Natural Affinity Driven Modification by Silicene to Construct a "Thermal Switch" for Tumorous Bone Loss.

Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.

Chemical structures, biosynthesis, bioactivities, and utilisation values for the diterpenes produced in tobacco trichomes.

Cembranoids and labdanes are two important types of diterpenes in tobacco (Nicotiana genus) that are predominantly found in the leaf and flower glandular trichome secretions. This is the first systematic review of the biosynthesis, chemical structures, bioactivities, and utilisation values of cembranoid and labdane diterpenes in tobacco. A total of 131 natural cembranoid diterpenes have been reported in tobacco since 1962; these were summarised and classified according to their chemical structure characteristics as isopropyl cembranoids (1-88), seco-cembranoids (89-103), chain cembranoids (104-123), and polycyclic cembranoids (124-131). Forty natural labdane diterpenes reported since 1961 were also summarised and divided into epoxy side chain labdanes (132-150) and epoxy-free side chain labdanes (151-171). Tobacco cembranoid and labdane diterpenes are both formed via the methylerythritol 4-phosphate pathway and are synthesised from geranylgeranyl diphosphate. Their biosynthetic pathways and the four key enzymes (cembratrienol synthase, cytochrome P450 hydroxylase, copalyl diphosphate synthase, and Z-abienol cyclase) that affect their biosynthesis have been described in detail. A systematic summary of the bioactivity and utilisation values of the cembranoid and labdane diterpenes is also provided. The agricultural bioactivities associated with cembranoid and labdane diterpenes include antimicrobial and insecticidal activities as well as induced resistance, while the medical bioactivities include cytotoxic and neuroprotective activities. Further research into the cembranoid and labdane diterpenes will help to promote their development and utilisation as plant-derived pesticides and medicines.

Comparison of anterior cervical diskectomy with fusion (ACDF) and laminoplasty treating multilevel cervical spondylotic myelopathy with developmental canal stenosis: a retrospective study.

PURPOSE: To evaluate clinical effectiveness and radiologic results of anterior cervical diskectomy with fusion (ACDF) comparing with laminoplasty (LP) in treating multilevel cervical spondylotic myelopathy (MCSM) with developmental canal stenosis (DCS). METHODS: This was a retrospective analysis of 41 patients who had MCSM with DCS treated with ACDF or LP from December 2018 to April 2023. Patients were split into ACDF and LP groups for comparison, and patients were further separated into subgroups based on whether or not a reserving canal space was present. The operation time, hemoglobin, hospital stay, modified Japanese Orthopaedic Association (mJOA) score, and visual analog scale (VAS) score were used to assess clinical efficacy. The C2-C7 Cobb angle, C2-C7 sagittal vertical axis, T1 slope, and cervical range of motion were applied to evaluate imaging changes. RESULTS: Of the 41 patients, 19 received ACDF, and 22 received LP. At the final follow-up, both groups' mJOA scores significantly improved, and the intercomparison showed no differences; the VAS score was much lower in the ACDF group but remained unchanged in the LP group. At the final follow-up, the C2-C7 Cobb angle and T1 slope had significantly increased in the ACDF group, while the LP group showed no change; the cervical range of motion had significantly decreased in both groups, with the ACDF group exhibiting a more marked reduction. Within the ACDF subgroup, there was no postoperative symptom improvement for those with reserving space, whereas there was postoperative symptom resolution for those with non-reserving space; however, postoperative symptom in the LP subgroup was resolved. CONCLUSIONS: Both ACDF and LP were efficacious for MCSM patients with DCS. While ACDF could improve cervical lordosis and alleviate neck pain more effectively, it can also result in cervical sagittal imbalance and decreased mobility. Furthermore, the recovery from LP was superior to that from ACDF for patients with reserving space. In contrast, the recovery from both decompression techniques was comparable for individuals in non-reserving space.

Different interventions for the treatment of patent ductus arteriosus in children: a protocol for a network meta-analysis.

