- Evaluation of the hepatoprotective, anti-inflammatory, antinociceptive and antiepileptic activities of Chrysanthemum trifurcatum. [Journal Article]
- BPBiomed Pharmacother 2019 Jun 21; 117:109123
- Chrysanthemum trifurcatum is common to Mediterranean countries and widely-used in traditional medicine. Due to the scarcity of data about the pharmacological properties of C. trifurcatum, this presen…
Chrysanthemum trifurcatum is common to Mediterranean countries and widely-used in traditional medicine. Due to the scarcity of data about the pharmacological properties of C. trifurcatum, this present study was designed to determine the effects of C. trifurcatumethanolic extract (CEE) for its anti-nociceptive, anti-epileptic, anti-inflammatory, and hepatoprotective activities in mice and rat models. We demonstrate that CEE contains alkaloids, carbohydrates, and flavonoids, and in a dose-dependent (300 and 500 mg/kg) manner exhibited significant reductions in paracetamol (PCM; 500 mg/kg)-induced increased serum AST, ALT and ALP levels, similar to as seen by silymarin (25 mg/kg). Additionally, CEE (300 mg/kg) elicited inhibition in acetic acid-induced abdominal writhes, delayed latency time to paw's licking in hot plate tests, exerted an anti-convulsant effect by prolonging the onset of clonic and tonic convulsions, and reduced pentylenetetrazole (PTZ; 80 mg/kg)-induced mortality. Moreover, CEE (500 mg/kg) exhibited a prominent reduction in carrageenan-induced paw edema. These studies indicate that CEE possesses profound central and peripheral analgesic, anti-convulsant, anti-inflammatory, and hepatoprotective activities.
- Orexin-A protects against oxygen-glucose deprivation/reoxygenation-induced cell damage by inhibiting endoplasmic reticulum stress-mediated apoptosis via the Gi and PI3K signaling pathways. [Journal Article]
- CSCell Signal 2019 Jun 21; :109348
- The neuropeptide orexin-A (OXA) has a neuroprotective effect, acting as an anti-apoptotic factor in response to multiple stimuli. Apoptosis induced by endoplasmic reticulum stress (ERS) underlies oxy…
The neuropeptide orexin-A (OXA) has a neuroprotective effect, acting as an anti-apoptotic factor in response to multiple stimuli. Apoptosis induced by endoplasmic reticulum stress (ERS) underlies oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell damage, an in vitro model of ischemia/reperfusion injury. However, that OXA inhibits ERS-induced apoptosis in the OGD/R model has not been reported. In the present study, we investigated the neuroprotective effect of OXA (0.1 μM) on OGD/R-induced damage in the human neuroblastoma cell line SH-SY5Y. After OXA treatment following 4 h oxygen-glucose deprivation (OGD) and then 4 h reoxygenation (R), cell morphology, viability, and apoptosis were analyzed by histology, Cell Counting Kit-8 assay, and flow cytometry, respectively. Western blotting was used to measure expression levels of ERS- and apoptosis-related proteins. To determine signaling pathways involved in OXA-mediated neuroprotection, the Gi pathway inhibitor pertussis toxin (PTX; 100 ng/mL) and PI3K inhibitor LY294002 (LY; 10 μM) were added. In addition, in order to prove the specificity of these characteristics, the OXA antagonist Suvorexant (DORA; Ki of 0.55 nM and 0.35 nM for OX1R and OX2R) was used for intervention. Our results showed that OGD/R induced cell damage, manifested as morphological changes and a significant decrease in viability. Furthermore, Western blotting detected an increase in ERS-related proteins GRP78, p-IRE1α, p-JNK, and Cleaved caspase-12, as well as apoptosis-related proteins Cleaved caspase-3 and Bax, and a decrease in the anti-apoptosis factor Bcl-2. OXA intervention alleviated the degree of cellular damage, and protein expression was also reversed. In addition, the protective effect of OXA was reduced by adding PTX and LY. Meanwhile, after the use of DORA, changes in the expression of related proteins were detected, and it was found that the protective effect of OXA was weakened. Collectively, our results indicate that OXA has a neuroprotective effect on OGD/R-induced cell damage by inhibiting ERS-induced apoptosis through the combined action of Gi and PI3K signaling pathways. These findings help to clarify the mechanism underlying the neuroprotective action of OXA, which should aid the development of further candidate drugs, and provide a new therapeutic direction for the treatment of ischemic stroke.
