Mechanism understanding of PIKfyve inhibitor YM201636 with human serum albumin: Insights from molecular modeling and multiple spectroscopic techniques.

YM201636 is the potent PIKfyve inhibitor that is being actively investigated for liver cancer efficacy. In this study, computer simulations and experiments were conducted to investigate the interaction mechanism between YM201636 and the transport protein HSA. Results indicated that YM201636 is stably bound between the subdomains IIA and IIIA of HSA, supported by site marker displacement experiments. YM201636 quenched the endogenous fluorescence of HSA by static quenching since a decrease in quenching constants was observed from 7.74 to 2.39 × 104 M-1. UV-vis and time-resolved fluorescence spectroscopy confirmed the YM201636-HSA complex formation and this binding followed a static mechanism. Thermodynamic parameters ΔG, ΔH, and ΔS obtained negative values suggesting the binding was a spontaneous process driven by Van der Waals interactions and hydrogen binding. Binding constants ranged between 5.71 and 0.33 × 104 M-1, which demonstrated a moderately strong affinity of YM201636 to HSA. CD, synchronous, and 3D fluorescence spectroscopy revealed that YM201636 showed a slight change in secondary structure. The increase of Kapp and a decrease of PSH with YM201636 addition showed that YM201636 changed the surface hydrophobicity of HSA. The research provides reasonable models helping us further understand the transportation and distribution of YM201636 when it absorbs into the blood circulatory system.

Promising therapeutic targets for ischemic stroke identified from plasma and cerebrospinal fluid proteomes: a multicenter Mendelian randomization study.

BACKGROUND: Ischemic stroke (IS) is more common every year, the condition is serious, and have a poor prognosis. New, efficient, and safe therapeutic targets are desperately needed as early treatment especially prevention and reperfusion is the key to lowering the occurrence of poorer prognosis. Generally circulating proteins are attractive therapeutic targets, this study aims to identify potential pharmacological targets among plasma and cerebrospinal fluid (CSF) proteins for the prevention and treatment of IS using a multicenter Mendelian randomization (MR) approach. METHODS: First, the genetic instruments of 734 plasma and 151 CSF proteins were assessed for causative connections with IS from MEGASTROKE consortium by MR to identify prospective therapeutic targets. Then, for additional validation, plasma proteins from the deCODE consortium and the Fenland consortium, as well as IS GWAS data from the FinnGen cohort, the ISGC consortium and UK biobank, were employed. A thorough evaluation of the aforementioned possible pharmacological targets was carried out using meta-analysis. The robustness of MR results was then confirmed through sensitivity analysis using several techniques, such as bidirectional MR analysis, Steiger filtering, and Bayesian colocalization. Finally, methods like Protein-Protein Interaction (PPI) Networking were utilized to investigate the relationship between putative drug targets and therapeutic agents. RESULTS: The authors discovered three proteins that may function as promising therapeutic targets for IS and meet the Bonferroni correction ( P <0.05/885=5.65×10 -5 ). Prekallikrein (OR=0.41, 95% CI: 0.27-0.63, P =3.61×10 -5 ), a protein found in CSF, has a 10-fold protective impact in IS, while the plasma proteins SWAP70 (OR=0.85, 95% CI: 0.80-0.91, P =1.64×10 -6 ) and MMP-12 (OR=0.92, 95% CI: 0.89-0.95, P =4.49×10 -6 ) of each SD play a protective role in IS. Prekallikrein, MMP-12, SWAP70 was replicated in the FinnGen cohort and ISGC database. MMP-12 (OR=0.93, 95% CI: 0.91-0.94, P <0.001), SWAP70 (OR=0.92, 95% CI: 0.90-0.94, P <0.001), and prekallikrein (OR=0.53, 95% CI: 0.33-0.72, P <0.001) may all be viable targets for IS, according to the combined meta-analysis results. Additionally, no evidence of reverse causality was identified, and Bayesian colocalization revealed MMP-12 (PPH 4 =0.995), SWAP70 (PPH 4 =0.987), and prekallikrein (PPH 4 =0.894) shared the same variant with IS, supporting the robustness of the aforementioned causation. Prekallikrein and MMP-12 were associated with the target protein of the current treatment of IS. Among them, Lanadelumab, a new drug whose target protein is a prekallikrein, may be a promising new drug for the treatment of IS. CONCLUSION: The prekallikrein, MMP-12, and SWAP70 are causally associated with the risk of IS. Moreover, MMP-12 and prekallikrein may be treated as promising therapeutic targets for medical intervention of IS.

