ASB3 promotes hepatocellular carcinoma progression by mediating DR5 ubiquitination in TRAIL resistance.

Ankyrin-repeat proteins with a suppressor of cytokine signaling box (ASB) proteins belong to the E3 ubiquitin ligase family. 18 ASB members have been identified whose biological functions are mostly unexplored. Here, we discovered that ASB3 was essential for hepatocellular carcinoma (HCC) development and high ASB3 expression predicted poor clinical outcomes. ASB3 silencing induced HCC cell growth arrest and apoptosis in vitro and in vivo. Liver-specific deletion of Asb3 gene suppressed diethylnitrosamine (DEN)-induced liver cancer development. Mechanistically, ASB3 interacted with death receptor 5 (DR5), which promoted ubiquitination and degradation of DR5. We further showed that ASB3 knockdown stabilized DR5 and increased the sensitivity of liver cancer cells to the treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a DR5-dependent manner in cellular and in animal models. In summary, we demonstrated that ASB3 promoted ubiquitination and degradation of DR5 in HCC, suggesting the potential of targeting ASB3 to HCC treatment and overcome TRAIL resistance.

Data-Driven Evolutionary Design of Multienzyme-like Nanozymes.

Multienzyme-like nanozymes are nanomaterials with multiple enzyme-like activities and are the focus of nanozyme research owing to their ability to facilitate cascaded reactions, leverage synergistic effects, and exhibit environmentally responsive selectivity. However, multienzyme-like nanozymes exhibit varying enzyme-like activities under different conditions, making them difficult to precisely regulate according to the design requirements. Moreover, individual enzyme-like activity in a multienzyme-like activity may accelerate, compete, or antagonize each other, rendering the overall activity a complex interplay of these factors rather than a simple sum of single enzyme-like activity. A theoretically guided strategy is highly desired to accelerate the design of multienzyme-like nanozymes. Herein, nanozyme information was collected from 4159 publications to build a nanozyme database covering element type, element ratio, chemical valence, shape, pH, etc. Based on the clustering correlation coefficients of the nanozyme information, the material features in distinct nanozyme classifications were reorganized to generate compositional factors for multienzyme-like nanozymes. Moreover, advanced methods were developed, including the quantum mechanics/molecular mechanics method for analyzing the surface adsorption and binding energies of substrates, transition states, and products in the reaction pathways, along with machine learning algorithms to identify the optimal reaction pathway, to aid the evolutionary design of multienzyme-like nanozymes. This approach culminated in creating CuMnCo7O12, a highly active multienzyme-like nanozyme. This process is named the genetic-like evolutionary design of nanozymes because it resembles biological genetic evolution in nature and offers a feasible protocol and theoretical foundation for constructing multienzyme-like nanozymes.

Multienzyme-Like Nanozyme Encapsulated Ocular Microneedles for Keratitis Treatment.

Keratitis, an inflammation of the cornea caused by bacterial or fungal infections, is one of the leading causes of severe visual disability and blindness. Keratitis treatment requires both the prevention of infection and the reduction of inflammation. However, owing to their limited therapeutic functions, in addition to the ocular barrier, existing conventional medications are characterized by poor efficacy and low bioavailability, requiring high dosages or frequent topical treatment, which represents a burden on patients and increases the risk of side effects. In this study, manganese oxide nanocluster-decorated graphdiyne nanosheets (MnOx/GDY) are developed as multienzyme-like nanozymes for the treatment of infectious keratitis and loaded into hyaluronic acid and polymethyl methacrylate-based ocular microneedles (MGMN). MGMN not only exhibits antimicrobial and anti-inflammatory effects owing to its multienzyme-like activities, including oxidase, peroxidase, catalase, and superoxide dismutase mimics but also crosses the ocular barrier and shows increased bioavailability via the microneedle system. Moreover, MGMN is demonstrated to eliminate pathogens, prevent biofilm formation, reduce inflammation, alleviate ocular hypoxia, and promote the repair of corneal epithelial damage in in vitro, ex vivo, and in vivo experiments, thus providing a better therapeutic effect than commercial ophthalmic voriconazole, with no obvious microbial resistance or cytotoxicity.

