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Glycyrrhizic acid (GA) is the main active ingredient extracted from Chinese herb licorice root, and it shows anti-tumor effects in many cancer types, while its role in gastric cancer (GC) is still unknown. In this study, we evaluated the effects of GA on GC cells and explored the underlying mechanisms. Methods: The anti-proliferation effect of GA on GC cells was assessed by CCK-8, colony formation, and EdU assay. The effects of GA on cell cycle and apoptosis were detected by flow cytometer. Western blotting was performed to explore the underlying mechanisms. Results: Our results showed that GA had a time-and dose-dependent inhibitory effect on proliferation of GC cells. Flow cytometer analysis demonstrated that GA would lead to G1/ S-phase arrest and apoptosis. GA treatment down-regulated the levels of G1 phase-related proteins, including cyclin D1, D2, D3, E1, and E2. In terms of apoptosis, GA treatment upregulated the levels of Bax, cleaved PARP, and pro-caspase-3,-8,-9, but did not influence their cleavage patterns. The expression of Bcl-2, survivin and p65 was attenuated after treatment. Besides, GA would down-regulate the phosphorylation of PI3K/AKT pathway. Conclusion: This study focused on inhibitory effect of GA on GC cells by inducing cell cycle arrest and apoptosis. Several important cyclins-and apoptosis-related proteins were involved in the regulation of GA to GC cells, and phosphorylated PI3K and AKT were attenuated. The results of this study indicated that GA is a potential and promising anticancer drug for GC.

The dysfunction of endothelial cells (ECs) plays crucial roles in vascular remodeling during hypertension. Researches suggested that ECs are regulated by the circulating platelets in vivo, which may participate in abnormal EC apoptosis in hypertension. However the molecular mechanism in this process is still unclear. Here we focused on the microRNAs (miRs) in platelets, and detected the potential role and delivery mechanism of platelet-derived miRs in ECs. Using microarray, the differentially expressed profile of miRs between platelets and ECs was detected. The results revealed that compared with ECs, 67 miRs highly expressed in platelets including the most significant one- miR-142-3p. Since platelets are activated by thrombin in hypertension, we detected the miR-142-3p transferring mechanism of activated platelet, and proved that platelet-derived microparticles (PMPs), but not platelets directly, delivered miR-142-3p into ECs via cellular adherent. Furthermore, BCL2L1, an important molecule in cell apoptosis, was predicted to be a putative target of miR-142-3p by multiple algorithms. Dual luciferase reporter assays, as well as miR-142-3p mimics treatment were used to confirm the interplay between miR-142-3p and BCL2L1. Meanwhile, using in vivo hypertensive rat model, our results showed that the expression of platelet-derived miR-142-3p and the apoptosis were both significantly increased in ECs during hypertension. The present results suggested that platelet-derived miR-142-3p is delivered into ECs via PMPs, and may modulate the expression of target molecule- BCL2L1, which may subsequently display a negative function by modulating EC apoptosis in hypertension.

Background. The syndrome of maternally inherited diabetes and deafness (MIDD) is typically caused by the m.3243A>G mutation and widely considered maternally inherited. In our study, we aimed to investigate the heredity way of the m.3243A>G among pedigrees with MIDD and discover novel mitochondrial DNA mutations related to atypical clinical phenotypes. Methods. Heteroplasmy levels of the m.3243A>G mutation in peripheral blood, saliva, and urine sediment of 31 individuals from 10 unrelated pedigrees were measured by pyrosequencing. Clinical evaluations including endocrinological, audiological, and magnetic resonance imaging (MRI) examinations, mitochondrial function evaluation in peripheral blood mononuclear cells (PBMCs), and whole mitochondrial DNA (mtDNA) sequencing were performed among the spontaneous mutant pedigrees. Results. Among the 10 unrelated MIDD pedigrees, we found that the de novo m.3243A>G mutation occurred in the family 1957 (F1957). The proband (F1957-II-1) and her son (F1957-III-1) both manifested diabetes with mild bilateral sensorineural hearing loss (SNHL) and abnormal brain MRI, and F1957-III-1 also complained of severe nausea and vomiting. Mitochondrial function evaluation in PBMCs revealed an increased level of ROS generation and decreased levels of ATP and mitochondrial membrane potential (ΔΨm) in the two m.3243A>G carriers. Whole mtDNA sequencing also revealed a de novo heteroplasmic substitution at m.16093T>C in both the proband and her son. Conclusions. Our study showed that de novo m.3243A>G mutation accompanied by other point mutations may occur in the very early embryonic or germ cell stage without maternal inheritance, bringing about both typical and atypical clinical features.