INTRODUCTION: Patent ductus arteriosus (PDA) is one of the most common congenital heart diseases. Once the PDA is diagnosed, it needs to be dealt with in time. At present, main methods include pharmacological treatment, surgical closure, and interventional closure for treatment of PDA. However, the effect of different interventions in PDA management is still controversial. Thus, our study aims to assess the effectiveness of different interventions together and estimate the sequence of these therapies for PDA children. Meanwhile, it is necessary to conduct a Bayesian network meta-analysis to compare the safety of different interventions comprehensively. METHODS AND ANALYSIS: To the best of our knowledge, this is the first Bayesian network meta-analysis comparing the efficacy and safety of different interventions for the treatment of PDA. PubMed, Embase, Cochrane Library, Web of Science, gray literature, and trial registry databases were searched from inception to December 2022. We will extract and report data according to methodological guidelines for Bayesian network meta-analysis by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Primary PDA closure, overall PDA closure, technical success, surgical success rate, mortality during hospital stay, operation time, intensive care unit stay, intraoperative radiation dose, radiation exposure time, total postoperative complication rate, and postoperative major complication rate will be defined as the outcomes. The quality of all random studies will be assessed using ROB, and quality of evidence for all outcomes will be judged by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). ETHICS AND DISSEMINATION: The results will be disseminated through peer-reviewed publication. Since no private and confidential patient data will be contained in the reporting, there are no ethical considerations associated with this protocol. SYSTEMATIC REVIEW REGISTRATION: INPLASY2020110067.

Treatment of acetabular fracture involving anterior and posterior columns using a single pararectus approach: surgical experience and preliminary results.

PURPOSE: This study aims to evaluate the efficacy of single pararectus approach in patients confirmed with acetabular fracture involving anterior and posterior columns. METHODS: A total of 58 patients confirmed with acetabular fracture involving anterior and posterior columns and treated at our hospital between January 2015 and January 2020 were retrospectively analyzed. A single pararectus approach was applied for all patients. Routine X-rays were performed at follow-up of one, three, six, 12, and 18 months, and three-dimensional CT scans were added at six and 18 months. Fracture reduction quality was assessed using the Matta score system, and functional assessment used the Modified Merle D'Aubigné and Postel score system. Post-operative complications, including fat liquefaction and deep vein thrombosis, were recorded and analyzed. RESULTS: The median operation time was 186 min while the intra-operative blood loss was 421 mL. The rate of good-to-excellent reduction was 94.8%, and the rate of good-to-excellent hip function score reached 93.1%. Seven patients presented with post-operative complications, including three intra-operative small vascular injuries, two peritoneal small perforations, one fat liquefaction, and one deep vein thrombosis. CONCLUSION: Using a single pararectus approach is convenient and effective for treating acetabular fracture involving anterior and posterior columns, especially those involving the quadrilateral area. TRIAL REGISTRATION: ChiCTR, ChiCTR2100054604. Registered 21 December 2022. Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=144783 .

Calcium Phosphate-Based Biomaterials for Bone Repair.

Traumatic, tumoral, and infectious bone defects are common in clinics, and create a big burden on patient's families and society. Calcium phosphate (CaP)-based biomaterials have superior properties and have been widely used for bone defect repair, due to their similarities to the inorganic components of human bones. The biological performance of CaPs, as a determining factor for their applications, are dependent on their physicochemical properties. Hydroxyapatite (HAP) as the most thermally stable crystalline phase of CaP is mostly used in the form of ceramics or composites scaffolds with polymers. Nanostructured CaPs with large surface areas are suitable for drug/gene delivery systems. Additionally, CaP scaffolds with hierarchical nano-/microstructures have demonstrated excellent ability in promoting bone regeneration. This review focuses on the relationships and interactions between the physicochemical/biological properties of CaP biomaterials and their species, sizes, and morphologies in bone regeneration, including synthesis strategies, structure control, biological behavior, and the mechanisms of CaP in promoting osteogenesis. This review will be helpful for scientists and engineers to further understand CaP-based biomaterials (CaPs), and be useful in developing new high-performance biomaterials for bone repair.

Discovery of the Biosynthetic Pathway of Beticolin 1 Reveals a Novel Non-Heme Iron-Dependent Oxygenase for Anthraquinone Ring Cleavage.