Comprehensive study of the combined effects of biochar and iron-based conductive materials on alleviating long chain fatty acids inhibition in anaerobic digestion.

This study investigated the feasibility of alleviating the negative influence of long-chain fatty acids (LCFAs) on anaerobic digestion by biochar, micron zero-valent iron, micron-magnetite (mFe3O4) and their combination. The results demonstrate that co-addition of biochar and 6 g/L mFe3O4 (BC+6 g/L mFe3O4) increased cumulative methane production by 50% as suffered from LCFAs inhibition exerted by 2 g/L glycerol trioleate. The BC+6 g/L mFe3O4 did best in accelerating total organic carbon degradation and volatile fatty acids conversion, through successively enriching Bacteroides, Corynebacterium, and DMER64 to dominant the bacterial community. The proportion of acetotrophic Methanothrix that could alternatively reduce CO2 to methane by accepting electrons via direct interspecies electron transfer (DIET) was 0.09% with BC+6 g/L mFe3O4, nine times more than the proportion in control. Prediction of functional genes revealed the enrichment of the bacterial secretion system, indicating that BC+6 g/L mFe3O4 promoted DIET by stimulating the secretion of extracellular polymeric substances. This study provided novel insights into combining biochar and iron-based conductive materials to enhance AD performance under LCFAs inhibition.

Lappaconitine sulfate inhibits proliferation and induces mitochondrial-mediated apoptosis via regulating PI3K/AKT/GSK3ß signaling pathway in HeLa cells.

Lappaconitine (LA), a diterpenoid alkaloid extracted from the root of Aconitum sinomontanum Nakai, exhibits broad pharmacological effects, including anti-tumor activity. The inhibitory effect of lappaconitine hydrochloride (LH) on HepG2 and HCT-116 cells and the toxicity of lappaconitine sulfate (LS) on HT-29, A549, and HepG2 cells have been described. But the mechanisms of LA against human cervical cancer HeLa cells still need to be clarified. This study was designed to investigate the effects and molecular mechanisms of lappaconitine sulfate (LS) on the growth inhibition and apoptosis in HeLa cells. The cell viability and proliferation were evaluated using the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2´-deoxyuridine (EdU) assay, respectively. The cell cycle distribution and apoptosis were detected by flow cytometry analysis and 4', 6-diamidino-2-phenylindole (DAPI) staining. The mitochondrial membrane potential (MMP) was determined through the 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimi-dazolyl carbocyanine iodide (JC-1) staining. The cell cycle arrest-, apoptosis-, and the phosphatidylinositol-3-kinase/protein kinase B/glycogen synthase kinase 3ß (PI3K/AKT/GSK3ß) pathway-related proteins were estimated by western blot analysis. LS markedly reduced the viability and suppressed the proliferation of HeLa cells. LS induced G0/G1 cell cycle arrest through the inhibition of Cyclin D1, p-Rb, and induction of p21 and p53. Furthermore, LS triggered apoptosis through the activation of mitochondrial-mediated pathway based on decrease of Bcl-2/Bax ratio and MMP and activation of caspase-9/7/3. Additionally, LS led to constitutive downregulation of the PI3K/AKT/GSK3ß signaling pathway. Collectively, LS inhibited cell proliferation and induced apoptosis through mitochondrial-mediated pathway by suppression of the PI3K/AKT/GSK3ß signaling pathway in HeLa cells.

Nardoguaianone L Isolated from Nardostachys jatamansi Improved the Effect of Gemcitabine Chemotherapy via Regulating AGE Signaling Pathway in SW1990 Cells.

