Gastric Acid-Responsive ROS Nanogenerators for Effective Treatment of Helicobacter pylori Infection without Disrupting Homeostasis of Intestinal Flora.

Helicobacter pylori (H. pylori) has infected more than half of the world's population, and is the major cause of gastric cancer. The efficacy of standard antibiotic-based triple therapy is declining due to drug resistance development. Herein, a pH-responsive reactive oxygen species (ROS) nanogenerator (Fe-HMME@DHA@MPN) composed of acid-responsive metal polyphenol network (MPN) shell and mesoporous metal-organic nanostructure core [Fe-HMME (hematoporphyrin monomethyl ether, sonosensitizer)] loaded with dihydroartemisinin (DHA) is reported. These nanoparticles generate more ROS singlet oxygen than sonosensitizer HMME under ultrasonication, and this sonodynamic process is fueled by oxygen generated through Fenton/Fenton-like reactions of the degraded product in gastric acid Fe (II) and hydrogen peroxide (H2 O2 ) in the infection microenvironment. The encapsulated DHA, as a hydroperoxide source, is found to enhance the peroxidase-like activity of the Fe-HMME@DHA@MPN to generate ROS hydroxyl radical, beneficial for the microenvironment without sufficient H2 O2 . In vitro experiments demonstrate that the ROS nanogenerators are capable of killing multidrug-resistant H. pylori and removing biofilm, and ROS nanogenerators show high therapeutic efficacy in a H. pylori infection mouse model. Unlike the triple therapy, the nanogenerators display negligible side effects toward the normal gut microbiota. Taken together, these self-enhanced ROS nanogenerators have a great potential for treatment of H. pylori infection.

MicroRNA­194­5p attenuates hypoxia/reoxygenation­induced apoptosis in H9C2 cardiomyocytes by inhibiting the over­activation of RAC1 protein.

Ras­related C3 botulinum toxin substrate 1 (RAC1), a member of the Rac family of guanosine triphosphate phosphohydrolases, has been suggested to be a regulator of myocardial injury during ischemia and reperfusion (I/R). Whether microRNAs (miRs) are involved in the regulation of the aforementioned process remains to be elucidated. In the present study, an in vitro model of H9C2 cardiomyocytes was used to establish the overexpression of RAC1 following hypoxia and reoxygenation (H/R). Overexpression of RAC1 in H/R­cultured cardiomyocytes could lead to cellular accumulation of reactive oxygen species (ROS) and facilitate the induction of apoptosis of H9C2 cardiomyocytes during H/R. Subsequent bioinformatic analysis indicated that RAC1 was the target of miRNA­194­5p. Further experiments showed that miR­194­5p attenuated the accumulation of cellular ROS and alleviated the induction of apoptosis of H9C2 cardiomyocytes caused by H/R, which was accompanied by the reduction in the expression levels of the RAC1 protein. Taken together, these results indicated that upregulation of miR­194­5p may function as a self­regulated cardioprotective response against RAC1­mediated ROS accumulation and cardiomyocyte apoptosis. Exogenous administration of miR­194­5p may be a novel target to ameliorate I/R injury­induced myocardial apoptosis.

Identification of an unrecognized circRNA associated with development of renal fibrosis.

Backgroud: Renal fibrosis is the common characteristic of chronic kidney disease. Circular RNA plays an essential role in the occurrence and development of Renal fibrosis, but its regulative mechanism remains elusive. Methods: The animal and cell model of Renal fibrosis was established, and RNA-sequencing and real-time polymerase chain reaction (qRT-PCR) experiments were implemented. Subsequently, experiments for detecting apoptosis and proliferation of cell, were carried out, and the isobaric tags for relative and absolute quantification proteomics analyses were performed accordingly. Results: It was found that a newly discovered Circular RNA (circRNA_0002158), is highly expressed in kidneys or cells with fibrosis, implying that this Circular RNA might be associated with the occurrence and development of Renal fibrosis. Subsequently, the overexpression and knockdown of circRNA_0002158 were conducted in the human kidney epithelial cell line (HK-2) cells, and the results indicated that the circRNA_0002158 could inhibit apoptosis, and promote proliferation of cells. The kidney injury-related factors, including Fibronectin and plasminogen activator inhibitor-1 (PAI-1), were decreased in HK-2 cells with overexpression of circRNA_0002158, while the results were reversed in cells with knockdown of circRNA_0002158. Finally, to explore the regulative mechanism of circRNA_0002158, the iTRAQ proteomics analyses were implemented for the cell samples with OE of circRNA_0002158 and its control, it showed that multiple genes and functional pathways were associated with the occurrence and development of Renal fibrosis. Conclusion: CircRNA_0002158 is associated with regulating Renal fibrosis, and may contribute to ameliorating the progression of Renal fibrosis in the future.

