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We aimed to examine the effects of antibiotic and probiotic usage on the gut microbiota structure and the presence of antibiotic-resistance genes (ARGs) in infants during the first six months of life. Questionnaires and fecal samples were collected within three days of birth, two months, and six months to assess antibiotic and probiotic exposure. Gut microbiotas were sequenced via 16S rRNA, and ARGs were conducted by qPCR, including beta-lactam (mecA, blaTEM), tetracycline (tetM), fluoroquinolone (qnrS), aminoglycoside (aac(6')-Ib), and macrolide (ermB). Infants were categorized by antibiotic and probiotic usage and stratified by delivery mode, microbial composition, and ARG abundances were compared, and potential correlations were explored. A total of 189 fecal samples were analyzed in this study. The gut microbiota diversity (Chao1 index) was significantly lower in the "only probiotics" (PRO) group compared to the "neither antibiotics nor probiotics" (CON) group at six months for the CS stratification (p = 0.029). Compositionally, the abundance of core genus Bifidobacterium_pseudocatenulatum was less abundant for the antibiotic during delivery (IAP) group than that in the CON group within the first three days (p = 0.009), while core genus Enterococcus_faecium was more abundant in the PRO than that in the CON group (p = 0.021) at two months. ARGs were highly detected, with Enterococcus hosting tetM and Escherichia associated with blaTEM within three days of birth, though no correlation was found between Bifidobacterium and ARGs. These findings emphasized the critical importance of carefully managing antibiotic and probiotic exposures in early life, with implications for promoting lifelong health through preserving a healthy infant gut ecosystem.
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This study aimed to reveal harm of exposure to indoor air pollution to cognitive function through "gut-brain-axis" among rural elderly residents. There were 120 participants recruited in rural villages of northwest China from December 2021 to February 2022. The cognitive level was assessed by eight-item ascertain dementia (AD) questionnaire, and indoor air pollution exposure was measured by air quality sensor. Inflammatory cytokines and oxidative stress-related index were detected in blood serum. Fecal samples were collected for gut microbiota analysis. The 120 participants were divided into impaired cognition (AD8) (81/67.5%) and cognition normal (NG) (39/32.5%). And there had more female in AD8 (FAD) (55/67.9%) than NG (FNG) (18/46.2%) (P = 0.003). Exposure of air pollution in FAD was higher than FNG (PM1, PM2.5, PM10, P < 0.001; NO2, P < 0.001; CO, P = 0.014; O3, P = 0.002). The risk of cognitive impairment increases 6.8%, 3.6%, 2.6%, 11%, and 2.4% in female for every 1 µg/m3 increased in exposure of PM1, PM2.5, PM10, NO2, and O3, separately. And GSH-Px and T-SOD in FAD were significantly lower than the FNG group (P = 0.011, P = 0.019). Gut microbiota in FAD is disordered with lower richness and diversity. Relative abundance of core bacteria Faecalibacterium (top 1 genus) in FAD was reduced (13.65% vs 19.81%, P = 0.0235), while Escherichia_Shigella and Akkermansia was increased. Correlation analysis showed Faecalibacterium was negatively correlated with age, and exposure of O3, PM1, PM2.5, and PM10; Akkermansia and Monoglobus were positively correlated with exposure of PM1, PM2.5 and PM10; Escherichia_Shigella was significantly positively correlated with NO2. Indoor air pollution exposure impaired cognitive function in elderly people, especially female, which may cause systemic inflammation, dysbiosis of the gut microbiota, and ultimately leading to early cognitive impairment through the gut-brain axis.
