Enrichment and Evaluation of Antitumor Properties of Total Flavonoids from Juglans mandshurica Maxim.

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer.

Epigenetic regulation of papillary thyroid carcinoma by long non-coding RNAs.

Thyroid cancer is the most common primary endocrine malignancy with papillary thyroid carcinoma (PTC) its most common subtype. The jump in diagnoses over last many years has prompted re-assessment of molecularly targeted therapies and the discovery of novel targets. Long non-coding RNAs (lncRNAs) are increasingly being assessed for their expression in various PTC models. Interestingly, in addition to cell line models, a large proportion of the reported studies have evaluated lncRNA levels in PTC patient samples providing an immediate clinical relevance of their findings. While most lncRNAs either promote or suppress PTC pathogenesis, data on individual lncRNAs is not very clear. As expected, lncRNAs function in PTC through sponging of microRNAs as well as modulation of several signaling pathways. The process of epithelial-mesenchymal transition and the PI3K/Akt and wnt signaling pathways have emerged as the primary targets of lncRNAs in PTC. This comprehensive review discusses all the information that is available on lncRNAs in PTC, ranging from in vitro and in vivo findings to the possible role of lncRNAs as diagnostic and/or prognostic biomarkers.

Epigenetic signature associated with thyroid cancer progression and metastasis.

Thyroid cancer is not among the top cancers in terms of diagnosis or mortality but it still ranks fifth among the cancers diagnosed in women. Infact, women are more likely to be diagnosed with thyroid cancer than the males. The burden of thyroid cancer has dramatically increased in last two decades in China and, in the United States, it is the most diagnosed cancer in young adults under the age of twenty-nine. All these factors make it worthwhile to fully understand the pathogenesis of thyroid cancer. Towards this end, microRNAs (miRNAs) have constantly emerged as the non-coding RNAs of interest in various thyroid cancer subtypes on which there have been numerous investigations over the last decade and half. This comprehensive review takes a look at the current knowledge on the topic with cataloging of miRNAs known so far, particularly related to their utility as epigenetic signatures of thyroid cancer progression and metastasis. Such information could be of immense use for the eventual development of miRNAs as therapeutic targets or even therapeutic agents for thyroid cancer therapy.

Retraction notice to "MicroRNA-27a regulates the proliferation, chemosensitivity and invasion of human ovarian cancer cell lines by targeting Cullin 5" [YABBI 688C (2019) 9-15 / 7995].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The entire 'Reason' text must be identical to that in the XML version (Box 6).

LncRNA SNHG14 Sponges miR-206 to Affect Proliferation, Apoptosis, and Metastasis of Hepatocellular Carcinoma Cells by Regulating SOX9.

OBJECTIVE: To explore how lncRNA SNHG14 modulates the biological features of hepatocellular carcinoma (HCC) cells by regulating SOX9 via mediating miR-206. METHODS: HCC tissues were collected to perform the quantitative reverse transcriptase polymerase chain reaction to determine the expressions of SNHG14, miR-206, and SOX9. HCC cell line SMCC7721 was selected for co-transfection by si-SNHG14/miR-206 inhibitor/si-SOX9, followed by the measurement of cell proliferation using Cell Count Kit-8 (CCK-8) assay and clone formation assay. The migration and invasion were evaluated by wound healing test and Transwell assay. The apoptotic rate was determined by flow cytometry. Levels of the apoptosis-related proteins were measured through Western blotting. RESULTS: SNHG14 and SOX9 were up-regulated in HCC tumor tissues compared with adjacent normal tissues, with decreased miR-206 expression. Moreover, SNHG14 expression was significantly associated with the TNM stage, lymphatic metastasis, and histological differentiation of HCC patients. Besides, inverse correlations between SNHG14 and miR-206, as well as between miR-206 and SOX9, were noted. The dual luciferase reporter gene assay, RIP, and RNA pull-down experiments also revealed the targeting relationship between SNHG14 and miR-206 or between miR-206 and SOX9. Silencing SNHG14 and SOX9 inhibited the proliferation, invasion, and migration of HCC cells, with increased apoptosis, which was all abolished by silencing miR-206. CONCLUSION: Inhibition of SNHG14 suppresses SOX9 by up-regulating miR-206, to further inhibit the proliferation, migration, and invasion of HCC cells with the promoted apoptosis, which is a novel target for the treatment of HCC.

Ultrasonic-Assisted Extraction of Flavonoids from Juglans mandshurica Maxim.: Artificial Intelligence-Based Optimization, Kinetics Estimation, and Antioxidant Potential.

