Anti-inflammatory effects of quinolinyl analog of resveratrol targeting TLR4 in MCAO/R ischemic stroke rat model.

BACKGROUND: Among adults, stroke is the main causes of mortality and permanent disability. Neuroinflammation is one of the main causes of stoke-mediated neuronal death. Our previous study revealed that (E)-5-(2-(Quinolin-4-yl) vinyl) benzene-1, 3-diol (RV01), a quinolinyl analog of resveratrol, inhibits microglia-induced neuroinflammation and safeguards neurons from inflammatory harm. The preventive role of RV01 in ischemic stroke and its underlying cellular mechanisms and molecular targets remain poorly understood. PURPOSE: To investigate whether RV01 alleviates ischemia-reperfusion (I/R) injury by inhibiting microglia-mediated neuroinflammation and determine the potential molecular mechanisms and targets by which RV01 inhibits the I/R-mediated microglia activation. METHODS: Rat middle cerebral artery occlusion and reperfusion (MCAO/R) and BV-2 or primary microglial cells oxygen-glucose deprivation and reperfusion (OGD/R) models were established. The neurological behavior scores, 2, 3, 5-triphenyl tetrazolium chloride staining and immunofluorescence were used to detect the neuroprotective effect of RV01 in the MCAO/R rats. In addition, the mRNA expression levels of IL-6, TNF-α, and IL-1ß were detected to reveal the antineuroinflammatory effect of RV01. Moreover, a western blot assay was performed to explore the protein expression changes in NF-κB-mediated neuroinflammation. Finally, we identified TLR4 as an RV01 target through molecular docking, drug sensitivity target stability analysis, cellular thermal shift analysis, and surface plasmon resonance techniques. RESULTS: RV01 reduced the infarct volume and neurological deficits, increased the rotarod duration, and decreased the number of rightward deflections in the MCAO/R rats. RV01 inhibited the NF-κB signaling pathway in vitro and in vivo, as demonstrated by the reduction in the transcription factor p65-mediated expression of several inflammatory factors including IL-6, TNF-α, and IL-1ß. Further studies showed that its protective effect was associated with targeting the TLR4 protein. Notably, the anti-inflammatory effect of RV01 was markedly reinforced by the TLR4 knockdown, but inhibited by the overexpression of TLR4. Results revealed that the conditioned medium derived from the RV01-treated BV-2 cells significantly decreased the OGD/R-mediated neuronal damage. CONCLUSION: Our results are the first to reveal the protective effects of RV01 on cerebral ischemia, depending on its inhibitory effect on the NF-κB pathway by targeting TLR4. RV01 could be a potential protective agent in ischemic stroke treatment.

Evaluating the value of progressive muscle relaxation therapy for patients with lumbar disc herniation after surgery based on a difference-in-differences model.

We evaluate the value of progressive muscle relaxation (PMR) for patients with lumbar disc herniation after surgery based on a difference-in-differences model. A total of 128 patients with lumbar disc herniation who underwent surgery were randomly assigned to undergo either conventional intervention (conventional intervention group, n = 64) or conventional intervention combined with PMR (PMR group, n = 64). Perioperative anxiety level, stress level and lumbar function were compared between the two groups and compared pain between the two groups before and 1 week and 1 and 3 months after surgery. After 3 months, no one was lost to follow-up. At 1 day before surgery and 3 days after surgery, Self-rating Anxiety Scale score in the PMR group was significantly lower than that in the conventional intervention group (P < 0.05). At 30 min before surgery, heart rate and systolic blood pressure in the PMR group were significantly lower than those in the conventional intervention group (P < 0.05). After intervention, the scores of subjective symptoms, clinical signs and restrictions on activities of daily living were significantly higher in the PMR group than those in the conventional intervention group (all P < 0.05). Visual Analogue Scale score in the PMR group was significantly lower than that in the conventional intervention group (all P < 0.05). The amplitude of change in VAS score in the PMR group was greater than that in the conventional intervention group (P < 0.05). PMR can relieve perioperative anxiety and stress in patients with lumbar disc herniation, reduce postoperative pain and improve lumbar function.

Traffic light-type ratiometric fluorescence visual sensing of Cs+ in soybean oil based on dimension regulation of 2D perovskite nanosheets.

