Portable Saliva Sensor Based on Dual Recognition Elements for Detection of Caries Pathogenic Bacteria.

Dental caries is one of the most common diseases affecting more than 2 billion people's health worldwide. In a clinical setting, it is challenging to predict and proactively guard against dental cavities prior to receiving a confirmed diagnosis. Streptococcus mutans (S. mutans) in saliva has been recognized as the main causative bacterial agent that causes dental caries. High sensitivity, good selectivity, and a wide detection range are incredibly important factors to affect S. mutans detection in practical applications. In this study, we present a portable saliva biosensor designed for the early detection of S. mutans with the potential to predict the occurrence of dental cavities. The biosensor was fabricated using a S. mutans-specific DNA aptamer and S. mutans-imprinted polymers. Methylene blue was utilized as a redox probe in the sensor to generate current signals for analysis. When S. mutans enters complementarily S. mutans cavities, it blocks electron transfer between methylene blue and the electrode, resulting in decreases in the reduction current signal. The signal variations are associated with S. mutans concentrations that are useful for quantitative analysis. The linear detection range of S. mutans is 102-109 cfu mL-1, which covers the critical concentration of high caries risk. The biosensor exhibited excellent selectivity toward S. mutans in the presence of other common oral bacteria. The biosensor's wide detection range, excellent selectivity, and low limit of detection (2.6 cfu mL-1) are attributed to the synergistic effect of aptamer and S. mutans-imprinted polymers. The sensor demonstrates the potential to prevent dental caries.

Synergistic antibacterial effect of ginsenoside Rh2 and calcium hydroxide on Enterococcus faecalis.

Treatment of root canal infections becomes more challenging due to the extremely high tolerance of Enterococcus faecalis (E. faecalis) to calcium hydroxide (Ca(OH)2). Ginsenoside is a Chinese herbal extract that has been proven to have antimicrobial properties and synergistic activities. And this study evaluated the antibacterial activity of ginsenoside Rh2 in combination with Ca(OH)2 against E. faecalis and its preliminary mechanism of action. Broth microdilution method, checkerboard dilution method, time-inhibition curve, drug resistance assays, scanning electron microscopy, and biofilm inhibition and removal assays indicated that Rh2 in combination with Ca(OH)2 exhibited potent antibacterial activity against E. faecalis. Rh2 exerted significant in vitro antibacterial activity against E. faecalis, with a minimum inhibitory concentration (MIC) of 3.125 µg/mL and minimum bactericidal concentration (MBC) of 6.25 µg/mL, and significantly enhanced the susceptibility of E. faecalis to Ca(OH)2 (FICI = 0.5). Furthermore, cell membrane permeability assays, surface hydrophobicity assays, ATPase activity assays, and intra-biofilm extracellular polysaccharides (EPS) assays revealed that Rh2 and Ca(OH)2 synergistically inhibit bacteria mainly by increasing membrane permeability. Ultimately, cytotoxicity assays showed that Rh2 exhibited only low toxicity, the half maximal inhibitory concentration (IC50) of Rh2 was 19.75 µg/mL. This study confirmed the synergistic antibacterial activities of Rh2 and Ca(OH)2 against E. faecalis. Our findings indicate that the Rh2 and Ca(OH)2 combination may be a promising alternative approach to treating root canal infections.

Research progress of the mechanisms and applications of ginsenosides in promoting bone formation.

