Lifelong impacts of puberty timing on human plasma metabolic profiles: A metabolome-wide Mendelian randomization study.

AIM: The aim was to investigate the causal relationship between puberty timing and plasma metabolites, accounting for birth weight, childhood and adulthood adiposity. MATERIALS AND METHODS: The meta-analysis of genome-wide association studies (GWAS) for puberty timing was extracted from the ReproGen Consortium, involving 329 345 women of European ancestry. Summary data for 174 plasma metabolites were retrieved from a recently conducted cross-platform GWAS that involved a meta-analysis of three cohort studies (i.e. the Fenland, European Prospective Investigation into Cancer-Norfolk and INTERVAL studies) and three publicly available studies and included up to 86 507 participants. We conducted a two-sample Mendelian randomization (MR) analysis to infer the causal relationship of puberty timing on 174 plasma metabolites, complemented by a two-step and multivariable Mendelian randomization (MVMR) analysis to assess direct and indirect effects. Additionally, summary-level data from the UK Biobank were used for our replication analysis. RESULTS: The results of the two-sample MR provide moderate evidence supporting a causal relationship between puberty timing and 23 of 174 plasma metabolites (i.e. 7 acylcarnitines, 8 amino acids, 2 biogenic amines and 6 lysophosphatidylcholines). Even after single-nucleotide polymorphisms associated with birth weight and childhood adiposity were excluded, causal effects persisted for 16 metabolites (i.e. 8 acylcarnitines, 4 amino acids, 2 biogenic amines and 2 lysophosphatidylcholines). The two-step MR analysis provided evidence that the relationship between puberty timing and plasma metabolites was mediated by adulthood adiposity. Additionally, moderate evidence emerged for an independent causal effect of puberty timing on 10 metabolites through an MVMR analysis (i.e. 5 acylcarnitines, 2 amino acids, 1 biogenic amine, 1 lysophosphatidylcholine and 1 phosphatidylcholine). Furthermore, the replication analysis suggested the robustness of our results. CONCLUSIONS: In summary, our study provides compelling evidence that puberty timing has a causal influence on certain plasma metabolites, although this influence is largely mediated by adulthood adiposity.

Synthesis of Hexabenzocoronene-Cored Graphdiyne Nanosheets through Dehydrogenative Coupling on Au(111) Surface.

Thermally-induced dehydrogenative coupling of polyphenylenes on metal surfaces is an important technique to synthesize π ${\pi }$ -conjugated carbon nanostructures with atomic precision. However, this protocol has rarely been utilized to fabricate structurally defined carbon nanosheets composed of sp- and sp2-hybridized carbon atoms. Here, we present the synthesis of butadiyne-linked hexabenzocoronenes (HBCs) on Au(111) surfaces as core-expanded graphdiynes. The reaction started from hexa(4-ethylphenyl)benzene, which undergoes dehydrogenation toward hexa(4-vinylphenyl)benzene, followed by planarization to hexabenzocoronene, coupling between the vinyl groups, and further dehydrogenation. In addition to butadiyne linkages, benzene groups were also found as another type of linker. The reaction sequences were monitored by scanning tunneling microscopy and bond-resolved non-contact atomic force microscopy, which disclose the structures of intermediates and final products. In combination with density functional theory simulations, the key steps from ethyl substituents to butadiyne and benzene linkers were elucidated. This is a new on-surface synthesis of core-expanded graphdiynes with unprecedented electronic properties.

Pyridinic Nitrogen Modification for Selective Acetylenic Homocoupling on Au(111).

On-surface acetylenic homocoupling has been proposed to construct carbon nanostructures featuring sp hybridization. However, the efficiency of linear acetylenic coupling is far from satisfactory, often resulting in undesired enyne products or cyclotrimerization products due to the lack of strategies to enhance chemical selectivity. Herein, we inspect the acetylenic homocoupling reaction of polarized terminal alkynes (TAs) on Au(111) with bond-resolved scanning probe microscopy. The replacement of benzene with pyridine moieties significantly prohibits the cyclotrimerization pathway and facilitates the linear coupling to produce well-aligned N-doped graphdiyne nanowires. Combined with density functional theory calculations, we reveal that the pyridinic nitrogen modification substantially differentiates the coupling motifs at the initial C-C coupling stage (head-to-head vs head-to-tail), which is decisive for the preference of linear coupling over cyclotrimerization.