Ultrasonic-assisted extraction (UAE) of flavonoids (JMBF) from Juglans mandshurica Maxim., an important industrial crop in China, was investigated in the present study. To improve the extraction efficiency of JMBF, suitable UAE was proposed after optimization using a hybrid response surface methodology-artificial neural network-genetic algorithm approach (RSM-ANN-GA). The maximum extraction yield (6.28 mg·g-1) of JMBF was achieved using the following optimum UAE conditions: ethanol concentration, 62%; solid-liquid ratio, 1:20 g·mL-1; ultrasonic power, 228 W; extraction temperature, 60 °C; extraction time, 40 min; total number of extractions, 1. Through the investigation of extraction kinetics, UAE offered a higher saturated concentration (Cs) for JMBF in comparison to traditional solvent extraction (TSE). Scanning electron microscopy (SEM) images showed that deeper holes were generated in J. mandshurica powder under the action of ultrasound, indicating that ultrasound significantly changed the structure of the plant materials to facilitate the dissolution of active substances. Extracts obtained using UAE and TSE were compared by Fourier-transform infrared spectroscopy analysis, the results of which revealed that the functional group of bioactive compounds in the extract was unaffected by the ultrasonication process. Moreover, JMBF was further shown to exhibit significant antioxidant properties in vitro. This study provides a basis for the application of JMBF as a natural antioxidant.

MicroRNA-27a regulates the proliferation, chemosensitivity and invasion of human ovarian cancer cell lines by targeting Cullin 5.

Reports suggest that microRNAs have implications in the development of several diseases including cancer. It is therefore believed that miRs may act as therapeutic targets for cancer treatment. The treatment of ovarian cancer is mainly obstructed by lack of biomarkers and efficient drug targets. Against this backdrop, this study was undertaken to unveil the therapeutic implications of miR-27a in ovarian cancer. The results showed that the expression of miR-27a was significantly elevated in ovarian cancer tissues and cell lines. Inhibition of miR-27a expression resulted in the decrease of proliferation rate and colony formation potential of the SK-OV-3 and OVACAR-3 cells via G2/M arrest. The miR-27a inhibition triggered G2/M arrest of SK-OV-3 and OVACAR-3 cells was accompanied with depletion of cyclin A and B1 expression levels. TargetScan analysis together with dual reporter assay revealed that miR-27a exerts its effects via modulation of CUL5 expression. The CUL5 was shown to be suppressed in the ovarian cancer tissues and cell lines and suppression of miR-27a expression caused upregulation of CUL5 expression. Overexpression of CUL5 caused inhibition of SK-OV-3 and OVACAR-3 cell proliferation via induction of G2/M arrest, similar to that of miR-27a inhibition. Interestingly, CUL5 overexpression reversed the effects of miR-27a inhibition on the viability of SK-OV-3 cells. Finally, the suppression of miR-27a could enhance the chemosensitivity of the SK-OV-3 cells to cisplatin and docetaxel anticancer drugs and also decreased their migration and invasion. The findings of this study revealed that miR-27a suppression inhibits the growth, chemosensitivity and invasion of ovarian cancer and may prove beneficial in the ovarian cancer management.

Mefloquine targets ß-catenin pathway and thus can play a role in the treatment of liver cancer.

The current study was designed and performed to investigate the effect of mefloquine on the proliferation and tumor formation potential of liver cancer stem cells. CD133 + HepG2 cells were identified using MACS and showed markedly higher tumor formation potential compared to the parental cells. The secondary tumors formed by CD133 + cells were markedly large in size and more in number compared to the parental cells. Mefloquine treatment of CD133 + HepG2 cells inhibited the proliferation selectively in concentration based manner. The rate of proliferation was inhibited to 82 and 12% in parental and CD133 + sphere forming cells, respectively on treatment with 10 µM concentration of mefloquine. The number of secondary tumors formed by primary tumors was decreased significantly on treatment with 10 µM mefloquine concentration. Treatment of the liver cancer stem cells with mefloquine markedly decreased the potential to undergo self-renewal at 10 µM concentration after 48 h. The results from western blot analysis showed significantly higher expression of cancer stem cell molecules ß-catenin and cyclin D1 in LCSCs. Treatment of the LCSCs with various concentrations of mefloquine reduced the expression levels of ß-catenin and cyclin D1. Administration of the CD133 + cell tumor xenografts in the mice led to the formation of large sized tumors in the control group. However, the tumor growth was inhibited significantly in the mice on treatment with 10 mg/kg doses of mefloquine after day 21. The tumor weight was significantly lower in the animals of mefloquine treatment group compared to the control group. Thus, mefloquine treatment inhibits self-renewal and proliferation potential of cells through targeting ß-catenin pathway.

