Significance of non-DLVO interactions on the co-transport of levofloxacin and titanium dioxide nanoparticles in porous media.

With the application of engineered nanomaterials and antibiotics in the fields of medicine, aerospace, new energy and agriculture, the associated contamination is detected widely in soil-groundwater systems. It is of great scientific and practical significance to deeply explore the environmental interface process between nanoparticles and antibiotics for the scientific assessment of environmental fate and ecological environmental risks, as well as the development of new composite pollution control technologies. In this study, the co-transport behaviors of positively charged titanium dioxide nanoparticles (TiO2-NPs) and negatively charged levofloxacin (LEV) in quartz sand (QS) are investigated in this study. The results show that TiO2-NPs hardly flow out when transported alone in the column because of its positive charge, which creates a strong attraction with the negatively charged quartz sand on the surface. When TiO2-NPs co-migrate with LEV in porous media, the presence of LEV promotes the transport of TiO2-NPs, while the presence of TiO2-NPs inhibits LEV transport. Non-XDLVO interactions based on molecular dynamics (MD) simulations can help explain the observed promotion and inhibition phenomena as well as the correlation between TiO2-NPs and LEV. The results indicate that TiO2-LEV complexes or aggregates can be formed during the co-transportation process of TiO2-NPs and LEV in porous media. As flow velocity increases from 0.204 cm min-1 to 1.630 cm min-1, both the transport capacities of TiO2-NPs and LEV are enhanced significantly. Under the condition of high citric acid (CA) concentration (15 mmol L-1), the transport capacity of TiO2-NPs is slightly inhibited, while the transport capacity of LEV is enhanced. This study provides new insights into the transport of nanometallic oxides and antibiotics in porous media, which suggests that non-XDLVO interactions should be considered together when assessing the environmental risks and fate of nanometallic oxides and antibiotics in soil-groundwater systems.

Unraveling the mechanisms behind sodium persulphate-induced changes in petroleum-contaminated aquifers' biogeochemical parameters and microbial communities.

Sodium persulphate (PS) is a highly effective oxidising agent widely used in groundwater remediation and wastewater treatment. Although numerous studies have examined the impact of PS with respect to the removal efficiency of organic pollutants, the residual effects of PS exposure on the biogeochemical parameters and microbial ecosystems of contaminated aquifers are not well understood. This study investigates the effects of exposure to different concentrations of PS on the biogeochemical parameters of petroleum-contaminated aquifers using microcosm batch experiments. The results demonstrate that PS exposure increases the oxidation-reduction potential (ORP) and electrical conductivity (EC), while decreasing total organic carbon (TOC), dehydrogenase (DE), and polyphenol oxidase (PO) in the aquifer. Three-dimensional excitation-emission matrix (3D-EEM) analysis indicates PS is effective at reducing fulvic acid-like and humic acid-like substances and promoting microbial metabolic activity. In addition, PS exposure reduces the abundance of bacterial community species and the diversity index of evolutionary distance, with a more pronounced effect at high PS concentrations (31.25 mmol/L). Long-term (90 d) PS exposure results in an increase in the abundance of microorganisms with environmental resistance, organic matter degradation, and the ability to promote functional genes related to biological processes such as basal metabolism, transmission of genetic information, and cell motility of microorganisms. Structural equation modeling (SEM) further confirms that ORP and TOC are important drivers of change in the abundance of dominant phyla and functional genes. These results suggest exposure to different concentrations of PS has both direct and indirect effects on the dominant phyla and functional genes by influencing the geochemical parameters and enzymatic activity of the aquifer. This study provides a valuable reference for the application of PS in ecological engineering.

Seroprevalence of five diarrhea-related pathogens in bovine herds of scattered households in Inner Mongolia, China between 2019 and 2022.

