OBJECTIVETo investigate the association between M235T variant of angiotensinogen (AGT) gene and the blood pressure response to benazepril in a hypertensive cohort.

METHODSBenazepril (10-20 mg/day) was administered for 6 weeks to 251 essential hypertensives. Polymerase chain reaction (PCR) combined with restriction enzyme digestion was used to detect the polymorphism and the patients were classified as MM, MT or TT genotype. The changes in systolic and diastolic blood pressure (SBP and DBP) were analyzed for association with genotypes at the AGT gene locus.

RESULTSThe MM genotype was observed in 23 patients (9.2%), the MT genotype in 104 patients (41.4%) and the TT genotype in 124 patients (49.4%). There was no association between these polymorphisms and the blood pressure responses in the total 251 patients. But based on the analysis stratified by age, the association between these polymorphism and the DBP responses was found in the old patients (> or = 60 years old) subgroup, the reduction in DBP was significantly greater in patients carrying the MM compared to MT or TT genotypes (14.8 +/- 4.8 mm Hg vs. 7.9 +/- 7.7 mm Hg or 9.8 +/- 6.4 mm Hg respectively; ANOVA, P = 0.034).

CONCLUSIONThe M235T polymorphism of the AGT gene was shown to influence the responses to benazepril in old hypertensive patients (> or = 60 years old). Thus, specific genotypes might predict the response to specific antihypertensive treatment.

Aged ; Angiotensinogen ; genetics ; Antihypertensive Agents ; therapeutic use ; Benzazepines ; therapeutic use ; Female ; Genotype ; Humans ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

BACKGROUNDThere is a significant association between obesity and breast cancer, which is possibly due to the expression of leptin. Therefore, it is important to clarify the role of leptin/ObR (leptin receptor) signaling during the progression of human breast cancer.

METHODSNude mice with xenografts of MCF-7 human breast cancer cells were administered recombinant human leptin subcutaneous via injection around the tumor site. Mice in the experimental group were intratumorally injected with ObR-RNAi-lentivirus, while negative control group mice were injected with the same dose of negative-lentivirus. Tumor size was blindly measured every other day, and mRNA and protein expression levels of ObR, estrogen receptor a (ERa), and vascular endothelial growth factor (VEGF) for each group were determined.

RESULTSKnockdown of ObR-treated xenografted nude mice with a high leptin microenvironment was successfully established. Local injection of ObR-RNAi-lentivirus significantly suppressed the established tumor growth in nude mice. ObR level was significantly lower in the experimental group than in the negative control group, while the amounts of ERa and VEGF expression were significantly lower in the leptin group than in the control group (P < 0.01 for all).

CONCLUSIONSInhibition of leptin/ObR signaling is essential to breast cancer proliferation and possible crosstalk between ObR and ERa, and VEGF, and may lead to novel therapeutic treatments aiming at targeting ObR in breast cancers.

Animals ; Breast Neoplasms ; genetics ; metabolism ; therapy ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Humans ; Lentivirus ; genetics ; MCF-7 Cells ; Mice ; Mice, Nude ; RNA Interference ; physiology ; Receptors, Leptin ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Xenograft Model Antitumor Assays

The breakthrough progress of implantable brain-computer interfaces (iBCIs) technology in the field of clinical trials has attracted widespread attention from both academia and industry. The development and advancement of this technology have provided new solutions for the rehabilitation of patients with movement disorders. However, challenges from many aspects make it difficult for iBCIs to further implement and transform technologies. This paper illustrates the key challenges restricting the large-scale development of iBCIs from the perspective of system implementation, then discusses the latest clinical application progress in depth, aiming to provide new ideas for researchers. For the system implementation part, we have elaborated the front-end signal collector, signal processing and decoder, then the effector. The most important part of the front-end module is the neural electrode, which can be divided into two types: piercing and attached. These two types of electrodes are newly classified and described. In the signal processing and decoder section, we have discussed the experimental paradigm together with signal processing and decoder for the first time and believed that the experimental paradigm acts as a learning benchmark for decoders that play a pivotal role in iBCIs systems. In addition, the characteristics and roles of the effectors commonly used in iBCIs systems, including cursors and robotic arms, are analyzed in detail. In the clinical progress section, we have divided the latest clinical progress into two categories: functional rehabilitation and functional replacement from the perspective of the application scenarios of iBCIs. Functional rehabilitation and functional replacement are two different types of application, though the boundary between the two is not absolute. To this end, we have first introduced the corresponding clinical trial progress from the three levels: application field, research team, and clinical timeline, and then conducted an in-depth discussion and analysis of their functional boundaries, in order to provide guidance for future research. Finally, this paper mentions that the key technical challenges in the development of iBCIs technology come from multiple aspects. First of all, from the signal acquisition level, high-throughput and highly bio-compatible neural interface designing is essential to ensure long-term stable signal acquisition. The electrode surface modification method and electrode packaging were discussed. Secondly, in terms of decoding performance, real-time, accurate, and robust algorithms have a decisive impact on improving the reliability of iBCIs systems. The third key technology is from the perspective of practicality, we believe that the signal transmission mode of wireless communication is the trend of the future, but it still needs to overcome challenges such as data transmission rate and battery life. Finally, we believe that issues such as ethics, privacy, and security need to be addressed through legal, policy, and technological innovation. In summary, the development of iBCIs technology requires not only the unremitting efforts of scientific researchers, but also the participation and support of policymakers, medical professionals, technology developers, and all sectors of society. Through interdisciplinary collaboration and innovation, iBCIs technology will achieve wider clinical applications in the future and make important contributions to improving the quality of life of patients.