A comprehensive overview of exosome lncRNAs: emerging biomarkers and potential therapeutics in endometriosis.

Endometriosis is a gynecological condition that significantly impacting women's daily lives. In recent years, the incidence of endometriosis has been rising yearly and is now an essential contributor to female infertility. Exosomes are extracellular vesicles (EVs) that carry long noncoding RNA (lncRNA) and shield lncRNA from the outside environment thanks to their vesicle-like structure. The role of exosome-derived lncRNAs in endometriosis is also receiving more study as high-throughput sequencing technology develops. Several lncRNAs with variable expression may be crucial to the emergence and growth of endometriosis. The early diagnosis of endometriosis will be considerably improved by further high specificity and sensitivity Exosome lncRNA screening. Exosomes assist lncRNAs in carrying out their roles, offering a new target for creating endometriosis-specific medications. In order to serve as a reference for clinical research on the pathogenesis, diagnosis, and treatment options of endometriosis, this paper covers the role of exosome lncRNAs in endometriosis and related molecular mechanisms.

Biogenesis and function of exosome lncRNAs and their role in female pathological pregnancy.

Preeclampsia, gestational diabetes mellitus, and recurrent spontaneous abortion are common maternal pregnancy complications that seriously endanger women's lives and health, and their occurrence is increasing year after year with a rejuvenation trend. In contrast to biomarkers found freely in tissues or body fluids, exosomes exist in a relatively independent environment and provide a higher level of stability. As backbone molecules, guidance molecules, and signaling molecules in the nucleus, lncRNAs can regulate gene expression. In the cytoplasm, lncRNAs can influence gene expression levels by modifying mRNA stability, acting as competitive endogenous RNAs to bind miRNAs, and so on. Exosomal lncRNAs can exist indefinitely and are important in intercellular communication and signal transduction. Changes in maternal serum exosome lncRNA expression can accurately and timely reflect the progression and regression of pregnancy-related diseases. The purpose of this paper is to provide a reference for clinical research on the pathogenesis, diagnosis, and treatment methods of pregnancy-related diseases by reviewing the role of exosome lncRNAs in female pathological pregnancy and related molecular mechanisms.

Cuproptosis: emerging biomarkers and potential therapeutics in cancers.

The sustenance of human life activities depends on copper, which also serves as a crucial factor for vital enzymes. Under typical circumstances, active homeostatic mechanisms keep the intracellular copper ion concentration low. Excess copper ions cause excessive cellular respiration, which causes cytotoxicity and cell death as levels steadily rise above a threshold. It is a novel cell death that depends on mitochondrial respiration, copper ions, and regulation. Cuproptosis is now understood to play a role in several pathogenic processes, including inflammation, oxidative stress, and apoptosis. Copper death is a type of regulatory cell death(RCD).Numerous diseases are correlated with the development of copper homeostasis imbalances. One of the most popular areas of study in the field of cancer is cuproptosis. It has been discovered that cancer angiogenesis, proliferation, growth, and metastasis are all correlated with accumulation of copper ions. Copper ion concentrations can serve as a crucial marker for cancer development. In order to serve as a reference for clinical research on the product, diagnosis, and treatment of cancer, this paper covers the function of copper ion homeostasis imbalance in malignant cancers and related molecular pathways.

Black phosphorus-enhanced injectable hydrogel for infected soft tissue healing.

The misuse of antibiotics makes clinical treatment of soft tissue infection a huge challenge in prosthesis replacement. In this study, a black phosphorus (BP)-enhanced antibacterial injectable hydrogel (HAABP) was developed by the dynamic coordinative cross-linking among thiolated hyaluronic acid, silver ion (Ag+), and BP. HAABP has been proven to possess typical porous structures, excellent injectability, and rapid self-healing properties. In addition, the shear modulus was positive correlative to the concentration of BP. In vitro, HAABP maintained good cytocompatibility and showed a highly efficient synergistic inhibitory effect on Staphylococcus aureus through the irradiation of near infrared light and the release of Ag+. In vivo, HAABP not only inhibited the persistent infection but also accelerated the deposition of collagen fibers and angiogenesis by down-regulating the inflammatory factor TNF-α in the infectious wound defect, thereby repairing the natural barrier of tissue. This study developed a BP-enhanced injectable hydrogel that provided a simple and efficient synergistic antibacterial strategy to treat soft tissue infections around prostheses.