Bovine diarrhea is a multi-factorial disease and remains one of the biggest health problems in animal husbandry. The endemic trends of the main pathogens responsible for bovine diarrhea in Inner Mongolia have not been analyzed systematically before. Therefore, the purpose of this study was to estimate the prevalence of bovine diarrhea pathogens found in the scattered households of Inner Mongolia in China. Additionally, we assessed for differences in the prevalence of infection based on age and region, as well as determined local prevalence rates and the rates of mixed infections. Using a two-stage random sampling strategy, 3,050 serum samples were collected from 72 bovine herds in 11 leagues and cities in Inner Mongolia, and the positive rates of BVDV, BRV, BCoV, K99, and Mycobacterium paratuberculosis (M. paratuberculosis) antibodies in the samples were detected by ELISA to determine the epidemic trends and epidemic differences of the five pathogens in Inner Mongolia. The positive rates of antibodies based on serum samples were: BVDV, 18.79% (95% CI [17.44-20.22]); BRV, 12.39% (95% CI [11.27-13.61]); BCoV, 12.82% (95% CI [11.68-14.05]); K99, 13.80% (95% CI [12.62-15.07]); and M. paratuberculosis, 10.79% (95% CI [9.74-11.94]). The prevalence rates of BRV, BCoV and K99 at 0-2 months were significantly different from that at 2-6 months, 6-18 months and adult cattle (P < 0.05). The prevalence of BVDV and M. paratuberculosis was the highest in adult cattle, which was significantly different from that in other age groups (P < 0.05). Furthermore, obvious regional epidemiological differences among the five diseases were observed. There was a mixed infection of BRV+BCoV in each age stage, the highest mixed infection being BVDV+BRV+K99 at 0-2 months of age. Our results showed that the cattle of scattered households in the Inner Mongolia of China were endemicly infected with several important cattle pathogens. Most of the pathogens studied occurred between 0-2 months of age and were mixed infections, which greatly influences the health of the cattle and leads to economic loss. These findings are of practical significance for the future prevention and control of bovine diarrhea in the Inner Mongolia or other regions of China.

Mixotrophic denitrification process driven by lime sulfur and butanediol: Denitrification performance and metagenomic analysis.

Heterotrophic sulfur-based autotrophic denitrification is a promising biological denitrification technology for low COD/TN (C/N) wastewater due to its high efficiency and low cost. Compared to the conventional autotrophic denitrification process driven by elemental sulfur, the presence of polysulfide in the system can promote high-speed nitrogen removal. However, autotrophic denitrification mediated by polysulfide has not been reported. This study investigated the denitrification performance and microbial metabolic mechanism of heterotrophic denitrification, sulfur-based autotrophic denitrification, and mixotrophic denitrification using lime sulfur and butanediol as electron donors. When the influent C/N was 1, the total nitrogen removal efficiency of the mixotrophic denitrification process was 1.67 and 1.14 times higher than that of the heterotrophic and sulfur-based autotrophic denitrification processes, respectively. Microbial community alpha diversity and principal component analysis indicated different electron donors lead to different evolutionary directions in microbial communities. Metagenomic analysis showed the enriched denitrifying bacteria (Thauera, Pseudomonas, and Pseudoxanthomonas), dissimilatory nitrate reduction to ammonia bacteria (Hydrogenophaga), and sulfur oxidizing bacteria (Thiobacillus) can stably support nitrate reduction. Analysis of metabolic pathways revealed that complete denitrification, dissimilatory nitrate reduction to ammonia, and sulfur disproportionation are the main pathways of the N and S cycle. This study demonstrates the feasibility of a mixotrophic denitrification process driven by a combination of lime sulfur and butanediol as a cost-effective solution for treating nitrogen pollution in low C/N wastewater and elucidates the N and S metabolic pathways involved.

Quantification of two-site kinetic transport parameters of polystyrene nanoplastics in porous media.

