The clinical value of combining shear wave elastography, VOCAL technique, and T2* MRI of early gestation placenta to predict pre-eclampsia.

OBJECTIVE: To investigate the clinical value of combining shear wave elastography (SWE) with the Volumetric Organ Computer-Aided AnaLysis (VOCAL) technique and T2* magnetic resonance imaging (MRI) to predict pre-eclampsia (PE). METHODS: From December 2022 to March 2023, we recruited 31 pregnant women diagnosed with PE at our hospital as the observation group and 85 normal pregnant women as the control group. Differences in placental elasticity, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and T2* MRI perfusion fraction (f) were compared between the two groups. Received operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of placental elasticity, VI, FI, VFI, f, and their combination for predicting PE. RESULTS: Placental elasticity was higher in the observation group than in the control group, while VI, FI, VFI, and f were lower in the observation group (all p < 0.05). The area under the curve (AUC) for placental elasticity, VI, FI, VFI, f, and their combination for predicting PE were 0.85, 0.77, 0.78, 0.84, 0.65, and 0.94, respectively. The sensitivity was 71%, 55%, 94%, 65%, 55%, and 81%. The specificity was 92%, 91%, 60%, 92%, 79%, and 98%. The combined prediction model had a higher AUC than the individual predictors (p < 0.05). CONCLUSION: SWE combined with VOCAL technique and T2* MRI has high value for predicting PE and can provide reference information for clinical diagnosis.

Pers reverse angiotensin II -induced vascular smooth muscle cell proliferation by targeting cyclin E expression via inhibition of the MAPK signaling pathway.

The circadian rhythm of blood pressure (BP) is believed to be regulated by the clock system, which is closely linked to levels of angiotensin II (Ang II). This study aimed to investigate whether Ang II mediates the proliferation of vascular smooth muscle cells (VSMCs) through the interaction between the clock system and the mitogen-activated protein kinase (MAPK) signaling pathway. Primary rat aortic VSMCs were treated with Ang II, with or without MAPK inhibitors. VSMC proliferation, expression of clock genes, CYCLIN E, and MAPK pathways were assessed. Ang II treatment resulted in increased VSMC proliferation and rapid upregulation of clock gene Periods (Pers) expression. Compared to the non-diseased control (NC) group, VSMCs incubated with Ang II displayed a noticeable delay in the G1/S phase transition and downregulation of CYCLIN E upon silencing of Per1 and Per2 genes. Importantly, silencing Per1 or Per2 in VSMCs led to decreased expression of key MAPK pathway proteins, including RAS, phosphorylated mitogen-activated protein kinase (P-MEK), and phosphorylated extracellular signal-regulated protein kinase (P-ERK). Moreover, the MEK and ERK inhibitors, U0126 and SCH772986, significantly attenuated the Ang II-induced proliferation of VSMCs, as evidenced by an increased G1/S phase transition and decreased CYCLIN E expression. The MAPK pathway plays a critical role in regulating VSMC proliferation in response to Ang II stimulation. This regulation is controlled by the expression of circadian clock genes involved in the cell cycle. These findings provide novel insights for further research on diseases associated with abnormal VSMC proliferation.

Valsartan-mediated chronotherapy in spontaneously hypertensive rats via targeting clock gene expression in vascular smooth muscle cells.

OBJECTIVE: This study was to investigate the underlying mechanisms of valsartan chronotherapy in regulating blood pressure variability. METHODS: RT-PCR was used to assay clock genes expression rhythm in the hypothalamus, aortic vessels, and target organs after valsartan chronotherapy. WB was used to measure Period 1 (Per1), Period 2 (Per2) protein expression in aortic vessels, as well as to measure phosphorylation of 20-kDa regulatory myosin light chain (MLC20) in VSMCs. RESULTS: Specific clock genes in the hypothalamus, and Per1 and Per2 in aorta abdominalis, exhibited disordered circadian expression in vivo. Valsartan asleep time administration (VSA) restored circadian clock gene expression in a tissue- and gene-specific manner. In vitro, VSA was more efficient in blocking angiotensin II relative to VWA, which led to differential circadian rhythms of Per1 and Per2, ultimately corrected MLC20 phosphorylation. CONCLUSION: VSA may be efficacious in regulating circadian clock genes rhythm, then concomitantly correct circadian blood pressure rhythms.

Stable Eu3+/Cu2+-Functionalized Supramolecular Zinc(II) Complexes as Fluorescent Probes for Turn-On and Ratiometric Detection of Hydrogen Sulfide.

Fabrication of dual-emitting materials for H2S sensing under environmental and biological conditions is currently of great interest. In this work, a new chemically stable metal supramolecular complex [Zn2(pda)2(H2O)3]·(H2O)0.5 (Znpda, pda = 1,10-phenanthroline-2,9-dicarboxylic acid), with accessible uncoordinated carboxylic oxygen sites, is solvothermally synthesized. It can serve as a host in luminescent hybrid composites. By incorporating Eu3+ and Cu2+ in the supramolecular coordination network, we obtained the dual-emitting hybrid material Eu3+/Cu2+@Znpda, which simultaneously shows intense ligand and weak Eu3+ emissions in HEPES buffer solution. Since H2S can easily chelate with Cu2+ and recover the blocked "antenna effect" between the ligand and Eu3+, Eu3+/Cu2+@Znpda possesses both the turn-on and ratiomectric fluorescence response to H2S. Accordingly, we designed an IMPLICATION logic gate for H2S recognition by employing the fluorescence intensity ratio between the ligand and Eu3+ as the output signal. In addition, Eu3+/Cu2+@Znpda shows a fast response (<1 min) and high sensitivity (1.45 µM) to H2S over other interfering species in the HEPES buffer solution, highlighting its potential use for H2S sensing under environmental and biological conditions.