Prognostic role of the peritoneal cancer index in ovarian cancer patients who undergo cytoreductive surgery: a meta-analysis.

Advanced-stage ovarian cancer is usually associated with peritoneal carcinomatosis. This study evaluates the prognostic role of the Peritoneal Cancer Index (PCI) in predicting the survival of patients with ovarian cancer. A literature search was conducted in electronic databases (Google Scholar, PubMed, Ovid, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to estimate survival with low and high PCI scores and to pool hazard ratios (HR) of survival between lower and higher PCI scores. A total of 20 studies (2588 patients) were included. Median follow-up was 39 months [95%CI: 25, 54]. Complete cytoreduction rate was 80% [95% CI: 73, 87]. The median PCI score was 11.3 [95% CI: 9.9, 12.7]. Median survival was 56.7 months [95% CI: 45.2, 68.2] with below and 28.8 months [95% CI: 23.0, 34.6] with above any PCI cutoff. Most studies used PCI cutoffs between 10 and 20. The median progression-free survival was 23.7 months [95% CI: 16.5, 30.8] with below and 11.9 months [95% CI: 5.9, 17.9] with above any PCI cutoff. 5-year survival rates were 61.3% [95% CI: 49.9, 72.8] with PCI<10 cutoffs, 21.7% [95% CI: 11.6, 31.8] with PCI>10 cutoffs, 50.1% [95% CI: 39.0, 61.2] with PCI<20 cutoffs, and 21.7% [95% CI: 16.2, 27.1] with PCI>20 cutoffs. Pooled analysis of HRs showed that a higher PCI score was associated with worse survival in both univariate (HR 2.14 [95%CI: 1.63, 2.66]) and multivariate (HR 1.10 [95% CI: 1.02, 1.18]) analyses. In a set of studies that used varying PCI cutoffs, the PCI has been found to have a significant inverse association with the survival of patients with advanced ovarian cancer who underwent cytoreductive surgery.

Epigenetic Regulation in Knee Osteoarthritis.

Osteoarthritis (OA) is a complicated disease with both hereditary and environmental causes. Despite an increase in reports of possible OA risk loci, it has become clear that genetics is not the sole cause of osteoarthritis. Epigenetics, which can be triggered by environmental influences and result in transcriptional alterations, may have a role in OA pathogenesis. The majority of recent research on the epigenetics of OA has been focused on DNA methylation, histone modification, and non-coding RNAs. However, this study will explore epigenetic regulation in OA at the present stage. How genetics, environmental variables, and epigenetics interact will be researched, shedding light for future studies. Their possible interaction and control processes open up new avenues for the development of innovative osteoarthritis treatment and diagnostic techniques.

An essential technique for modern hepato-pancreato-biliary surgery: minimally invasive biliary reconstruction.

Introduction: Minimally invasive reconstruction of the biliary tract is complex and involves multiple steps. The procedure is challenging and has been an essential technique in modern hepato-pancreato-biliary surgery in recent years. Additionally, the quality of the reconstruction directly affects long-and short-term complications and affects the prognosis and quality of life. Various minimally invasive reconstruction methods have been developed to improve the reconstruction effect; however, the optimal method remains controversial. Areas covered: In this study, were viewed published studies of minimally invasive biliary reconstruction within the last 5 years and discussed the current status and main complications of minimally invasive biliary reconstruction. More importantly, we introduced the current reconstruction strategies and technical details of minimally invasive biliary reconstruction, which may be potentially helpful for surgeons to choose reconstruction methods and improve reconstruction quality. Expert opinion: Although several improved and modified methods for biliary reconstruction have been developed recently, no single approach is optimal or adaptable to all situations. Patient-specific selection of appropriate technical strategies according to different situations combined with sophisticated and skilled minimally invasive techniques effectively improves the quality of anastomosis and reduces complications.

Endoplasmic reticulum stress: Multiple regulatory roles in hepatocellular carcinoma.

