Anti-inflammatory activity and chemical composition of the essential oils from Senecio flammeus

Many species from Senecio genus have been used in traditional medicine, and their pharmacological activities have been demonstrated. This study investigated the chemical composition and anti-inflammatory activities of essential oils from Senecio flammeus. A total of 48 components representing 98.41 % of the total oils were identified. The main compounds in the oils were α-farnesene (11.26 %), caryophyllene (8.69 %), n-hexadecanoic acid (7.23 %), and α-pinene (6.36 %). The anti-inflammatory activity of the essential oils was evaluated in rodents (10–90 mg/kg bw) in classical models of inflammation [carrageenan-induced paw edema, 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ear edema, and cotton pellet-induced granuloma]. The essential oils at doses of 10, 30, and 90 mg/kg bw significantly reduced carrageenan-induced paw edema by 17.42 % (P < 0.05), 52.90 % (P < 0.05), and 66.45 % (P < 0.05) 4 h after carrageenan injection, respectively, and significantly reduced myeloperoxidase activity (P < 0.05). The essential oils (10, 30, and 90 mg/kg) also produced asignificant dose-dependent response to reduce TPA-induced ear edema by 20.27 % (P < 0.05), 33.06 % (P < 0.05), and 53.90 % (P < 0.05), respectively. The essential oils produced significant dose-response anti-inflammatory activity against cotton pellet-induced granuloma that peaked at the highest dose of 90 mg/kg (49.08 % wet weight and 47.29 % dry weight). Results demonstrate that the essential oils of S. flammeus were effective in the treatment of both acute and chronic inflammatory conditions, there by supporting the traditional use of this herb

Anti-inflammatory effect of selagin-7-O-(6''-O-acetyl-)-ß-D-glycoside isolated from Cancrinia discoidea on lipopolysaccharide-induced mouse macrophage RAW 264.7 cells

Selagin-7-O-(6''-O-acetyl-)-β-D-glycoside, a new flavone glycoside isolated from Cancrinia discoidea, is known to exhibit anti-inflammatory activity in vivo. This study aimed to investigate the protection of this flavone glycoside on inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The effects of selagin-7-O-(6''-O-acetyl-)-β-D-glycoside on inflammatory cytokines and signaling pathways were analyzed by enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and western blot. Results show that selagin-7-O-(6''-O-acetyl-)-β-D-glycoside protected LPS-induced macrophage RAW 264.7 cells from injury. The flavone glycoside markedly inhibited the LPS-induced production of tumor necrosis factor-α, interleukin-1β, and interleukin-6 and increased interleukin-10 release in a concentration-dependent manner. Furthermore, treatment with the flavone glycoside decreased nitric oxide and prostaglandin E2 in LPS-challenged RAW 264.7 cells. These decreases were associated with the down-regulation of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and nuclear factor kappa B (NF-κB) activity. These findings suggest that the anti-inflammatory effects of selagin-7-O-(6''-O-acetyl-)-β-D-glycoside were associated with the adjustment of in flammatory cytokines, and attributed to the down-regulation of NF-κB and consequent suppression of the expression of iNOS and COX-2

The Role of Deubiquitinases in DNA Double-Strand Break Repair

DNA double-strand break (DSB) is a type of the most critical DNA lesions, and if not repaired promptly, it can result in cell death or a wide variety of genetic alterations including genome instability, large- or small-scale deletions, chromosome loss, loss of heterozygosity, and translocations. DSBs are repaired by double-strand break repair (DSBR), including nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathway, and defects in these pathways cause genome instability and promote tumorigenesis. Accumulating evidence has demonstrated that the superfamily of deubiquitinases (DUBs) can regulate the action and stability of DNA repair enzymes involving in DSBR via modifying ubiquitination levels, a reversible posttranslational modification pathway. In this review, we will discuss ubiquitination/deubiquitination modification involving in DSBR genes, the role of DUBs in DSBR and corresponding mechanisms, and the potential effects of this modification on human diseases

LC/MS Guided Isolation of Alkaloids from Lotus Leaves by pH-Zone-Refining Counter-Current Chromatography

