Release of Additives from Agricultural Plastic Films in Water: Experiment and Modeling.

Globally, more than 6 million metric tons of agricultural plastic films are used to increase crop yields and reduce the use of water and herbicides, resulting in the contamination of soil and water by plastic debris and additives. However, knowledge of the occurrence and release of additives from agricultural films is limited. In this study, suspect screening with high-resolution mass spectrometry, one-dimensional Fickian diffusion models, and linear free energy relationships (LFERs) were used to determine the occurrence and mass transfer of various additives from agricultural plastic films. A total of 89 additives were tentatively identified in 40 films, and 62 of them were further validated and quantified. The aqueous concentrations of 26 released additives reached mg L-1 after a 28 day incubation at 25 °C. Diffusion models and LFERs demonstrated that the film-water partition coefficient and the diffusivity in the polymer, the two critical parameters controlling the mass transfer, could be predicted using Abraham descriptors. The findings of this study highlighted the need for future research on the environmental fate and risk assessment of previously neglected additives in agricultural plastic films and other similar products.

Metal-organic framework materials promote neural differentiation of dental pulp stem cells in spinal cord injury.

Spinal cord injury (SCI) is accompanied by loss of Zn2+, which is an important cause of glutamate excitotoxicity and death of local neurons as well as transplanted stem cells. Dental pulp stem cells (DPSCs) have the potential for neural differentiation and play an immunomodulatory role in the microenvironment, making them an ideal cell source for the repair of central nerve injury, including SCI. The zeolitic imidazolate framework 8 (ZIF-8) is usually used as a drug and gene delivery carrier, which can release Zn2+ sustainedly in acidic environment. However, the roles of ZIF-8 on neural differentiation of DPSCs and the effect of combined treatment on SCI have not been explored. ZIF-8-introduced DPSCs were loaded into gelatin methacryloyl (GelMA) hydrogel and in situ injected into the injured site of SCI rats. Under the effect of ZIF-8, axon number and axon length of DPSCs-differentiated neuro-like cells were significantly increased. In addition, ZIF-8 protected transplanted DPSCs from apoptosis in the damaged microenvironment. ZIF-8 promotes neural differentiation and angiogenesis of DPSCs by activating the Mitogen-activated protein kinase (MAPK) signaling pathway, which is a promising transport nanomaterial for nerve repair.

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models.

BACKGROUND: Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. METHODS: The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. RESULTS: DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. CONCLUSIONS: DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.

Unveiling interactions of norfloxacin with microplastic in surface water by 2D FTIR correlation spectroscopy and X-ray photoelectron spectroscopy analyses.

Microplastics (MPs) has shown adsorption of hydrophilic organic matters (HOMs) in aqueous environments. However, it is still difficult to predict the adsorption behaviors of HOMs by different MPs, especially in authentic water systems. In this study, the adsorption behaviors and mechanisms of norfloxacin (NOR) onto polyamide (PA) MPs were investigated in both simulated and real surface water. The results showed that the adsorption equilibrium of NOR by PA in simulated surface water could be achieved within 15 h, while the adsorption rate of NOR in real surface was slowed down, with the equilibrium time of 25 h. Pseudo-second-order model could well describe the adsorption kinetics data. The experimental maximum adsorption capacity of NOR on PA in real surface water (e. g. 132.54 ug/g) was dramatically reduced by 37.5 % compared with that in simulated surface water (e. g. 212.25 ug/g), and the adsorption isotherm would obey Freundlich model. Besides, the leaching of NOR from the surface of PA could occur obviously at acidic environment. Furthermore, the salinity and natural organic matter exhibited significantly adverse effects on the NOR adsorption. Finally, the results of 2D Fourier transform infrared correlation spectroscopy and X-ray photoelectron spectroscopy indicated that the electrostatic, H-bond and van der Waals interactions were involved in the adsorption. More importantly, the sequential functional groups in the adsorption process followed the orders: 1638 (CO) > 1542 amide II (-NH-CO) > 717 (CH2) > 1445 (CO) > 973 amide IV (CONH). This study could provide an insight into the interactions between PA and NOR in different water environments.

