A Review on The Pathogenesis of Cardiovascular Disease of Flaviviridea Viruses Infection.

Members of the Flaviviridae family, encompassing the Flavivirus and Hepacivirus genera, are implicated in a spectrum of severe human pathologies. These diseases span a diverse spectrum, including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, and adverse fetal outcomes, such as congenital heart defects and increased mortality rates. Notably, infections by Flaviviridae viruses have been associated with substantial cardiovascular compromise, yet the exploration into the attendant cardiovascular sequelae and underlying mechanisms remains relatively underexplored. This review aims to explore the epidemiology of Flaviviridae virus infections and synthesize their cardiovascular morbidities. Leveraging current research trajectories and our investigative contributions, we aspire to construct a cogent theoretical framework elucidating the pathogenesis of Flaviviridae-induced cardiovascular injury and illuminate prospective therapeutic avenues.

Investigating the impact of protein S-sulfhydration modification on vascular diseases: A comprehensive review.

The post-translational modification of cysteine through redox reactions, especially S-sulfhydration, plays a critical role in regulating protein activity, interactions, and spatial arrangement. This review focuses on the impact of protein S-sulfhydration on vascular function and its implications in vascular diseases. Dysregulated S-sulfhydration has been linked to the development of vascular pathologies, including aortic aneurysms and dissections, atherosclerosis, and thrombotic diseases. The H2S signaling pathway and the enzyme cystathionine γ-lyase (CSE), which is responsible for H2S generation, are identified as key regulators of vascular function. Additionally, potential therapeutic targets for the treatment of vascular diseases, such as the H2S donor GYY4137 and the HDAC inhibitor entinostat, are discussed. The review also emphasizes the antithrombotic effects of H2S in regulating platelet aggregation and thrombosis. The aim of this review is to enhance our understanding of the function and mechanism of protein S-sulfhydration modification in vascular diseases, and to provide new insights into the clinical application of this modification.

The hydroxamic acid derivative YPX-C-05 alleviates hypertension and vascular dysfunction through the PI3K/Akt/eNOS pathway.

BACKGROUND: Hypertension is a prevalent cardiovascular disease characterized by elevated blood pressure and increased vascular resistance. HDAC inhibitors have emerged as potential therapeutic agents due to their ability to modulate gene expression and cellular processes. YPX-C-05, a novel hydroxamic acid-based HDAC inhibitor, shows promise in its vasodilatory effects and potential targets for hypertension treatment. In this study, we aimed to elucidate the mechanisms underlying YPX-C-05's vasodilatory effects and explore its therapeutic potential in hypertension. METHODS: To determine the ex vivo vasodilatory effects of YPX-C-05, isolated aortic rings precontracted with phenylephrine were used. We assessed YPX-C-05's inhibitory effects on HDACs and its impact on histone H4 deacetylation levels in endothelial cells. Network pharmacology analysis was employed to predict putative targets of YPX-C-05 for hypertension treatment. To investigate the involvement of the PI3K/Akt/eNOS pathway, we employed enzyme-linked immunosorbent assay and to assess the levels of NO, ET-1, BH2, and BH4 in human umbilical vein endothelial cells. And we also analyzed the mRNA expression of eNOS and ET-1. Furthermore, Western blotting was conducted to quantify the phosphorylated and total Akt and eNOS levels in human umbilical vein endothelial cell lysates following treatment with YPX-C-05. In order to elucidate the vasodilatory mechanism of YPX-C-05, we employed pharmacological inhibitors for evaluation purposes. Furthermore, we evaluated the chronic antihypertensive effects of YPX-C-05 on N-omega-nitro-L-arginine-induced hypertensive mice in an in vivo model. Vascular remodeling was assessed through histological analysis. RESULTS: Our findings demonstrated that YPX-C-05 exerts significant vasodilatory effects in isolated aortic rings precontracted with phenylephrine. Furthermore, YPX-C-05 exhibited inhibitory effects on HDACs and increased histone H4 acetylation in endothelial cells. Network pharmacology analysis predicted YPX-C-05 might activate endothelial eNOS via PI3K/Akt signaling pathway. Inhibition of the PI3K/Akt/eNOS pathway attenuated the vasodilatory effects of YPX-C-05, as evidenced by reduced levels of phosphorylated Akt and eNOS in human umbilical vein endothelial cell lysates. The chronic administration of YPX-C-05 in N-omega-nitro-L-arginine-induced hypertensive mice resulted in significant antihypertensive effects. Histological analysis demonstrated a reduction in vascular remodeling, further supporting the therapeutic potential of YPX-C-05 in hypertension. CONCLUSION: This study demonstrates for the first time that the novel hydroxamic acid-based HDAC inhibitor YPX-C-05 produces significant antihypertensive and vasodilatory effects through the PI3K/Akt/eNOS pathway. Our findings support the developing prospect of YPX-C-05 as a novel antihypertensive drug.

IBIL Measurement and Optical Simulation of the DI Center in 4H-SiC.

In this paper, DI defects are studied via experiments and calculations. The 2 MeV H+ is used to carry on an ion-beam-induced luminescence (IBIL) experiment to measure the in-situ luminescence of untreated and annealed 4H-SiC at 100 K. The results show that the luminescence intensity decreases rapidly with increasing H+ fluence, which means the losses of optical defect centers. In addition, the evident peak at 597 nm (2.07 eV) is the characteristic peak of 4H-SiC, and the weak peak between 400 nm and 450 nm is attributed to the DI optical center. Moreover, the first-principles calculation of 4H-SiC is adopted to discuss the origin of DI defects. The optical transition of the defect SiC(CSi)2 from q = 0 to q = 1 is considered the experimental value of the DI defect center.