In this study, a combination of column experiments, interface chemistry theory and transport model with two-site kinetics was used to systematically investigate the effect of pH on the transport of polystyrene nanoparticles (PSNPs) in porous media. The porous media containing quartz sand (QS) and three kinds of clay minerals (CMs)-kaolinite (KL), illite (IL) and montmorillonite (MT), was used in column experiments to simulate the porous media in the soil-groundwater systems. Experimental results showed that the inhibitory effect of CMs on the transport of PSNPs is weakened as pH increases. The two-dimensional (2D) surface of the DLVO interaction energy (2D-pH-DLVO) was built to calculate the interactions between PSNPs and CMs under different conditions of pH. Results suggested the inflection point of PSNP-QS, PSNP-KL, PSNP-IL and PSNP-MT are 2.42, 3.30, 2.84 and 3.69, respectively. Most importantly, there was a significant correlation between the two-site kinetic parameters related to PSNPs transport and the DLVO energy barrier (DB). The contributions of the interactions of PSNPs-PSNPs and PSNPs-minerals were determined for PSNPs transport in porous media. The critical values of pH related to the migration ability of PSNPs in porous media could be determined by a combination of column experiments, 2D-pH-DLVO and PSNPs transport model. The critical values of pH were 2.95-3.01, 3.22-3.51, 2.98-3.02, 3.31-3.33 for the migration ability of PSNPs in QS, QS + KL, QS + IL and QS + MT porous media, respectively. The stronger migration ability of PSNPs under high pH conditions is attributed to the enhanced deprotonation of the media surface and increased negative surface charge, which increases the electrostatic repulsion between PSNPs and porous media (QS, CMs). Moreover, the agglomeration of PSNPs usually is weaker and the average particle size of agglomerates is smaller under the condition of high pH, thus leading to the stronger migration ability of PSNPs under high pH conditions.

Investigating transport kinetics of polystyrene nanoplastics in saturated porous media.

Understanding the fate and transport of polystyrene nanoparticles (PSNPs) in porous media under various conditions is necessary for evaluating and predicting environmental risks caused by microplastics. The transport kinetics of PSNPs are investigated by column experiment and numerical model. The surface of DLVO interaction energy is calculated to analyze and predict the adsorption and aggregation of PSNPs in porous media, which the critical ionic strength of PSNPs can be accurately investigated. The results of the DLVO energy surface suggest that when the concentration of Na+ increases from 1 mM to 50 mM, the DLVO energy barrier of PSNPs-silica sand (SS) decreases from 78.37 kT to 5.46 kT. As a result, PSNPs are easily adsorbed on the surface of SS and the mobility of PSNPs is reduced under the condition of a high concentration of Na+ (PSNPs recovery rate decreases from 62.16% to 3.65%). When the concentration of Ca2+ increases from 0.1 mM to 5 mM, the DLVO energy barrier of PSNPs-SS decreases from 12.10 kT to 1.90 kT, and PSNPs recovery rate decreases from 82.46% to 4.27%. Experimental and model results showed that PSNPs mobility is enhanced by increasing initial concentration, flow velocity and grain size of SS, while the mobility of PSNPs with larger particle diameter is lower. Regression analysis suggests that kinetic parameters related to PSNPs mobility are correlated with DLVO energy barriers. The environmental behavior and mechanism of PSNPs transport in porous media are further investigated in this study, which provides a scientific basis for the systematic and comprehensive evaluation of the environmental risk and ecological safety of nano-plastic particles in the groundwater system.

Effects of clay minerals on the transport of polystyrene nanoplastic in groundwater.

Microplastics are widely detected in the soil-groundwater environment, which has attracted more and more attention. Clay mineral is an important component of the porous media contained in aquifers. The transport experiments of polystyrene nanoparticles (PSNPs) in quartz sand (QS) mixed with three kinds of clay minerals are conducted to investigate the effects of kaolinite (KL), montmorillonite (MT) and illite (IL) on the mobility of PSNPs in groundwater. Two-dimensional (2D) distributions of DLVO interaction energy are calculated to quantify the interactions between PSNPs and three kinds of clay minerals. The critical ionic strengths (CIS) of PSNPs-KL, PSNPs-MT and PSNPs-IL are 17.0 mM, 19.3 mM and 21.0 mM, respectively. Experimental results suggest KL has the strongest inhibition effect on the mobility of PSNPs, followed by MT and IL. Simultaneously, the change of ionic strength can alter the surface charge of PSNPs and clay minerals, thus affecting the interaction energy. Experimental and model results indicate both the deposition rate coefficient (k) and maximum deposition (Smax) linearly decrease with the logarithm of the DLVO energy barrier, while the mass recovery rate of PSNPs (Rm) exponentially increases with the logarithm of the DLVO energy barrier. Therefore, the mobility and associated kinetic parameters of PSNPs in complex porous media containing clay minerals can be predicted by 2D distributions of DLVO interaction energy. These findings could help to gain insight into understanding the environmental behavior and transport mechanism of microplastics in the multicomponent porous media, and provide a scientific basis for the accurate simulation and prediction of microplastic contamination in the groundwater system.

Low-grade fibromyxoid sarcoma in the middle ear as a rare location: a case report.

