RESULTS: QRT-PCR results showed that the expression level of PCAT6 in ovarian cancer was higher than that in the adjacent normal tissues. The incidence of distant metastasis and lymph node metastasis in patients with high expression of PCAT6 was higher than those with low PCAT6 expression. Compared with the NC group, the proliferation, metastasis and invasion ability of ovarian cancer cells in si-PCAT6 group decreased significantly. QRT-PCR results demonstrated that the PTEN expression was increased after the knockdown of PCAT6. In addition, the recovery experiment also revealed that PCAT6 and PTEN have a mutual regulation, which can jointly regulate the development of ovarian cancer. CONCLUSIONS: LncRNA PCAT6 was up-regulated in ovarian cancer tissues and was closely related to distant metastasis or lymph node metastasis. Additionally, lncRNA PCAT6 might promote the proliferation, migration and invasion of ovarian tumor cells by inhibiting PTEN.

MiR-199 inhibits EMT and invasion of hepatoma cells through inhibition of Snail expression.

OBJECTIVE: MiR-199 expression is associated with liver cancer. Bioinformatics analysis revealed that miR-199 has a complementary binding site to the 3'-UTR region of Snail mRNA. This study investigated whether miR-199 plays a role in regulating Snail expression and affecting epithelial-mesenchymal transition (EMT) and invasion of hepatoma cells. PATIENTS AND METHODS: The Dual-Luciferase reporter gene assay validated the targeted regulation between miR-199 and Snail. QRT-PCR was used to detect and compare the expression of miR-199 and Snail mRNA in human normal liver HL7702 cells, low metastatic MHCC97L cells, and high metastatic MHCC97H cells. MHCC97H cells were cultured in vitro and divided into two groups: miR-NC group and the miR-199 mimic group followed by the analysis of the expression of Snail, E-cadherin, and N-cadherin, as well as cell invasion ability by transwell assay. RESULTS: There was a targeted regulatory relationship between miR-199 and Snail mRNA. Compared with HL7702 cells, miR-199 expression was significantly decreased, and Snail expression was significantly increased in MHCC97L and MHCC97H cells, with more changes being observed in high metastatic MHCC97H cells. The transfection of miR-199 mimic significantly downregulated the expression of Snail and N-cadherin in MHCC97H cells, increased E-cadherin expression, inhibited the cell's EMT process, and invasion. CONCLUSIONS: The decrease of miR-199 expression plays a role in upregulating the expression of Snail and promoting EMT and invasion of hepatocarcinoma cells. The increase of the expression of miR-199 can inhibit the expression of Snail and inhibit the EMT process and invasion ability of hepatoma cells.

Hsa-miR-337 inhibits non-small cell lung cancer cell invasion and migration by targeting TCF7.

OBJECTIVE: Recent studies have revealed that microRNAs (miRNAs) play a crucial role in the progression of tumorigenesis. Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide. The aim of this study was to identify the exact role of hsa-miR-337 in the progression of NSCLC and to investigate the possible underlying mechanism. PATIENTS AND METHODS: Hsa-miR-337 expression in NSCLC cells and 60 paired tissue samples were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Moreover, the functions of hsa-miR-337 in vitro were identified by transwell assay and wound healing assay, respectively. Furthermore, the underlying mechanism was explored by RT-qPCR, Western blot assay, and luciferase assay. RESULTS: The expression level of hsa-miR-337 in NSCLC tissues was remarkably down-regulated when compared with that of adjacent normal samples. Moreover, the invasion and migration of NSCLC cells were significantly inhibited after overexpression of hsa-miR-337 in vitro. Moreover, after overexpression of hsa-miR-337 in vitro, the mRNA and protein levels of TCF7 were significantly down-regulated. Besides, the expression of TCF7 in NSCLC tissues was negatively correlated with the expression of hsa-miR-337. CONCLUSIONS: The above results suggested that hsa-miR-337 could repress the migration and invasion of NSCLC cells through directly targeting TCF7. Furthermore, hsa-miR-337 might offer a new therapeutic intervention for NSCLC patients.

Different surgical outcomes in a patient with bilateral atypical femoral fracture related to bisphosphonate use with or without teriparatide treatment.