BACKGROUND: Bone deficiency-related diseases caused by various factors have disrupted the normal function of the skeleton and imposed a heavy burden globally, urgently requiring potential new treatments. The multi-faceted role of compounds like ginsenosides and their interaction with the bone microenvironment, particularly osteoblasts can promote bone formation and exhibit anti-inflammatory, vascular remodeling, and antibacterial properties, holding potential value in the treatment of bone deficiency-related diseases and bone tissue engineering. PURPOSE: This review summarizes the interaction between ginsenosides and osteoblasts and the bone microenvironment in bone formation, including vascular remodeling and immune regulation, as well as their therapeutic potential and toxicity in the broad treatment applications of bone deficiency-related diseases and bone tissue engineering, to provide novel insights and treatment strategies. METHODS: The literature focusing on the mechanisms and applications of ginsenosides in promoting bone formation before March 2024 was searched in PubMed, Web of Science, Google Scholar, Scopus, and Science Direct databases. Keywords such as "phytochemicals", "ginsenosides", "biomaterials", "bone", "diseases", "bone formation", "microenvironment", "bone tissue engineering", "rheumatoid arthritis", "periodontitis", "osteoarthritis", "osteoporosis", "fracture", "toxicology", "pharmacology", and combinations of these keywords were used. RESULTS: Ginsenoside monomers regulate signaling pathways such as WNT/ß-catenin, FGF, and BMP/TGF-ß, stimulating osteoblast generation and differentiation. It exerts angiogenic and anti-inflammatory effects by regulating the bone surrounding microenvironment through signaling such as WNT/ß-catenin, NF-κB, MAPK, PI3K/Akt, and Notch. It shows therapeutic effects and biological safety in the treatment of bone deficiency-related diseases, including rheumatoid arthritis, osteoarthritis, periodontitis, osteoporosis, and fractures, and bone tissue engineering by promoting osteogenesis and improving the microenvironment of bone formation. CONCLUSION: The functions of ginsenosides are diverse and promising in treating bone deficiency-related diseases and bone tissue engineering. Moreover, potential exists in regulating the bone microenvironment, modifying biomaterials, and treating inflammatory-related bone diseases and dental material applications. However, the mechanisms and effects of some ginsenoside monomers are still unclear, and the lack of clinical research limits their clinical application. Further exploration and evaluation of the potential of ginsenosides in these areas are expected to provide more effective methods for treating bone defects.

Advances in Electrochemical Biosensors for the Detection of Common Oral Diseases.

Limiting and preventing oral diseases remains a major challenge to the health of populations around the world, so finding ways to detect early-stage diseases (e.g., caries, periodontal disease, and oral cancer) and aiding in their prevention has always been an important clinical treatment concept. The development and application of electrochemical detection technology can provide important support for the early detection and non-invasive diagnosis of oral diseases and make up for the shortcomings of traditional diagnostic methods, which are highly sensitive, non-invasive, cost-effective, and less labor-intensive. It detects specific disease markers in body fluids through electrochemical reactions, discovers early warning signals of diseases, and realizes rapid and reliable diagnosis. This paper comprehensively summarizes the development and application of electrochemical biosensors in the detection and diagnosis of common oral diseases in terms of application platforms, sensing types, and disease detection, and discusses the challenges faced by electrochemical biosensors in the detection of oral diseases as well as the great prospects for future applications, in the hope of providing important insights for the future development of electrochemical biosensors for the early detection of oral diseases.

Barriers to healthcare-worker adherence to infection prevention and control practices in British Columbia during the coronavirus disease 2019 (COVID-19) pandemic: A cross-sectional study.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of robust infection prevention and control (IPAC) practices to maintain patient and staff safety. However, healthcare workers (HCWs) face many barriers that affect their ability to follow these practices. We identified barriers affecting HCW adherence to IPAC practices during the pandemic in British Columbia, Canada. DESIGN: Cross-sectional web-based survey. SETTING: Acute care, long-term care or assisted living, outpatient, mental health, prehospital care, and home care. PARTICIPANTS: Eligible respondents included direct-care providers and IPAC professionals working in these settings in all health authorities across British Columbia. METHODS: We conducted a web-based survey from August to September 2021 to assess respondent knowledge and attitudes toward IPAC within the context of the COVID-19 pandemic. Respondents were asked to rate the extent to which various barriers affected their ability to follow IPAC practices throughout the pandemic and to make suggestions for improvement. RESULTS: The final analysis included 2,488 responses; 36% of respondents worked in acute care. Overall, perceptions of IPAC practice among non-IPAC professionals were positive. The main self-perceived barriers to adherence included inadequate staffing to cover absences (58%), limited space in staff rooms (57%), multibed rooms (51%), and confusing messages about IPAC practices (51%). Common suggestions for improvement included receiving more support from IPAC leadership and clearer communication about required IPAC practices. CONCLUSIONS: Our findings highlight frontline HCW perspectives regarding priority areas of improvement for IPAC practices. They will inform policy and guideline development to prevent transmission of COVID-19 and future emerging infections.