This study used light-mediated comparative transcriptomics to identify the biosynthetic gene cluster of beticolin 1 in Cercospora. It contains an anthraquinone moiety and an unusual halogenated xanthone moiety connected by a bicyclo[3.2.2]nonane. During elucidation of the biosynthetic pathway of beticolin 1, a novel non-heme iron oxygenase BTG13 responsible for anthraquinone ring cleavage was discovered. More importantly, the discovery of non-heme iron oxygenase BTG13 is well supported by experimental evidence: (i) crystal structure and the inductively coupled plasma mass spectrometry revealed that its reactive site is built by an atypical iron ion coordination, where the iron ion is uncommonly coordinated by four histidine residues, an unusual carboxylated-lysine (Kcx377) and water; (ii) Kcx377 is mediated by His58 and Thr299 to modulate the catalytic activity of BTG13. Therefore, we believed this study updates our knowledge of metalloenzymes.

O-Arm-Navigated, Robot-Assisted Versus Conventional CT Guided Radiofrequency Ablation in Treatment of Osteoid Osteoma: A Retrospective Cohort Study.

Background: Osteoid osteoma is a common benign bone tumor, and clinically there is severe local pain that typically worsens at night. The conventional CT-guided radiofrequency ablation (RFA) was widely used in the treatment of osteoid osteoma (OO), which could result in some radiation-related and imprecise complications due to the overdose of radiation exposure. This study aimed to compare the surgical effect of robot-assisted RFA with O-arm navigation and conventional CT-guided RFA in the treatment of OO. Methods: Sixty-two patients who underwent robot-assisted RFA with O-arm navigation (Robot-RFA, n = 24) or CT-guided RFA (CT-RFA, n = 38) were included in this retrospective cohort study. The mean follow-up time was 23.3 months. The intra-operative data, primary technical success rate, visual analog scale (VAS), and post-operative complications were analyzed. Results: Primary technical success was obtained in 23 patients who had robot-assisted RFA, and 35 patients who had conventional CT-guided RFA. One patient in Robot-RFA group and three patients in CT-RFA group with pain recurrence received repeat-RFA and had a secondary success. Mean operation time and dose of radiation exposure were lower in Robot-RFA group than that in CT-RFA group. The Robot-RFA group took fewer K-wire adjustment times for each patient than the CT-RFA group. There was a statistically significant difference in the mean operation time, dose of radiation exposure, and K-wire adjustment times between the groups (p < 0.05). No complications associated with the procedure were reported in the two groups during the follow-up period. Conclusion: Robot-assisted RFA with O-arm navigation is a safer and more precise strategy in the treatment of osteoid osteoma with less operation time and radiation exposure compared with the conventional CT-guided radiofrequency ablation.

Synthesis of Highly Near-Infrared Fluorescent Graphene Quantum Dots Using Biomass-Derived Materials for In Vitro Cell Imaging and Metal Ion Detection.

Graphene quantum dots (GQDs) are a subset of fluorescent nanomaterials that have gained recent interest due to their photoluminescence properties and low toxicity and biocompatibility features for bioanalysis and bioimaging. However, it is still a challenge to prepare highly near-infrared (NIR) fluorescent GQDs using a facile pathway. In this study, NIR GQDs were synthesized from the biomass-derived organic molecule cis-cyclobutane-1,2-dicarboxylic acid via one-step pyrolysis. The resulting GQDs were then characterized by various analytical methods such as UV-Vis absorption spectroscopy, fluorescence spectroscopy, dynamic light scattering, high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. Moreover, the photostability and stability over a wide pH range were also investigated, which indicated the excellent stability of the prepared GQDs. Most importantly, two peaks were found in the fluorescence emission spectra of the GQDs, one of which was located in the NIR region of about 860 nm. Finally, the GQDs were applied for cell imaging with human breast cancer cell line, MCF-7, and cytotoxicity analysis with mouse macrophage cell line, RAW 246.7. The results showed that the GQDs entered the cells through endocytosis on the fluorescence images and were not toxic to the cells up to a concentration of 200 µg/mL. Thus, the developed GQDs could be a potential effective fluorescent bioimaging agent. Finally, the GQDs depicted fluorescence quenching when treated with mercury metal ions, indicating that the GQDs could be used for mercury detection in biological samples as well.

