Qiliqiangxin Affects L Type Current in the Normal and Hypertrophied Rat Heart

Qiliqiangxin capsule is newly developed Chinese patent drug and proved to be effective and safe for the treatment of patients with chronic heart failure. We compared the effects of different dose Qiliqiangxin on L type Ca2+ current between normal and hypertrophied myocytes. A total of 40 healthy Sprague—Dawley rats were used in the study. The rats were randomly divided into two groups (control group and hypertrophy group). Cardiac hypertrophy was induced by pressure overload produced by partial ligation of the abdominal aorta. The control group was the sham-operated group. After 1 month, cardiac ventricular myocytes were isolated from the hearts of rats. Ventricular myocytes were exposed to 10 and 50 μmol/L Qiliqiangxin, and whole cell patch-clamp technique was used to study the effects of Qiliqiangxin on . The current densities of were similar in control group and in hypertrophy group . They were not statistically significant. 10 and 50 μmol/L Qiliqiangxin can decrease peak current and in control group. However, the peak current was only reduced by 50 μmol/L Qiliqiangxin in hypertrophied myocytes. The inhibited action of Qiliqiangxin on of hypertrophy group was lower than in control group. Qiliqiangxin affected L-type Ca2+ channel and blocked , as well as affected cardiac function finally. Qiliqiangxin has diphasic action that is either class IV antiarrhythmic agent or the agent of effect cardiac function

Inhibition of Aurora B by CCT137690 sensitizes colorectal cells to radiotherapy

Colorectal cancer is the third most commonly diagnosed cancer worldwide. Although surgery remains the best treatment for this disease, adjuvant chemotherapy and radiotherapy are also very important in clinical practice. However, the notorious refractory lack of responses to radiochemotherapy greatly limits the application of radiochemotherapy in the context of colorectal cancer. There is a growing interest in the role that Aurora B may play in colorectal cancer cell survival as well as other cancer subtypes. In the current study, we sought to ascertain whether blocking of Aurora B signaling machinery by a small molecule inhibitor, CCT137690, could synergize radiation-induced colorectal cancer cell death. Results showed that CCT137690 increases the sensitivity of SW620 cells to radiation. Mechanistic studies revealed that Aurora B-Survivin pathway may be involved in this synergistic effect. Taken together, our results for the first time show that Aurora B inhibition and radiation exert a synergistic effect, resulting in enhanced colorectal cancer cell death. This synergistic effect is clinically relevant as lower doses of radiation could be used for cancer treatment, and could provide significant clinical benefits in terms of colorectal cancer management, while reducing unwanted side-effects

Exploring interfacial exchange coupling and sublattice effect in heavy metal/ferrimagnetic insulator heterostructures using Hall measurements, x-ray magnetic circular dichroism, and neutron reflectometry

We use temperature-dependent Hall measurements to identify contributions of spin Hall, magnetic proximity, and sublattice effects to the anomalous Hall signal in heavy metal/ferrimagnetic insulator heterostructures with perpendicular magnetic anisotropy. This approach enables detection of both the magnetic proximity effect onset temperature and the magnetization compensation temperature and provides essential information regarding the interfacial exchange coupling. Onset of a magnetic proximity effect yields a local extremum in the temperature-dependent anomalous Hall signal, which occurs at higher temperature as magnetic insulator thickness increases. This magnetic proximity effect onset occurs at much higher temperature in Pt than W. The magnetization compensation point is identified by a sharp anomalous Hall sign change and divergent coercive field. We directly probe the magnetic proximity effect using x-ray magnetic circular dichroism and polarized neutron reflectometry, which reveal an antiferromagnetic coupling between W and the magnetic insulator. Finally, we summarize the exchange-coupling configurations and the anomalous Hall-effect sign of the magnetized heavy metal in various heavy metal/magnetic insulator heterostructures

Non-Isolated Neural Tube Defects with Comorbid Malformations Are Responsive to Population-Level Folic Acid Supplementation in Northern China