Genetically predicted plasma levels of amino acids and metabolic dysfunction-associated fatty liver disease risk: a Mendelian randomization study.

BACKGROUND: Emerging metabolomics-based studies suggested links between amino acid metabolism and metabolic dysfunction-associated fatty liver disease (MAFLD) risk; however, whether there exists an aetiological role of amino acid metabolism in MAFLD development remains unknown. The aim of the present study was to assess the causal relationship between circulating levels of amino acids and MAFLD risk. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using summary-level data from genome-wide association studies (GWAS) to evaluate the causal relationship between genetically predicted circulating levels of amino acids and the risk of MAFLD. In the discovery MR analysis, we used data from the largest MAFLD GWAS (8434 cases and 770,180 controls), while in the replication MR analysis, we used data from a GWAS on MAFLD (1483 cases and 17,781 controls) where MAFLD cases were diagnosed using liver biopsy. We used Wald ratios or inverse variance-weighted (IVW) methods in the MR main analysis and weighted median and MR-Egger regression analyses in sensitivity analyses. Furthermore, we performed a conservative MR analysis by restricting genetic instruments to those directly involved in amino acid metabolism pathways. RESULTS: We found that genetically predicted higher alanine (OR = 1.43, 95% CI 1.13-1.81) and lower glutamine (OR = 0.83, 95% CI 0.73-0.96) levels were associated with a higher risk of developing MAFLD based on the results from the MR main and conservative analysis. The results from MR sensitivity analyses and complementary analysis using liver proton density fat fraction as a continuous outcome proxying for MAFLD supported the main findings. CONCLUSIONS: Novel causal metabolites related to MAFLD development were uncovered through MR analysis, suggesting future potential for evaluating these metabolites as targets for MAFLD prevention or treatment.

Significantly anisotropic Raman response of the (110) surface in quasi-one-dimensional system (TaSe4)2I by polarized Raman spectroscopy.

Quasi-one-dimensional materials are usually characterized by optical response spectroscopy methods, which show significant polarization dependence. Herein, we report a systematical investigation of polarized Raman scattering on the (110) crystal surface of the layered (TaSe4)2I compound. Taking into account group theory analysis of the crystal structure and the Raman tensor transformation technique, the vibrational mode of the Raman peaks can be differentiated by the angular dependence of the Raman peak intensity in parallel and vertical polarization Raman scattering tests. Moreover, density functional perturbation theory (DFPT) calculation confirmed the form of the Raman tensor of the (110) crystal surface, which was consistent with the result of the Raman tensor transformation technique, and the Raman spectrum and phonon dispersion curve calculations were also performed based on the Vienna ab initio simulation package (VASP). This new method provides useful insight for accurately identifying the lattice vibration behavior in new 2D layered structures.

Development and validation of a 3D-convolutional neural network model based on chest CT for differentiating active pulmonary tuberculosis from community-acquired pneumonia.

PURPOSE: To develop and validate a 3D-convolutional neural network (3D-CNN) model based on chest CT for differentiating active pulmonary tuberculosis (APTB) from community-acquired pneumonia (CAP). MATERIALS AND METHODS: Chest CT images of APTB and CAP patients diagnosed in two imaging centers (n = 432 in center A and n = 61 in center B) were collected retrospectively. The data in center A were divided into training, validation and internal test sets, and the data in center B were used as an external test set. A 3D-CNN was built using Keras deep learning framework. After the training, the 3D-CNN selected the model with the highest accuracy in the validation set as the optimal model, which was applied to the two test sets in centers A and B. In addition, the two test sets were independently diagnosed by two radiologists. The 3D-CNN optimal model was compared with the discrimination, calibration and net benefit of the two radiologists in differentiating APTB from CAP using chest CT images. RESULTS: The accuracy of the 3D-CNN optimal model was 0.989 and 0.934 with the internal and external test set, respectively. The area-under-the-curve values with the 3D-CNN model in the two test sets were statistically higher than that of the two radiologists (all P < 0.05), and there was a high calibration degree. The decision curve analysis showed that the 3D-CNN optimal model had significantly higher net benefit for patients than the two radiologists. CONCLUSIONS: 3D-CNN has high classification performance in differentiating APTB from CAP using chest CT images. The application of 3D-CNN provides a new automatic and rapid diagnosis method for identifying patients with APTB from CAP using chest CT images.