Synthesis and vasorelaxant evaluation of novel 7-methoxyl-2,3-disubstituted-quinoxaline derivatives.

An array of novel 7-methoxyl-2,3-disubstituted quinoxaline derivatives was designed, synthesized and their potential antihypertensive activities were examined, in an attempt to discover potent small molecules with vasorelaxant effects. The vasoactivities of these compounds on vascular tone, as well as underlying mechanisms were hereby explored. Results showed that five compounds (7s, 7t, 7v, 7w, 7γ) could induce endothelium-independent relaxation in high extracellular K+- and phenylephrine-precontracted C57 mice aortic rings. These five compounds, unlike other commonly used vasodilators, could slowly but effectively inhibit vasoconstriction.

The Immunogenicity of OMP31 Peptides and Its Protection Against Brucella melitensis Infection in Mice.

Given brucellosis is a widespread zoonosis in the world, a safe and effective vaccine is urgently needed. Recent trend in vaccine design has shifted to epitope-based vaccines that are safe and specific. In this study, peptide containing both T-cell and B-cell epitopes of OMP31 was synthesized and used to immunize the mice by nasal administration. The protective efficacy was evaluated. Mice immunized with the B epitope or TB epitope peptides of OMP31 had higher levels of IgG1 and IgG2a in the serum. While the BALB/c mice immunized with peptides containing T cell epitope or TB epitope of OMP31 showed high degree of IFN-γ-producing T cells in the lymphocytes from the respiratory draining lymph nodes and spleen. After intranasally challenged with 5 × 105 CFU of Brucella melitensis (strain 16 M), the bacterial loads in lung of the immunized mice were significantly lower than control group. These data demonstrate for the first time that peptides of OMP31 containing T epitope, B epitope or TB epitopes are of high immunogenicity and thus can protect host from Brucella melitensis infection in lung.

Seizure syndrome as a first manifestation of solitary tumor-like mass lesion of PACNS: Two case reports.

RATIONALE: Primary angiitis of the central nervous system (PACNS) is an inflammatory disease involving cerebrovascular and parenchymal, and solitary tumor-like mass lesion of PACNS (TLML-PACNS) is frequently misdiagnosed as neoplastic or other inflammatory diseases. However, seizure syndrome as a first manifestation of TLML-PACNS has rarely reported before. PATIENT CONCERNS: Here, we report 2 cases of seizure syndrome, which was the first sign that presented prior to the diagnosis of TLML-PACNS by brain biopsy. DIAGNOSES: A mass lesion in the white and gray matters was detected by magnetic resonance imaging. The pathology for leptomeningeal lesion biopsy observed a transmural inflammation of the artery, with T lymphocyte infiltration. Patients were diagnosed with PACNS and epileptic seizure by biopsy and electroencephalogram. INTERVENTIONS: Patients were treated with glucocorticoid pulse therapy for 3 days, and subsequently oral prednisone was continued, in combination with immunosuppressant. OUTCOMES: Luckily, both two patients were improved after treatment, and only mild cognitive impairment remained without adverse event. LESSONS: Patient with mass lesion in CNS, which is similar to tumor, presented with seizure, headache, or cerebrovascular events without any other risk factors for stroke or tumor, should be considered the feasible with the disease of TLML-PACNS.

[Increased serum levels of soluble programmed death-1 (sPD-1) and sPD-ligand 1 in patients infected with Brucella].

Objective To investigate the alterations of soluble molecule programmed death 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1), as well as related Th1 cytokines IFN-γ and Th2 cytokines IL-4 in patients infected with Brucella. Methods The study enrolled 56 patients infected with Brucella and 48 healthy controls. Serum sPD-1 and sPD-L1 were detected by ELISA and the levels of Th1/Th2 cytokines were measured with cytometric bead array (CBA). Among them, 37 patients received follow-up. Results Compared with the control group, the serum levels of sPD-1/sPD-L1 and IL-4 increased significantly, while the level of IFN-γ decreased significantly. In the 37 patients receiving follow-up after treatment, serum levels of sPD-1/sPD-L1 and IL-4 were remarkably lower than those in pretherapy, while the level of IFN-γ was obviously higher than that in pretherapy. Conclusion The increase of sPD-1 and sPD-L1 may be involved in the process of Brucella infection.

[Increased expressions of Blimp-1 and Bcl-6 in the deciduas of patients with unexplained recurrent spontaneous abortion].

Objective To oberseve the expressions of B cell lymphoma 6 (Bcl-6) and B lymphocyte-induced maturation protein 1 (Blimp-1) in the decidua of patients with unexplained recurrent spontaneous abortion (URSA), and investigate the roles that Bcl-6 and Blimp-1 act in URSA. Methods Decidual tissues were collected from patients with URSA (URSA group) and normal pregnant women (control group). Then, we detected the expressions of Bcl-6 and Blimp-1 in the deciduas of the two groups using real-time fluorescent quantitative PCR and immunohistochemistry. The relationship between Blimp-1 and Bcl-6 was estimated by Pearson's correlation analysis. Results Compared with the control group, the levels of Blimp-1 mRNA and protein, Bcl-6 mRNA significantly increased in the URSA group. However, Bcl-6 protein was raised insignificantly in URSA group. Furthermore, there was a positive correlation between Bcl-6 and Blimp-1 at the level of mRNA. Conclusion The expressions of Bcl-6 and Blimp-1 are enhanced in the deciduas of URSA patients.