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is known as "the king of cancers". Currently, gemcitabine (GEM) as the clinical drug of choice for chemotherapy of advanced pancreatic cancer has poor drug sensitivity and ineffective chemotherapy. Nardoguaianone L (G-6) is a novel guaiane-type sesquiterpenoid isolated from Nardostachys jatamansi DC., and it exhibits anti-tumor activity. Based on the newly discovered G-6 with anti-pancreatic cancer activity in our laboratory, this paper aimed to evaluate the potential value of the combination of G-6 and GEM in SW1990 cells, including cell viability, cell apoptosis, colony assay and tandem mass tags (TMT) marker-based proteomic technology. These results showed that G-6 combined with GEM significantly inhibited cell viability, and the effect was more obvious than that with single drug. In addition, the use of TMT marker-based proteomic technology demonstrated that the AGE-RAGE signaling pathway was activated after medication-combination. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays were used to validate the proteomic results. Finally, apoptosis was detected by flow cytometry. In conclusion, G-6 combined with GEM induced an increase in ROS level and a decrease in MMP in SW1990 cells through the AGE-RAGE signaling pathway, ultimately leading to apoptosis. G-6 improved the effect of GEM chemotherapy and may be used as a potential combination therapy for pancreatic cancer.

A Carabrane-Type Sesquiterpenolide Carabrone from Carpesium cernuum Inhibits SW1990 Pancreatic Cancer Cells by Inducing Ferroptosis.

Pancreatic cancer has an extremely poor prognosis, and the clinical drugs for the treatment of pancreatic cancer are usually multi-drug combinations. Therefore, it is necessary to search for and find specific new bioactive agents against pancreatic cancer. Carabrone is a carabrane-type sesquiterpenolide extracted from Carpesium cernuum L., and this natural compound has been reported to be a potential anti-tumor agent. However, there are few reports on the function of carabrone related to anti-tumor activity in pancreatic cancer. Herein, cell experiments indicated that carabrone had anti-proliferation inhibition and anti-migration and anti-invasion activity against SW1990 cells. Furthermore, the tandem mass spectrometry and network pharmacology analysis showed that this activity may be related to the ferroptosis and Hippo signaling pathway. Taken together, our results demonstrated that carabrone exhibited prominent anti-pancreatic cancer activity and could be a promising agent against pancreatic cancer.

PI3K/mTOR Dual Inhibitor Pictilisib Stably Binds to Site I of Human Serum Albumin as Observed by Computer Simulation, Multispectroscopic, and Microscopic Studies.

Pictilisib (GDC-0941) is a well-known dual inhibitor of class I PI3K and mTOR and is presently undergoing phase 2 clinical trials for cancer treatment. The present work investigated the dynamic behaviors and interaction mechanism between GDC-0941 and human serum albumin (HSA). Molecular docking and MD trajectory analyses revealed that GDC-0941 bound to HSA and that the binding site was positioned in subdomain IIA at Sudlow's site I of HSA. The fluorescence intensity of HSA was strongly quenched by GDC-0941, and results showed that the HSA-GDC-0941 interaction was a static process caused by ground-state complex formation. The association constant of the HSA-GDC-0941 complex was approximately 105 M-1, reflecting moderate affinity. Thermodynamic analysis conclusions were identical with MD simulation results, which revealed that van der Waals interactions were the vital forces involved in the binding process. CD, synchronous, and 3D fluorescence spectroscopic results revealed that GDC-0941 induced the structural change in HSA. Moreover, the conformational change of HSA affected its molecular sizes, as evidenced by AFM. This work provides a useful research strategy for exploring the interaction of GDC-0941 with HSA, thus helping in the understanding of the transport and delivery of dual inhibitors in the blood circulation system.

Changes in Quality and Antioxidant Properties of Virgin Olive Oil of 'Cornicabra' According to Fruit Maturation in Longnan, China.

This work aims to study the influence of olive fruit maturity on physicochemical properties and antioxidant activity which determine the quality of virgin olive oils (VOO). According to the results, the values of all parameters were within the range specified by the Codex Alimentarius (2017). With the increase of fruit maturity, the oil content continued to increase until reached the maximum value (20.05%) in the 7th maturity (M7). K232, K270 and peroxide value (PV) decreased with the increase of maturity, while ΔK increased linearly with the increase of maturity. Free fatty acidity (FFA) first decreased and then increased, until reached the maximum value of (0.52 ± 0.03) % in M7. The total polyphenols (TP) and total flavonoids (TF) that characterized the antioxidant properties of olive oil increased with the increase of fruit maturity, which indicated that the oxidative stability (OS) of VOO of 'Cornicabra' increased with the increase of fruit maturity. The oleic acid (C18:1) content remained above 70 % and reached the maximum of (76.68 ± 0.17) % at M7. The values of monounsaturated fatty acids (MUFA) / polyunsaturated fatty acids (PUFA) and oleic acid (C18:1) / linoleic acid (C18:2) showed a decreasing trend with the maturity stage. Principal component analysis (PCA) showed that the quality of FFA, PV, K232, K270, TP, TF and OS were higher at the 5th maturity (M5), the quality of fatty acid were higher at M7. It can be seen from the analysis that the olive fruit maturity was an important parameter to characterize and distinguish olive oil.