[Diagnosis and treatment of prostatic abscess: Report of 11 cases and review of the literature].

OBJECTIVE: To analyze the clinical features, imaging characteristics, treatment options and prognosis of prostatic abscess (PA), and provide some new ideas for the diagnosis and treatment of the disease. METHODS: This retrospective study included 11 cases of confirmed PA treated in the Fifth Medical Center of PLA General Hospital. We analyzed the clinical data obtained from the electronic medical records, including basic demographic statistics, risk factors, clinical symptoms, laboratory results, imaging findings, treatment methods, treatment-related complications and outcomes. RESULTS: The 11 patients diagnosed with PA between May 2016 and August 2022 were aged (64.18 ± 7.19) years and all had at least 1 comorbidity, including 5 cases of diabetes mellitus (45.5%) and 8 cases of dysuria (72.8%). PA was confirmed in 3 cases by CT and in 8 cases by MRI, 6 (54.5%) multifocal and 10 (90.9%) >2 cm in diameter, with a median size of 3.84 cm. After admission, positive urine culture was found in 3 cases, positive blood culture in 1, Klebsiella pneumoniae in 2 and Enterococcus Faecalis in 1. Three of the patients were treated by intravenous administration of antibiotics alone, and the other 8 by transurethral PA unroofing in addition. Antibiotics medication lasted for a median of (12.9 ± 3.88) d and hospital stay averaged (19.18 ± 8.20) d. The patients were followed up for 3 months, which revealed the presence of PA in 2 of the cases treated with antibiotics alone, but not in any of the cases treated by surgery. CONCLUSION: PA is relatively rare and has no specific symptoms clinically. Imaging examination is very important for accurate diagnosis, and transurethral PA unroofing plus antibiotics administration could be considered as an optimal management of the disease.

On-Surface Debromination of 2,3-Bis(dibromomethyl)- and 2,3-Bis(bromomethyl)naphthalene: Dimerization or Polymerization?

We describe the on-surface dehalogenative homocoupling of benzylic bromides, namely bis-bromomethyl- and bis-gem-(dibromomethyl) naphthalene as a potential route to either hydrocarbon dimers or conjugated polymers on Au(111). While bis-gem-(dibromomethyl) naphthalene affords different dimers with naphthocyclobutadiene as the key intermediate, bis-bromomethyl naphthalene furnishes a poly(o-naphthylene vinylidene) as a non-conjugated polymer which undergoes dehydrogenation toward its conjugated derivative poly(o-naphthylene vinylene) upon mild annealing. A combination of scanning tunneling microscopy, non-contact atomic force microscopy and density functional theory calculations provides deep insights into the prevailing mechanisms.

Activation of BDNF/TrkB pathway promotes prostate cancer progression via induction of epithelial-mesenchymal transition and anoikis resistance.

Prostate cancer (PCa) is one of the most common malignant diseases in male worldwide, yet, the molecular mechanisms involved in PCa progression are still poorly understood. This study aimed to investigate the roles of the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) pathway in PCa progression. It was demonstrated by immunohistochemical analysis that both BDNF and TrkB were overexpressed in PCa tissues and elevated TrkB expression was tightly related with lymph node metastasis and advanced stage of PCa. In vitro studies showed that stimulation with rhBDNF or overexpression of TrkB in PCa cells promoted cell migration, invasion, and anoikis resistance. Overexpression of TrkB also resulted in epithelial-mesenchymal transition (EMT)-like transformation in cell morphology, whereas RNA interference-mediated TrkB depletion caused reversion of EMT. Further investigation demonstrated that protein kinase B (AKT) was responsible for BDNF/TrkB signaling-induced pro-migratory and pro-invasive effects, EMT, and anoikis resistance. Finally, in vivo studies confirmed that enhanced TrkB expression facilitated tumor growth, whereas downregulation of TrkB suppressed tumor growth. Our findings illustrate that BDNF/TrkB pathway is crucial for PCa progression, which may provide a novel therapeutic strategy for the treatment of advanced PCa.