The traditional methods used in natural product separation primarily target the major components and the minor components may thus be lost during the separation procedure. Consequently, it’s necessary to develop efficient methods for the preparative separation and purification of relatively minor bioactive components. In this paper, a LC/MS method was applied to guide the separation of crude extract of lotus (Nelumbo nucifera Gaertn.) leaves whereby a minor component was identified in the LC/MS analysis. Afterwards, an optimized pH-zone-refining CCC method was performed to isolate this product, identified as N-demethylarmepavine. The separation procedure was carried out with a biphasic solvent system composed of hexane-ethyl acetate-methyl alcohol-water (1:6:1:6, v/v) with triethylamine (10 mM) added to the upper organic phase as a retainer and hydrochloric acid (5 mM) to the aqueous mobile phase eluent. Two structurally similar compounds – nuciferine and roemerine – were also obtained from the crude lotus leaves extract. In total 500 mg of crude extract furnished 7.4 mg of N-demethylarmepavine, 45.3 mg of nuciferine and 26.6 mg of roemerine with purities of 90%, 92% and 96%, respectively. Their structures were further identified by HPLC/ESI-MSn, FTICR/MS and the comparison with reference compounds

Hepatocarcinoma Angiogenesis and DNA Damage Repair Response: An Update

Hepatocarcinoma is one of the most common lethal human malignant tumors, mainly because of active angiogenesis. This kind of high angiogenesis often accounts for early metastasis, rapid recurrence, and poor survival. Growing evidence has proved that hepatocarcinoma angiogenesis is closely associated with multiple risk factors, such as DNA damages resulting from hepatitis B and C virus infection, aflatoxin B1 exposure, ethanol intake, and obesity. Genetic alterations and genomic instability, probably resulting from low DNA damage repair response (DRR) and the following unrepaired DNA lesions, are also increasingly recognized as important risk factors of hepatocarcinoma angiogenesis. Dysregulation of DRRs and signaling to cell cycle checkpoints involving in DRR pathways may accelerate the accumulation of DNA damages and trigger the dysregulation of angiogenesis-related genes and the progression of hepatocarcinoma. In this review, we discussed DNA damages/DRRs and angiogenesis during hepatocarcinogenesis and their interactive regulations. Hopefully, the review will also remind the medical researchers and clinic doctors of further understanding and validating the values of DNA damages/DRRs in hepatocarcinoma angiogenesis

Ulinastatin attenuates oxidation, inflammation and neural apoptosis in the cerebral cortex of adult rats with ventricular fibrillation after cardiopulmonary resuscitation

OBJECTIVE: The role of Ulinastatin in neuronal injury after cardiopulmonary resuscitation has not been elucidated. We aim to evaluate the effects of Ulinastatin on inflammation, oxidation, and neuronal injury in the cerebral cortex after cardiopulmonary resuscitation. METHODS: Ventricular fibrillation was induced in 76 adult male Wistar rats for 6 min, after which cardiopulmonary resuscitation was initiated. After spontaneous circulation returned, the rats were split into two groups: the Ulinastatin 100,000 unit/kg group or the PBS-treated control group. Blood and cerebral cortex samples were obtained and compared at 2, 4, and 8 h after return of spontaneous circulation. The protein levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were assayed using an enzyme-linked immunosorbent assay, and mRNA levels were quantified via real-time polymerase chain reaction. Myeloperoxidase and Malondialdehyde were measured by spectrophotometry. The translocation of nuclear factor-κB p65 was assayed by Western blot. The viable and apoptotic neurons were detected by Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). RESULTS: Ulinastatin treatment decreased plasma levels of TNF-α and IL-6, expression of mRNA, and Myeloperoxidase and Malondialdehyde in the cerebral cortex. In addition, Ulinastatin attenuated the translocation of nuclear factor-κB p65 at 2, 4, and 8 hours after the return of spontaneous circulation. Ulinastatin increased the number of living neurons and decreased TUNEL-positive neuron numbers in the cortex at 72 h after the return of spontaneous circulation. CONCLUSIONS: Ulinastatin preserved neuronal survival and inhibited neuron apoptosis after the return of spontaneous circulation in Wistar rats via attenuation of the oxidative stress response and translocation of nuclear factor-κB p65 in the cortex. In addition, Ulinastatin decreased the production of TNF-α, IL-6, Myeloperoxidase, and Malondialdehyde

Nogo-66 Promotes the Differentiation of Neural Progenitors into Astroglial Lineage Cells through mTOR-STAT3 Pathway