The predictive value of Holter monitoring in the risk of obstructive sleep apnea.

BACKGROUND: Patients with obstructive sleep apnea (OSA) often present with cardiovascular symptoms. Holter monitors were reported to predict sleep apnea, though were rarely used in everyday clinical practice. In this study, by comparing Holter monitoring to polysomnography (PSG), we try to find out an operable way for clinicians to use Holter to predict OSA risk. METHODS: Patients (n=63) suspected of OSA underwent Holter monitoring with concurrent PSG at a sleep center. Respiration and heart rate variability (HRV) indices were calculated from the Holter and compared with PSG indices. RESULTS: The sensitivity of the Holter-derived respiratory waveform for OSA was 90.0%, and the specificity was 82.6%. The time domain indices including standard deviation of all NN intervals during 24 hours, mean of standard deviation of the averages of NN intervals in all 5-minute segments, square root of the mean squared differences of successive NN intervals, percentage of beat-to-beat NN interval differences that were more than 50 milliseconds, and the frequency domain index of high frequency decreased in participants with OSA and correlated with the PSG derived indices including apnea-hypopnea index (AHI), oxygen reduction index (ODI) and nadir SaO2. Logistic regression showed that standard deviation of all NN intervals during 24 hours and gender could predict the risk of OSA (P<0.001), with a sensitivity for diagnosing moderate to severe OSA of 87.5% and could accurately distinguish the risk of OSA in 77.8% of patients. Males with standard deviation of all NN intervals during 24 hours ≤177 ms or females with standard deviation of all NN intervals during 24 hours ≤80.9 ms were considered to be at high risk for OSA. CONCLUSIONS: Commercial and common parameters from Holter monitoring could predict the risk of OSA with high sensitivity. Therefore, the risk of OSA may be assessed using the Holter examination to improve the diagnosis and treatment rate of OSA.

PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer.

OBJECTIVE: This study aimed to develop aptamer-anchored hyperbranched poly(amido amine) (HPAA) for the systemic delivery of miRNA-133a-3p and to evaluate its therapeutic potential against bone metastasis of prostate cancer in vivo and in vitro. METHODS: A glutathione (GSH)-responsive cationic HPAA was prepared by the Michael addition reaction. Furthermore, HPAA-PEG was produced by PEGylation, and then the aptamer targeted to prostate-specific membrane antigen (PSMA) was conjugated to the HPAA-PEG. The obtained HPAA-PEG-APT could form nanocomplexes with miRNA-133a-3p through electrostatic adsorption. RESULTS: The results of immunocytochemistry indicated that the complexes could target PSMA-expressing LNCaP cells. The ability of HPAA-PEG-APT to facilitate the delivery of miRNA-133a-3p into LNCaP cells was proven, and HPAA-PEG-APT/miRNA-133a-3p demonstrated enhanced antitumor activity, lower cytotoxicity and better biocompatibility in vitro. Moreover, in a mouse tibial injection tumor model, the intravenous injection of the HPAA-PEG-APT/miRNA-133a-3p complex significantly inhibited cancer growth and extended the survival time. CONCLUSION: This study provided an aptamer-anchored HPAA-loaded gene system to deliver miRNA-133a-3p for better therapeutic efficacy of bone metastasis of prostate cancer.

DNA methylation modulates H19 and IGF2 expression in porcine female eye.

