PMID: 

Onco Targets Ther. 2019 ;12:8601-8609. Epub 2019 Oct 17. PMID: 31802896

Abstract Title: 

Resveratrol As A Natural Regulator Of Autophagy For Prevention And Treatment Of Cancer.

Abstract: 

Resveratrol, as a natural product compound, has been recently attracted much attention for its potent effects on cancer. Cancer is a serious disease threatening human survival and social development. Autophagy is a cellular pathway to realize the metabolic needs of the cell itself and the renewal of some organelles and plays opposing, context-dependent role in tumorigenesis. So the regulation of autophagy is of great significance in the treatment of cancer. p62, as an autophagy adaptor protein, is a preferred target for autophagy and is constantly controlled by constitutive autophagy. As a tumor-suppression mechanism, autophagy deficiency is common in tumors, which results in aberrant accumulation of p62 and activates p62-regulated pathways, such as activation of mTOR in nutrient sensing, and the activation of the Keap1-Nrf2 pathway for antioxidant stress, which are associated with cancer development. In this review, we emphasize that resveratrol can induce autophagy in the treatment of cancer and accelerates the degradation of p62, and then, the mTOR activation is blocked and Nrf2 activation is suppressed. As a result, the multidrug resistance of cancer cells can be reversed by resveratrol.

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PMID: 

Med Sci Monit. 2019 Dec 6 ;25:9290-9298. Epub 2019 Dec 6. PMID: 31806860

Abstract Title: 

Resveratrol Protects the Myocardium in Sepsis by Activating the Phosphatidylinositol 3-Kinases (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway and Inhibiting the Nuclear Factor-κB (NF-κB) Signaling Pathway.

Abstract: 

BACKGROUND Sepsis combined with myocardial injury is an important cause of septic shock and multiple organ failure. However, the molecular mechanism of sepsis-induced myocardial dysfunction has not yet been thoroughly studied. Resveratrol has been an important research topic due its organ-protection function, but the specific mechanism is unclear. The purpose of this study was to explore the mechanism of organ injury in sepsis and to investigate the molecular mechanism of resveratrol in myocardial protection in sepsis. MATERIAL AND METHODS A classical Sprague-Dawley rat model of sepsis peritonitis was constructed for further experiments. The PI3K inhibitor LY294002 and resveratrol were used to intervene in a rat model of cardiomyopathy. HE staining was used to observe pathological changes. Cardiomyocyte apoptosis was detected by TUNEL assay. Western blot analysis was used to detect the level of maker proteins. RESULTS The PI3K inhibitors could promote cardiac abnormalities and apoptosis, but resveratrol showed the opposite effect. The upregulation function of the PI3K inhibitor on the expression of NF-kappaB, IL-6, IL-1ß, and TLR4 in LPS rats was not obvious, but the expression of TNF-a in LPS+LY294002 rats was increased by 22.85% compared with that in LPS rats (P

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PMID: 

Biol Trace Elem Res. 2019 Nov 20. Epub 2019 Nov 20. PMID: 31749063

Abstract Title: 

Selenium Deficiency Induces Inflammation via the iNOS/NF-κB Pathway in the Brain of Pigs.

Abstract: 

Selenium (Se) is an essential trace element to maintain homeostasis in humans and animals. The aim of the present study was to clarify the mechanism of Se deficiency-induced inflammation in the pig's brain. Twenty-four healthy pigs were randomly divided into two groups (n = 12/group): control group (group C) was fed diet with 0.3 mg/kg inorganic Se, and Se-deficient group (group L) was fed diet with 0.007 mg/kg inorganic Se. At the 90th day of the experiment, the histology in the pig's brain was observed by the microscope, the NO levels and iNOS activity wereassayed, and the mRNA and protein expression levels of inflammatory cytokines (iNOS, COX-2, NF-κB, and PTGEs) and HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90) were detected by real-time quantitative PCR and Western blot. Compared with group C, both of NO levels and iNOS activity were increased in group L, and the mRNA and protein expression levels of inflammatory cytokines (iNOS, COX-2, NF-κB, and PTGEs) and HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90) were also upregulated; histological observation displayed inflammatory response in the brain of pig. In summary, diet with Se deficiency canactivate the iNOS/NF-κB pathway to upregulate the expression of inflammatory cytokines, thereby leading to inflammatory lesions in the pig's brain, and HSPs are involved in the compensatory regulation of inflammation. This study provides a reference for the prevention of pig brain inflammation fromthe perspective of nutrition.

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PMID: 

Cell Signal. 2019 Dec 3:109491. Epub 2019 Dec 3. PMID: 31809873

Abstract Title: 

Photobiomodulation therapy decreases free fatty acid generation and release in adipocytes to ameliorate insulin resistance in type 2 diabetes.