Dronabinol inhibits alveolar bone remodeling in tooth movement of rats.

INTRODUCTION: Orthodontic tooth movement is reliant on the process of bone remodeling, and a variety of medications impact the ability of teeth to move through bone. Marijuana is the most widely used recreational drug in the world, and early studies suggest the drug impacts bone remodeling as tetrahydrocannabinol binds to cannabinoid receptors which play a role in bone homeostasis. This study aimed to assess the impact of dronabinol on alveolar bone remodeling in rats with otherwise healthy tissue when subjected to orthodontic forces. METHODS: Thirty male Sprague Dawley rats were equally allocated into 2 groups. Orthodontic appliances were placed in all animals, which consisted of a nickel-titanium coil ligated from the maxillary first molar to the central incisor. The appliance was activated to deliver a force to move teeth together. Over 21 days, daily injections of either dronabinol or the control (solvent) were given to the rats. Cephalometric analysis, histology, and bone remodeling profiles of both groups were analyzed and compared. RESULTS: Teeth moved in both the dronabinol and control groups (P <0.05). Tooth movement in the control group followed the typical process of orthodontic tooth movement: periodontal width narrowing and bone resorption on the compression side of the tooth, with an overall decrease in the height of the alveolar bone. In contrast, the dronabinol group showed an abnormal response to tooth movement: no bone resorption on the compression side of the tooth, increased bone formation on the tension side, and the maintenance of the height of the alveolar crest. In the dronabinol group, there were also significantly more osteoclasts and osteoblasts in the alveolar bone than in the control group. CONCLUSIONS: These results demonstrate that dronabinol attenuates orthodontic tooth movement by decreasing bone resorption, which could have implications for other bone-related recovery processes.

Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

Pretreatment quality of life as a predictor of survival for patients with nasopharyngeal carcinoma treated with IMRT.

BACKGROUND: To evaluate the prognostic significance of pretreatment quality of life for patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy. METHODS: We performed a prospective, longitudinal study on 554 newly diagnosed patients with NPC from April 2011 to January 2015. A total of 501 consecutive NPC patients were included. Patients were asked to complete the EORTC QLQ-C30 (version 3.0) and QLQ-H&N35 questionnaires before treatment. RESULTS: Global health status among QLQ-C30 correlates with EBV DNA(P = 0.019). In addition, pretreatment appetite loss was significantly correlated with EBV DNA(P = 0.02). Pretreatment teeth, opening mouth, feeding tube was significantly correlated with EBV DNA, with P value of 0.003, < 0.0001, and 0.031, respectively. In multivariate analysis, pretreatment cognitive functioning of QLQ-C30 was significantly associated with LRFS, with HR of 0.971(95%CI 0.951-0.990), P = 0.004. Among scales of QLQ-H&N35 for multivariate analysis, pretreatment teeth (P = 0.026) and felt ill (P = 0.012) was significantly associated with PFS, with HR of 0.984 (95%CI 0.971-.998) and 1.004 (95%CI 1.001-1.007), respectively. Felt ill of QLQ-H&N35 was significantly associated with DMFS, with HR of 1.004(95%CI 1.000-1.007), P = 0.043. There is no QoL scale significantly associated with OS after multivariate analysis. CONCLUSIONS: In conclusion, our analysis confirms that pretreatment teeth and felt ill was significantly associated with PFS in NPC patients treated with IMRT. In addition, the posttreatment EBV DNA was significantly associated with OS.

Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells.

Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC50 values of CD20-SA-NPs were reduced to 5.7 and 2.6 µg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg-1·d-1, iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.

An outbreak of Coxsackievirus A6-associated hand, foot, and mouth disease in a kindergarten in Beijing in 2015.