Aims To investigate the associations among heteroplasmy levels (i.e. the proportions of mutant and wild-type mitochondrial DNA in the same cell), mitochondrial function and clinical severity of the m.3243A>G mutation.Methods A total of 17 participants carrying the m.3243A>G mutation and 17 sex-and age-matched healthy controls were included in this study. Heteroplasmy levels of the m.3243A>G mutation in leukocytes, saliva and urine sediment were determined by pyrosequencing. The clinical evaluation included endocrinological, audiological and ophthalmological examinations. Mitochondrial function was determined in peripheral blood mononuclear cells isolated from participants.Results Heteroplasmy levels in urine sediment were higher than those in leukocytes and saliva. Reduced levels of adenosine triphosphate and mitochondrial membrane potential, and increased reactive oxygen species production were observed in mutant peripheral blood mononuclear cells (all P < 0.05). Linear regression analysis indicated that higher heteroplasmy levels in peripheral blood leukocytes were associated with increased levels of glycated albumin and HbA 1c , and decreased total hip bone mineral density T-score after adjustment for age and sex (all P < 0.05). Furthermore, mitochondrial membrane potential was independently associated with bone mineral density T-score at the femoral neck (P < 0.05).Conclusions Heteroplasmy levels in peripheral blood leukocytes and mitochondrial membrane potential in peripheral blood mononuclear cells were closely associated with clinical manifestations and were valuable for evaluation of the clinical severity of the m.3243A>G mutation.

Object: We aimed to identify the relationship between vertigo symptoms and the involvement of vestibular dysfunction in sudden sensorineural hearing loss (SSNHL) and the contribution of audiogram classification.Methods: A total of 50 patients with unilateral SSNHL were retrospectively divided into the vertigo group and non-vertigo group depending on the presence of vertigo. The involved vestibular end organs (VEOs) were verified by a battery of vestibular function tests including video head impulse test (vHIT), cervical vestibular-evoked myogenic potential (cVEMP), and ocular VEMP (oVEMP). The correlations of audiogram configurations, initial pure-tone average (PTA), number of involved VEOs, prognosis (complete recovery rate), and vestibular functions were analyzed between the two groups. Additionally, the vestibular functions in a subgroup of profound SSNHL patients were further compared within groups with or without vertigo.Results: Significant differences in the initial audiogram configurations (p = 0.033) and the abnormal rates of the posterior semicircular canal (PSC) (p = 0.035) and oVEMP (p = 0.046) were found between the two groups. The number of involved VEOs was related to the initial PTA in the vertigo group (p = 0.002, r = 0.541) and non-vertigo group (p = 0.042, r = 0.446). The prognosis was related to the abnormal rate of cVEMP and the number of involved VEOs in both vertigo group (p = 0.008, r = 0.482; p = 0.039, r = 0.385, respectively) and non-vertigo group (p = 0.016, r = 0.520; p = 0.022, r = 0.495, respectively), and it was especially related to the audiogram configurations in the vertigo group (p &lt; 0.001, r = 0.692). However, after classification by audiogram configurations, there was no statistical difference in the abnormal rates of all vestibular function tests or the number of involved VEOs between the profound SSNHL patients with or without vertigo.Conclusion: The relationship between the involvement of vestibular dysfunction and vertigo symptoms in patients with SSNHL was significantly different before and after audiogram classification. When evaluating the vestibular dysfunction in SSNHL patients, more attention should be paid to the audiogram configuration.

Drug treatment for prehypertension may help stem the current epidemic of hypertension among Chinese adults free of CVD, which may in turn reduce CVD complications and potentially be cost effective.

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