Bisphosphonates (BPs) are first-line drugs for the treatment of osteoporotic fractures, but long-term use of BP reduces bone turnover and is associated with atypical femur fractures (AFFs). Additionally, BP treatment may cause delayed fracture healing or nonunion, which makes AFF treatment difficult. The incidence of AFF is generally low. In fact, there are only a few clinical reports of AFF and there is no controlled study on AFF treatment. Herein, we report a case of multiple osteoporotic fractures. After 5 years of BP treatment, left and right AFFs occurred within 2 years. The fracture types and surgical operations were the same, but the level of bone metabolism and drug treatment were different. The right AFF healed well following teriparatide initiation compared with non-healed left AFF with BP continuation; thus, our case can be considered a self-controlled study. Furthermore, we have reviewed the diagnosis and treatment of this case in detail and analyzed and investigated the potential causes of the different outcomes of AFFs between the two sides to inform the clinical treatment of atypical fractures. Mini Abstract We report a case of bilateral AFFs. The surgical treatments were the same, but the final treatment outcomes were different with or without teriparatide treatment. We investigated the potential causes of the different outcomes of AFFs between the two sides to inform the clinical treatment of AFFs.

Upregulation of lncRNA CALML3-AS1 promotes cell proliferation and metastasis in cervical cancer via activation of the Wnt/ß-catenin pathway.

OBJECTIVE: It is well verified that lncRNA are emerging as imperative regulators in various tumors. LncRNA CALML3-AS1 (CALML3-AS1), a freshly discovered lncRNA, has been confirmed as a tumor promoter in bladder cancer. This present study aimed to explore the biological functions and molecular mechanisms of CALML3-AS1 in cervical cancer (CC). PATIENTS AND METHODS: We analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) datasets to determine dysregulated lncRNAs in CC. Real Time-Polymerase Chain Reaction (RT-PCR) was applied for the assays of CALML3-AS1 amplification in CC samples and cell lines. Kaplan-Meier analysis and multivariate assays were carried out for determination of the prognostic values. The functions of CALML3-AS1 on cell proliferation, invasion, migration, and apoptosis were determined by a series of cells experiments by knocking down CALML3-AS1. MRNA and protein expressions of signaling pathways were examined using Western blot. RESULTS: We found that CALML3-AS1 was upregulated in CC tissues and this upregulation was associated with FIGO stage, histological grade, and reduced overall survival. Multivariate assays indicated that high CALML3-AS1 expression was an independent prognostic parameter indicating poorer clinical outcome for CC patients. Functional assays suggested that knockdown of CALML3-AS1 suppressed the proliferation, migration, and invasion of CC cells, and induced apoptosis. Mechanistic investigations revealed that inhibiting the expression of CALML3-AS1 decreased the levels of ß-catenin, cyclin D1, and c-myc via Western blot. CONCLUSIONS: Our study revealed that CALML3-AS1 could be an oncogenic lncRNA promoting the growth and metastasis of CC by modulating Wnt/ß-catenin pathway, suggesting that CALML3-AS1 may be an important contributor to CC progression.

miR-21 regulates the proliferation and apoptosis of ovarian cancer cells through PTEN/PI3K/AKT.

OBJECTIVE: Phosphatase and tensin homologue deleted on chromosome ten (PTEN) regulates cell proliferation and apoptosis by inhibiting phosphatidylinositol-3 kinase (PI3K) and protein kinase (AKT) signaling. High expression of miR-21 was associated with ovarian cancer. This study aims to investigate whether miR-21 regulates PTEN/PI3K/AKT signaling as well as its role in the proliferation and apoptosis of ovarian cancer cells. MATERIALS AND METHODS: Bioinformatics analysis was used to identify the binding site between miR-21 and the 3'-UTR of PTEN mRNA. A dual-luciferase reporter gene assay was performed to confirm the relationship between miR-21 and PTEN. The expression of miR-21, PTEN, and p-AKT was measured in normal ovarian cell IOSE80, ovarian cancer cell lines A2780, and SKOV3. miR-NC or miR-21 inhibitor was transfected into A2780 or SKOV3 cells followed by the analysis of the expression of miR-21, PTEN, p-AKT, cell apoptosis by flow cytometry, and proliferation by EdU assay. RESULTS: There was a targeted relationship between miR-21 and PTEN. Compared with IOSE80 cell, levels of miR-21 and p-AKT were significantly elevated in A2780 and SKOV3 cells, with the statistical reduction of PTEN expression (p<0.05). The inhibition of miR-21 significantly reduced the expressions of miR-21 and p-AKT and induced PTEN level in A2780 and SKOV3 cells, which also restricted cell proliferation and promoted cell apoptosis. CONCLUSIONS: The miR-21 expression is found elevated in ovarian cancer cells. The suppression of miR-21 increases PTEN expression, inhibits PI3K/AKT activity, promotes cell apoptosis, and reduces cell proliferation. This finding provides new leads to the future treatment of ovarian cancer.