BACKGROUND: Coxsackievirus A6 (CVA6) is one of the major agents to cause hand, foot and mouth disease (HFMD) outbreaks globally. The objective of this study is to investigate the epidemiologic and clinical manifestations of CVA6 outbreak, and thus guide the diagnosis and treatment of the disease, as well as disease prevention. METHODS: An HFMD outbreak in a kindergarten was reported to Shijingshan District Center for Disease Control and Prevention (SCDC) on November 2, 2015 in Beijing, China. Epidemiological investigation was conducted. We performed a nine-week follow-up study to collect and analyze the clinical manifestations of HFMD cases. RESULTS: The outbreak yield 56 (15.7%) clinical diagnosed HFMD cases out of 357 registered children in the kindergarten with the mean age of 3.5 years old. This outbreak lasted for three days and ceased after initiating infectious disease controlling procedures, including periodical suspension of the kindergarten activities, environmental disinfection, and family health education. Fifty-one cases were followed for nine weeks. The positive rate of clinical manifestations of rash, fever, desquamation, pigmentation and onychomadesis were 100.0%, 84.3%, 68.6%, 17.6% and 43.1%, respectively. Children developed desquamation within the first 4 weeks after disease onset and developed onychomadesis between the 3th and 8th week after disease onset. Children with desquamation had 9.3 (95%CI: 1.836-47.437) times higher odds of developing onychomadesis compared to those without this manifestation. Ten out of 14 collected samples were CVA6 positive, and five positive samples shared a high degree of similarity in the VP1 nucleotide and amino acid sequences (99.9-100.0% and 100%). CONCLUSION: This HFMD outbreak was caused by CVA6, featured with delayed symptoms. Emerging CVA6-associated HFMD and its delayed symptoms should be paid more attention to reduce outbreaks and provide more information to doctors and parents.

Relationship Between the Comprehensive Nutritional Index and the EORTC QLQ-H&N35 in Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiation Therapy.

This study aimed to explore the relationship between the comprehensive nutritional index (CNI) and quality of life in nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiation therapy (IMRT). The nutritional index, which includes total lymphocyte count, hemoglobin and albumin levels, body mass index, and usual body weight percentage, was evaluated pre-treatment and post-treatment in patients who underwent IMRT. The quality of life of NPC patients was measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Cancer Module (EORTC QLQ-H&N35) at four time points: pre-treatment, post-treatment, and 3 and 6 mo after IMRT. A comprehensive nutritional model was used to assess the correlation with QLQ-H&N35. The nutritional index decreased significantly post-treatment. The CNI was associated with immunotherapy; the International Union Against Cancer (UICC) stage; concurrent chemotherapy; speech problems, trouble with social contact, feeling ill and having dental problems at pre-treatment; sexuality at 3 mos post-treatment; and sensory problems and xerostomia at 6 mo post-treatment (P < 0.05). The nutritional status and QLQ-H&N35 scores in NPC patients decreased during IMRT. Our study provides an alternative measure of the CNI to improve the QLQ-H&N35 evaluation system for patients with NPC.

Individualized intervention to reduce anxiety in adult orthodontic patients based on Q methodology.

INTRODUCTION: In this study, we used Q methodology to assess the concerns of adults seeking orthodontic treatment and to determine individualized interventions to reduce their anxiety. METHODS: Statements of concern were derived by in-depth interviews with 70 adult patients. Q sorting methodology was then used to identify the main factors associated with anxiety in a cohort of 40 adults who had not been involved in the first part of the study. The final stage involved a randomized study in which 160 new adult patients were recruited and randomized into intervention and control groups. Participants in the intervention group sorted the statements, after which individualized interventions were implemented. Participants in the control group received routine treatment. The State-Trait Anxiety Inventory was used to measure changes in participants' anxiety levels before and during treatment. RESULTS: In total, 41 statements were identified, and participants were classified according to 5 factors. Factor 1 participants were concerned about the lack of treatment information; factor 2 represented concerns about cost and other people's opinions; factor 3 represented concerns about impact on work related to wearing braces; factor 4 encompassed concerns about treatment effects, pain, and dental fears; and factor 5 reflected concerns about side effects and finding a partner. The mean state anxiety inventory scores for both the intervention and control groups were highest 24 hours after bonding (intervention group, 44.63 ± 4.49; control group, 49.43 ± 5.42). The intragroup state anxiety inventory scores differed significantly across the 6 time points (P <0.01), with the state anxiety inventory scores of the intervention group significantly lower than those of the control group (P <0.01) at all time points except baseline. No significant intergroup or intragroup differences were found in relation to trait anxiety. CONCLUSIONS: Adult orthodontic patients expressed diverse concerns. Individualized interventions based on Q methodology may reduce anxiety in this patient population.