Organic and inorganic amendments for the remediation of nickel contaminated soil and its improvement on Brassica napus growth and oxidative defense.

In-situ stabilization has been considered an effective way to remediate metal contaminated soil. Thus, pot experiments were undertaken to investigate the effectiveness of multiple stabilization agents such as biochar (BC), mussel shell (MS), zeolite (ZE) and limestone (LS) on the immobilization of Ni, physicochemical features and enzyme activities in polluted soil. Results showed that the sole application of Ni adversely affected the rapeseed growth, photosynthetic pigments, and antioxidative defense. However, the addition of amendments to the contaminated soil significantly reduced Ni bioavailability. The XRD analysis confirmed the formation of Ni related ligands and FTIR showed the presence of hydroxyl, carboxyl and sulfur functional groups, as well as complexation and adsorption of Ni on amendments. Among multiple amendments, biochar significantly enhanced plant biomass attributes and total chlorophyll content. Moreover, addition of amendments also strengthened the antioxidant defense by decreasing Ni induced oxidative stress (H2O2 and O2.-), increased macronutrient availability, reduced Ni uptake and improved soil health. The qPCR analysis showed that the Ni transporters were significantly suppressed by amendments, which is correlated with the lower accumulation of Ni in rapeseed. The present study showed that immobilizing agents, especially biochar, is an effective amendment to immobilize Ni in soil, which restricts its entry into the food chain.

Lappaconitine hydrochloride inhibits proliferation and induces apoptosis in human colon cancer HCT-116 cells via mitochondrial and MAPK pathway.

Lappaconitine hydrochloride (LH), as a new synthetic alkaloid, exhibits antitumor activity, whereas its antitumor effect on colorectal cancer (CRC) has not been investigated. In this study, the effect of LH on HCT-116 cell proliferation and apoptosis in vivo and in vitro and underlying molecular mechanism were explored. The Cell Counting Kit-8 (CCK-8) was used to assess cell viability. Morphological change was observed by Hoechst 33342 staining. Cell cycle and apoptosis were performed using a flow cytometer. The western blot method was used to screen for related protein expression. The mitochondrial membrane potential (MMP) was confirmed using the 5, 5, 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimi-dazolyl carbo cyanine iodide (JC-1) staining assay. Reactive oxygen species (ROS) was evaluated by a 20-70-dichlorofluorescein diacetate (DCFH-DA) staining assay. The antitumor effect was evaluated in vivo by the xenograft HCT-116 model. The results showed that LH significantly inhibited cell viability in a time- and concentration-dependent manner. LH induced apoptosis and S phase cell cycle arrest. LH promoted the reduction of MMP and ROS accumulation. Moreover, LH activated the mitochondrial and MAPK pathway. The experiments in vivo showed that LH had significant antitumor effect in tumor-bearing mice, and had virtually no effect on the weight and internal organs of the mice. In conclusion, LH could induce apoptosis in HCT-116 cells through mitochondrial and MAPK signaling pathways. LH may be a promising treatment for CRC.

Improving anaerobic digestion of chicken manure under optimized biochar supplementation strategies.

Anaerobic digestion of chicken manure was carried out in this study basing on central composite design to identify the most optimal strategy for biochar supplementation. Model of cumulative methane production (CMP) was established by using response surface methodology. The optimal conditions predicted accordingly, including manure loading of 51.8 g VS/L, biochar dosage of 3.3% VSmanure, and cellulose loading of 98.0 g VS/L, were expected to maximize CMP, i.e., 294 mL/g VSmanure. The results also demonstrated that biochar dosage and its interaction with manure loading were key factors with significant impact on CMP. Biochar dosage higher than 3.5% VSmanure was observed to weaken the transformation of organic substances to methane. Higher dosage of biochar could considerably reduce concentration of organic acids, total ammonia nitrogen, as well as soluble salts. Verification experiment supported validity of the optimal strategy and provided data for cost assessment, which showed positive cost balances from biochar supplementation.