Modified Laparoscopic and Robotic Flap Pyeloplasty for Recurrent Ureteropelvic Junction Obstruction with a Long Proximal Ureteral Stricture: The "Wishbone" Anastomosis and the "Ureteral Plate" Technique.

OBJECTIVES: The aim of the study was to present our modified flap pyeloplasty techniques for recurrent ureteropelvic junction obstruction (UPJO) with a long proximal ureteral stricture and compare outcomes of laparoscopic and robotic procedures. MATERIALS AND METHODS: Between March 2018 and January 2020, 21 patients underwent modified laparoscopic or robotic flap pyeloplasty for recurrent UPJO with a long proximal ureteral stricture. Our surgical modifications included the "wishbone" anastomosis and "ureteral plate" technique. Demographic, perioperative, and follow-up data were recorded and compared retrospectively between the groups. Success was defined as subjective pain alleviation and hydronephrosis improvement. RESULTS: Thirteen modified laparoscopic flap pyeloplasty (mLFP) and 8 modified robotic flap pyeloplasty (mRFP) were performed successfully without conversion. mRFP tended to have shorter overall operative time (142.4 vs. 179.1 min, p = 0.122) and anastomosis time (43.1 vs. 61.0 min, p = 0.093) than mLFP. No difference was found in estimated blood loss (p = 0.723) and pararenal draining time (p = 0.175) between the groups. The mean postoperative hospital stay of mRFP was significantly shorter than that of mLFP (5.0 vs. 8.2 days, p = 0.015). No major complications occurred. During the mean follow-up of 17.9 months, the overall success rate was 90.5%, and there was no significant difference between 2 groups. CONCLUSIONS: The modified flap pyeloplasty could be considered a practical and effective treatment option with a high success rate for recurrent UPJO with a long proximal ureteral stricture, and the robotic procedures showed advantages of higher efficiency and faster recovery.

On-Surface Synthesis of 8- and 10-Armchair Graphene Nanoribbons.

Armchair graphene nanoribbons (AGNRs) with 8 and 10 carbon atoms in width (8- and 10-AGNRs) are synthesized on Au (111) surfaces via lateral fusion of nanoribbons that belong to different subfamilies. Poly-para-phenylene (3-AGNR) chains are pre-synthesized as ladder ribbons on Au (111). Subsequently, synthesized 5- and 7-AGNRs can laterally fuse with 3-AGNRs upon annealing at higher temperature, producing 8- and 10-AGNRs, respectively. The synthetic process, and their geometric and electronic structures are characterized by scanning tunneling microscopy/spectroscopy (STM/STS). STS investigations reveal the band gap of 10-AGNR (2.0 ± 0.1 eV) and a large apparent band gap of 8-AGNRs (2.3 ± 0.1 eV) on Au (111) surface.

AMPK/GSK3ß/ß-catenin cascade-triggered overexpression of CEMIP promotes migration and invasion in anoikis-resistant prostate cancer cells by enhancing metabolic reprogramming.