Psychosocial impact of dental esthetics regulates motivation to seek orthodontic treatment.

INTRODUCTION: The aim of this study was to evaluate the psychosocial impact of dental esthetics for adults seeking orthodontic treatment. METHODS: The Chinese version of the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) was administered to 393 adults, aged 18 to 30 years. The participants were divided into 2 groups: an intervention group (received orthodontic treatment) and a control group (rejected orthodontic treatment). Baseline malocclusion severity was assessed using the Index of Orthodontic Treatment Need (IOTN). RESULTS: The Wilcoxon signed rank test showed no statistically significant difference between the groups for the dental health component (DHC) of the IOTN (P = 0.134). Total and subscale PIDAQ scores of the intervention group were higher than those of the control group and differed significantly in each group among the 4 IOTN-DHC grades; self-confidence scores in the control group (F = 1.802; P >0.05) were the exception. Correlations between the PIDAQ scores and the IOTN-DHC grades were strong in each group. DHC grades, psychological impact, social impact, and aesthetic concern had significant impacts on patients accepting orthodontic treatment. CONCLUSIONS: The psychosocial impact of dental esthetics played an important role in the decision-making process of adults seeking orthodontic treatment. Importantly, participants with low self-awareness of the potential psychosocial impact rejected orthodontic treatment, despite the need for severe normative treatment.

Preparation and evaluation of a novel bioactive glass/lysozyme/PLGA composite microsphere.

OBJECTIVE: The objective of this study was to fabricate a novel nano-bioceramics incorporated lysozyme poly (d, l-lactide-co-glycolide) (PLGA) microsphere. METHODS: The nano-bioceramics was used as a biodegradable and sustained-release antacid to stabilize the lysozyme in the drug release process. First, the nano-bioceramics were prepared by sol-gel method, and then were characterized by energy dispersive X-ray analysis, dynamic light scattering and in vitro degradation test. Second, the lysozyme PLGA microsphere incorporated with nano-bioceramic was fabricated by the S/W/O/W emulsion solvent evaporation method. The microsphere was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and UV circular dichroism (UV CD). Finally the in vitro drug release and bioactivity test was carried out. RESULTS: The composition of the nano-bioceramics was 58% SiO2, 36% CaO, 6% P2O5, and the average particle size was 295 nm. The nano-bioceramics incorporated lysozyme PLGA microspheres were prepared by the multi-emulsion method. The SEM results showed that the bioceramics was uniformly distributed in the PLGA microsphere. Results from in vitro lysozyme release test exhibited a prolonged release time for 1month. The FTIR and UVCD results suggested that the lysozyme in the drug release process had a similar secondary structure conformation to the native one. The Micrococcus lysodeikticus test showed that the microspheres incorporated with bioceramics provided long-term protein stability against the acidic environment resulted from PLGA's degradates and more than 90% of the lysozyme released over the 1 month period was preserved in a bioactive form. CONCLUSION: A novel bioceramics incorporated lysozyme PLGA microsphere was prepared with potentials for sustained protein release formulation.

Sensitive and selective detection of copper ions with highly stable polyethyleneimine-protected silver nanoclusters.