- Short-term and long-term prognosis after cardiac surgery: Do anaesthetics protect against ischemia-reperfusion injury? [Editorial]
- ACAnaesth Crit Care Pain Med 2019 Jun 13
- Butyrate promotes slow-twitch myofiber formation and mitochondrial biogenesis in finishing pigs via inducing specific microRNAs and PGC-1α expression1. [Journal Article]
- JAJ Anim Sci 2019 Jun 22
- The present study aimed to investigate the influence of dietary butyrate supplementation on muscle fiber-type composition and mitochondrial biogenesis of finishing pigs, and the underlying mechanisms…
The present study aimed to investigate the influence of dietary butyrate supplementation on muscle fiber-type composition and mitochondrial biogenesis of finishing pigs, and the underlying mechanisms. Thirty-two LY (Landrace × Yorkshire) growing pigs with BW of 64.9 ± 5.7 kg were randomly allotted to either control (basal diet) or butyrate diets (0.3% butyrate sodium). Compared with the control group, diet supplemented with butyrate tended to increase average daily gain (P < 0.10). Pigs fed butyrate diet had higher intramuscular fat content, marbling score and pH24 h, and lower shear force and L*24 h in longissimus thoracis (LT) muscle than that fed control diet (P < 0.05). Interestingly, supplemented with butyrate increased (P < 0.05) the mRNA level of myosin heavy chain I (MyHC-I) and the percentage of slow-fibers, and decreased (P < 0.05) the mRNA level of MyHC-IIb in LT muscle. Meanwhile, pigs in butyrate group had an increase in mitochondrial DNA (mtDNA) copy number and the mRNA levels of mtDNA-encoded genes (P < 0.05). Moreover, feeding butyrate diet increased PGC-1α (PPAR γ coactivator 1α) level, decreased miR-133a-3p level and increased its target gene level (TEAD1, TEA domain transcription factor 1), increased miR-208b and miR-499-5p levels and decreased their target genes levels (Sp3 and Sox6, specificity protein 3 and SRY-box containing gene 6; P < 0.05) in the LT muscle. Collectively, these findings suggested that butyrate promoted slow-twitch myofiber formation and mitochondrial biogenesis, and the molecular mechanism may be via upgrading specific microRNAs and PGC-1α expression, finally improving meat quality.
- Congregate Meal Program-How Can We Make It More Appealing? (P16-014-19). [Journal Article]
- CDCurr Dev Nutr 2019; 3(Suppl 1)
- CONCLUSIONS: These findings provide insight as to how the CMP may be modified to be more appealing to older adults. We suggest CMP promotion highlight the value of a healthy meal and the opportunities for socialization.
- Mode of progression after first line treatment correlates with outcome of chronic lymphocytic leukemia (CLL). [Journal Article]
- AJAm J Hematol 2019 Jun 20
- In CLL, progressive disease (PD) following remission after first line treatment can present with varying phenotypes. We hypothesized that the mode of PD correlates with clinical outcomes. Data from t…
In CLL, progressive disease (PD) following remission after first line treatment can present with varying phenotypes. We hypothesized that the mode of PD correlates with clinical outcomes. Data from three phase III trials of the GCLLSG (CLL8, CLL10, CLL11) including a total of 2159 patients receiving first line (immuno)-chemotherapy (FCR, FC, CLB, CLB-R, CLB-Ob) were analyzed. Patients were categorized as "ALC" if PD was due to increasing absolute lymphocyte count, or as "Ly" if due to lymphadenopathy. 241 patients progressed with ALC and 727 progressed with Ly, including 329 who progressed on both modalities. In fit patients, median TTNT after PD in the Ly group was 12.3 months vs 17.0 months in the ALC group (HR 1.299 [1.036-1.628]; p=0.024). Median OS after PD was 45.1 months in the Ly group and 42.4 months in the ALC group (HR=1.023 [0.753-1.389]; p=0.885). For unfit patients, median TTNT in the Ly group was 11.7 months vs 21.4 months in the ALC group (HR 1.357 [1.051-1.753]; p=0.019). Median OS was 42.8 months in the Ly group and not reached in the ALC group (HR 1.851 [1.280-2.677]; p=0.001). Patients in the Ly group more frequently showed impairment of quality of life (QoL). This analysis demonstrates that patients with progressive lymphadenopathy have a significantly shorter TTNT, OS and less favorable QoL. Our findings might help physicians to better estimate the clinical course of a progressing CLL patient. This article is protected by copyright. All rights reserved.