Prostate cancer (PCa) represents one of the most common solid neoplasms, and metastasis is the second leading cause of death in adult males. Anoikis is a programmed cell death that is induced upon cell detachment from the extracellular matrix (ECM), which behaves as a critical protective mechanism for anchorage-independent cell growth and metastasis formation. However, in the absence of ECM attachment, shift of metabolic pattern and tolerance to anoikis facilitate the survival of aggressive cancer cells in the circulatory system as well as their metastasis to distant sites. Few molecular targets in PCa have thus far been reported to prevent anoikis resistance, metabolic reprogramming, and metastasis simultaneously. In the present study, elevated migration, invasion, pyruvate production, lactate generation, ATP level, and impaired detachment-induced apoptosis were found in anoikis-resistant PCa cells, and genome microarray analysis demonstrated that the cell migration-inducing protein (CEMIP) was a potential molecular target for the regulation of the aforementioned malignant behaviors. Additional investigation revealed that the AMPK/glycogen synthase kinase 3ß (GSK3ß)/ß-catenin cascade-triggered CEMIP overexpression in anoikis-resistant PCa cells might be implicated in local progression, metabolic shift, and cellular migration and invasion, whereas knockout of CEMIP by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 in anoikis-resistant PCa cells reversed the described bioeffects by reducing expressions of matrix metalloproteinase 2 (MMP2), VEGF, pyruvate dehydrogenase kinase isoform 4 (PDK4), and lactate dehydrogenase A. In addition, inhibition of glycolysis by CEMIP-mediated PDK4 down-regulation impaired the migration and invasion of anoikis-resistant PCa cells by attenuating MMP2 and VEGF expressions. Our findings establish that AMPK/GSK3ß/ß-catenin cascade-triggered CEMIP overexpression might promote migration and invasion in anoikis-resistant PCa cells by enhancing PDK4-associated metabolic reprogramming, which may provide a novel, promising therapeutic target for the treatment of advanced PCa.-Zhang, P., Song, Y., Sun, Y., Li, X., Chen, L., Yang, L., Xing, Y. AMPK/GSK3ß/ß-catenin cascade-triggered overexpression of CEMIP promotes migration and invasion in anoikis-resistant prostate cancer cells by enhancing metabolic reprogramming.

Biological roles of filamin a in prostate cancer cells.

OBJECTIVE: This study aims to investigate the association of filamin A with the function and morphology of prostate cancer (PCa) cells, and explore the role of filamin A in the development of PCa, in order to analyze its significance in the evolvement of PCa. MATERIALS AND METHODS: A stably transfected cell line, in which filamin A expression was suppressed by RNA interference, was first established. Then, the effects of the suppression of filamin A gene expression on the biological characteristics of human PCa LNCaP cells were observed through cell morphology, in vitro cell growth curve, soft agar cloning assay, and scratch test. RESULTS: A cell line model with a low expression of filamin A was successfully constructed on the basis of LNCaP cells. The morphology of cells transfected with plasmid pSilencer-filamin A was the following: Cells were loosely arranged, had less connection with each other, had fewer tentacles, and presented a fibrous look. The growth rate of LNCap cells was faster than cells transfected with plasmid pSilencer-filamin A (P<0.05). The clones of LNCap cells in the soft agar cloning assay was significantly fewer than that of cells stably transfected with plasmid pSilencer-filamin A (P<0.05). Cells stably transfected with plasmid pSilencer-filamin A presented with a stronger healing and migration ability compared to LNCap cells (healing rate was 32.2% and 12.1%, respectively; P<0.05). CONCLUSION: The expression of the filamin A gene inhibited the malignant development of LNCap cells. Therefore, the filamin A gene may be a tumor suppressor gene.

Viral etiologies and epidemiology of patients with acute respiratory infections based on sentinel hospitals in Gansu Province, Northwest China, 2011-2015.

Understanding etiological role and epidemiological profile is needed to improve clinical management and prevention of acute respiratory infections (ARIs). A 5-year prospective study about active surveillance for outpatients and inpatients with ARIs was conducted in Gansu province, China, from January 2011 to November 2015. Respiratory specimens were collected from patients and tested for eight respiratory viruses using polymerase chain reaction (PCR) or reverse transcription polymerase chain reaction (RT-PCR). In this study, 2768 eligible patients with median age of 43 years were enrolled including pneumonia (1368, 49.2%), bronchitis (435, 15.7%), upper respiratory tract infection or URTI (250, 9.0%), and unclassified ARI (715, 25.8%). Overall, 29.2% (808/2768) were positive for any one of eight viruses, of whom 130 cases were identified with two or more viruses. Human rhinovirus (HRV) showed the highest detection rate (8.6%), followed by influenza virus (Flu, 7.3%), respiratory syncytial virus (RSV, 6.1%), human coronavirus (hCoV, 4.3%), human parainfluenza (PIV, 4.0%), adenovirus (ADV, 2.1%), human metapneumovirus (hMPV, 1.6%), and human bocavirus (hBoV, 0.7%). Compared with URTI, RSV was more likely identified in pneumonia (χ2 = 12.720, P < 0.001) and hCoV was more commonly associated with bronchitis than pneumonia (χ2 = 15.019, P < 0.001). In patients aged less than 5 years, RSV showed the highest detection rate and hCoV was the most frequent virus detected in adults and elderly. The clear epidemical seasons were observed in HRV, Flu, and hCoV infections. These findings could serve as a reference for local health authorities in drawing up further plans to prevent and control ARIs associated with viral etiologies.