Collagen peptides from sturgeon swim bladder prolong the lifespan and healthspan in Caenorhabditis elegans.

BACKGROUND: Sturgeon is a popular aquaculture species in many countries. Its swim bladder is rich in collagen but has not yet been exploited scientifically. RESULTS: Collagen peptides (CPs) prepared from sturgeon swim bladder by trypsinolysis had an average molecular weight of 528.5 Da and consisted of 407 peptides, 16.1% of the content of which was GFPGADGSAGPK. The CPs at 25 mg mL-1 extended the lifespan of Caenorhabditis elegans by 22.6%, which was significantly higher than the extension achieved by other hydrolysis methods and source materials. They also improved fitness-related traits (body size, motor capacity, oxidative stress, cell apoptosis, and epidermal barrier function), indicating prolonged healthspan. Transcriptome analysis showed that the effect was mediated by the mitogen-activated protein kinase pathway, which enhanced stress resistance, the insulin/IGF-1 pathway, which inhibited protein aggregation, and the NHR-80/FAT-6 pathway, which regulated lipid metabolism. CONCLUSION: Collagen peptides from sturgeon swim bladder by trypsinolysis prolonged the lifespan and healthspan in C. elegans, and might be promising anti-aging agents. © 2024 Society of Chemical Industry.

Piezoelectric Effect Modulates Nanozyme Activity: Underlying Mechanism and Practical Application.

Nanozyme activity relies on surface electron transfer processes. Notably, the piezoelectric effect plays a vital role in influencing nanozyme activity by generating positive and negative charges on piezoelectric materials' surfaces. This article comprehensively reviews the potential mechanisms and practical applications of regulating nanozyme activity through the piezoelectric effect. The article first elucidates how the piezoelectric effect enables nanozymes to exhibit catalytic activity. It is highlighted that the positive and negative charges produced by this effect directly participate in redox reactions, leading to the conversion of materials from an inactive to an active state. Moreover, the piezoelectric field generated can enhance nanozyme activity by accelerating electron transfer rates or reducing binding energy between nanozymes and substrates. Practical applications of piezoelectric nanozymes are explored in the subsequent section, including water pollutant degradation, bacterial disinfection, biological detection, and tumor therapy, which demonstrate the versatile potentials of the piezoelectric effect in nanozyme applications. The review concludes by emphasizing the need for further research into the catalytic mechanisms of piezoelectric nanozymes, suggesting expanding the scope of catalytic types and exploring new application areas. Furthermore, the promising direction of synergistic catalytic therapy is discussed as an inspiring avenue for future research.

Effect of online intervention mode on breastfeeding results: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of Internet based intervention model on breastfeeding knowledge, attitude, self-confidence and breastfeeding rate. METHODS: An electronic literature search of PubMed, Embase, Web of Science, Cochrane Library, CINAHL, CNKI, Wanfang, CBM and VIP database was performed using combinations of the keywords "Breastfeeding," "Breastfeeding, Exclusive," "Internet," "Online," and "Website". The retrieval period was from their inception to March 31, 2023. Quality appraisal was performed using the Cochrane 5.1 for randomized controlled trials (RCTs). RevMan5.3 was used for data analysis. RESULTS: Thirty-two studies were included in the review, with a total of 9514 samples. The results of Meta-analysis showed that, compared with routine nursing, the intervention model based on the Internet can effectively improve breastfeeding knowledge and attitude of pregnant women, improve breastfeeding self-confidence (P < 0.05), and improve the rate of exclusive breastfeeding in the short term (within 6 weeks) and the long-term postpartum (3-6 months) had a positive effect on the rate of exclusive breastfeeding (P < 0.05). CONCLUSIONS: The Internet breastfeeding intervention model may be an effective intervention to improve the effect of exclusive breastfeeding. In the future, more high-quality, large-sample randomized controlled trials can be carried out to further explore the effect of the Internet intervention model on breastfeeding.

Telocytes and endometriosis.