BACKGROUND: Endoplasmic reticulum (ER) stress is a basic cellular stress response that maintains cellular protein homeostasis under endogenous or exogenous stimuli, which depends on the stimulus, its intensity, and action time. The ER produces a corresponding cascade reaction for crosstalk of adaptive and/or pro-death regulation with other organelles. Hepatocellular carcinoma(HCC) is one of the most common malignant solid tumors with an extremely poor prognosis. Viral hepatitis infection, cirrhosis, and steatohepatitis are closely related to the occurrence and development of HCC, and ER stress has gradually been shown to be a major mechanism. Moreover, an increasing need for protein and lipid products and relative deficiencies of oxygen and nutrients for rapid proliferation and endoplasmic reticulum stress are undoubtedly involved. Therefore, to fully and comprehensively understand the regulatory role of endoplasmic reticulum stress in the occurrence and progression of HCC is of vital importance to explore its pathogenesis and develop novel anti-cancer strategies. METHODOLOGY: We searched for relevant publications in the PubMed databases using the keywords "Endoplasmic reticulum stress", "hepatocellular carcinoma" in last five years,and present an overview of the current knowledge that links ER stress and HCC, which includes carcinogenesis, progression, and anti-cancer strategies, and propose directions of future research. RESULT: ER stress were confirmed to be multiple regulators or effectors of cancer, which also be confirmed to drive tumorigenesis and progression of HCC. Targeting ER stress signaling pathway and related molecules could play a critical role for anti-HCC and has become a research hotspot for anti-cancer in recent years. CONCLUSION: ER stress are critical for the processes of the tumorigenesis and progression of tumors. For HCC, ER stress was associated with tumorigenesis, development, metastasis, angiogenesis and drug resistance, targeting ER stress has emerged as a potential anti-tumor strategy.

Erratum: Role of ursolic acid chalcone, a synthetic analogue of ursolic acid, in inhibiting the properties of CD133(+) sphere-forming cells in liver stem cells.

[This corrects the article on p. 1427 in vol. 8, PMID: 25973027.].

Achilles'heel of laparoscopic pancreatectomy: reconstruction of the remnant pancreas.

INTRODUCTION: Laparoscopic pancreatic reconstruction is a challenging procedure and is considered the Achilles' heel of laparoscopic pancreatectomy. Multiple techniques of laparoscopic pancreatic reconstruction have been reported, but the optimal technique remains unclear. AREAS COVERED: This paper provides a brief introduction to the developmental status and major related complications of laparoscopic pancreatic reconstruction. We reviewed all published literature on the technology of laparoscopic pancreatic reconstruction within the last 5 years and herein discuss the advantages and disadvantages of different reconstruction methods. We also discuss several details of different reconstruction techniques in terms of their significance to the operation and complications. EXPERT OPINION: No individual method of laparoscopic pancreatic reconstruction is considered optimal for all conditions. The reconstruction strategy should be based on the surgeon's proficiency with laparoscopic technology and the patient's individual risk factors. Personalized methods of pancreatic reconstruction may more effectively reduce morbidity and mortality.

Preclinical evaluation of a mini-arthroplasty implant based on polyetheretherketone and Ti6AI4V for treatment of a focal osteochondral defect in the femoral head of the hip.

A mini or partial arthroplasty may offer the advantages of reduced pain, shorter hospital stay, and increased range of motion, which are beneficial for the treatment of large-sized focal osteochondral defects. We aimed to evaluate the in vivo histologic response and function of our nonresorbable, composite structure implant, developed using polyetheretherketone (PEEK) and Ti6AI4V alloy, as a treatment for full-thickness osteochondral defects in the femoral head of the hip using a goat model. The gross and imaging appearance and histologic results were compared to those of a similar size cobalt-chromium-molybdenum (CoCrMo) alloy implant placed in a defect in the femoral head and evaluated up to 12 weeks. The X radiographs showed that there was no evidence of loosening of the implants for both the PEEK-Ti6AI4V and CoCrMo groups. Magnetic resonance imaging results showed no inflammatory signal findings in both PEEK-Ti6AI4V and CoCrMo implants. Macroscopically and histologically, there was lesser cartilage degeneration in the PEEK-Ti6AI4V implant than in the CoCrMo implant. The modified macroscopic articular evaluation score was lower in the PEEK-Ti6AI4V group than in the CoCrMo group (p < 0.05), and the histological score of the periprosthetic and acetabular cartilage was lower in the PEEK-Ti6AI4V group than in the CoCrMo group (P < 0.05). The micro-computed tomography results showed that the uncemented PEEK-Ti6AI4V implant has better osseointegration and higher bone-implant contact than the cemented CoCrMo implant. The peri-implant bone mass was higher in the PEEK-Ti6AI4V implant(p < 0.05). Meanwhile, the optical profile analytical results showed that the surface roughness of the cartilage in the acetabulum was higher in the CoCrMo group. In conclusion, the mini-arthroplasty implant based on PEEK-Ti6AI4V was superior to an identical CoCrMo alloy implant as a treatment for local osteochondral defect in the femoral head, owing to its in vivo cartilage protection and better osseointegration.