Evolution of Phenotypic Traits and Main Functional Components in the Fruit of 'Chenggu-32' Olives (Olea europaea L.) Cultivated in Longnan (China).

China has taken olive cultivation as a significant part of its agricultural development. Longnan city of Gansu province was marked into the world olive distribution map by International Olive Oil Council in 1998. However, so far, little research has been done on the growth and development stages of Chinese olives. The objective of this study was to investigate the dynamics changes of several quality characteristics of olive oil at different sampling times. Olive fruit of 'Chenggu-32' grown in Longnan were harvested at twenty-four time periods and used for determination of phenotypic traits and oil quality characteristics: total polyphenols and flavonoids contents, as well as fatty acid composition by using Gas Chromatography-Mass Spectrometer (GC-MS) and analysed by using Principal Components Analysis (PCA). Towards maturation, fruit moisture content decreased while oil content increased. Levels of both total flavonoids and total polyphenols contents slightly decreased first then increased. The ratio of unsaturated to saturated fatty acids was close to three. The ratio of monounsaturated fatty acids (MUFA)/ polyunsaturated fatty acids (PUFA) was from 2.28 to 4.05. The oleic acid (C18:1)/linoleic acid (C18:2) ratio was varied between 5.23 and 10.67 according to different sampling dates. The olive oil had lower oleic acid (C18:1) levels, higher linoleic acid (C18:2), linolenic acid (C18:3), and palmitic acid (C16:0) levels compared to Codex values (2017) in some periods, which is the characteristics fatty acid composition of 'Chenggu-32' variety in Longnan, China.

Lappaconitine sulfate induces apoptosis and G0/G1 phase cell cycle arrest by PI3K/AKT signaling pathway in human non-small cell lung cancer A549 cells.

Lappaconitine sulfate (LS) has good solubility and bioavailability. We have previously studied the anti-proliferative activity of LS on colon cancer HT-29 cell, but its anti-proliferative activity and molecular mechanism on human non-small cell lung cancer A549 cells are still unclear. This study was to investigate the effects of LS on proliferation, cell cycle and apoptosis in human non-small cell lung cancer A549 cells, and its possible molecular mechanisms. Cell proliferation activity was measured by Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) cell proliferation kit. Cell cycle was detected by propidium iodide (PI) flow cytometry. Apoptosis was detected by Annexin-V-FITC/PI method. Western blot was used to detect cycle and apoptosis-related proteins expression. These results showed that the proliferation activity of LS was significantly decreased in A549 cells, showing a dose- and time-dependent manner (p < 0.05). LS could increase the proportion of G0/G1 phase cells and decrease the proportion of cells in S phase, showing obvious G0/G1 phase arrest. LS significantly inhibited the expression of p-PI3K/PI3K, p-AKT/AKT, Cyclin D1 and Bcl-2 proteins (p < 0.05), and increased the expression of p53, p21, Bax, caspase 3 and caspase 9 (p < 0.05). Moreover, PI3K inhibitor (LY294002) significantly decreased A549 cell viability rate induced by LS, abrogated the activation of p-PI3K/PI3K and p-AKT/AKT in the presence of LS. These results indicated that LS could block A549 cells in the G0/G1 phase, induce apoptosis, and inhibit cell proliferation through the PI3K/AKT signaling pathway.

Downregulation of TNFRSF19 and RAB43 by a novel miRNA, miR-HCC3, promotes proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma cells.