The sexually dimorphic expression of H19/IGF2 is evolutionarily conserved. To investigate whether the expression of H19/IGF2 in the female porcine eye is sex-dependent, gene expression and methylation status were evaluated using quantitative real-time PCR (qPCR) and bisulfite sequencing PCR (BSP). We hypothesized that H19/IGF2 might exhibit a different DNA methylation status in the female eye. In order to evaluate our hypothesis, parthenogenetic (PA) cells were used for analysis by qPCR and BSP. Our results showed that H19 and IGF2 were over-expressed in the female eye compared with the male eye (3-fold and 2-fold, respectively). We observed a normal monoallelic methylation pattern for H19 differentially methylated regions (DMRs). Compared with H19 DMRs, IGF2 DMRs showed a different methylation pattern in the eye. Taken together, these results suggest that elevated expression of H19/IGF2 is caused by a specific chromatin structure that is regulated by the DNA methylation status of IGF2 DMRs in the female eye.

DNA methylation modulates H19 and IGF2 expression in porcine female eye

Abstract The sexually dimorphic expression of H19/IGF2 is evolutionarily conserved. To investigate whether the expression of H19/IGF2 in the female porcine eye is sex-dependent, gene expression and methylation status were evaluated using quantitative real-time PCR (qPCR) and bisulfite sequencing PCR (BSP). We hypothesized that H19/IGF2 might exhibit a different DNA methylation status in the female eye. In order to evaluate our hypothesis, parthenogenetic (PA) cells were used for analysis by qPCR and BSP. Our results showed that H19 and IGF2 were over-expressed in the female eye compared with the male eye (3-fold and 2-fold, respectively). We observed a normal monoallelic methylation pattern for H19 differentially methylated regions (DMRs). Compared with H19 DMRs, IGF2 DMRs showed a different methylation pattern in the eye. Taken together, these results suggest that elevated expression of H19/IGF2 is caused by a specific chromatin structure that is regulated by the DNA methylation status of IGF2 DMRs in the female eye.

A voice acoustic analysis of thyroid adenoma patients after a unilateral thyroid lobectomy.

OBJECTIVE: The objective of this study was to investigate the features of voice changes in thyroid adenoma patients secondary to a unilateral thyroid lobectomy that did not result in laryngeal nerve injury. STUDY DESIGN: Prospective study. METHODS: Pre- and postoperative fiberlaryngoscopic and voice acoustic analyses were performed on 32 adult patients (eight males and 24 females) with unilateral thyroid adenoma. Forty adults (20 women and 20 men) with normal voice function were grouped as controls. RESULTS: The vocal folds before and after surgery in all patients appeared to be normal under the fiberlaryngoscope. The preoperative voice was slightly abnormal in female patients and normal in male patients. One week after surgery, the F0 levels of both male and female patients decreased significantly from the values recorded before surgery (P<0.05). One month after the surgery, the F0 standard deviation, fundamental frequency perturbation, amplitude perturbation, noise/harmonic ratio, voice turbulence index, and degree of subharmonics in female patients decreased significantly from the values observed before surgery (P<0.05). Three months after surgery, the values of these indicators returned to normal. CONCLUSIONS: The preoperative voice was slightly abnormal in female patients and normal in male patients. After a unilateral thyroid lobectomy, which did not result in injury of the laryngeal nerve, the acoustic measures of male patients consequently became slightly abnormal and returned to normal within 1 month. The indicators of female patients improved from that demonstrated before surgery and returned to normal within 3 months.

[An analysis on SCL-90 of pharyngeal paraesthesia].

OBJECTIVE: To explore the mental health of the patients who suffered from pharyngeal paraesthesia, and investigate the effect of mental factors during the happening, development, therapy and turnover of the disease. METHOD: The Symptom Checklist 90 (SCL-90) was used to collect information,and all the data was dealed with SPSS 12.0. RESULT: (1) The total score of SCL-90 of pharyngeal paraesthesia was higher than the norm, and the score of positive items and average score of positive symptom were both significantly higher than the norm; (2) There was no differences between pharyngeal paraesthesia and the norm in terror factor while significant differences in the others; (3) There was no difference between male and female patients who suffered from pharyngeal paraesthesia. CONCLUSION: Compared with the normal, patients who suffered from pharyngeal paraesthesia had obvious mental symptoms, such as somatization, anxiety, depression et al.