Sujet(s)
Polluants atmosphériques , Pollution de l'air , Dysfonctionnement cognitif , Microbiome gastro-intestinal , Humains , Femelle , Sujet âgé , Polluants atmosphériques/analyse , Matière particulaire/analyse , Axe cerveau-intestin , Dioxyde d'azote/analyse , Exposition environnementale/analyse , Pollution de l'air/analyse , Poussière/analyse , Dysfonctionnement cognitif/épidémiologie , Chine , CognitionRÉSUMÉ
(1) Background: Both tooth loss and diabetes have high global prevalence, and both have a significant influence on patients' general health and quality of life. Previous research has indicated a possible connection between tooth loss and diabetes, but it has been unclear whether tooth loss has an effect on the development of diabetes and how it affects it. We aim to investigate the relationship between insulin resistance (IR) and tooth loss and examine how the systemic immune-inflammation index (SII) level and diet quality mediate it. (2) Methods: The cross-sectional study data were obtained from the National Health and Nutrition Examination Survey (NHANES). After describing and comparing baseline data, we used regression models to evaluate the relationship between IR and tooth loss, diet quality and tooth loss and IR, SII and tooth loss and IR. Furthermore, we applied bootstrapping to test the mediation effect of diet quality and SII between tooth loss and IR. Diet quality is reflected by the HEI (Healthy Eating Index)-2015 score. (3) Results: The total number of subjects included was 8197, with 3861 individuals belonging to the IR group (HOMA-IR ≥ 2.5) and 4336 in the non-IR group (HOMA-IR < 2.5). In the model with all covariates adjusted, tooth loss in the fourth quartile was found to be positively correlated with an increase in HOMA-IR (OR = 1.301; 95% confidence interval (CI) = [1.102, 1.537]; p < 0.001) compared to the first quartile; tooth loss in the fourth quartile correlated with the HEI-2015 score compared to the first quantile (ß = -0.121, 95% CI = [-4.839, -2.974], p < 0.001); and the highest number of tooth loss was found to have a significant effect on SII (ß = 0.032; 95%CI = [1.777, 47.448]; p < 0.05). Compared to average diet quality, best diet quality acts as a safeguard against elevated HOMA-IR (OR = 0.776; 95% CI = [0.641, 0.939]; p < 0.01); inadequate diet quality is a risk factor (OR = 1.267; 95%CI = [1.138, 1.411]; p < 0.001) conversely. Meanwhile, it can be seen that compared with the first quantile of SII, the highest score is significantly correlated with the higher incidence of IR (OR = 1.363; 95%CI = [1.179, 1.575]; p < 0.001). Diet quality and SII played a partial mediating role in the relationship between HOMA-IR and tooth loss, and the mediating effect ratio for the total effect value was 4.731% and 4.576%, respectively. The mediating effect of SII and diet quality in the association of the relationship between HOMA-IR and tooth loss both was 0.003 (95%CI = [0.001, 0.004]). (4) Conclusions: Our study revealed the relationship between IR and tooth loss, and further explored the mediating role of SII and diet quality between the number of missing teeth and IR, emphasizing that improving diet quality and reducing SII can effectively prevent and treat IR and related diseases. It provides new theoretical support for the study of IR mechanisms and new ideas and approaches to deal with related diseases.
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Diabète , Insulinorésistance , Perte dentaire , Humains , Enquêtes nutritionnelles , Études transversales , Perte dentaire/épidémiologie , Qualité de vie , Régime alimentaire , Inflammation/épidémiologie , InsulineRÉSUMÉ
Introduction: An extended-spectrum beta-lactamase (ESBL)-hypervirulent Klebsiella pneumoniae (HvKP) strain HKE9 was isolated from the blood in an outpatient. Methods: The effect of the global regulatory factor RpoS on antimicrobial resistance, pathogenicity, and environmental adaptability was elucidated. Results: HKE9 is a novel ST3355 (K20/O2a) hypervirulent strain with a positive string test and resistant to cephems except cefotetan. It has a genome size of 5.6M, including two plasmids. CTX-M-15 was found in plasmid 2, and only ompk37 was found in the chromosome. HKE9 could produce bacterial siderophores, and genes of enterobactin, yersiniabactin, aerobactin, and salmochelin have been retrieved in the genome. As a global regulatory factor, knockout of rpoS did not change antimicrobial resistance or hemolytic phenotype while increasing the virulence to Galleria mellonella larvae and showing higher viscosity. Moreover, rpoS knockout can increase bacterial competitiveness and cell adhesion ability. Interestingly, HKE9-M-rpoS decreased resistance to acidic pH, high osmotic pressure, heat shock, and ultraviolet and became sensitive to disinfectants (H2O2, alcohol, and sodium hypochlorite). Although there were 13 Type 6 secretion system (T6SS) core genes divided into two segments with tle1 between segments in the chromosome, transcriptomic analysis showed that rpoS negatively regulated T4SS located on plasmid 2, type 1, and type 3 fimbriae and positively regulate genes responsible for acidic response, hyperosmotic pressure, heat shock, oxidative stress, alcohol and hypochlorous acid metabolism, and quorum sensing. Discussion: Here, this novel ST3355 ESBL-HvKP strain HKE9 may spread via various clonal types. The important regulation effect of rpoS is the enhanced tolerance and resistance to environmental stress and disinfectants, which may be at the cost of reducing virulence and regulated by T4SS.
