Overexpression of angiotensin-converting enzyme 2 attenuates tonically active glutamatergic input to the rostral ventrolateral medulla in hypertensive rats.

The rostral ventrolateral medulla (RVLM) plays a key role in cardiovascular regulation. It has been reported that tonically active glutamatergic input to the RVLM is increased in hypertensive rats, whereas angiotensin-converting enzyme 2 (ACE2) in the brain has been suggested to be beneficial to hypertension. This study was designed to determine the effect of ACE2 gene transfer into the RVLM on tonically active glutamatergic input in spontaneously hypertensive rats (SHRs). Lentiviral particles containing enhanced green fluorescent protein (lenti-GFP) or ACE2 (lenti-ACE2) were injected bilaterally into the RVLM. Both protein expression and activity of ACE2 in the RVLM were increased in SHRs after overexpression of ACE2. A significant reduction in blood pressure and heart rate in SHRs was observed 6 wk after lenti-ACE2 injected into the RVLM. The concentration of glutamate in microdialysis fluid from the RVLM was significantly reduced by an average of 61% in SHRs with lenti-ACE2 compared with lenti-GFP. ACE2 overexpression significantly attenuated the decrease in blood pressure and renal sympathetic nerve activity evoked by bilateral injection of the glutamate receptor antagonist kynurenic acid (2.7 nmol in 100 nl) into the RVLM in SHRs. Therefore, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced tonically active glutamatergic input in SHRs, which may be an important mechanism underlying the beneficial effect of central ACE2 to hypertension.

Comprehensive analysis of mitochondria-related genes indicates that PPP2R2B is a novel biomarker and promotes the progression of bladder cancer via Wnt signaling pathway.

Bladder cancer (BC) is the fourth and tenth most common malignancy in men and women worldwide, respectively. The complexity of the molecular biological mechanism behind BC is a major contributor to the lack of effective treatment management of the disease. The development and genesis of BC are influenced by mitochondrial retrograde control and mitochondria-nuclear cross-talk. However, the role of mitochondrial-related genes in BC remains unclear. In this study, we analyzed TCGA datasets and identified 752 DE-MRGs in BC samples, including 313 down-regulated MRGs and 439 up-regulated MRGs. Then, the results of machine-learning screened four critical diagnostic genes, including GLRX2, NMT1, PPP2R2B and TRAF3IP3. Moreover, we analyzed their prognostic value and confirmed that only PPP2R2B was associated with clinical prognosis of BC patients and Cox regression assays validated that PPP2R2B expression was a distinct predictor of overall survival in BC patients. Them, we performed RT-PCR and found that PPP2R2B expression was distinctly decreased in BC specimens and cell lines. Functional experiments revealed that overexpression of PPP2R2B distinctly suppressed the proliferation, migration and invasion of BC cells via Wnt signaling pathway. In summary, these research findings offer potential molecular markers for the diagnosis and prognosis of BC, with the discovery of PPP2R2B particularly holding significant biological and clinical significance. This study provides valuable clues for future in-depth investigations into the molecular mechanisms of BC, as well as the development of new diagnostic markers and therapeutic targets.

Growth history of hepatitis C virus among HIV/HCV co-infected patients in Guizhou Province.

Background: The evolutionary and epidemiological history and the regional differences of various hepatitis C virus (HCV) genotypes are complex. Our aim was to better understand the molecular epidemiology and evolutionary dynamics of HCV among HIV/HCV co-infected individuals in Guizhou Province. This information could contribute to improve HCV prevention and control strategies in Guizhou and surrounding provinces. Methods: The HCV RNA was extracted from the serum of HIV/HCV co-infected patients, and reverse transcription/nested PCR was performed to amplify nucleotide sequences of the C-E1 region. Then, the successfully amplified sequences were selected for phylogenetic analysis. The available C-E1 region reference sequences from the surrounding provinces of Guizhou (Guangxi, Yunnan, Hunan, and Sichuan) were retrieved in GenBank, and the evolutionary analysis by Bayesian Markov chain Monte Carlo (MCMC) algorithm was performed using BEAST software to reconstruct a phylogeographic tree in order to explore their migration patterns. Finally, the epidemiological history of HCV in the Guizhou region was retraced by reconstructing Bayesian skyline plots (BSPs) after excluding sequences from surrounding provinces. Results: Among 186 HIV/HCV co-infected patients, the C-E1 region sequence was successfully amplified in 177 cases. Phylogenetic analysis classified these sequences into six subtypes: 1a, 1b, 3a, 3b, 6a, and 6n. Among them, subtype 6a was the most dominant strain (n = 70), followed by 3b (n = 55), 1b (n = 31), 3a (n = 11), 1a (n = 8), and 6n (n = 2). By reconstructing the phylogeographic tree, we estimated that the 6a strain in Guizhou mainly originated from Yunnan and Guangxi, while the 3b strain emerged due to transmission from the IDU network in Yunnan. Subtypes 1b, 3a, 3b, and 6a, as the major subtypes of HCV in HIV/HCV co-infected individuals in Guizhou, emerged and later grew more rapidly than the national average. Notably, BSPs of the currently prevalent HCV predominant strain subtype 6a in Guizhou have shown a rapid population growth since 2004. Although the growth rate slowed down around 2010, this growth has continued to date. Conclusion: Overall, despite the improvement and implementation of a series of HCV prevention and control policies and measures, a delayed growth pattern may indicate a unique history of the spread of 6a in Guizhou. Its trend as the dominant strain in Guizhou in recent years may continue to increase slowly over subsequent years.