Physical mechanism of order between electric and magnetic dipoles in spoof plasmonic structures.

It has been recently shown that a solid-textured metal cylinder can support electric and magnetic dipolar resonances simultaneously [Phys. Rev. X4, 021003 (2014)PRXHAE2160-330810.1103/PhysRevX.4.021003] which are almost degenerate in a two-dimensional (2-D) structure and non-degenerate in a three-dimensional (3-D) structure, and with the magnetic dipole appearing at higher frequency. They are described as spoof localized plasmonic modes analogous to localized plasmonic resonances in optical frequencies. Here, we consider a hollow metal cylinder corrugated by periodic cut-through slits. Our results indicate that the magnetic dipole can be separated from the electric dipole in a 2-D structure, and magnetic dipolar resonance appears at lower frequency, rather than electric resonance in both 2-D and 3-D structures. In order to clarify the physical mechanism behind the abnormal phenomenon, we study the influence of the core material on the electric- and magnetic-dipole modes based on theoretical analysis and numerical simulation. It is discovered that there is a threshold of an imaginary part of permittivity for switching the order between electric and magnetic dipoles. These results may provide fundamental understanding and physical insight for spoof plasmonic modes supported in designer structures.

Tetraiodothyroacetic acid and transthyretin silencing inhibit pro-metastatic effect of L-thyroxin in anoikis-resistant prostate cancer cells through regulation of MAPK/ERK pathway.

UNLABELLED: Prostate cancer is one of the most common malignancies in adult males and metastasis is the leading cause of death cases without satisfactory treatment options. Anoikis-resistance and migration are crucial aspects for the metastasis of various human cancer cells including prostate cancer and L-thyroxin (T4) has been proved to play vital roles in tumor metastasis. The present study demonstrated that T4 promoted migration and depressed detachment-induced apoptosis in anoikis-resistant prostate cancer cells while tetraiodothyroacetic acid (tetrac), a competitive antagonist of T4 at integrin αvß3, reversed T4 induced effects through diminishing expressions of XIAP, MMP-2, VEGF together with inhibited activity of MAPK/ERK pathway. In addition, we illustrated that over-expression of transthyretin (TTR) was positively correlated to the progression and metastatic potential in prostate cancer. Similar to tetrac, TTR silencing also inverted T4 mediated bioeffects on anoikis-resistant PC-3 cells. The current study sheds light on novel therapeutic strategies for metastatic prostate cancer. IMPLICATIONS: This study identified novel compound and target for preventing metastasis in anoikis-resistant prostate cancer cells, which might offer potential therapeutic alternatives for advanced prostate cancer.

What sleep behaviors are associated with bruxism in children? A systematic review and meta-analysis.

PURPOSE: The aim of this article was to assess the sleep behaviors that serve as risk factors related to bruxism in children ages 0 to 12 years by performing a systematic review and meta-analysis of published studies. METHODS: Seven databases were searched to identify all peer-reviewed articles potentially relevant to the review. Data were pooled for random-effects modeling. Sleep risk factors related to bruxism in this age group are summarized using pooled odds ratios (ORs), 95% confidence intervals (CIs), and P values. RESULTS: Of 5637 initially identified articles, 14 met inclusion criteria. Study qualities of all case-control studies were high. Quality of cross-sectional studies was more variable. The pooled ORs, 95% CIs, and P values were as follows: snoring (2.86, 1.85-4.42, <0.0001), mouth breathing (1.51, 1.04-2.18, 0.029), restless sleep (2.31, 1.89-2.83, <0.0001), drooling (1.79, 1.07-2.97, 0.026), stomach position during sleep (1.70, 1.0-2.39, 0.003), and inadequate sleep time (2.56, 1.48-4.43, 0.001). CONCLUSIONS: Snoring, mouth breathing, restless sleep, drooling, stomach position during sleep, and lack of sleep were the risk factors related to bruxism in children.