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Anti-infectieux , Désinfectants , Animaux , Virulence/génétique , Klebsiella pneumoniae , Facteurs de virulence/génétique , Facteurs de virulence/pharmacologie , Transcriptome , Peroxyde d'hydrogène/pharmacologie , bêta-Lactamases/génétique , bêta-Lactamases/métabolisme , Phénotype , Désinfectants/pharmacologie , Anti-infectieux/pharmacologieRÉSUMÉ
A patented strain of Bacillus amyloliquefaciens C-1 in our laboratory could produce functional sodium selenite (Na2SeO3) under optimized fermentation conditions. With the strong stress resistance and abundant secondary metabolites, C-1 showed potential to be developed as selenium-enriched postbiotics. C-1 has the ability to synthesize SeNPs when incubated with 100 µg/ml Na2SeO3 for 30 h at 30 °C aerobically with 10% seeds-culture. The transformation rate from Na2SeO3 into SeNPs reached to 55.51%. After selenium enrichment, there were no significant morphology changes in C-1 cells but obvious SeNPs accumulated inside of cells, observed by scanning electron microscope and transmission electron microscope, verified by energy dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. SeNPs had antioxidant activity in radical scavenge of superoxide (O2-), Hydroxyl radical (OH-) and 1,1-diphenyl-2-picryl-hydrazine (DPPH), where scavenging ability of OH- is the highest. Selenium-enriched C-1 had obvious anti-inflammatory effect in protecting integrity of Caco-2 cell membrane destroyed by S. typhimurium; it could preventing inflammatory damage in Caco-2 stressed by 200 µM H2O2 for 4 h, with significantly reduced expression of IL-8 (1.687 vs. 3.487, P = 0.01), IL-1ß (1.031 vs. 5.000, P < 0.001), TNF-α (2.677 vs. 9.331, P < 0.001), increased Claudin-1 (0.971 vs. 0.611, P < 0.001) and Occludin (0.750 vs. 0.307, P < 0.001). Transcriptome data analysis showed that there were 381 differential genes in the vegetative growth stage and 1674 differential genes in the sporulation stage of C-1 with and without selenium-enrichment. A total of 22 ABC transporter protein-related genes at vegetative stage and 70 ABC transporter protein-related genes at sporulation stage were founded. Genes encoding MsrA, thiol, glutathione and thioredoxin reduction were significantly up-regulated; genes related to ATP synthase such as atpA and atpD genes showed down-regulated during vegetative stage; the flagellar-related genes (flgG, fliM, fliL, and fliJ) showed down-regulated during sporulation stage. The motility, chemotaxis and colonization ability were weakened along with synthesized SeNPs accumulated intracellular at sporulation stage. B. amyloliquefaciens C-1 could convert extracellular selenite into intracellular SeNPs through the oxidation-reduction pathway, with strong selenium-enriched metabolism. The SeNPs and selenium-enriched cells had potential to be developed as nano-selenium biomaterials and selenium-enriched postbiotics.