Determination of cesium ion in soybean oil is of high importance since the increasing risk from releasing of main component of nuclear waste cesium 137. The complex composition and high viscosity of soybean oil make it necessary to convert it into water phase by nitration before detection, so developing a simple, accurate and sensitive method for on-site sensing of Cs+ in soybean oil is still a big challenge. In this work, we report a traffic light-type ratiometric fluorescence strategy for the visual sensing of Cs+ in soybean oil based on dimensional regulation of two dimensional (PEA)2PbI4 perovskite nanosheets (NSs). The PEA+ in (PEA)2PbI4 NSs exchanged with Cs+ and lead to dimension of partial (PEA)2PbI4 NSs progressively increase from 2D to 3D CsPbI3 NCs. Resultantly, the fluorescence of (PEA)2PbI4 NSs decreases with a concomitant fluorescence enhancement of CsPbI3 NCs upon increasing the concentrations of Cs+, and the emission accordingly change from green, yellow to red with a high fluorescence colorimetric resolution up to 5.0 µM, make it successful to achieve on-site sensing of Cs+ in soybean oil just with naked eye in 5 min without any nitration, demonstrating a bright application future for determination of Cs+ in the soybean oil.

Hydrazine Hydrate Accelerates Neocuproine-Copper Complex Generation and Utilization in Alkyne Reduction, a Significant Supplement Method for Catalytic Hydrogenation.

Diimine (HN═NH) is a strong reducing agent, but the efficiency of diimine oxidized from hydrazine hydrate or its derivatives is still not good enough. Herein, we report an in situ neocuproine-copper complex formation method. The redox potential of this complex enable it can serve as an ideal redox catalyst in the synthesis of diimine by oxidation of hydrazine hydrate, and we successfully applied this technique in the reduction of alkynes. This reduction method displays a broad functional group tolerance and substrate adaptability as well as the advantages of safety and high efficiency. Especially, nitro, benzyl, boc, and sulfur containing alkynes can be reduced to the corresponding alkanes directly, which provides a useful complementary method to traditional catalytic hydrogenation. Besides, we applied this method in the preparation of the Alzheimer's disease drug CT-1812 and studied the mechanism.

[Efficacy of Shangbai ointment in alleviating pain in patients with acute ankle joint lateral collateral ligament injury: a randomized controlled trial].

OBJECTIVE: To investigate the effect of Shangbai ointment in relieving pain in patients with acute ankle joint lateral collateral ligament injury. METHODS: Fifty patients with unilateral ankle injury were randomized into Shangbai ointment treatment group and control group (n=25). The Visual Analog Scale (VAS) pain scores, ankle joint circumference, Kofoed score and self-rated lower limb function were recorded before and at 3, 7, and 14 days after the treatment. RESULTS: The baseline data were comparable between the two groups. The VAS pain score and swelling elimination in the treatment group were better than those in the control group at 3, 7, and 14 days after treatment; the Kofoed ankle score was higher in the treatment group than in the control group at 7 and 14 days after treatment. The patients in the treatment also reported better self-rated lower limb function than those in the control group at 7 and 14 days after the treatment. CONCLUSION: Shangbai ointment treatment can rapidly relieve pain in patients with acute ankle joint lateral collateral ligament injury and improve the functional scores of the joint.

A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.

Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer's disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the hippocampi of adult and aged mice as well as that of transgenic AD model mice. AT and its fractions also enhanced the proliferation of NPCs cultured in vitro. Further analysis identified α-asarone and ß-asarone as the two active constituents of AT in promoting neurogenesis. Our mechanistic study revealed that AT and asarones activated extracellular signal-regulated kinase (ERK) but not Akt, two critical kinase cascades for neurogenesis. Consistently, the inhibition of ERK activities effectively blocked the enhancement of NPC proliferation by AT or asarones. Our findings suggest that AT and asarones, which can be orally administrated, could serve as preventive and regenerative therapeutic agents to promote neurogenesis against age-related neurodegeneration and neurodegenerative disorders.

Small molecule 1'-acetoxychavicol acetate suppresses breast tumor metastasis by regulating the SHP-1/STAT3/MMPs signaling pathway.

Signal transducer and activator of transcription 3 (STAT3) is implicated breast cancer metastasis and represents a potential target for developing new anti-tumor metastasis drugs. The purpose of this study is to investigate whether the natural agent 1'-acetoxychavicol acetate (ACA), derived from the rhizomes and seeds of Languas galanga, could suppress breast cancer metastasis by targeting STAT3 signaling pathway. ACA was examined for its effects on breast cancer migration/invasion and metastasis using Transwell assays in vitro and breast cancer skeletal metastasis mouse model in vivo (n = 10 mice per group). The inhibitory effect of ACA on cellular STAT3 signaling pathway was investigated by series of biochemistry analysis. The chavicol preferentially suppressed cancer cell migration and invasion, and this activity was superior to its cytotoxic effects. ACA suppressed both constitutive and interleukin-6-inducible STAT3 activation and diminished the accumulation of STAT3 in the nucleus and its DNA-binding activity. More importantly, ACA treatment led to significant up-regulation of Src homology region 2 domain-containing phosphatase 1 (SHP-1), and the ACA-induced depression of cancer cell migration and STAT3 signaling could be apparently reversed by blockade of SHP-1. Matrix metalloproteinase (MMP)-2 and -9, gene products of STAT3 that regulate cell invasion, were specifically suppressed by ACA. In tumor metastasis model, ACA potently inhibited the human breast cancer cell-induced osteolysis, and had little apparent in vivo toxicity at the test concentrations. ACA is a novel drug candidate for the inhibition of tumor metastasis through interference with the SHP-1/STAT3/MMPs signaling pathway.