Disease diagnosis and application analysis of molecularly imprinted polymers (MIPs) in saliva detection.

Saliva has significantly evolved as a diagnostic fluid in recent years, giving a non-invasive alternative to blood analysis. A high protein concentration in saliva is delivered directly from the bloodstream, making it a "human mirror" that reflects the body's physiological state. It plays an essential role in detecting diseases in biomedical and fitness monitoring. Molecularly imprinted polymers (MIPs) are biomimetic materials with custom-designed synthetic recognition sites that imitate biological counterparts renowned for sensitive analyte detection. This paper reviews the progress made in research about MIP biosensors for detecting saliva biomarkers. Specifically, we investigate the link between saliva biomarkers and various diseases, providing detailed insights into the corresponding biosensors. Furthermore, we discuss the principles of molecular imprinting for disease diagnostics and application analysis, including recent advances in integrated MIP-sensor technologies for high-affinity analyte detection in saliva. Notably, these biosensors exhibit high discrimination, allowing for the detection of saliva biomarkers linked explicitly to chronic stress disorders, diabetes, cancer, bacterial or viral-induced illnesses, and exposure to illicit toxic substances or tobacco smoke. Our findings indicate that MIP-based biosensors match and perhaps surpass their counterparts featuring integrated natural antibodies in terms of stability, signal-to-noise ratios, and detection limits. Additionally, we highlight the design of MIP coatings, strategies for synthesizing polymers, and the integration of advanced biodevices. These tailored biodevices, designed to assess various salivary biomarkers, are emerging as promising screening or diagnostic tools for real-time monitoring and self-health management, improving quality of life.

Barriers to infection prevention and control in long-term care/assisted living settings in British Columbia during the COVID-19 pandemic: a cross-sectional survey.

BACKGROUND: The COVID-19 pandemic disproportionately impacted long-term care and assisted living (LTC/AL) facilities in Canada, where infection prevention and control (IPAC) programs had been suboptimal. We aimed to identify barriers affecting healthcare workers' (HCW) adherence to IPAC practices during the pandemic in British Columbia in LTC/AL compared to acute care settings. METHODS: We conducted a web-based survey of direct care providers and IPAC professionals across BC from August to September 2021, focused on knowledge and attitudes toward IPAC within the context of the COVID-19 pandemic, and barriers that affected respondents' abilities to follow IPAC practices throughout the pandemic. RESULTS: The final analysis included 896 acute care respondents and 441 from LTC/AL. More LTC/AL respondents reported experiencing the following barriers: following IPAC guidance was of lower priority compared to other tasks (29.1% vs. 14.7%, FDR = 0.001) and not their responsibility (28.0% vs. 11.2%, FDR = 0.001); limited supplies for personal protective equipment (PPE) (49.0% vs. 33.6%, FDR = 0.001), hand hygiene products (42.2% vs. 28.8%, FDR = 0.001), and cleaning/disinfection products (44.1% vs. 30.3%, FDR = 0.001); deficits in IPAC leadership support (46.2% vs. 38.9%, FDR = 0.012), IPAC education and training (46.9% vs. 32.0%, FDR = 0.001), and patient care knowledge for managing COVID-19 infections (46.6% vs. 36.0%, FDR = 0.001). CONCLUSIONS: This survey found that barriers to HCWs' adherence to IPAC practices during the COVID-19 pandemic were different in LTC/AL settings compared to acute care. Improvement efforts should focus on strengthening IPAC programs in LTC/AL, particularly enhanced IPAC staffing/leadership, increased training and education, and improving access to PPE, hand hygiene, and cleaning products.