Donut-like MOFs of copper/nicotinic acid and composite hydrogels with superior bioactivity for rh-bFGF delivering and skin wound healing.

BACKGROUND: Skin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis. RESULTS: Herein, we have prepared a new donut-like metal-organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers. CONCLUSIONS: Considering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration.

Hybrid locked medial plating in dual plate fixation optimizes the healing of comminuted distal femur fractures: A retrospective cohort study.

OBJECTIVES: Dual plate fixation has been reported to be effective in the treatment of comminuted distal femur fractures (DFFs). However, optimized use of the medial plate and screws is less studied. This study aimed to evaluate the effect of a hybrid configuration of the medial plate in dual plate fixation of comminuted DFFs in promoting fracture healing. MATERIALS AND METHODS: We retrospectively analyzed 62 patients with comminuted DFFs (AO/OTA 33-A3/33-C2/33-C3) from January 2015 to March 2020, who were either fixed with lateral locked plating augmented with hybrid locked medial plating (LP-HLMP, n = 32) or lateral locked plating (LLP, n = 30) alone. Specifically, compression screws were applied in the middle of the medial plate and flanked by locking ones at both ends. Baseline characteristics, radiological and clinical outcomes were reviewed and analyzed. Multivariate logistic regression analysis was used to identify predictive factors for early fracture healing, and risk factors for delayed union/nonunion. RESULTS: Demographics including age, gender, smoking, diabetes, and injury mechanism were comparable between the two groups. Reduction quality was better in the LP-HLMP group (p < 0.001). Although the LP-HLMP group experienced longer duration of surgery (125 min vs. 100 min, p < 0.001), sign of healing at 3 months was more obvious in this group (75%, 24/32 vs. 30%, 9/30; p < 0.001). The LP-HLMP group also presented with higher union rate (93.8%, 30/32 vs. 56.7%, 17/30; p = 0.001) and lower reoperation rate (0%, 0/32 vs. 13.3%, 4/30; p = 0.049). Kolment score showed no statistical significance between the two groups. Multivariate analysis revealed that younger age (< 60 years) (OR 5.99, 95%CI 1.16 - 31.03; p = 0.001) and LP-HLMP fixation (OR 45.90, 95% CI 4.78 - 440.56; p = 0.001) predict early healing; while smoking (OR 17.80, 95% CI 2.41 - 131.49; p = 0.01) and fracture translation (OR 3.49, 95% CI 1.46 - 8.32; p = 0.01) were identified as risk factors for delayed union/nonunion. CONCLUSION: Hybrid locked medial plating in this study favors the healing of comminuted DFFs and reduces reoperation. Additionally, smoking and suboptimal reduction (translation) predict delayed union/nonunion.

Transcriptome Profiling and Cytological Assessments for Identifying Regulatory Pathways Associated With Diorcinol N-Induced Autophagy in A3 Cells.

Fungal secondary metabolites serve as a rich resource for exploring lead compounds with medicinal importance. Diorcinol N (DN), a fungal secondary metabolite isolated from an endophytic fungus, Arthrinium arundinis, exhibits robust anticancer activity. However, the anticancer mechanism of DN remains unclear. In this study, we examined the growth-inhibitory effect of DN on different human cancer cell lines. We found that DN decreased the viability of A3 T-cell leukemia cells in a time- and concentration-dependent manner. Transcriptome analysis indicated that DN modulated the transcriptome of A3 cells. In total, 9,340 differentially expressed genes were found, among which 4,378 downregulated genes and 4,962 upregulated genes were mainly involved in autophagy, cell cycle, and DNA replication. Furthermore, we demonstrated that DN induced autophagy, cell cycle arrest in the G1/S phase, and downregulated the expression of autophagy- and cell cycle-related genes in A3 cells. By labeling A3 cells with acridine orange/ethidium bromide, Hoechst 33,258, and monodansylcadaverine and via transmission electron microscopy, we found that DN increased plasma membrane permeability, structural disorganization, vacuolation, and autophagosome formation. Our study provides evidence for the mechanism of anticancer activity of DN in T-cell leukemia (A3) cells and demonstrates the promise of DN as a lead or even candidate molecule for the treatment of acute lymphoblastic leukemia.