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor with a misleadingly bland histological appearance and fully malignant behavior, typically occurring in the deep soft tissues of the proximal extremities or trunk of young adults. However, no cases of primary middle ear LGFMS have been reported previously. LGFMS is characterized by high rates of local recurrence and metastatic spread, which should be attached of great importance to clinical diagnosis and treatment. Case Description: Herein, we report an unusual case of LGFMS occurring primarily in the middle ear of a 12-year-old boy, who presented with aural fullness and gradually progressive hearing loss in the left ear for 6 months, without other related symptoms and family history. Preoperative imaging examination suggested that the lesions were located in the tympanic cavity, tympanic antrum, and mastoid portion, with equisignal or hypointense on T1 weighted image (T1WI), apparent hyperintense on T2 weighted image (T2WI), and slight enhancement on T1WI following administration of gadolinium. A decision was made to perform mastoidectomy, as the lesion was limited to the middle ear and did not invade the facial nerve canal or the inner ear. During the surgery, the mass exhibited a hard texture and smooth surface that was approximately 1.0 cm × 1.5 cm in size, not easy to bleed, and non-adherent to surrounding tissues. After consultation, a diagnosis of LGFMS was made by postoperative pathology. The patient showed an excellent recovery from surgery without any complications. At present, the patient has been followed up for 24 months, and no local recurrence or distant metastasis has been observed. Conclusions: The primary LGFMS in the middle ear is very rare, and the clinical manifestations and related examinations lack specificity, so a clinical diagnosis of LGFMS is very difficult, and the final diagnosis is mainly determined by pathological diagnosis. Due to its malignant behavior, clinical diagnosis and treatment should be vigilant against it. Treatment of LGFMS mainly requires extensive resection combined with radiotherapy and chemotherapy if necessary, and long-term follow-up is essential. Reporting and identification of this rare case are imperative to improving our understanding of LGFMS and reducing misdiagnosis.

Effects of polyamide microplastic on the transport of graphene oxide in porous media.

With the rapid development of the nano-material and chemical industry, more and more microplastic (MP) and nano-material were discharged into the environment. In this study, a two-dimensional (2D) surface of Extended Darjaguin-Landau-Verwe-Overbeek (XDLVO) is proposed to quantitatively investigate the effect of polyamide (PA) on the transport of graphene oxide (GO) in porous media. The influences of mass fraction of PA, flow rate, GO concentration, ionic type and strength on the migration of GO in saturated porous media are investigated by column experiments and numerical models. The two-dimensional (2D) surfaces of XDLVO interaction energy between GO and GO, GO and QS, GO and PA, are firstly calculated to analyze the transport of GO in saturated porous media. Experimental results suggest the mobility of GO is enhanced when flow velocity and initial concentration of GO are increased. However, the mobility of GO is inhibited when the mass fraction of PA and ionic strength are increased. More important, the inhibitory effect of divalent cations on GO migration is stronger than that of monovalent cations. Simultaneously, XDLVO results suggest that ionic types and strengths are important factors affecting the mobility of GO in porous media, and the critical ionic strength is observed from the continuous variation of the secondary minimum trap of XDLVO interaction energy. Model results show that there is a linear relationship between the logarithm of the secondary minimum trap of XDLVO interaction energy and the parameters related to GO mobility, which suggests XDLVO energy surface has an important application significance in the accurate quantification of GO mobility in porous media. These findings contribute to GO transport affected by microplastic in porous media, thus laying a significant foundation for the environmental risk and contamination remediation.

Evaluating salinity variation and origin in coastal aquifer systems with integrated geophysical and hydrochemical approaches.

Public concerns have been dramatically increased over potential saltwater intrusion resulting in freshwater resources shortage in coastal aquifers in the past decades. Investigating the distribution and origin of saline water is a key factor to understand coastal groundwater evolution and further assist its management. Here we evaluate the horizontal and vertical spatial variability of the coastal groundwater salinity and its potential key influencing factors based on integrated hydrochemical and geoelectrical approaches in the Pearl River Estuary (PRE), South China. The electrical resistivity tomography and geochemical data show a decrease of salinity from the coast to the inland with a water type varying from Cl-Na to HCO3-Ca at the regional scale. Points with higher/lower salinity values than those in the surrounding environment occasionally exist in the study region. In the cross section, the zone 2-90 m below the surface has low resistivity values, which correspond to high-salinity values in the subsurface. The moderate resistivity values at 0-2 m depth illustrate an infiltration of freshwater. The complex salinity distribution pattern is mainly controlled by the heterogeneity of formation and distribution of primary flow paths, while the coastal groundwater salinity evolution is shaped by the joint influence of paleo-seawater intrusion, the ion mixing processes, and the water-rock interaction.