Endometriosis involving the presence and growth of glands and stroma outside the uterine cavity is a common, inflammatory, benign gynecologic disease. Nevertheless, no single theory can exactly account for the pathogenesis of endometriosis. Telocytes, a kind of novel mesenchymal cells, have been suggested to be crucial in promoting angiogenesis and increasing the activity of endometrial interstitial cells and inflammatory cells. Given above roles, telocytes may be considered as the possible pathogenesis of endometriosis. We reviewed the current literature on telocytes. The following aspects were considered: (A) the telocytes' typical characteristics, function, and morphological changes in endometriosis; (B) the potential role of telocytes in endometriosis by impacting the inflammation, invasion, and angiogenesis; (C) telocytes as the potential treatment options for endometriosis.

Machine Learning Guided Discovery of Superoxide Dismutase Nanozymes for Androgenetic Alopecia.

Androgenetic alopecia (AGA) is a common form of hair loss, which is mainly caused by oxidative stress induced dysregulation of hair follicles (HF). Herein, a highly efficient manganese thiophosphite (MnPS3) based superoxide dismutase (SOD) mimic was discovered using machine learning (ML) tools. Remarkably, the IC50 of MnPS3 is 3.61 µg·mL-1, up to 12-fold lower than most reported SOD-like nanozymes. Moreover, a MnPS3 microneedle patch (MnMNP) was constructed to treat AGA that could diffuse into the deep skin where HFs exist and remove excess reactive oxygen species. Compared with the widely used minoxidil, MnMNP exhibits higher ability on hair regeneration, even at a reduced frequency of application. This study not only provides a general guideline for the accelerated discovery of SOD-like nanozymes by ML techniques, but also shows a great potential as a next generation approach for rational design of nanozymes.

Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis.

Iron overload and oxidative stress have been reported to contribute to ferroptosis in endometriotic lesions. However, the possible roles of iron overload on macrophages in endometriosis (EMs) remain unknown. Based on recent reports by single-cell sequencing data of endometriosis, here we found significant upregulations of ferroptosis-associated genes in the macrophage of the endometriotic lesion. Additionally, there was an elevated expression of HMOX1, FTH1, and FTL in macrophages of peritoneal fluid in EMs, as well as iron accumulation in the endometriotic lesions. Notably, cyst fluid significantly up-regulated levels of intracellular iron and ferroptosis in Phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. Additionally, high iron-induced ferroptosis obviously reduced PMA-stimulated THP-1 cells' phagocytosis and increased the expression of angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8). Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of EMs by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA). Baicalein displays the potential for the treatment of EMs, especially in patients with high ferroptosis and low phagocytosis of macrophages.

Ultrathin Graphdiyne/Graphene Heterostructure as a Robust Electrochemical Sensing Platform.

Graphdiyne (GDY) has been considered as an appealing electrode material for electrochemical sensing because of its alkyne-rich structure and high degrees of π-conjugation, which shows great affinity to heavy metal ions and pollutant molecules via d-π and π-π interactions. However, the low surface area and poor conductivity of bulk GDY limit its electrochemical performance. Herein, a two-dimensional ultrathin GDY/graphene (GDY/G) nanostructure was synthesized and used as an electrode material for electrochemical sensing. Graphene plays the role of an epitaxy template for few-layered GDY growth and conductive layers. The formed few-layered GDY with a high surface area possesses abundant affinity sites toward heavy metal ions (Cd2+, Pb2+) and toxic molecules, for example, nitrobenzene and 4-nitrophenol, via d-π and π-π interactions, respectively. Moreover, hemin as a key part of the enzyme catalytic motif was immobilized on GDY/G via π-π interactions. The artificial enzyme mimic hemin/GDY/G-modified electrode exhibited promising ascorbic acid and uric acid detection performance with excellent sensitivity and selectivity, a good linear range, and reproducibility. More importantly, real sample detection and the feasibility of this electrochemical sensor as a wearable biosensor were demonstrated.

Silver Peroxide Nanoparticles for Combined Antibacterial Sonodynamic and Photothermal Therapy.