Tumor necrosis factor receptor superfamily 19 (TNFRSF19) is a transmembrane protein involved in tumorigenesis. RAB43 is a small molecule GTP-binding protein contributing to the occurrence and development of tumors. However, TNFRSF19/RAB43 dysregulation and their role in hepatocellular carcinoma cells are unknown. Herein, we found that TNFRSF19 and RAB43 were downregulated in hepatocellular carcinoma tissues. TNFRSF19/RAB43 overexpression suppressed, whereas TNFRSF19/RAB43 knockdown promoted cell proliferation and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells. Previously, using deep sequencing technology, a new miRNA, miR-HCC3, was identified and found to suppress the expression of TNFRSF19 and RAB43 by binding to their 3'untranslated regions (3'UTRs) directly. miR-HCC3 was upregulated in hepatocellular carcinoma (HCC) tissues compared with adjacent noncancerous tissues and promoted proliferation and epithelial-mesenchymal transition in HCC cells. Furthermore, TNFRSF19/RAB43 suppressed but miR-HCC3 promoted tumor growth in vivo. Collectively, our results indicated that downregulation of TNFRSF19 and RAB43 by miR-HCC3 contributes to oncogenic activities in HCC, which sheds light on tumorigenesis and might provide potential therapeutic targets for HCC.

Lappaconitine Sulfate Inhibits Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells through the Reactive Oxygen Species-Dependent Mitochondrial Pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of tumor-related deaths in the word. Lappaconitine (LA), a diterpenoid alkaloid, exerts antitumor activities. However, the effects and mechanisms of LA sulfate (LS) on HCC remain unclear. This study evaluated the activities and explored the underlying mechanisms of LS in HCC cell line HepG2 cells. MATERIALS AND METHODS: The cell viability and proliferation were evaluated using the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assay, respectively. The cell cycle distribution was detected by propidium iodide (PI) staining assay. The apoptosis was detected by Annexin -V-fluorescein isothiocyanate (FITC)/PI double staining assay. The cell cycle arrest and apoptosis-related proteins were estimated by western blot analysis. The mitochondrial membrane potential (MMP) was -determined through the 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimi-dazolyl carbocyanine iodide (JC-1) staining assay. The reactive oxygen species (ROS) was monitored by 20-70-dichlorofluorescein diacetate (DCFH-DA) staining assay. In vivo antitumor activities were investigated by HepG2 xenograft model. RESULTS: Our results showed that LS significantly -inhibited the viability and proliferation of HepG2 cells. LS triggered G0/G1 cell cycle arrest, apoptosis and caspase activation. Furthermore, LS induced MMP loss and ROS accumulation. Additionally, LS suppressed the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3ß (GSK3ß) signaling pathway. An in vivo assay showed that LS exhibited a pronounced antitumor effect in nude mice bearing HepG2 xenografts. CONCLUSIONS: Our results demonstrated that LS is a promising therapeutic agent for HCC directed -toward the proliferation inhibition and the induction of apoptosis.

TNF-α-induced lncRNA LOC105374902 promotes the malignant behavior of cervical cancer cells by acting as a sponge of miR-1285-3p.

Long noncoding RNAs (lncRNAs) regulate gene expression at epigenetic, transcriptional, post-transcriptional levels and play important roles in tumorigenesis and inflammation. In order to explore the effects of lncRNAs on the malignant behavior of cervical cancer (CC) which may be involved in mechanism stimulated by inflammatory factors, we screened a differential expression profile of lncRNAs in CC cells stimulated by TNF-α by deep sequencing. We characterized a significantly upregulated lncRNA LOC105374902 induced by TNF-α. Then, we found that TNF-α accelerated the binding of STAT3 to the promoter region of lncRNA LOC105374902 and promoted its expression. Mechanistically, lncRNA LOC105374902 directly bond to miR-1285-3p as a competing endogenous RNA (ceRNA) to derepress RPL14; functional analysis indicated that both lncRNA LOC105374902 and RPL14 promoted migration, invasion and epithelial-mesenchymal transition (EMT) of CC cells. Taken together, TNF-α-induced lncRNA LOC105374902 may function as a ceRNA for miR-1285-3p to promote the expression of RPL14, promoting the migration, invasion and EMT of CC cells. These findings may provide new insights into the molecular pathogenesis of CC.

Positron emission tomography/computed tomography for osseous and soft tissue sarcomas: A systematic review of the literature and meta-analysis.