Exercise Ameliorates Fluoride-induced Anxiety- and Depression-like Behavior in Mice: Role of GABA.

Fluoride exposure caused anxiety- and depression-like behavior in mice. Meanwhile, exercise contributes to relieve anxiety and depression. However, the effects of exercise on anxiety- and depression-like behavior in fluorosis mice remain unclear. In the current study, thirty-six Institute of Cancer Research (ICR) female mice were randomly assigned to four groups: control group (C, gavage with distilled water); exercise group (E, gavage with distilled water and treadmill exercise (speed, 10 m/min; time, 30 min/day)); fluoride group (F, gavage with 24 mg/kg sodium fluoride (NaF)); and exercise plus fluoride group (EF, gavage with 24 mg/kg NaF and treadmill exercise). All treatments lasted for 8 weeks. A number of entries into and time spent in the open zone in the elevated zero maze (EZM), resting time in the tail suspension test (TST) and levels of serotonin (5-HT) and gamma-aminobutyric acid (GABA), were significantly altered in F when compared to C. Meanwhile, the anxiety-like behavior in the EZM and the depression-like behavior in the TST were significantly improved in EF when compared to group F. Exercise significantly enhanced fluoride-induced low GABA level, with less effect on the concentration of 5-HT. Moreover, the mRNA and protein expressions of GABA synthesis and transport-related proteins of glutamic acid decarboxylase (GAD) 65 and GAD67 and vesicular GABA transporter (VGAT) were all strikingly decreased in F, while those in EF were increased. In conclusion, exercise ameliorates anxiety- and depression-like behavior in fluorosis mice through increasing the expressions of GABA synthesis and transport-related proteins, rather than 5-HT system.

Seasonal Variation of Nonsyndromic Orofacial Clefts in Northern Chinese Population.

BACKGROUND: Nonsyndromic orofacial clefts (NSOC) comprise a range of disorders affecting the lips and oral cavity. Various authors evaluated seasonal influence on the occurrence of NSOC differently. The aim of present study was to investigate seasonal variation in birth of individuals with orofacial cleft in northern China. METHODS: A retrospective study comprised 499 cases and 452 controls were conducted. Children with NSOC operated in The First Affiliated Hospital of Harbin Medical University from 2009 to 2015 were investigated. Controls were children patients with trauma and bone fracture from the same hospital during the same period. Data on sex, birth time, area of residence was retrospectively collected from patients' records. Chi-squared test was used for comparisons. P values less than or equal to 0.05 were considered to be significant. RESULTS: Seasonal distribution was significantly different between cases and controls (P < 0.05). Birth time peaks of cases, especially males, occurred in winter. Furthermore, compared with controls, more cases with cleft lip/palate were born in winter (P < 0.05). There was no significant seasonal difference between female cases and controls (P > 0.05), and no statistical difference was found between cases with cleft palate and controls (P > 0.05). CONCLUSIONS: Our study revealed the presence of seasonal variation in individuals with orofacial cleft in northern Chinese population. We found a peak incidence of birth time for NSOC during winter.

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.

A novel missense mutation in SMPX causes a rare form of X-linked postlingual sensorineural hearing loss in a Chinese family.