[Chemical constituents from Cirsium pendulum Fisch. ex DC].

To study the chemical constituents of Cirsium pendulum Fisch. ex DC. Thirteen compounds were obtained from ethanol extract of Cirsium pendulum Fisch. ex DC. These compounds were characterized by spectroscopic analysis and comparison with published data to be beta-sitosterol(1), alpha-spinastenorl(2), taraxasterol(3), triacontanol(4), chlorophylla(5), lutein(6), linarin(7), 3-sitosterol-3-O-beta-D-glucopyranoside (8), 3', 4'-dihydroxy phenylethanol glucoside(9),3-(4'-methoxy-3',5'-dihydroxyphenyl)-allyl alcohol glucoside (10), uracil (11), methyl chlorogenate (12), chlorogenic (13). All of them were isolated from this plant for the first time.

Effects of water-soluble Ganoderma lucidum polysaccharides on the immune functions of patients with advanced lung cancer.

Preclinical studies have established that the polysaccharide fractions of Ganoderma lucidum have potential antitumor activity. Recent clinical studies have demonstrated that G. lucidum polysaccharides enhance host immune functions [e.g., enhanced natural killer (NK) cell activity] in patients with advanced solid tumors, although an objective response was not observed. This open-label study aimed to evaluate the effects of water-soluble G. lucidum polysaccharides (Ganopoly, Encore International Corp., Auckland, New Zealand) on immune functions in patients with advanced lung cancer. Thirty-six patients were enrolled and treated with 5.4 g/day Ganopoly for 12 weeks. In the 30 cancer patients who completed the trial, treatment with Ganopoly did not significantly alter the mean mitogenic reactivity to phytohemagglutinin, mean counts of CD3, CD4, CD8, and CD56, mean plasma concentrations of interleukin (IL)-2, IL-6, and interferon (IFN)-gamma, or NK activity in the patients, but the results were significantly variable. However, some cancer patients demonstrated markedly modulated immune functions. The changes in IL-1 were correlated with those for IL-6, IFN-gamma, CD3, CD8, and NK activity (P < .05), and IL-2 changes were correlated with those for IL-6, CD8, and NK activity. The results suggest that subgroups of cancer patients might be responsive to Ganopoly in combination with chemotherapy/radiotherapy. Further studies are needed to explore the efficacy and safety of Ganopoly used alone or in combination with chemotherapy/radiotherapy in lung cancer patients.

A randomized, double-blind and placebo-controlled study of a Ganoderma lucidum polysaccharide extract in neurasthenia.

Ganoderma lucidum has been widely used to treat various diseases, including cancer, diabetes, and neurasthenia in many Asian countries. This randomized, double-blind, placebo-controlled parallel study aimed to investigate the efficacy and safety of a polysaccharide extract of G. lucidum (Ganopoly) in Chinese patients with neurasthenia. One hundred thirty-two patients with neurasthenia according to the diagnosis criteria of the 10th International Classification of Diseases were included in this study. Written consents were obtained from the patients, and the study was conducted in accordance with Good Clinical Practice guidelines. Patients were randomized to receive Ganopoly or placebo orally at 1,800 mg three times a day for 8 weeks. Efficacy assessments comprised the Clinical Global Impression (CGI) improvement of severity scale and the Visual Analogues Scales for the sense of fatigue and well-being. In 123 assessable patients in two treatment groups at the end of the study, Ganopoly treatment for 8 weeks resulted in significantly lower scores after 8 weeks in the CGI severity score and sense of fatigue, with a respective reduction of 15.5% and 28.3% from baseline, whereas the reductions in the placebo group were 4.9% and 20.1%, respectively. The score at day 56 in the sense of well-being increased from baseline to 38.7% in the Ganopoly group compared with 29.7% in the placebo group. The distribution of the five possible outcomes from very much improved to minimally worse was significantly different (X (2) = 10.55; df = 4; P = .0322) after treatment with Ganopoly or placebo. There was a percentage of 51.6% (32 of 62) in the Ganopoly group rated as more than minimally improved compared with 24.6% (15 of 61) in the placebo group (X (2) = 9.51; df = 1; P = .002). Ganopoly was well tolerated in the study patients. These findings indicated that Ganopoly was significantly superior to placebo with respect to the clinical improvement of symptoms in neurasthenia.