CircRNA ITCH increases bortezomib sensitivity through regulating the miR-615-3p/PRKCD axis in multiple myeloma.

AIMS: Bortezomib (BTZ) is described as the first-line agent for multiple myeloma (MM) chemotherapy, but the emergence of BTZ resistance usually results in the failure of chemotherapy in MM. Circular RNA (circRNA) itchy E3 ubiquitin protein ligase (circITCH) is a novel identified circRNA that plays a vital role in the development of human cancers. However, the role of circITCH in the development of BTZ resistance in MM remains elusive. MATERIALS AND METHODS: The expression of circITCH, miR-615-3p, and protein kinase C, delta (PRKCD) was detected with quantitative reverse transcription PCR and western blot. The effects of circITCH on the sensitivity of MM cells to BTZ were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, flow cytometry, and xenograft tumor assay. The interaction of circITCH, microRNA-615-3p, and PRKCD was explored using luciferase reporter assay and RNA immunoprecipitation assay. KEY FINDINGS: circITCH was downregulated in MM bone marrow specimens and cell lines, as well as BTZ-resistant MM cells. Reduced expression of circITCH was indicative of poor prognosis in MM patients. Upregulation of circITCH enhanced the sensitivity of BTZ-resistant MM cells to BTZ in vitro and in vivo. Furthermore, circITCH was identified as a sponge for miR-615-3p, and PRKCD is confirmed as a direct target of miR-615-3p. Besides, circITCH overexpression enhanced the sensitivity of MM cells to BTZ through miR-615-3p/PRKCD axis. SIGNIFICANCE: circITCH overexpression enhanced the sensitivity of MM cells to BTZ through miR-615-3p/PRKCD axis, providing a novel potential target for combating BTZ resistance in patients with MM.

Bone morphogenetic protein-9 promotes the proliferation of non-small cell lung cancer cells by activating PI3K/Akt and Smad1/5 pathways.

Non-small-cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small cell lung carcinoma (SCLC), which accounts for about 85% of all lung cancers. Bone morphogenetic protein (BMP)-9 in humans is encoded by the growth differentiation factor 2 gene, which belongs to the transforming growth factor-beta superfamily. In the present study, we explored the role of BMP-9 in A549 and NCI-H1650 cell proliferation and its possible molecular mechanisms. 25 NSCLC patients were recruited to evaluate mRNA expression of BMP-9 to determine its clinicopathologic significance. We found that recombinant protein BMP-9 and overexpression of BMP-9 promoted A549 and NCI-H1650 cell proliferation in vitro, which was abolished by phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002). Western blot results revealed that BMP-9 significantly activated the PI3K/Akt and Smad1/5 pathway signaling. In vivo, BMP-9 promoted tumor growth and PI3K/Akt and Smad1/5 signaling pathways in an A549 or NCI-H1650 cell line-derived xenograft model. Knockdown BMP-9 or BMP-9 receptor ALK1 inhibited A549 cell growth in vitro and in vivo, which was associated with regulating the PI3K/Akt and Smad1/5 signaling pathways. These results demonstrated that BMP-9 promoted A549 and NCI-H1650 cell proliferation via PI3K/Akt and Smad1/5 signaling pathways.

Standard median sternotomy, right minithoracotomy, totally thoracoscopic surgery, percutaneous closure, and transthoracic closure for atrial septal defects in children: A protocol for a network meta-analysis.

BACKGROUND: Atrial septal defect (ASD) is one of the most common congenital heart diseases, with an average of 1.64 per 1000 newborns with the ASD. Empirical studies suggest that surgery should be performed early in the presence of right atrium and or right ventricular enlargement, even for asymptomatic patients. Many surgical procedures can be used to treat ASD. But which method is the best choice remains unclear. This study aims to compare the efficacy and safety of standard median sternotomy, right minithoracotomy, totally thoracoscopic surgery, percutaneous closure, transcutaneous by echocardiography, and transcutaneous by radiotherapy for ASDs in children using Bayesian network meta-analysis (NMA). METHODS: We will perform a comprehensive literature search using PubMed, EMBASE.com, the Cochrane Library, Web of Science, and Chinese Biomedical Literature Database to identify relevant studies from inception to April 2019. Randomized controlled trials, prospective or retrospective cohort studies that reported the efficacy and safety of surgical procedures for the treatment of atrial septal defects will be included. Risk of bias of the included randomized controlled trials and prospective or retrospective cohort studies will be evaluated according to the Cochrane Handbook 5.1.0 and the risk of bias in non-randomized studies of interventions, respectively. A Bayesian NMA will be performed using R 3.4.1. RESULTS: The results of this NMA will be submitted to a peer-reviewed journal for publication. CONCLUSION: This NMA will summarize the direct and indirect evidence to assess the efficacy and safety of different surgical procedures for the treatment of ASDs. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is a network meta-analysis based on published trials. PROSPERO REGISTRATION NUMBER: CRD42019130902.