Blood metabolomic profiling predicts postoperative gastrointestinal function of colorectal surgical patients under the guidance of goal-directed fluid therapy.

Postoperative gastrointestinal function influences postoperative recovery and length of hospital stay for patients undergoing colorectal surgery. Goal-directed fluid therapy (GDFT) restricts fluid administration to an amount required to prevent dehydration. Although the fluid management of GDFT could decrease the incidence of postoperative complications in patients who undergo high-risk surgery, certain patients may not respond to GDFT. Thus, to achieve optimal treatment, identification of patients suitable for GDFT is necessary. Metabolomic profiling of 48 patients undergoing surgery for colorectal cancer was performed. Patients were divided into delayed- and enhanced-recovered groups based on gastrointestinal function within 72 hours, and the results of omics analysis showed differential serum metabolites between the two groups of patients in the post anesthesia care unit 24 hours after surgery. A support vector machine model was applied to evaluate the curative effects of GDFT in different patients. Four metabolites, oleamide, ubiquinone-1, acetylcholine, and oleic acid, were found to be highly associated with postoperative gastrointestinal function and could be used as potential biomarkers. Moreover, four pathways were found to be highly related to postoperative gastrointestinal recovery. Among them, the vitamin B6 metabolism pathway may be a common pathway for improving postoperative recovery in various diseases. Our findings proposed a novel method to predict postoperative recovery of gastrointestinal function based on metabolomic profiling and suggested the potential mechanisms contributing to gastrointestinal function after surgical resection of colorectal cancer under the fluid management of GDFT.

Exercise Training Improves the Altered Renin-Angiotensin System in the Rostral Ventrolateral Medulla of Hypertensive Rats.

The imbalance between angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7) in the brain has been reported to contribute to cardiovascular dysfunction in hypertension. Exercise training (ExT) is beneficial to hypertension and the mechanism is unclear. This study was aimed to determine if ExT improves hypertension via adjusting renin angiotensin system in cardiovascular centers including the rostral ventrolateral medulla (RVLM). Spontaneously hypertensive rats (SHR, 8 weeks old) were subjected to low-intensity ExT or kept sedentary (Sed) for 12 weeks. Blood pressure elevation coupled with increase in age was significantly decreased in SHR received ExT compared with Sed. The results in vivo showed that ExT significantly reduced or increased the cardiovascular responses to central application of sarthran (antagonist of Ang II) or A779 (antagonist of Ang 1-7), respectively. The protein expression of the Ang II acting receptor AT1R and the Ang 1-7 acting receptor Mas in the RVLM was significantly reduced and elevated in SHR following ExT, respectively. Moreover, production of reactive oxygen species in the RVLM was significantly decreased in SHR following ExT. The current data suggest that ExT improves hypertension via improving the balance of Ang II and Ang 1-7 and antioxidative stress at the level of RVLM.

Verification of the Westervelt equation for focused transducers.

This study investigates the validity of the Westervelt equation for focused transducers. The angular spectrum method is employed to analyze the second-harmonic acoustic field under the weakly nonlinear approximation. Although it is well known that the Westervelt equation is accurate for the case of quasi-plane waves, the present work demonstrates accurate solution for the highly focused case of a spherically-curved ultrasound transducer having an aperture angle of 80°. It is further found that the solution error is inversely dependent on the nonlinearity coefficient.