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Bacillus amyloliquefaciens , Sélénium , Humains , Sélénium/pharmacologie , Cellules Caco-2 , Peroxyde d'hydrogène , Transporteurs ABC , Anti-inflammatoiresRÉSUMÉ
BACKGROUND: Unreasonable use of antibiotics and probiotics can alter the gut ecology, leading to antibiotic resistance and suboptimal health outcomes during early life. Our study aims are to clarify the association among antibiotic and probiotic exposure in early life, the microecology of the gut microbiota, and the development of antibiotic resistance; to investigate the long-term impact of antibiotics and probiotics on the health outcomes of infants and young children; and to provide a theoretical basis for the rational use of antibiotics and probiotics from a life course perspective. METHODS: The study is a prospective, longitudinal birth cohort study conducted in Shaanxi Province, China from 2018 to 2024. A total of 3,000 eligible mother-child pairs will be enrolled from rural, suburban, and urban areas. The recruitment of the participants begins at pregnancy, and the newborns will be followed up for 2 years at successive timepoints: within 3 days after birth, 42 days after birth, and at 3, 6, 12, 18, and 24 months of age. Sociodemographic data, environmental exposures, dietary patterns, psychological conditions, and medical and drug histories are collected. Cognitive and behavioural development among infants and young children and questionnaires on antibiotic knowledge and behaviour among caregivers will be collected at 12 and 24 months of age. The faecal samples are collected and analysed by 16S rRNA high-throughput sequencing and quantitative PCR (qPCR) for antibiotic resistance genes. DISCUSSION: The findings will inform antibiotic and probiotic use for pregnant women and infants and contribute to establishing rational use strategies of antibiotics and probiotics for paediatricians, health practitioners, and drug administration policy-makers. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Registry (ChiCTR) platform, http://www.chictr.org.cn (Record ID: ChiCTR2100047531, June 20, 2021).
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Microbiome gastro-intestinal , Probiotiques , Nourrisson , Nouveau-né , Humains , Femelle , Grossesse , Enfant d'âge préscolaire , Antibactériens/usage thérapeutique , Santé infantile , ARN ribosomique 16S/génétique , Études prospectives , Cohorte de naissance , Études de cohortes , Probiotiques/usage thérapeutiqueRÉSUMÉ
[This retracts the article DOI: 10.3892/etm.2019.7226.].
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As the use of strategies facilitates the tedious process of language learning, a multitude of studies have been conducted on language learning strategies and their educational consequences. Nonetheless, grammar learning strategies (GLSs) have not been widely studied. Moreover, no review study has been carried out to illustrate the role of individual differences in the use of GLSs. To address the existing gaps, the present review study intends to explain the role of English as a foreign language (EFL) learners' individual differences (i.e., desire to learn a second language, motivation, and willingness to communicate) in their employment of GLSs. The favorable impact of individual difference variables on grammar learning strategy use was proved using the theoretical and empirical evidence. Future research directions and pedagogical implications are also discussed.
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[This retracts the article DOI: 10.3892/etm.2018.6223.].
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Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cellcycle data shown in Fig. 4A and Transwell cell migration data shown in Fig. 5A were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 9: 23932399, 2014; DOI: 10.3892/mmr.2014.2123].
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Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Fig. 1A and Transwell cell migration data shown in Fig. 4A were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 9: 17031708, 2014; DOI: 10.3892/mmr.2014.2021].
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Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell apoptosis assay data shown in Figs. 1C and 4D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 12: 39233929, 2015; DOI: 10.3892/mmr.2015.3826].
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Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Fig. 4A and B were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 12: 37753780, 2015; DOI: 10.3892/mmr.2015.3827].