Experimental Realization of Robust Geometric Quantum Gates with Solid-State Spins.

We experimentally realize a universal set of single-bit and two-bit geometric quantum gates by adiabatically controlling solid-state spins in a diamond defect. Compared with the nonadiabatic approach, the adiabatic scheme for geometric quantum computation offers a unique advantage of inherent robustness to parameter variations, which is explicitly demonstrated in our experiment by showing that the single-bit gates remain unchanged when the driving field amplitude varies by a factor of 2 or the detuning fluctuates in a range comparable to the inverse of the gate time. The reported adiabatic control technique and its convenient implementation offer a paradigm for achieving quantum computation through robust geometric quantum gates, which is important for quantum information systems with parameter-fluctuation noise such as those from the inhomogeneous coupling or the spectral diffusion.

ICOS/ICOSL upregulation mediates inflammatory response and endothelial dysfunction in type 2 diabetes mellitus.

OBJECTIVE: ICOS/ICOSL plays a crucial part in various disease-mediated immune responses. However, the exact role of ICOS/ICOSL in type 2 diabetes mellitus (T2DM) development remains unexplored. This study aims to investigate the role of ICOS/ICOSL in the pathogenesis of T2DM. MATERIALS AND METHODS: Human peripheral blood T-lymphocytes (CD3) and umbilical vein endothelial cells (HUVECs) were treated with high-glucose (HG) or advanced glycation end products (AGEs). A portion of CD3 cells was co-cultured with HUVECs and treated with different mediums or anti-ICOS mAbs. The ICOS/ICOSL and caspase-3 protein expression was measured by Western blotting. ELISA (enzyme-linked immunosorbent assay), MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and NOx production assays were respectively used to detect cytokines level, cell viability and the production of NOx. RESULTS: HG and AGEs significantly upregulated ICOS/ICOSL expressions in T cells and HUVECs. T cell contact with HUVECs secreted more IFN-γ, IL-4, and IL-10 compared to non-contact cells, while cytokines from IL-6-, IL-1ß-, and CM- (the conditioned medium) treated cells did not differ from the control. A significant increase of IL-8 and IL-6 was found in HUVECs under both contact and non-contact conditions vs. control cells. Similar results were also observed in the comparison between CM1- (T cell condition medium) or CM2- (co-culture condition medium) treated cells and control cells. However, CM1 and CM2 treatment significantly inhibited cell viability and increased caspase-3 and NOx production; blocking ICOS/ICOSL remarkably decreased cytokines secretion, enhanced cell viability and reduced caspase-3 and NOx production. CONCLUSIONS: HG and AGEs cause T cell inflammatory response and vascular endothelial dysfunction by upregulating ICOS/ICOSL, which may be one of the possible mechanisms of cardiovascular complications development in T2DM patients.

Effect of siglidine on glucose lipid metabolism and the expression of iNOS and GLP-1 receptors in diabetic rats.

OBJECTIVE: Diabetic nephropathy (DN) has become the major complication of diabetes. The progression of the disease impedes the efficacy of DN treatment. Therefore, the strategies to inhibit or reverse kidney damage in DN patients are of critical importance. We aim to investigate the effect of sitagliptin on DN within rat model and analyze the associated metabolism and expression of iNOS/GLP-1 receptor. MATERIALS AND METHODS: Diabetic model was generated by using Sprague-Dawley (SD) rats, which received an intra-peritoneal injection of 30 mg/kg streptozotocin. Rats were then treated with saline or 15 mg/(kg.d) sitagliptin by gavage. After 12 weeks, fasting blood glucose and insulin resistance were measured. Rat glucose and lipid metabolism were evaluated by high triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Western blot was used to measure expression of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) related with glucose-lipid metabolism, and expression of iNOS and GLP-1 expression in kidney tissues. RESULTS: After 12 weeks of feeding, the levels of blood glucose and lipid in sitagliptin group were significantly decreased compared to those in control group (p<0.05), whilst insulin sensitivity was enhanced (p<0.05). Western blot showed that sitagliptin downregulated the expressions of glucose-lipid metabolism proteins such as G6Pase, PEPCK, ACC and FAS in rat livers, inhibited iNOS expression in kidneys and elevated GLP-1 receptor activity (p<0.05). CONCLUSIONS: Sitagliptin effectively stabilizes blood glucose and lipid levels in DN rats, significantly improves glucose-lipid metabolism and protects kidney and vascular endothelial cells during DN pathogenesis through inhibiting iNOS expression and elevating GLP-1 receptor activity.