BACKGROUND: X-linked deafness-4 (DFNX4) caused by the functional loss of the SMPX gene is one form of nonsyndromic hearing loss with postlingual onset. This study aimed to investigate the cause of X-linked inherited sensorineural nonsyndromic hearing loss in a four-generation Chinese family and to explain the reason for extremely different hearing phenotypes between the proband and other family members. METHODS: Whole-exome sequencing (WES) and co-segregation analysis were used to identify the pathogenic variants. Furthermore, methylation differences among the androgen receptor genes were utilized to investigate whether the severe phenotype of the proband is related to X-chromosome inactivation (Xi). RESULTS: We described in detail the clinical characteristics of the family and identified a novel missense mutation (c.262C>G: p.Gln88Glu) in SMPX by WES. This variant was co-segregated with the postlingual hearing loss phenotype and was absent in 300 normal controls. Also, we found that the proband, a 4-year-old female, carries two new compound heterozygous mutations (c.9259G>A: p.Val3087Ile and c.8576G>A: p.Arg2859His) in the USH2A gene, but to date without any other symptoms except profound sensorineural hearing loss. Additionally, analysis of X-chromosome inactivation indicated moderate skewing in the proband, which is probably related to the heterogeneity of clinical characteristics. CONCLUSIONS: This is the first study to report a missense mutation of SMPX in a Chinese family. Our findings have enriched the mutation and phenotypic spectrum of the SMPX gene.

miR-488-3p sponged by circ-0000495 and mediated upregulation of TROP2 in head and neck squamous cell carcinoma development.

TROP2 (trophoblast cell surface antigen 2) overexpression has been reported in many human cancers. The correlation between TROP2 and tumor aggressiveness has implied it could be a prognostic indicator. However, the roles of TROP2 and their underlying mechanisms remain of great interest in head and neck squamous cell carcinoma (HNSCC) biology. In the current study, the prognostic significance of TROP2 in HNSCC archival samples was determined using immunohistochemistry. Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure the phenotypic effects of TROP2 knockdown, miR-488-3p re-expression, and circRNAs expression. Cell viability, migration/invasion as well as in vivo tumor formation assays were accessed. The interactions of miRNAs-TROP2 or circRNAs-miRNAs were determined by qRT-PCR, western blot analysis and luciferase assays. TROP2 was demonstrated overexpression in HNSCC patients and cancer cell lines. High expression of TROP2 was significantly associated with patient relapse. TROP2 promoted tumor cell proliferation, migration, invasion, and tumor growth, through AKT and MAPK pathways. Further investigation revealed that TROP2 is a direct target of miR-488-3p, while circ-0000495 bounds to miR-488-3p. Our study unraveled a novel mechanism by which down-regulation of miR-488-3p sponged by circ-0000495 releases its epigenetic silencing to TROP2. The increased TROP2 promotes tumor proliferation, therefore, providing evidence in support of targeting the circ-0000495/miR-488-3p/TROP2 axis in contributing to HNSCC therapy and preventing tumor metastasis.

MicroRNA-205 targets HER3 and suppresses the growth, chemosensitivity and metastasis of human nasopharyngeal carcinoma cells.

PURPOSE: Nasopharyngeal carcinoma is one of the lethal cancers prevalent in Southeast Asia and Southern China. The frequent relapses, development of drug resistance, the adverse effects of chemotherapy and lack of therapeutic targets form the major hurdles in nasopharyngeal carcinoma treatment. This study was undertaken to investigate the role and therapeutic potential of miR-205 in human nasopharyngeal carcinoma cells. METHODS: Expression analysis was performed by qRT-PCR. The WST-1 and colony formation assays were used for the assessment of the cell viability. Autophagy was detected by electron microscopy and apoptosis was detected by DAPI staining. Protein expression was determined by western blot analysis. RESULTS: The expression of miR-205 was significantly downregulated in human nasopharyngeal carcinoma cells. Overexpression of miR-205 caused significant inhibition in the proliferation of CNE1 nasopharyngeal carcinoma cells. The miR-205-triggered growth inhibition was found to be mainly due to the induction of autophagy which was associated with increase in LC3B II and decrease in p62 expression. The miR-205 overexpression also caused apoptotic cell death of CNE1 cells which was concomitant with increase in the Bax/Bcl-2 ratio. Additionally, miR-205 enhanced the chemosensitivity of the nasopharyngeal carcinoma cells to cisplatin and suppressed their migration and invasiveness. In silico analysis showed that miR-205 exerts its effects by inhibiting human epidermal growth factor receptor 3 (HER3). The expression of HER3 was found to be significantly upregulated in nasopharyngeal carcinoma cells and overexpression of HER3 could nullify the effects of miR-205 on the proliferation of nasopharyngeal carcinoma cells. CONCLUSION: miR-205 may exhibit therapeutic implications in the treatment of nasopharyngeal carcinoma.