PUF60 accelerates the progression of breast cancer through downregulation of PTEN expression.

BACKGROUND: PUF60 is a splicing variant of far upstream element binding protein 1-interacting repressor, which is abnormally expressed in a variety of tumors and is closely involved in their progression. However, whether PUF60 participates in the occurrence and development of breast cancer remains unknown. Therefore, the objective of the current study is to explore the effects and mechanism of PUF60 in the progression of breast cancer. METHODS: PUF60 expression patterns in breast cancer tissues and cells were determined by RT-PCR and Western blotting. The relationship between PUF60 expression and patients' clinical features and outcome was evaluated to assess the potential of PUF60 as a marker for progression and prognosis prediction. CCK-8, flow cytometry, transwell and in vivo tumor formation assays were used to detect cell proliferation, apoptosis, migration, invasion and tumorigenesis. The effects of PUF60 on the activation of PTEN/PI3K/AKT were also evaluated by Western blotting and immunofluorescence assays. RESULTS: The expression of PUF60 was elevated in breast cancer tissue samples and cell lines, and its high expression was closely associated with the high incidence of lymph node metastasis and advanced TNM stage. Besides, upregulation of PUF60 with lentivirus infection significantly increased the growth, migration, and invasion and repressed the apoptosis of breast cancer HCC1937 and MDA-MB-231 cells, while silencing of PUF60 with shRNA showed the opposite results. Moreover, PUF60 upregulation promoted the expression of p-AKT, PI3K, and mTOR, while decreased PTEN expression through inhibiting its stability and enhancing its ubiquitination. Furthermore, upregulation of PUF60 promoted the tumorigenesis in vivo, whereas this effect was impaired when PTEN expression was upregulated in MDA-MB-231 and HCC1937 cells. CONCLUSION: This study demonstrates that PUF60 is highly expressed in breast cancer; upregulation of PUF60 accelerates the progression of breast cancer through PTEN inhibition.

Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L.

Recently, the incidence of hepatocellular carcinoma has increased worldwide. Cembranoid-type diterpenes (CBDs) from tobacco exhibit good antimicrobial, antitumor, and neuroprotective activities. Therefore, in this study, we isolated CBDs from Nicotiana tabacum L. and evaluated their antitumor activity against hepatoma cell lines. Particularly, the anti-tumor activity of α-2,7,11-cyprotermine-4,6-diol (α-CBD) was investigated against HepG2, SMMC-7721, and HL-7702 cells. The MTT assay revealed that α-CBD reduced the formation of cell clones and inhibited the proliferation of hepatocellular carcinoma cells. Morphological observations showed that α-CBD altered cell morphology and membrane permeability before inducing apoptosis. To further explore the antitumor mechanism of α-CBD, flow cytometry and transcriptome analysis were performed using HepG2 cells. The results showed that the number of HepG2 cells increased from 10.4% to 29.8%, indicating that α-CBD inhibits the proliferation of hepatocellular carcinoma cells in the S phase. The gene expression analysis of HepG2 cells treated with α-CBD showed 3068 genes with altered expression, among which 1289 were upregulated and 1779 were downregulated. Apoptosis induced by these differentially expressed genes might be mediated by the p53-PUMA, PI3K-Akt, and IL-1-NF-κB-IAP pathways. Comprehensively, our study shows that α-CBD isolated from N. tabacum L. can be potentially used as a natural antitumor agent.