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BACKGROUND: Evidence on anemia and associated factors among young adolescent girls and boys in rural western China is limited. METHODS: We used data from a follow-up study of adolescents (10-14 years) born to women who participated in a randomized trial of antenatal micronutrient supplementation in western China. Anemia was defined by World Health Organization standards. Logistic regression was used to examine the factors associated with anemia. RESULTS: The overall prevalence of anemia was 11.7% (178/1517). Female adolescents were 1.73 (95% CI 1.21, 2.48) times more likely to have anemia as compared to males. Adolescents whose mothers had completed high school were 0.35 (95% CI 0.13, 0.93) times less likely to be anemic, compared to those of whom had < 3 years of formal education. Household wealth was also inversely associated with anemia. The association of puberty status with anemia was modified by adolescent sex (P-value for interaction was 0.04); males with greater than mild pubertal development had reduced odds (OR 0.35, 95% CI 0.15, 0.83) of anemia while there was no association among females (OR 0.72, 95% CI 0.29, 1.78). Consumption of flesh foods (OR 0.58, 95% CI 0.38, 0.89), eggs (OR 0.60, 95% CI 0.38, 0.93), and having a meal frequency of three times or more per day (OR 0.68, 95% CI 0.48, 0.96) were also associated with a lower likelihood of anemia. CONCLUSIONS: Anemia was a mild public health problem among young adolescents in rural western China. Nutritional and social determinants were identified as predictors, warranting interventions to reduce the risk of anemia among this critical age group.
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Anémie , Adolescent , Anémie/épidémiologie , Chine/épidémiologie , Études transversales , Femelle , Études de suivi , Humains , Mâle , Grossesse , Prévalence , Population rurale , Établissements scolairesRÉSUMÉ
We aimed to comprehensively examine the association of breast-feeding, types and initial timing of complementary foods with adolescent cognitive development in low- and middle-income countries. We conducted a prospective cohort study of 745 adolescents aged 10-12 years who were born to women who participated in a randomised trial of prenatal micronutrient supplementation in rural Western China. An infant feeding index was constructed based on the current WHO recommendations. Full-scale intelligence quotient (FSIQ) was assessed and derived by the fourth edition of the Wechsler Intelligence Scale for Children. The duration of exclusive or any breast-feeding was not significantly associated with adolescent cognitive development. Participants who regularly consumed Fe-rich or Fe-fortified foods during 6-23 months of age had higher FSIQ than those who did not (adjusted mean differences 4·25; 95 % CI 1·99, 6·51). For cows'/goats' milk and high protein-based food, the highest FSIQ was found in participants who initially consumed at 10-12 and 7-9 months, respectively. A strong dose-response relationship of the composite infant feeding index was also identified, with participants in the highest tertile of overall feeding quality having 3·03 (95 % CI 1·37, 4·70) points higher FSIQ than those in the lowest tertile. These findings suggest that appropriate infant feeding practices (breast-feeding plus timely introduction of appropriate complementary foods) were associated with significantly improved early adolescent cognitive development scores in rural China. In addition, improvement in Fe-rich or Fe-fortified foods complementary feeding may produce better adolescent cognitive development outcomes.
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Développement de l'enfant , Phénomènes physiologiques nutritionnels chez l'enfant , Cognition/physiologie , Tests d'intelligence , Allaitement naturel , Enfant , Chine , Études de cohortes , Compléments alimentaires , Relation dose-effet des médicaments , Femelle , Aliment enrichi , Humains , Nourrisson , Aliment du nourrisson au cours de la première année , Phénomènes physiologiques nutritionnels chez le nourrisson , Nouveau-né , Mâle , Grossesse , Phénomènes physiologiques nutritionnels prénatals , Population ruraleRÉSUMÉ
The relationship of cognitive developmental trajectories during the dynamic first years with later life development outcomes remains unclear in low- and middle-income countries. 1388 Children born to women who participated in a randomized trial of antenatal micronutrient supplementation in rural China were prospectively followed. Cognitive development was assessed six times between 3 and 30 months of age using Bayley Scales of Infant Development, and then in mid-childhood (7-9 years) and early adolescence (10-12 years) using Wechsler Intelligence Scale for Children. We identified four distinct infant cognitive development trajectory subgroups using group-based trajectory modeling: (i) consistently above average, (ii) consistently average, (iii) started below average and then improved, and (iv) started below average and then declined. LBW infants (<2500 g) were 10.60 times (95% CI 3.57, 31.49) more likely to be in the trajectory group that started below average and then declined, while each grade increase in maternal education decreased the risk of being in this group by 73% (95% CI 54%, 84%). Infants who performed consistently above average had 8.02 (95% CI 1.46, 14.59) points higher IQ in adolescence versus the declining trajectory group. These findings suggest that interventions to improve early child development trajectories may produce long-term human capital benefits.