Copper is a highly toxic environmental pollutant with bioaccumulative properties. Therefore, sensitive Cu(2+) detection is very important to prevent over-ingestion, and visual detection using unaugmented vision is preferred for practical applications. In this study, hyperbranched polyethyleneimine-protected silver nanoclusters (hPEI-AgNCs) were successfully synthesized using a facile, one-pot reaction under mild conditions. The hPEI-AgNCs were very stable against extreme pH, ionic strength, temperature, and photoillumination and could act as sensitive and selective Cu(2+) sensing nanoprobes in aqueous solutions with a 10 nM limit of detection. In addition, hPEI-AgNCs-doped agarose hydrogels were developed as an instrument-free and regenerable platform for visual Cu(2+) and water quality monitoring.

PVP and surfactant combined carrier as an effective absorption enhancer of poorly soluble astilbin in vitro and in vivo.

CONTEXT: Astilbin is considered to be a new and promising immunosuppressant for immune related diseases, but limited in clinical application due to its poor water solubility, difficult oral absorption and low bioavailability. OBJECTIVE: The present work studied the effect of PVP and surfactant combined carrier on its capability to improve drug absorption. MATERIALS AND METHODS: PVP K30-Tween 80 combined carries was applied into the astilbin solid dispersions, tested both in vivo in beagle dogs and in vitro in transport experiments across Caco-2 cell monolayers. RESULTS AND DISCUSSION: In the animal studies a many fold increase in plasma AUC was observed for the solid dispersions of drug in PVP K30-Tween 80 combined carries compared to active pharmaceutical ingredient (API). The applicability of Caco-2 monolayers as a tool for predicting the in vivo transport behavior of Astilbin in combination with a solubility enhancing carries was shown. In vitro transport studies confirmed the effect of combined carries on the absorption behavior of the astilbin. MTT studies showed the cell viability gradually decreased with the increase of the drug concentration in a dose dependent manner for astilbin and that in solid dispersions. The permeability and apparent permeability coefficients (Papp) increased with drug in the Caco-2 cell. CONCLUSION: In this study, it was found that PVP K30 and Tween 80 promoted the permeability of drugs best within a certain amount. For astilbin PVP K30 and surfactant combined carrier had a strong potential to improve oral bioavailability.

Preparation and characterization of curcumin thermosensitive hydrogels for intratumoral injection treatment.

OBJECTIVES: This paper describes the development and optimization of curcumin thermosensitive hydrogels (CTH), a kind of gel injection for intratumoral injection treatment. METHODS: Aimed at increasing the content and stability of effective components, an optimal formulation of CTH was chosen based on the results from orthogonal tests and the optimal pH was determined by stability test. To investigate the hydrogels drug release in vitro, residence time by RP-HPLC and therapeutic effects on ascitic hepatocarcinoma cell strain with high metastasis potential in lymphatic system (HCA-F) solid tumors in mice. KEY FINDINGS: The selected optimal formulation of CTH was: 0.2% curcumin, 20% poloxamer 407, 4% poloxamer 188, 8% polyethylene glycol 400, 12% 1,2-propanediol and pH was 6.0. The drug release determined by RP-HPLC fit to the Higuchi model. The residence time of CTH was longer than the curcumin suspensions. Intratumoral injection of the CTH can effectively inhibit the growth of HCA-F solid tumors in mice. CONCLUSIONS: The CTH prepared in this test demonstrates proper gel temperature and viscosity. It improves the solubility of curcumin with a relatively long period of drug release in vitro and residence time. Intratumoral injection of the CTH can effectively inhibit the growth of HCA-F solid tumors in mice.

Elevated Level of PINK1/Parkin-Mediated Mitophagy Pathway Involved to the Inhibited Activity of Mitochondrial Superoxide Dismutase in Rat Brains and Primary Hippocampal Neurons Exposed to High Level of Fluoride.