Background: Neural stem/progenitor cells (NPCs) can differentiate into neurons, astrocytes and oligodendrocytes. NPCs are considered valuable for the cell therapy of injuries in the central nervous system (CNS). However, when NPCs are transplanted into the adult mammalian spinal cord, they mostly differentiate into glial lineage. The same results have been observed for endogenous NPCs during spinal cord injury. However, little is known about the mechanism of such fate decision of NPCs. Methodology/Principal Findings: In the present study, we have found that myelin protein and Nogo-66 promoted the differentiation of NPCs into glial lineage. NgR and mTOR-Stat3 pathway were involved in this process. Releasing NgR from cell membranes or blocking mTOR-STAT3 could rescue the enhanced glial differentiation by Nogo-66. Conclusions/Significance: These results revealed a novel function of Nogo-66 in the fate decision of NPCs. This discover

GradedDAG: An Asynchronous DAG-based BFT Consensus with Lower Latency

To enable parallel processing, the Directed Acyclic Graph (DAG) structure is introduced to the design of asynchronous Byzantine Fault Tolerant (BFT) consensus protocols, known as DAG-based BFT. Existing DAG-based BFT protocols operate in successive waves, with each wave containing three or four Reliable Broadcast (RBC) rounds to broadcast data, resulting in high latency due to the three communication steps required in each RBC. For instance, Tusk, a state-of-the-art DAG-based BFT protocol, has a good-case latency of 7 communication steps and an expected worst latency of 21 communication steps. To reduce latency, we propose GradedDAG, a new DAG-based BFT consensus protocol based on our adapted RBC called Graded RBC (GRBC) and the Consistent Broadcast (CBC), with each wave consisting of only one GRBC round and one CBC round. Through GRBC, a replica can deliver data with a grade of 1 or 2, and a non-faulty replica delivering the data with grade 2 can ensure that more than 2/3 of replicas have delivered the same data. Meanwhile, through CBC, data delivered by different non-faulty replicas must be identical. In each wave, a block in the GRBC round will be elected as the leader. If a leader block has been delivered with grade 2, it and all its ancestor blocks can be committed. GradedDAG offers a good-case latency of 4 communication steps and an expected worst latency of 7.5 communication steps, significantly lower than the state-of-theart. Experimental results demonstrate GradedDAG’s feasibility and efficiency

Characteristics and outcomes of heart failure with recovered left ventricular ejection fraction

Aims There is an emerging interest in elucidating the natural history and prognosis for patients with heart failure with reduced ejection fraction (HFrEF) in whom left ventricular ejection fraction (LVEF) subsequently improves. The characteristics and outcomes were compared between heart failure with recovered ejection fraction (HFrecEF) and persistent HFrEF. Methods and results This is a retrospective study of adults who underwent at least two echocardiograms 3 months apart between 1 November 2015 and 31 October 2019 with an initial diagnosis of HFrEF. The subjects were divided into HFrecEF group (second LVEF > 40%, ≥10% absolute improvement in LVEF) and persistent HFrEF group (20% subgroups. The primary outcomes were all-cause mortality and rehospitalization. A total of 1160 HFrEF patients were included [70.2% male, mean (standard deviation) age: 62 ± 13 years]. On the second echocardiogram, 284 patients (24.5%) showed HFrecEF and 876 patients (75.5%) showed persistent HFrEF. All-cause mortality was identified in 23 (8.10%) HFrecEF and 165 (18.84%) persistent HFrEF, whilst 76 (26.76%) and 426 (48.63%) showed rehospitalizations, respectively. Survival analysis showed that the persistent HFrEF subgroup experienced a significantly higher mortality at 12 and 24 months and a higher hospitalization at 12, 24, 48, and more than 48 months following discharge. Multivariate Cox regression showed that persistent HFrEF had a higher risk of all-cause mortality [hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.49–3.56, P = 0.000] and rehospitalization (HR 1.85, 95% CI 1.45–2.36, P = 0.000) than the HFrecEF group. Subgroup analysis showed that the LVEF ≥ 20% improvement subgroup had lower rates of adverse outcomes compared with those with less improvement of 10–20%. Conclusions Heart failure with recovered ejection fraction is a distinct HF phenotype with better clinical outcomes compared with those with persistent HFrEF. HFrecEF patients have a relatively better short-term mortality at 24 months but not thereafter