Oleanolic acid inhibits cell survival and proliferation of prostate cancer cells in vitro and in vivo through the PI3K/Akt pathway.

Oleanolic acid (OA) is a naturally occurring pentacyclic triterpenoid and possesses diverse pharmacological activities, including anti-cancer effects that have been confirmed in multiple types of human cancers. However, the potential effect of natural OA on human prostate cancer is still unclear. The present study aimed to explore whether and how OA exerted anti-cancer effects in prostate cancer. Our data showed that OA inhibited cell viability and proliferation, and promoted cell apoptosis and G0/G1 phase cell cycle arrest in prostate cancer PC-3, DU145, and LNCaP cells, in a dose-dependent manner. In addition, OA was found to regulate the expression levels of apoptosis-related and cell cycle-related proteins, as well as the activity of PI3K/Akt pathway, in a dose-dependent manner. Mechanistically, our data revealed that OA exerted anti-cancer effects in vitro in PC-3 and DU145 cells by repressing the PI3K/Akt pathway. In agreement, OA also suppressed the tumor growth of PC-3 cells in vivo via inhibition of the PI3K/Akt pathway. In conclusion, our findings demonstrate the anti-cancer properties of OA in prostate cancer cells, both in vitro and in vivo, and provide the experimental evidence for the use of OA as an adjuvant agent for prostate cancer patients.

Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway.

Antisense non-coding RNA in the INK4 locus (ANRIL) is a member of long non-coding RNAs and has been reported to be dysregulated in several human cancers. However, the role of ANRIL in bladder cancer remains unclear. This present study aimed to investigate whether and how ANRIL involved in bladder cancer. Our results showed up-regulation of ANRIL in bladder cancer tissues versus the corresponding adjacent non-tumor tissues. To explore the specific mechanisms, ANRIL was silenced by small interfering RNA or short hairpin RNA transfection in human bladder cancer T24 and EJ cells. Knockdown of ANRIL repressed cell proliferation and increased cell apoptosis, along with decreased expression of Bcl-2 and increased expressions of Bax, cytoplasmic cytochrome c and Smac and cleaved caspase-9, caspase-3 and PARP. However, no change of cleaved caspase-8 level was observed. Furthermore, in vivo experiment confirmed that knockdown of ANRIL inhibited tumorigenic ability of EJ cells in nude mice. Meanwhile, in accordance with in vitro study, knockdown of ANRIL inhibited expression of Bcl-2 and up-regulated expressions of Bax and cleaved caspase-9, but did not affect cleaved caspase-8 level. In conclusion, we first report that ANRIL possibly serves as an oncogene in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic apoptosis pathway.

[Patient-derived renal pelvic carcinoma organoids: establishment and sensitivity to chemotherapeutic drugs].

Renal pelvic carcinoma is a common upper urothelial cancer. The lack of an ideal in vitro model seriously hinders the research progress in the treatment for this disease. This study established a pipeline for the culture of renal pelvic carcinoma organoids based on the tumor tissue samples derived from the patients and tested the organoids to chemotherapeutic drugs. The results of immunohistochemistry and fluorescence experiments confirmed that the renal pelvic carcinoma organoids obtained from culture presented obvious nuclear heteromorphism, which was consistent with the tissue samples from renal pelvic carcinoma patients. The tumor marker molecule CD44 and the cell proliferation marker molecule Ki67 were positive in the organoids, indicating that the organoids were enriched with tumor stem cells and had strong proliferative ability. The renal pelvic carcinoma organoids were highly sensitive to pirarubicin, which had obvious killing effects. In brief, this study successfully established an in vitro model of renal pelvic cancer organoids and tested the sensitivity of the model to chemotherapeutic drugs. The results provide a new laboratory model for the individualized diagnosis and treatment of epithelial carcinomas represented by renal pelvic carcinoma.