- Learning Curve for Endoscopic Submucosal Dissection With an Untutored, Prevalence-Based Approach in the United States. [Journal Article]
- CGClin Gastroenterol Hepatol 2019 Jun 17
- CONCLUSIONS: In an analysis of ESDs performed at a large referral center in the United States, we found that an untutored, prevalence-based approach allowed operators to achieve all proficiency benchmarks after ∼250 cases. Compared with Asia, ESD requires more time to learn in the West, where the untutored, prevalence-based approach requires resection of challenging lesions, such as colon lesions and previously manipulated lesions, in early stages of training.
- Metronomic combination chemotherapy using everolimus and etoposide for the treatment of non-Hodgkin lymphoma. [Journal Article]
- CMCancer Med 2019 Jun 20
- Patients with Non-Hodgkin lymphoma (NHL) treated by conventional chemotherapeutic drugs usually require a long recovery period. However, metronomic combination chemotherapy (MCC) enhances therapeutic…
Patients with Non-Hodgkin lymphoma (NHL) treated by conventional chemotherapeutic drugs usually require a long recovery period. However, metronomic combination chemotherapy (MCC) enhances therapeutic efficacy and decreases side effects in the treatment of NHL. In this study, we tested and compared the effects of metronomic chemotherapy (MC) using podophyllotoxin derivative etoposide (VP-16) alone and that of MCC using both VP-16 and everolimus (RAD001) in the treatment of NHL. Two types of NHL cells, OCI-LY-10 and SU-DHL-6, were employed for the experiments. Cell proliferation, apoptosis, and cell senescence were measured to test the effects of drugs in each experiment. In addition, the influences of MC and MCC on the cell cycle and autophagy pathway were evaluated to study the functional mechanisms behind their effects. Finally, we conducted analyses of the growth inhibitory effect and synergistic activity for different MCC. The results showed that MC using low-dose VP-16 alone demonstrated strong treatment effects in terms of inducing apoptosis, cell senescence, and reducing tumor cell proliferation, and this treatment also led to changes of the cell cycle. Compared with MC, MCC using VP-16 and RAD001 together demonstrated even stronger treatment effects, with both the cell cycle and autophagy-related proteins being affected. Considering the synergistic activity, our results showed the MCC of VP-16 48 hours + RAD001 24 hours is the optimal method for treating NHL.
- Cystic fibrosis disease severity correlates with plasma levels of desmosine and isodesmosine, biomarkers of elastin degradation. [Journal Article]
- EOERJ Open Res 2019; 5(2)
- Novel methodological approaches now demonstrate that the unique elastin degradation products desmosine and isodesmosine are detectable in plasma of cystic fibrosis patients and correlate to lung func…
Novel methodological approaches now demonstrate that the unique elastin degradation products desmosine and isodesmosine are detectable in plasma of cystic fibrosis patients and correlate to lung function, exacerbation frequency and disease progression http://bit.ly/2VwZOcx.
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- Airway obstruction is associated with reduced variability in specific parts of the tidal breathing flow-volume curve in young children. [Journal Article]
- EOERJ Open Res 2019; 5(2)
- Impedance pneumography recordings during sleep at night show reduced variability in specific parts of the expiratory flow-volume curve in children with recurrent wheeze http://bit.ly/2Wkfap0.
Impedance pneumography recordings during sleep at night show reduced variability in specific parts of the expiratory flow-volume curve in children with recurrent wheeze http://bit.ly/2Wkfap0.