Flexible and Wearable Biosensors for Monitoring Health Conditions.

Flexible and wearable biosensors have received tremendous attention over the past decade owing to their great potential applications in the field of health and medicine. Wearable biosensors serve as an ideal platform for real-time and continuous health monitoring, which exhibit unique properties such as self-powered, lightweight, low cost, high flexibility, detection convenience, and great conformability. This review introduces the recent research progress in wearable biosensors. First of all, the biological fluids often detected by wearable biosensors are proposed. Then, the existing micro-nanofabrication technologies and basic characteristics of wearable biosensors are summarized. Then, their application manners and information processing are also highlighted in the paper. Massive cutting-edge research examples are introduced such as wearable physiological pressure sensors, wearable sweat sensors, and wearable self-powered biosensors. As a significant content, the detection mechanism of these sensors was detailed with examples to help readers understand this area. Finally, the current challenges and future perspectives are proposed to push this research area forward and expand practical applications in the future.

Research progress of odontogenic extracellular vesicles in regeneration of dental pulp.

It is well understood that maintaining viable pulp is critical for tooth retention. This review focused on cell-free therapy based on extracellular vesicles (EVs), a novel minimally invasive treatment strategy for endodontic restoration. This study was conducted by searching mainstream electronic databases such as Web of Science and PubMed for relevant studies on the therapeutic role of odontogenic EVs in pulp healing published in the last five years. We selected 89 relevant articles and discovered that dental stem cells (DSCs) derived EVs (DSC-EVs) have become a research hotspot in oral regenerative medicine, with significant advantages over cell transplantation in terms of low immunogenicity, ease of isolation, preservation, and management. Here, we introduce in detail the therapeutic effects of DSC-EVs for pulp restoration from three perspectives: excellent odontogenic properties, clinical applications, and possible molecular mechanisms. This article contributes a new viewpoint to the field of regenerative endodontics.

Advances of Mesenchymal Stem Cells Released Extracellular Vesicles in Periodontal Bone Remodeling.

Extracellular vesicles (EVs) are nanoparticles that include exosomes, microvesicles, and apoptotic bodies; they interact with target cell surface receptors and transport contents, including mRNA, proteins, and enzymes into the cytoplasm of target cells to function. The biological fingerprints of EVs practically mirror those of the parental cells they originated from. In the bone remodeling microenvironment, EVs could act on osteoblasts to regulate the bone formation, promote osteoclast differentiation, and regulate bone resorption. Therefore, there have been many attempts wherein EVs were used to achieve targeted therapy in bone-related diseases. Periodontitis, a common bacterial infectious disease, could cause severe alveolar bone resorption, resulting in tooth loss, whereas research on periodontal bone regeneration is also an urgent question. Therefore, EVs-related studies are important for periodontal bone remodeling. In this review, we summarize the current knowledge of mesenchymal stem cell-EVs involved in periodontal bone remodeling and explore the functional gene expression through a comparative analysis of transcriptomic content.

(20S) Ginsenoside Rh2-Activated, Distinct Apoptosis Pathways in Highly and Poorly Differentiated Human Esophageal Cancer Cells.