Metal peroxide nanoparticles designed to elevate the oxidative stress are considered a promising nanotherapeutics in biomedical applications, including chemotherapy, photodynamic therapy, and bacterial disinfection. However, their lack of specificity towards the therapeutic target can cause toxic side effects to healthy tissues. Here, silver peroxide nanoparticles (Ag2 O2 NPs) capable of controlled reactive oxygen species (ROS) release are synthesized. The release of bactericidal Ag+ ions and ROS is strictly regulated by external stimuli of ultrasound (US) and near-infrared (NIR) light. In vitro and in vivo investigations show that the Ag2 O2 NPs present enhanced antibacterial and antibiofilm capabilities with a killing efficiency >99.9999% in 10 min, significantly accelerate multi-drug resistant Staphylococcus aureus infected skin wound closure with excellent cytocompatibility and hemocompatibility. This work not only provides the first paradigm for fabricating silver peroxide nanoparticle but also introduces a highly efficient noninvasive and safe therapeutic modality for combating bacterial infectious diseases.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IA1 with LVSI, IA2): study protocol of the LAUNCH 1 trial.

BACKGROUND: A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial. METHODS: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life. DISCUSSION: The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04934982 , Registered on 22 June 2021).

Analysis of Cross-Reactivity and Allergic Symptoms of 19 Allergens: Results from NHANES 2005-2006.

INTRODUCTION: We explored the cross-reactivity among 19 common allergen sources and evaluated the influence of serum IgE concentrations and the number of sensitized allergens on the incidence of allergic symptoms. METHODS: We conducted this cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 which is a program of studies designed to assess the health and nutritional status of adults and children in the USA. After excluding participants with missing data from the allergen IgE test, allergy questionnaire, and respiratory health questionnaire, a total of 7,224 participants aged 6 years and older were included, as children younger than 6 years old did not complete all 19 allergen-specific IgE tests. Spearman correlation analysis was used to analyze the cross-reactivity between allergen sources. An independent sample Kruskal-Wallis test was performed to investigate the relationship between the serum-specific IgE levels of 19 allergens and the incidence of allergic symptoms. RESULTS: The cross-reactivity between D. farinae and D. pteronyssinus was the strongest (ρ = 0.88), and cross-reactivity of cross-species was universal. With the increase in serum-specific IgE levels of D. farinae, D. pteronyssinus, oak, and birch, the incidence of sneezing increased (p < 0.05). With the increase in serum-specific IgE levels of cats, dogs, peanuts, Aspergillus, and Alternaria, the incidence of wheezing increased (p < 0.05). The incidence of rash was positively correlated with serum-specific IgE levels of D. farinae, D. pteronyssinus, shrimp, and peanut (p < 0.05). The incidence of wheezing continued to increase with an increase in sensitized allergens. When participants were sensitized to <10 allergens, the incidence of sneezing continued to increase as the number of sensitized allergens increased, whereas the incidence of rash did not have a clear association with the number of sensitized allergens. CONCLUSION: Species that are biologically close are more likely to have antigen cross-reactivity, while cross-reactivity among different species is common. Different allergens tend to cause different allergic symptoms. Different allergic sites in the body have inconsistent responses to the number of sensitized allergens.

Anatomical Partition-Based Deep Learning: An Automatic Nasopharyngeal MRI Recognition Scheme.