Comparison of transcatheter closure, mini-invasive closure, and open-heart surgical repair for treatment of perimembranous ventricular septal defects in children: A PRISMA-compliant network meta-analysis of randomized and observational studies.

OBJECTIVE: Our study was aimed to comprehensively compare the relative efficacy, safety, and the cost of transcatheter closure, mini-invasive closure, and open-heart surgical repair to treat perimembranous ventricular septal defects (pmVSDs) in children using network meta-analysis method. METHODS: Five databases were systematically searched including Chinese Biomedical Literature Database, China National Knowledge Infrastructure, PubMed, EMBASE.com, and the Cochrane Central Register of Controlled Trials from the starting date of each database to February 2017. Tools for assessing the risk of bias in nonrandomized studies of interventions (ROBINS-I) were used to evaluate the risk of bias in observational studies and Cochrane Handbook version 5.1.0 was used for randomized controlled trials (RCTs). Data were analyzed using R-3.4.0 software and Review Manager 5.2. RESULTS: Three RCTs and 24 observational studies were included in our study. Network meta-analysis result demonstrated that transcatheter closure was the most effective treatment in terms of operative time [standardized mean difference (SMD) = -2.02, 95% confidence interval (CI): -3.92 to -0.12], major complications [odds ratio (OR) = 0.52, 95% CI = 0.30-0.91], ICU stay (SMD = -1.11, 95% CI = -2.13 to -0.08), and hospital stay (SMD = -1.81, 95% CI = -2.24 to -1.39). However, open-heart surgical repair showed a higher success rate of the procedure than transcatheter closure (OR = 0.36, 95% CI = 0.17-0.77).Statistical analysis result demonstrated that transcatheter closure had the best potential to lessen major complications, ICU stay, hospital stay, operative time, and significant residual shunt. CONCLUSIONS: Transcatheter closure has more benefit than mini-invasive closure and open-heart surgical repair to treat pmVSDs.

Preparation of porous calcium phosphate microspheres with phosphate-containing molecules at room temperature for drug delivery and osteogenic differentiation.

Calcium phosphate (CaP) has similar chemical properties to those of the inorganic component of human bone tissue, for potential application in drug delivery for the chemotherapy of osteosarcoma. In this work, CaP with a porous microsphere structure has been synthesized using fructose-1,6-bisphosphate (FBP) as the phosphorus source by a simple wet-chemical strategy at room temperature. The CaP porous microspheres, as an organic-inorganic hybrid nano-platform, exhibit good doxorubicin (Dox) loading capacity, and Dox-loading CaP, enhancing the in vitro chemotherapy of osteosarcoma cells. The CaP porous microspheres show high biocompatibility, and induce the osteogenic differentiation of MC3T3-E1. These results indicate that the CaP porous microspheres reported in this study are promising for application as an anti-osteosarcoma drug carrier and osteoinductive material for bone regeneration in the treatment of osteosarcoma.

Cytological Assessments and Transcriptome Profiling Demonstrate that Evodiamine Inhibits Growth and Induces Apoptosis in a Renal Carcinoma Cell Line.

Chinese medicines are an important source of secondary metabolites with excellent antitumour activity. Evodia rutaecarpa, from the family Rutaceae, exhibits antitumour activity. Evodiamine (EVO), which was isolated from the fruit of E. rutaecarpa, exhibits robust antitumour activity. However, the antitumour mechanism of EVO remains unclear. In this study, we assessed the growth-inhibiting effect of EVO on two renal carcinoma cell lines. We found that EVO could change the morphology and decrease the viability and proliferation of cells in a time- and concentration-dependent manner in vitro. In addition, transcriptome analysis indicated that EVO can modulate the transcriptome of Caki-1 cells. In total, 7,243 differentially expressed genes were found, among which 3,347 downregulated genes and 3,896 upregulated genes were mainly involved in cell migration, apoptosis, cell cycle, and DNA replication. Furthermore, we demonstrated that EVO can cause apoptosis, arrest cells in the G2/M phase, and regulate the expression of apoptosis- and cell cycle-related genes in Caki-1 cells. Our study reveals the anticancer effects of EVO using cellular and molecular data, and indicates the potential uses of this compound as a resource to characterize the antitumour mechanisms of E. rutaecarpa.