Ginsenoside Rh2 (G-Rh2), a rare ginsenoside isolated from red ginseng, has considerable anti-cancer activity and induces apoptosis in a variety of cancer cells, but its activity in esophageal cancer cells is unclear. In this study, we examined the cytotoxic activity of (20S) G-Rh2 in highly differentiated esophageal squamous ECA109 cells and poorly differentiated esophageal squamous TE-13 cells. (20S) G-Rh2 exerted intense cytotoxicity in ECA109 and TE-13 cells with an IC50 of 2.9 and 3.7 µg/mL, respectively. After treatment with G-Rh2, Bcl-2, and Bcl-xL, the two main anti-apoptosis Bcl-2 family proteins upregulated, and Bax and Bak, the two key pro-apoptosis proteins translocated to mitochondria in both cell lines. At the same time, cytochrome c and Smac released from mitochondria, followed by caspase-9 activation, indicating that a mitochondria-mediated intrinsic apoptosis pathway was activated in both cell lines upon treatment with (20S) G-Rh2. It is noteworthy that (20S) G-Rh2 upregulated the transcription and protein expression of two death receptors, Fas and DR5, and subsequently activated Caspase-8 in the TE-13 cells but not in the ECA109 cells. Taken together, we demonstrated the potent anti-esophageal cancer cell activity of (20S) G-Rh2 and showed its working mechanism in two differentiated esophageal cancer cells, which can provide important evidence for developing an effective strategy for anti-esophageal cancer treatment.

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults, Canada, 2015-2019.

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015-2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015-2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.

Highly Stretchable Hydrogels as Wearable and Implantable Sensors for Recording Physiological and Brain Neural Signals.

Recording electrophysiological information such as brain neural signals is of great importance in health monitoring and disease diagnosis. However, foreign body response and performance loss over time are major challenges stemming from the chemomechanical mismatch between sensors and tissues. Herein, microgels are utilized as large crosslinking centers in hydrogel networks to modulate the tradeoff between modulus and fatigue resistance/stretchability for producing hydrogels that closely match chemomechanical properties of neural tissues. The hydrogels exhibit notably different characteristics compared to nanoparticles reinforced hydrogels. The hydrogels exhibit relatively low modulus, good stretchability, and outstanding fatigue resistance. It is demonstrated that the hydrogels are well suited for fashioning into wearable and implantable sensors that can obtain physiological pressure signals, record the local field potentials in rat brains, and transmit signals through the injured peripheral nerves of rats. The hydrogels exhibit good chemomechanical match to tissues, negligible foreign body response, and minimal signal attenuation over an extended time, and as such is successfully demonstrated for use as long-term implantable sensory devices. This work facilitates a deeper understanding of biohybrid interfaces, while also advancing the technical design concepts for implantable neural probes that efficiently obtain physiological information.

Correlations among spiritual care competence, spiritual care perceptions and spiritual health of Chinese nurses: A cross-sectional correlational study.

BACKGROUND: The significance of spiritual care competence among nurses has been emphasized across countries and cultures in many studies. However, there were few studies on correlations among spiritual care competence, spiritual care perceptions, and spiritual health of nurses in China. OBJECTIVE: To investigate spiritual care competence, spiritual care perceptions, and spiritual health, and examine the correlations among spiritual care competence, spiritual care perceptions and spiritual health, and the mediating role of spiritual health between other two variables of Chinese nurses. METHODS: A cross-sectional and correlational design was implemented, and the STROBE Checklist was used to report the study. A convenience sample of 2,181 nurses were selected from 17 hospitals in 3 provinces, China. Participants provided data on sociodemographic by completing the Chinese Version of the Spiritual Care Competence Scale, the Chinese Version of the Spiritual Care-Giving Scale, and the Spiritual Health Scale Short Form. Descriptive statistics, univariate, multiple linear regression, and Pearson correlation analysis were used to analyze data. RESULTS: The total scores of spiritual care competence, spiritual care perceptions, and spiritual health were 58.25 ± 16.21, 144.49 ± 16.87, and 84.88 ± 10.57, respectively, which both were moderate. Spiritual care competence was positively correlated with spiritual care perceptions (r = 0.653, p < 0.01) and spiritual health (r = 0.587, p < 0.01). And spiritual health played a mediating role between the other two variables (accounting for 35.6%). SIGNIFICANCE OF RESULTS: The spiritual care competence, spiritual care perceptions, and spiritual health of Chinese nurses need to be improved. It is recommended that nursing managers should pay attention to spiritual care education of nurses, and improve spiritual care perceptions and spiritual health in multiple ways, so as to improve their spiritual care competence and to maximize the satisfy spiritual care needs of patients in China.

Activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts.

The (pro)renin receptor (PRR) is a multifunctional integral membrane protein that serves as a component of the vacuolar H+-ATPase (V-ATPase) and also activates (pro)renin. We recently showed that full-length PRR, found as part of a V-ATPase sub-complex, is abundant in extracellular vesicles shed by osteoclasts. Here, we tested whether these extracellular vesicles stimulate (pro)renin. Extracellular vesicles isolated from the conditioned media of RAW 264.7 osteoclast-like cells or primary osteoclasts were characterized and counted by nanoparticle tracking. Immunoblotting confirmed that full-length PRR was present. Extracellular vesicles from osteoclasts dose-dependently stimulated (pro)renin activity, while extracellular vesicles from 4T1 cancer cells, in which we did not detect PRR, did not activate (pro)renin. To confirm that the ability of extracellular vesicles from osteoclasts to stimulate (pro)renin activity was due to the PRR, the "handle region peptide" from the PRR, a competitive inhibitor of PRR activity, was tested. It dose-dependently blocked the ability of extracellular vesicles to stimulate the enzymatic activity of (pro)renin. In summary, the PRR, an abundant component of extracellular vesicles shed by osteoclasts, stimulates (pro)renin activity. This represents a novel mechanism by which extracellular vesicles can function in intercellular regulation, with direct implications for bone biology.

Effects of deltamethrin subacute exposure in snakehead fish, Channa argus: Biochemicals, antioxidants and immune responses.

To evaluate the effects on biochemicals, antioxidants, immune responses and disease resistance of the snakehead fish, following exposure to deltamethrin at 0.061, 0.121, 0.242, 0.485 and 0.970 µg/L. After 28 d, the biochemical, the levels of antioxidant enzymes and immune enzymes in liver, spleen, kidney and intestine were negatively related to the concentrations of deltamethrin exposure. Likewise, the survival rates of the fish after 7 d challenge with Aeromonas veronii were negatively related. The levels of IL-1ß, IL-8, TNF-α, Hsp70 and malondialdehyde in liver, spleen, kidney and intestine were positively connected to the concentrations of deltamethrin exposure. Results demonstrated that environmentally relevant concentrations (0.121, 0.242, 0.485 and 0.970 µg/L) inhibited the biochemicals, antioxidants and immune responses and disease resistance of snakehead fish.

Correlation between emotional intelligence and negative emotions of front-line nurses during the COVID-19 epidemic: A cross-sectional study.

AIMS AND OBJECTIVES: The purpose of this study was to understand the emotional intelligence level (EI) and negative emotional status of the front-line nurses in the epidemic situation and to further explore the relationship between them. BACKGROUND: During the COVID-19 epidemic, under the influence of multiple factors, nurses were vulnerable to negative emotions. While previous studies have explored, the role of emotional intelligence in negative emotions, the relationship between the two has not been sufficiently discussed in the context of COVID-19. DESIGN: The study carried out a cross-sectional survey. The STROBE was selected as the checklist in this study. METHODS: 202 nurses from Wuhan makeshift hospital participated in the questionnaire survey. Data collection tools included a general data questionnaire designed by the researchers, Chinese version of EI scale (WLEIS-C) and Chinese version of Depression Anxiety Stress Scale (DASS-21). Descriptive statistics, single factor analysis and correlation analysis were used to analyse the data. RESULTS: The emotional intelligence of the front-line nurses was in the upper middle range. Among the negative emotions, anxiety was the most prominent symptom. CONCLUSIONS: Managers should pay attention to the negative emotional problems of front-line nurses, improve their EI level and promote mental health and the progress of epidemic prevention. RELEVANCE TO CLINICAL PRACTICE: Improving the level of emotional intelligence can reduce the frequency and intensity of negative emotions. In clinical work, emotional intelligence can be used as a skill to carry out relevant training, which is conducive to playing a positive role in future emergencies.