In order to elucidate the value of positron emission tomography (PET)/computed tomography (CT) in the clinical diagnosis and treatment of osseous and soft tissue malignancies, two authors independently searched the PubMed, Medline, Elsevier, Embase and Cochrane Library databases for literature published between January 2003 and February 2016, using the key words 'PET/CT', 'positron emission tomography/computed tomography', 'osseous sarcoma', 'bone tumor', 'soft tissue sarcoma' and 'neoadjuvant', to identify prospective and retrospective studies on the applicability of PET/CT on the clinical diagnosis of bone and soft tissue lesions, and evaluation of their response to neoadjuvant therapies. Data were independently extracted by the two authors and any disagreements were resolved by a third author when necessary. Extracted data were analyzed by Meta-Disc 1.6 software. As a result, 16 trials with a total of 883 patients and 2,214 lesions were included in the present study. The overall diagnostic accuracy of PET/CT exhibited a sensitivity and specificity of 0.90 (0.86-0.92) and 0.89 (0.85-0.92), respectively, and the effect of neoadjuvant therapy was assessed with a sensitivity and specificity of 0.79 (0.30-0.93) and 0.79 (0.69-0.89), respectively. Thus, it may be concluded from the present study that PET/CT is a reliable imaging method to be applied in the diagnosis and treatment of osseous and soft tissue malignancies.

Halo-pelvic traction for severe kyphotic deformity secondary to spinal tuberculosis.

To evaluate the efficacy and safety of Halo-pelvic ring traction in the treatment of severe kyphotic deformity secondary to spinal tuberculosis.Eighty patients with severe kyphotic deformity due to spinal tuberculosis were included in the study. Forty of those patients (experimental group) received Halo- pelvic ring traction before surgery and the rest (control group) received surgical treatment directly. Two groups were compared by means of the duration of surgery, intraoperative blood loss, correction of Cobb angle, change in patient height, and American Spinal Injury Association (ASIA) impairment scale.Halo-pelvic traction group achieved significantly (P < .05) better results than direct surgical treatment group by means of the time of surgery (244 ±â€Š58 minutes vs 276 ±â€Š47 minutes, P = .036), intraoperative blood loss (950 ±â€Š236 mL 1150 ±â€Š305 mL, P = .018), correction of Cobb angle (68.3 ±â€Š12.6 vs 55.6 ±â€Š13.8, P = .001), change in patient height (9.4 ±â€Š4.0 cm vs 6.8 ±â€Š3.8 cm, P = .024). The mean improvement of ASIA scale was more in the experimental group than in the control group (0.23 ±â€Š0.07 vs 0.15 ±â€Š0.06); however, the difference is not statistically significant (P = .09).Halo-pelvic ring traction before osteotomy can be applied in patients with severe spinal kyphotic deformity due to spinal tuberculosis to increase efficacy and safety of surgical treatment.

Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo.

A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD) is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA) and cryopreserved in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage. To test therapeutic efficacy, cryopreserved iPSC-mDA neurons were transplanted without subculturing into the 6-OHDA-lesioned rat and MPTP-lesioned non-human-primate models of PD. Grafted neurons retained midbrain lineage with extensive fiber innervation in both rodents and monkeys. Behavioral assessment in 6-OHDA-lesioned rats demonstrated significant reversal in functional deficits up to 6 months post transplantation with reinnervation of the host striatum and no aberrant growth, supporting the translational development of pluripotent cell-based therapies in PD.

Establishment of a three-dimensional finite element model of severe kyphotic deformity secondary to ankylosing spondylitis.

Objective To establish a three-dimensional (3D) finite element (FE) model of ankylosing spondylitis (AS) kyphosis that is a digital platform for further studies. Methods A 30-year-old man with AS kyphosis underwent computed tomography transverse scanning from T1 to the sacrococcyx. The images were imported into Mimics® 17.0 software to establish a 3D model of the posterior spine, which was then imported into Studio Geomagic 2013 software. Posterior spine convex geometry was established on the 3D geometric model for subsequent optimization of image processing. Unigraphics NX 8.5 produced the spinal kyphosis surface model. Modeled calcification of ligaments and partial resection of useless sacral bone were added. The model was imported into ANSYS 15.0 FE analysis software. Ligaments were added. Parameters were set to generate a 3D FE model of AS. Results and Conclusion A 3D FE model of AS was successfully established, providing a reliable digital platform for subsequent biomechanical analysis.