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Développement de l'enfant , Cognition , Enfant , Enfant d'âge préscolaire , Chine , Niveau d'instruction , Femelle , Humains , Nourrisson , Intelligence , Mâle , Phénomènes physiologiques nutritionnels maternels , Essais contrôlés randomisés comme sujet , Population ruraleRÉSUMÉ
Human papillomaviruses (HPVs) have important roles in the development and progression of cervical cancer, but the underlying mechanisms are yet to be fully elucidated. MicroRNA-130a (miR-130a) has previously been reported to promote cervical cancer growth. However, the underlying molecular mechanisms by which miR-130a promotes cervical cancer progression have remained largely elusive. In the present study, polymerase chain reaction and western blot analyses were performed to examine the expression levels of miR-130a and associated proteins. A wound healing assay and a Transwell assay were applied to study cell migration and invasion. A luciferase reporter gene assay was performed to confirm the targeting associations of miR-130a. It was observed that miR-130a was significantly upregulated in cervical cancer tissues compared with that in adjacent non-tumorous tissues. High expression of miR-130a was significantly associated with lymph node metastasis and an advanced clinical stage of cervical cancer. Furthermore, the expression of miR-130a was also higher in HPV(+) cervical cancer cell lines compared with that in HPV(-) cells. Knockdown of HPV18 E6 significantly inhibited the expression of miR-130a in HeLa cervical cancer cells. Furthermore, knockdown of miR-130a reduced the migration and invasion of HeLa cells. Tissue inhibitor of metalloproteinase 2 (TIMP2), an antagonist of matrix metalloproteinase 2 (MMP2), was identified as a novel, direct target gene of miR-130a. The expression of TIMP2 was negatively mediated by miR-130a, and HPV18 E6 inhibited the expression of TIMP2 in HeLa cells. Furthermore, knockdown of TIMP2 rescued the suppressive effects of miR-130a downregulation on the migration and invasion of HeLa cells. In summary, the present study suggests that HPV18 E6 promotes the expression of miR-130a, which further inhibits the expression of TIMP2 and promotes cervical cancer cell invasion. Therefore, HPV/miR-130a/TIMP2 signaling may be a potential target for the prevention of cervical cancer metastasis.
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MicroRNA serve crucial roles in a variety of human cancer types. The miR-302-367 cluster has been reported to suppress the proliferation of cervical carcinoma cells through the novel target AKT1; however, the molecular mechanism of miR-302 in cervical cancer metastasis remains unclear. The present study aimed to investigate the clinical significance of miR-302-3p expression in cervical cancer, and to examine the regulatory mechanism of miR-302-3p in the malignant phenotypes of cervical cancer cells. The present data indicated that miR-302-3p was significantly downregulated in cervical cancer tissues compared with the level in adjacent non-tumor tissues, and low expression of miR-302-3p was significantly associated with node metastasis, advanced clinical stage, and poor prognosis in patients with cervical cancer. Restoration of miR-302-3p expression caused a significant reduction in cervical cancer cell migration and invasion. Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was identified as a novel target gene of miR-302-3p, and miR-302-3p negatively regulated the mRNA and protein expression of DCUN1D1 in cervical cancer HeLa cells. Additionally, overexpression of DCUN1D1 rescued the effects of miR-302-3p on the migration and invasion of cervical cancer cells. Furthermore, DCUN1D1 was upregulated in cervical cancer tissues compared with the levels in adjacent tissues, and its high expression was associated with node metastasis, advanced clinical stage, and shorter survival time in patients with cervical cancer. Notably, a negative correlation between miR-302-3p and DCUN1D1 expression in cervical cancer tissues was observed. Taken together, the present study suggests that miR-302-3p serves a suppressive role in cervical cancer metastasis, partly at least, via directly targeting DCUN1D1. Therefore, miR-302-3p/DCUN1D1 may be a potential therapeutic target for cervical cancer treatment.