Long non-coding RNA ANRIL promotes proliferation, clonogenicity, invasion and migration of laryngeal squamous cell carcinoma by regulating miR-181a/Snai2 axis.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the common cancer with poor prognosis. Long non-coding RNA (lncRNA) ANRIL has been proven to play an important role in many cancers. However up to now, the role of ANRIL in LSCC is still poorly understood. The present study aimed to investigate the role and underlying mechanisms of ANRIL and miR-181a in LSCC. METHODS: Expression of ANRIL, miR-181a and Snai2 in both LSCC tissues and cells was determined by qRT-PCR. CCK-8 assay, colony formation assay, flow cytometry analysis and transwell assay were conducted to detect cell proliferation, clonogenicity, apoptosis, invasion and migration, respectively. The binding between ANRIL and miR-181a, as well miR-181a and Snai2 was confirmed by dual luciferase reporter assay. Western blotting was used to determine the protein levels of Snail, Slug, E-cadherin, N-cadherin and Vimentin. RESULTS: ANRIL was up-regulated while miR-181a was down-regulated in LSCC tissues. ANRIL was negatively correlated with miR-181a and was positively correlated with Snai1 and Snai2. Dual luciferase reporter assay showed ANRIL could directly sponge miR-181a to counteract its suppression on Snai2, serving as a positive regulator of Snai2. Either knockdown of ANRIL or overexpression of miR-181a significantly inhibited the proliferation, clonogenicity, invasion, migration and epithelial mesenchymal transformation (EMT), as well as promoted the apoptosis of LSCC cells, and knockdown of miR-181a reversed the effects. CONCLUSION: Inhibition of ANRIL could suppress cell proliferation, clonogenicity, invasion and migration, as well as enhance cell apoptosis of LSCC cells through regulation of miR-181a/Snai2 axis, indicating that ANRIL might be a promising therapeutic target during the treatment of LSCC.

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.

Synergistic combination of PEGylated selenium nanoparticles and X-ray-induced radiotherapy for enhanced anticancer effect in human lung carcinoma.

In this study, PEGylated selenium nanoparticles (PSNP) was successfully prepared and combined with X-ray for effective anticancer efficacy in lung cancer cells. The particles were nanosized and observed in spherical shape. The combination of PSNP and X-ray effectively killed the cancer cells and decreased the cell viability in a concentration dependent manner. PSNP combined with X-ray showed a significantly higher apoptosis of cancer cells with around 23% of cells in late apoptosis stage. Consistently, Caspase-3 activity was significantly higher when exposed to X-ray than in the absence of X-ray. The caspase-3 activity has been doubled in the presence of X-ray and PSNPs were actively involved in the activation of effector caspase-3 and downstream target. Importantly, treatment with the combination of PSNP and X-ray showed predominant red fluorescence which is indicative of dead cells. The results clearly indicate the cytotoxic potential of PSNP + X-ray combination against lung cancer cells. Overall, novel strategy of combination of PSNP and X-ray could be an alternative and effective chemo-radiotherapy.

Association between a single-nucleotide polymorphism in the GREM1 gene and non-syndromic orofacial cleft in the Chinese population.

BACKGROUND: Non-syndromic orofacial cleft (NSOC) is a common craniofacial deformity among newborns. The GREM1 gene is correlated with orofacial development. The aim of our study was to investigate the association between a single-nucleotide polymorphism in the GREM1 gene and this malformation in the Chinese population. METHODS: The SNaPshot mini-sequencing technique was used to genotype the locus rs1258763 of the GREM1 gene in 331 patients with NSOC and 271 individuals in a control group. RESULTS: For GREM1 rs1258763, there was a significant difference between the NSOC case group and control group (P = .022). Children carrying GA and GA/AA genotypes had an increased risk of NSOC (OR=1.62, 95%CI: 1.15-2.30; OR=1.52, 95%CI: 1.09-2.12). In the cleft subgroup, we found that the GREM1 rs1258763 GA genotype might contribute to the elevated risk of the cleft lip with or without cleft palate (CL/P) (P = .029). Non-significant differences were found between the cleft palate only (CPO) and control groups (P = .077). CONCLUSION: Our findings revealed that the GREM1 polymorphism was significantly associated with the risk of NSOC in the Chinese population.