Gender Differences in Depression: Evidence From Genetics.

Compared with men, female accounts for a larger proportion of patients with depression. Behavioral genetics researches find gender differences in genetic underpinnings of depression. We found that gender differences exist in heritability and the gene associated with depression after reviewing relevant research. Both genes and gene-environment interactions contribute to the risk of depression in a gender-specific manner. We detailed the relationships between serotonin transporter gene-linked promoter region (5-HTTLPR) and depression. However, the results of these studies are very different. We explored the reasons for the contradictory conclusions and provided some suggestions for future research on the gender differences in genetic underpinnings of depression.

Downregulation of MicroRNA-494 inhibits the TGF-ß1/Smads signaling pathway and prevents the development of hypospadias through upregulating Nedd4L.

BACKGROUND: Hypospadias, as a congenital disorder of the urethra, is the second most common birth abnormality of the male reproductive system. This study primarily investigates the effects of microRNA-494 (miR-494) on the transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathway and on the development of hypospadias by binding to neural precursor cell expressed developmentally downregulated gene 4-like (Nedd4L). METHODS: We induced a mouse model of hypospadias through di-(2-ethylhexyl) phthalate treatment. The underlying regulatory mechanisms of miR-494 in this model were analyzed upon treatment of miR-494 mimic, miR-494 inhibitor, or small interfering RNA against Nedd4L in urethral epithelial cells isolated from mice with hypospadias. We then verified the binding site between miR-494 and Nedd4L and applied a gain- and loss-of-function approach to determine the effects of miR-494 on cell proliferation, cycle distribution, and apoptosis. RESULTS: Male mice with hypospadias exhibited significantly higher miR-494 expression and lower Nedd4L expression in urethral tissues than normal male mice. Nedd4L was verified as a target gene of miR-494. Treatment with miR-494 inhibitor suppressed the activation of the TGF-ß1/Smads signaling pathway, whereas down-regulation of miR-494 exerted protective effects on urethral epithelial cells by impeding cell proliferation and inducing cell apoptosis. CONCLUSIONS: The study indicates that downregulation of miR-494 inhibits the TGF-ß1/Smads signaling pathway and prevents the development of hypospadias through upregulating Nedd4L.

Extreme intrusive force affects the expression of c-Fos and matrix metallopeptidase 9 in human dental pulp tissues.

This study aimed to investigate the expression of c-Fos and matrix metallopeptidase 9 (MMP-9) in dental pulp of patients receiving orthodontic treatment via wire appliance.Fifteen patients (30 teeth in total) were randomly assigned to five groups: t = 0, t = 1, t = 4, t = 8 and t = 12 (n = 6). The first maxillary premolars of patients in the t = 0 group were extracted without any orthodontic treatment. An intrusive force of 300 g was applied on first maxillary premolars in the other four groups via wire appliances. This force was maintained for 1 week for t = 1 group, 4 weeks for t = 4 group, 8 weeks for t = 8 group, or 12 weeks for t = 12 group, before the teeth were extracted.The expression of c-Fos and MMP-9 in the pulps of each group was analyzed by immunohistochemical staining and real-time PCR. The relationship in the protein expression between c-Fos and MMP-9 in the dental pulp was analyzed by Pearson correlation analysis.Intrusive force of 300 g increased the expression of both c-Fos and MMP-9 in the dental pulp. The protein expression of MMP-9 in the dental pulp was significantly correlated with the expression of c-Fos (P < .001).Extreme intrusive force upregulates c-Fos and MMP-9 expression in the dental pulp. Moreover, protein expression of c-Fos and MMP-9 is significantly correlated under intrusive force.