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In recent decades, numerous long non-coding (lnc)RNAs, including growth arrest-specific transcript 5 (GAS5), have been demonstrated to exert promoting or suppressive effects in human cancers. Decreased expression of the lncRNA GAS5 was reported to promote cell proliferation, migration and invasion and indicate poor prognosis in ovarian cancer. However, the exact underlying molecular mechanism through which GAS5 is involved in ovarian cancer growth remains unknown. The present study aimed to investigate the regulatory mechanism of GAS5 in ovarian cancer cell proliferation. Quantitative polymerase chain reaction and western blot analysis were used to examine RNA and protein expression, respectively. An MTT assay was used to examine cell proliferation. A luciferase reporter gene assay was conducted to verify the targeting relationship. It was identified that the expression levels of GAS5 and Sprouty homolog 2 (SPRY2) were significantly downregulated, while the expression level of microRNA (miR)-21 was significantly upregulated in ovarian cancer tissues and cell lines compared with adjacent non-tumor tissues and normal ovarian epithelial cells, respectively. Downregulation of GAS5 was significantly associated with advanced clinical stage. Luciferase assay data indicated that miR-21 was a direct target of GAS5 and that SPRY2 was a target gene of miR-21 in ovarian cancer-derived A2780 cells. GAS5 overexpression significantly inhibited the proliferation of ovarian cancer cells, which was accompanied by the downregulation of miR-21 and the upregulation of SPRY2. The overexpression of miR-21 caused a significant decrease in A2780 cell proliferation, which was accompanied by reduced SPRY2 expression. Furthermore, miR-21 overexpression attenuated the suppressive effects of GAS5 on A2780 cell proliferation and rescued the promoting effects of GAS5 on SPRY2 expression. In addition, the knockdown of SPRY2 also rescued the suppressive effects of GAS5 on the proliferation of A2780 cells. In summary, our study demonstrates that GAS5 exerts a suppressive effect on the proliferation of ovarian cancer cells, at least in part via the inhibition of miR-21 expression and subsequent increased SPRY2 expression. These findings suggest that the GAS5/miR-21/SPRY2 signaling pathway may be a potential therapeutic target in ovarian cancer.
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MicroRNAs (miRs) serve promoting or suppressive roles in various human cancer types, including ovarian cancer; however, the role of miR-142-3p in ovarian cancer growth and chemoresistance has not previously been studied. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to examine miR and protein expression levels. An MTT assay was used to examine cell proliferation. A luciferase reporter gene assay was used to clarify the target gene of miR-142-3p. The present study reported that miR-142-3p expression levels were significantly lower in ovarian cancer tissues and cell lines, when compared with those in adjacent tissues and the normal human ovarian epithelial cell line IOSE386, respectively. The reduced expression of miR-142-3p was significantly associated with poor cell differentiation. Ectopic expression of miR-142-3p significantly inhibited the proliferation of ovarian cancer cells and increased the sensitivity of SKOV3/DDP cells to cisplatin. Sirtuin 1 (SIRT1) was identified as a target gene of miR-142-3p; SIRT1 expression was negatively regulated by miR-142-3p in ovarian cancer cells. Further investigation demonstrated that SIRT1 reversed the suppressive effects of miR-142-3p on the proliferation and chemoresistance of ovarian cancer cells. In addition, SIRT1 was significantly upregulated in ovarian cancer. A negative correlation between the expression of SIRT1 and miR-142-3p in ovarian cancer tissues was also observed. In summary, the present study indicated that miR-142-3p inhibits the proliferation and chemoresistance of ovarian cancer cells by targeting SIRT1. This suggests that miR-142-3p may be a promising therapeutic candidate for the treatment of ovarian cancer.