Objective: Comorbid congenital malformation of multiple organs may indicate a shared genetic/teratogenic causality. Folic acid supplementation reduces the population-level prevalence of isolated neural tube defects (NTDs), but whether complex cases involving independent malformations are also responsive is unknown. We aimed to describe the epidemiology of NTDs with comorbid malformations in a Chinese population and assess the impact of folic acid supplementation. Study Design: Data from five counties in Northern China were obtained between 2002 and 2021 through a population-based birth defects surveillance system. All live births, stillbirths, and terminations because of NTDs at any gestational age were recorded. NTDs were classified as spina bifida, anencephaly, or encephalocele. Isolated NTDs included spina bifida cases with presumed secondary malformations (hydrocephalus, hip dislocation, talipes). Non-isolated NTDs were those with independent concomitant malformations. Results: A total of 296,306 births and 2031 cases of NTDs were recorded from 2002–2021. A total of 4.8% of NTDs (97/2031) had comorbid defects, which primarily affected the abdominal wall (25/97), musculoskeletal system (24/97), central nervous system (22/97), and face (15/97). The relative risk of cleft lip and/or palate, limb reduction defects, hip dislocation, gastroschisis, omphalocele, hydrocephalus, and urogenital system defects was significantly greater in infants with NTDs than in the general population. Population-level folic acid supplementation significantly reduced the prevalence of both isolated and non-isolated NTDs. Conclusion: Epidemiologically, non-isolated NTDs follow similar trends as isolated cases and are responsive to primary prevention by folic acid supplementation. Various clinically-important congenital malformations are over-represented in individuals with NTDs, suggesting a common etiology

Up-regulated serum lactate dehydrogenase could become a poor prognostic marker in patients with bladder cancer by an evidence-based analysis of 2,182 patients

BackgroundA growing number of studies have considered serum lactate dehydrogenase (LDH) as an indicator of bladder cancer (BC) prognosis. However, a meta-analysis of the serum LDH’s influence on BC prognosis is still missing.MethodsPubMed, EMBASE, Web of Science and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between high-LDH and low-LDH patients. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3) for overall survival (OS) in patients with BC.ResultsSix studies involving 2,182 patients were selected according to predefined eligibility criteria. The results showed that serum LDH level was significantly associated with OS (HR = 1.86, 95%CI = 1.54-2.25, p<0.0001) in BC. Sensitivity analysis showed the stability of the results. Subgroup analysis revealed that the levels of serum LDH had a significant impact on the OS of BC patients among different groups including publication time, research country, sample size, tumor stage, LDH cut-off value, therapy and follow-up time (all HR>1 and p<0.05), revealing that the ability of serum LDH is not affected by other factors.ConclusionOur findings indicated that a high level of serum LDH was associated with inferior OS in patients with BC. However, caution must be taken before recommendations are given because this interpretation is based upon very few clinical studies and a small sample

Detection of zoonotic pathogens and characterization of novel viruses carried by commensal Rattus norvegicus in New York City

Norway rats (Rattus norvegicus) are globally distributed and concentrate in urban environments, where they live and feed in closer proximity to human populations than most other mammals. Despite the potential role of rats as reservoirs of zoonotic diseases, the microbial diversity present in urban rat populations remains unexplored. In this study, we used targeted molecular assays to detect known bacterial, viral, and protozoan human pathogens and unbiased high-throughput sequencing to identify novel viruses related to agents of human disease in commensal Norway rats in New York City. We found that these rats are infected with bacterial pathogens known to cause acute or mild gastroenteritis in people, including atypical enteropathogenic Escherichia coli, Clostridium difficile, and Salmonella enterica, as well as infectious agents that have been associated with undifferentiated febrile illnesses, including Bartonella spp., Streptobacillus moniliformis, Leptospira interrogans, and Seoul hantavirus. We also identified a wide range of known and novel viruses from groups that contain important human pathogens, including sapoviruses, cardioviruses, kobuviruses, parechoviruses, rotaviruses, and hepaciviruses. The two novel hepaciviruses discovered in this study replicate in the liver of Norway rats and may have utility in establishing a small animal model of human hepatitis C virus infection. The results of this study demonstrate the diversity of microbes carried by commensal rodent species and highlight the need for improved pathogen surveillance and disease monitoring in urban environments. Importance: The observation that most emerging infectious diseases of humans originate in animal reservoirs has led to wide-scale microbial surveillance and discovery programs in wildlife, particularly in the developing world. Strikingly, less attention has been focused on commensal animals like rats, despite their abundance in urban centers and close proximity to human populations. To begin to explore the zoonotic disease risk posed by urban rat populations, we trapped and surveyed Norway rats collected in New York City over a 1-year period. This analysis revealed a striking diversity of known pathogens and novel viruses in our study population, including multiple agents associated with acute gastroenteritis or febrile illnesses in people. Our findings indicate that urban rats are reservoirs for a vast diversity of microbes that may affect human health and indicate a need for increased surveillance and awareness of the disease risks associated with urban rodent infestation