BACKGROUND: Training deep learning (DL) models to automatically recognize diseases in nasopharyngeal MRI is a challenging task, and optimizing the performance of DL models is difficult. PURPOSE: To develop a method of training anatomical partition-based DL model which integrates knowledge of clinical anatomical regions in otorhinolaryngology to automatically recognize diseases in nasopharyngeal MRI. STUDY TYPE: Single-center retrospective study. POPULATION: A total of 2485 patients with nasopharyngeal diseases (age range 14-82 years, female, 779[31.3%]) and 600 people with normal nasopharynx (age range 18-78 years, female, 281[46.8%]) were included. SEQUENCE: 3.0 T; T2WI fast spin-echo sequence. ASSESSMENT: Full images (512 × 512) of 3085 patients constituted 100% of the dataset, 50% and 25% of which were randomly retained as two new datasets. Two new series of images (seg112 image [112 × 112] and seg224 image [224 × 224]) were automatically generated by a segmentation model. Four pretrained neural networks for nasopharyngeal diseases classification were trained under the nine datasets (full image, seg112 image, and seg224 image, each with 100% dataset, 50% dataset, and 25% dataset). STATISTICAL TESTS: The receiver operating characteristic curve was used to evaluate the performance of the models. Analysis of variance was used to compare the performance of the models built with different datasets. Statistical significance was set at P < 0.05. RESULTS: When the 100% dataset was used for training, the performances of the models trained with the seg112 images (average area under the curve [aAUC] 0.949 ± 0.052), seg224 images (aAUC 0.948 ± 0.053), and full images (aAUC 0.935 ± 0.053) were similar (P = 0.611). When the 25% dataset was used for training, the mean aAUC of the models that were trained with seg112 images (0.823 ± 0.116) and seg224 images (0.765 ± 0.155) was significantly higher than the models that were trained with full images (0.640 ± 0.154). DATA CONCLUSION: The proposed method can potentially improve the performance of the DL model for automatic recognition of diseases in nasopharyngeal MRI. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.

Retracted: Mukonal Inhibits Cell Proliferation, Alters Mitochondrial Membrane Potential and Induces Apoptosis and Autophagy in Human CNE1 Nasopharyngeal Carcinoma Cells.

Retracted, due to breach of publishing guidelines, following the identification of non-original content. Reference: Mukonal Inhibits Cell Proliferation, Alters Mitochondrial Membrane Potential and Induces Apoptosis and Autophagy in Human CNE1 Nasopharyngeal Carcinoma Cells Yingyuan Guo, Yanru Hao, Guofang Guan, Shuaishuai Ma, Zhiling Zhu, Fang Guo, Jie Bai Med Sci Monit 2019; 25:1976-1983 10.12659/MSM.913915.

Antibacterial Activity of Graphdiyne and Graphdiyne Oxide.

From manufacture to disposal, the interaction of graphdiyne based nanomaterials with living organisms is inevitable and crucial. However, the cytotoxic properties of this novel carbon nanomaterial are rarely investigated, and the mechanisms behind their cytotoxicity are totally unknown. In this study, the antibacterial activity of graphdiyne (GDY) and graphdiyne oxide (GDYO) is reported. GDY is capable of inhibiting broad-spectrum bacterial growth while exerting moderate cytotoxicity on mammalian cells. In comparison, GDYO exhibits lower antibacterial activity than that of GDY. Then an alterable, synergetic antibacterial mechanism of GDY, involving wrapping bacterial membrane, membrane insertion and disruption, and reactive oxygen species generation is demonstrated, while the differential gene expression analysis indicates that GDY could only alter the bacterial metabolism slightly and the oxidative stress route may be a minor bactericidal factor. The investigation of the antibacterial behaviors of GDY based nanomaterials may provide useful guidelines for the future design and application of this novel molecular allotrope of carbon.

Subsequent monitoring of ferric ion and ascorbic acid using graphdiyne quantum dots-based optical sensors.

Graphdiyne (GDY) as an emerging carbon nanomaterial has attracted increasing attention because of its uniformly distributed pores, highly π-conjugated, and tunable electronic properties. These excellent characteristics have been widely explored in the fields of energy storage and catalysts, yet there is no report on the development of sensors based on the outstanding optical property of GDY. In this paper, a new sensing mechanism is reported built upon the synergistic effect between inner filter effect and photoinduced electron transfer. We constructed a novel nanosensor based upon the newly-synthesized nanomaterial and demonstrated a sensitive and selective detection for both Fe3+ ion and ascorbic acid, enabling the measurements in real clinical samples. For the first time fluorescent graphdiyne oxide quantum dots (GDYO-QDs) were prepared using a facile ultrasonic protocol and they were characterized with a range of techniques, showing a strong blue-green emission with 14.6% quantum yield. The emission is quenched efficiently by Fe3+ and recovered by ascorbic acid (AA). We have fabricated an off/on fluorescent nanosensors based on this unique property. The nanosensors are able to detect Fe3+ as low as 95 nmol L-1 with a promising dynamic range from 0.25 to 200 µmol L-1. The LOD of AA was 2.5 µmol L-1, with range of 10-500 µmol L-1. It showed a promising capability to detect Fe3+ and AA in serum samples. Graphical abstract.

Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology.

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (KD, µM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 µM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.

Mukonal Inhibits Cell Proliferation, Alters Mitochondrial Membrane Potential and Induces Apoptosis and Autophagy in Human CNE1 Nasopharyngeal Carcinoma Cells.

BACKGROUND Nasopharyngeal carcinoma results in high patient morbidity and mortality, due to early metastasis, and toxicity due to chemotherapy. Mukonal is plant-derived carbazole alkaloid that has been used in traditional Chinese medicine to treat several types of cancer. This study aimed to investigate the effects of mukonal on cell proliferation, apoptosis, autophagy, and the mitochondrial membrane potential of nasopharyngeal carcinoma cells in vitro. MATERIAL AND METHODS CNE1 human nasopharyngeal carcinoma cells and NP69 normal nasopharyngeal epithelial cells were cultured with and without treatment with increasing doses of mukonal. Cell viability was determined by the MTT assay. Fluorescence microscopy was used to detect reactive oxygen species (ROS), mitochondrial membrane potential, and the release of cytochrome C. Flow cytometry was used to examine changes in the cell cycle, electron microscopy examined cell autophagy, and Western blot was performed to measure levels of proteins associated with autophagy and apoptosis. RESULTS Mukonal had an antiproliferative effect on CNE1 cells, with an IC50 of 9 µM and there were effects of toxicity on normal NP69 cells. Mukonal triggered ROS-mediated changes in mitochondrial membrane potential which was also accompanied by the discharge of cytochrome C in the CNE1 cells. Mukonal activated autophagy and apoptosis in CNE1 cells, which was also associated with upregulation of the autophagy-related proteins, LC3 II and beclin-1, as well as apoptosis-associated proteins, Bax, cleaved caspase-3 and -9. Mukonal treatment also resulted in CNE1 cells cycle arrest at G2/M. CONCLUSIONS Mukonal inhibited the growth of human CNE1 nasopharyngeal carcinoma cells in vitro.

Intranasal Vasopressin Relieves Orthopedic Pain After Surgery.

BACKGROUND: Orthopedic pain after surgery is very common and difficult to manage. Although intranasal arginine vasopressin (AVP) relieves headache (tension-type headache and migraine mostly), the effect of intranasal AVP on the orthopedic pain after surgery is unknown. AIMS: This study investigated the effect of intranasal AVP on orthopedic pain after surgery in a randomized controlled trial with a double-blind design. PARTICIPANTS: The study included 653 orthopedic patients and 661 health volunteers. METHODS: Orthopedic pain was analyzed by the visual analogue scales (VAS) and AVP concentration was determined by radioimmunoassay. RESULTS: (1) intranasal AVP decreased the VAS level in orthopedic patients 2-4 weeks after surgery in a dose-dependent manner; (2) the cerebrospinal fluid (CSF) AVP concentration in orthopedic patients after surgery was higher than that in the health volunteers (38.57 ± 6.11 pg/mL vs 11.74 ± 2.85 pg/mL, p < .01), but had no change in plasma (p > .05); (3) CSF AVP concentration increased significantly in orthopedic patients during 24 hours after the intranasal AVP (p < .05 or .01), which related with VAS level negatively (all p < .01); (4) during 24 hours, intranasal AVP did not influence not only plasma AVP concentration, but also blood pressure, heart rate, respiratory rate and body temperature in orthopedic patients. COUCLUSIONS: The findings contribute valuable information that intranasal AVP can treat orthopedic pain after surgery, and AVP could be an option for pain relief by intranasal administration.