To reveal the molecular mechanism of brain damage induced by chronic fluorosis, expression of PTEN-induced kinase 1 (PINK1)/parkin RBR E3 ubiquitin-protein ligase (Parkin)-mediated mitophagy pathway and activity of mitochondrial superoxide dismutase (SOD) were investigated in rat brains and primary cultured neurons exposed to high level of fluoride. Sprague-Dawley (SD) rats were treated with fluoride (0, 5, 50, and 100 ppm) for 3 and 6 months. The primary neurons were exposed to 0.4 mM (7.6 ppm) fluoride and thereafter treated with 100 nM rapamycin (a stimulator of mitophagy) or 50 µM 3-methyladenine (3-MA, an inhibitor of mitophagy) for 24 h. The expressions of PINK1/Parkin at the protein level and the activity of SOD in mitochondria of rat brains and cultured neurons were determined by Western blotting and biochemical method, respectively. The results showed that the rats exposed to fluoride exhibited different degrees of dental fluorosis. In comparison to controls, the expressions of PINK1 and Parkin were significantly higher in the rat brains and primary neurons exposed to high fluoride. In addition, a declined activity of mitochondrial SOD was determined. Interestingly, rapamycin treatment enhanced but 3-MA inhibited the changes of PINK1/Parkin pathway and SOD activity, and the correlations between the inhibited SOD activity and the elevated PINK1/Parkin proteins were observed. The results suggest that the inhibition of mitochondrial SOD activity induced by fluorosis may stimulate the expressions of mitophagy (PINK1/ Parkin) pathway to maintain the mitochondrial homeostasis.

Research progress on optimization of in vitro isolation, cultivation and preservation methods of dental pulp stem cells for clinical application.

Due to high proliferative capacity, multipotent differentiation, immunomodulatory abilities, and lack of ethical concerns, dental pulp stem cells (DPSCs) are promising candidates for clinical application. Currently, clinical research on DPSCs is in its early stages. The reason for the failure to obtain clinically effective results may be problems with the production process of DPSCs. Due to the different preparation methods and reagent formulations of DPSCs, cell characteristics may be affected and lead to inconsistent experimental results. Preparation of clinical-grade DPSCs is far from ready. To achieve clinical application, it is essential to transit the manufacturing of stem cells from laboratory grade to clinical grade. This review compares and analyzes experimental data on optimizing the preparation methods of DPSCs from extraction to resuscitation, including research articles, invention patents and clinical trials. The advantages and disadvantages of various methods and potential clinical applications are discussed, and factors that could improve the quality of DPSCs for clinical application are proposed. The aim is to summarize the current manufacture of DPSCs in the establishment of a standardized, reliable, safe, and economic method for future preparation of clinical-grade cell products.

Dietary habits and nutrition status in esophageal cancer patients after esophageal reconstruction.

Background: Surgery is the cornerstone of the treatment of esophageal cancer (EC). This study is to evaluate the dietary habits and nutrition status in EC patients who underwent esophagectomy followed by esophageal reconstruction. Methods: This retrospective study included patients with EC who underwent esophagectomy followed by esophageal reconstruction in the Department of Thoracic Surgery I of Peking University Cancer Hospital between February 2014 and December 2018. The primary outcomes were dietary habits and nutrition status. The secondary outcomes were gastrointestinal symptoms and quality of life (QoL). Results: A total of 346 patients were included. At 30 months after the operation, 90.2% of the patients had recovered to regular dietary habits, 72.8% of patients had a restored frequency of preoperative regular food intake, 2.3% of the patients ate more than six times a day, and 0.6% had semi-liquid food because of bad teeth. The nutrition status remained stable after 6 months postoperatively and recovered slightly 1 year after the surgery. At 30 months after the operation, the most common gastrointestinal symptoms were reflux (38.4%), dysphagia (15.3%), hoarseness (11.8%), abdominal distension (6.6%), diarrhea (2.9%), and nausea and vomiting (2.3%). According to the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-OG 25 (EORTC QLQ-OG 25), the factors that affected the life quality of patients during follow-up were anxiety, reflux, and dietary limitations. Conclusions: Most patients with EC who underwent esophageal reconstruction recovered to regular dietary habits and stable nutrition status, while some may still suffer from gastrointestinal symptoms, anxiety, and dietary limitations.