α-Mangostin reduced the viability of A594 cells in vitro by provoking ROS production through downregulation of NAMPT/NAD.

α-Mangostin (MAN) is a bioactive compound isolated from the inedible pericarp of a tropical fruit mangosteen (Garcinia mangostana Linn). It exhibits notable therapeutic potentials on lung cancers, but the underlying mechanisms are still largely unknown. This study was designed to further explore the mechanisms involved in cytotoxicity of MAN on A549 cells. Apoptosis and cell cycle distribution were analyzed by flow cytometry methods. The fluorescent probes DCFH-DA and JC-1 were used to assess the intracellular reactive oxidative species (ROS) and mitochondrial membrane potential statuses, respectively. The regulation of MAN on relevant pathways was investigated by immunoblotting assays. The results obtained indicated that MAN caused significant apoptosis and cell cycle arrest in A549 cells, which eventually resulted in inhibition on cell proliferation in vitro. All these phenomena were synchronized with escalated oxidative stress and downregulation of nicotinamide phosphoribosyltransferase/nicotinamide adenine dinucleotide (NAMPT/NAD). Supplementation with nicotinamide mononucleotide (NMN) and N-acetylcysteine (NAC) efficiently eased MAN-induced ROS accumulation, and potently antagonized MAN-elicited apoptosis and cell cycle arrest. The pro-apoptotic effect of MAN was further confirmed by increased expressions of cleaved caspase 3, 6, 7, and 9, and its effect on cell cycle progression was validated by the altered expressions of p-p38, p-p53, CDK4, and cyclin D1. The immunoblotting assays also demonstrated that NAC/NMN effectively restored these molecular changes elicited by MAN treatment. Collectively, this study revealed a unique anti-tumor mechanism of MAN by provoking ROS production through downregulation of NAMPT/NAD signaling and further validated MAN as a potential therapeutic reagent for lung cancer treatment.

Valsartan chronotherapy reverts the non-dipper pattern and improves blood pressure control through mediation of circadian rhythms of the renin-angiotensin system in spontaneous hypertension rats.

Background: Numerous clinical studies have evaluated valsartan and found more efficacious control of blood pressure (BP) variability when administered before sleep. The treatment leads to improved outcomes when compared to administration upon awakening. The mechanism underlying this etiology is not fully understood. The present study investigates the safety and efficacy of asleep administration of valsartan in spontaneously hypertensive rats (SHR) with a non-dipping blood pressure pattern compared to SHRs receiving administration during awake time. Materials and Methods: 84 Male SHRs and 28 male Wistar-Kyoto rats (WKY) were kept under a strict alternating 12-h light/dark cycle. WKYs were utilized as a non-disease control. Meanwhile, SHRs were randomly divided into three groups: untreated, Valsartan asleep administration (VSA) and Valsartan awake administration (VWA) respectively. The VSA group was treated with valsartan (30 mg/kg/d) after the light onset, while the VWA group was treated with valsartan (30 mg/kg/d) after light offset. Both groups were treated for 6 weeks. Tail artery blood pressure was measured every 4 h via a noninvasive tail cuff blood pressure measurement method. HE and Masson staining were used to evaluate any damage within the target organs. ELISA was used to determine the 24-h plasma renin-angiotensin system (RAS) concentration at 4-h intervals. Results: Based on our findings, VSA significantly reduced 24-h and evening mean BP and restored the abnormal circadian rhythm compared to VWA, which attenuated injuries in the majority of target organs except for the kidneys. Furthermore, VSA was found to activate RAS during the light cycle and inhibit it during the dark cycle. Conversely, VWA was found to deactivate RAS throughout the day which may be related to the circadian BP rhythm. Conclusion: VSA may be more efficacious than VWA in controlling BP, circadian BP rhythm and blood RAS rhythm. Recent cardiovascular outcome investigations substantiate that chronotherapy treatment might be a novel therapeutic strategy for hypertension therapy. Abbreviations: Angiotensin-converting enzyme (ACE); Angiotensin converting enzyme inhibitors (ACEIs); Angiotensin II (ANG II); Analysis of variance (ANOVA); Angiotensin receptor blockers (ARBs); Blood Pressure (BP); Calcium Antagonists Calcium Channel Blockers (CCB); Chronic kidney diseases (CKD); Sodium carboxyl methyl cellulose (CMC-Na); Cardiac mass index (CMI); Cardiovascular diseases (CVD); Diastolic blood pressure (DBP); Enzyme-linked immunosorbent assay (ELISA); Hematoxylin-eosin (H&E); Kidney mass index (KMI); Liver mass index (LMI); Mean arterial blood pressure (MAP); Plasma renin concentration (PRC); Renin-angiotensin system (RAS); Rennin (REN); Systolic blood pressure (SBP); Student-Newman-Keuls q test (SNK-q test); Spontaneous hypertension rats (SHR); Valsartan asleep Administration (VSA); Valsartan awake Administration (VWA); Wistar-Kyoto (WKY); Mesor (M); Amplitude (A); Phase (φ).