Abstract: 

Excessive circulating free fatty acids (FFA) cause insulin resistance in peripheral tissues by inhibiting the proximal insulin signaling pathway. White adipose tissue (WAT) is a primary source of FFA generation and release through triglyceride (TG) hydrolysis. Thus, reducing excessive lipolysis in adipocytes ameliorates whole-body insulin resistance in type 2 diabetes. Here, we found that a noninvasive photobiomodulation therapy (PBMT), decreased FFA generation and release in WATs from high-fat diet (HFD)-fed mice and diabetic db/db mice. Meanwhile, plasma FFA and TG levels were reduced in two mouse models after PBMT. PBMT promoted mitochondrial reactive oxygen species (ROS) generation, which inhibited phosphatase and tensin homologue (PTEN) and promoted protein kinase B (AKT) activation. Photoactivation of AKT inhibited the transcriptional activity of Forkhead box transcription factor O1 (FoxO1), reducing expression of lipolytic enzymes and FFA generation and release. Eliminating ROS elimination or inhibiting AKT blocked the effects of the laser therapy in vivo and in vitro. Taken together, PBMT suppresses FFA generation and release in insulin-resistant adipocytes, contributing to improvement of insulin resistance in mouse models of type 2 diabetes.

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PMID: 

Curr Drug Targets. 2019 Oct 24. Epub 2019 Oct 24. PMID: 31749425

Abstract Title: 

Cardiovascular Modulating Effects of Magnolol and Honokiol, two polyphenolic compounds from Traditional Chinese Medicine-Magnolia officinalis.

Abstract: 

Honokiol and its isomer magnolol are poly-phenolic compounds isolated from the Magnolia officinalis that exert cardiovascular modulating effects via a variety of mechanisms. They are used as a blood-quickening and stasis-dispelling agents in Traditional Chinese Medicine and confirmed to have therapeutic potential in atherosclerosis, thrombosis, hypertension, and cardiac hypertrophy. This comprehensive review summarizes the current date regarding the cardioprotective mechanisms of those compounds and identifies areas for further research.

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PMID: 

Life Sci. 2019 Nov 21 ;240:117096. Epub 2019 Nov 21. PMID: 31760097

Abstract Title: 

Mechanistic aspects of antifibrotic effects of honokiol in Con A-induced liver fibrosis in rats: Emphasis on TGF-β/SMAD/MAPK signaling pathways.

Abstract: 

: Aim Liver fibrosis represents a massive global health burden with limited therapeutic options. Thus, the need for curative options is evident. Thus, this study aimed to assess the potential antifibrotic effect of honokiol in Concanavalin A (Con A) induced immunological model of liver fibrosis as well the possible underlying molecular mechanisms.METHODS: Male Sprague-Dawley rats were treated with either Con A (20 mg/kg, IV) and/or honokiol (10 mg/kg, orally) for 4 weeks. Hepatotoxicity indices were as well as histopathological evaluation was done. Hepatic fibrosis was assessed by measuring alpha smooth muscle actin (α-SMA) expression and collagen fibers deposition by Masson's trichrome stain and hydroxyproline content. To elucidate the underlying molecular mechanisms, the effect of honokiol on oxidative stress, inflammatory markers as well as transforming growth factor beta (TGF-β)/SMAD and mitogen-activated protein kinase (MAPK) pathways was assessed.KEY FINDINGS: Honokiol effectively reversed the hepatotoxicity indices elevations and abnormal histopathological changes induced by Con A. Besides, honokiol attenuated Con A-induced liver fibrosis by down-regulation of hydroxyproline levels,α-SMA expression together with a marked decrease in collagen fibers deposition. Mechanistically Con A induced oxidative stress, provocation of inflammatory responses and activation of TGF-β/SMAD/MAPK pathways. Contrariwise, honokiol co-treatment significantly restored antioxidant defence mechanisms, down-regulated inflammatory cascades and inhibited TGF-β/SMAD/MAPK signaling pathways.CONCLUSION: The results provide an evidence for the promising antifibrotic effect of honokiol that could be partially due to suppressing oxidative stress and inflammatory processes as well as inhibition of TGF-β/SMAD/MAPK signaling pathways.

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PMID: 

BMC Pulm Med. 2019 Nov 11 ;19(1):210. Epub 2019 Nov 11. PMID: 31711463

Abstract Title: 

Spontaneous remission of advanced progressive poorly differentiated non-small cell lung cancer: a case report and review of literature.

Abstract: 

BACKGROUND: Spontaneous remission (SR) of cancer is a very rare phenomenon of unknown mechanism. In particular, SR of non-small cell lung cancer (NSCLC) has been scarcely reported. We present the case of a 74-year-old woman with advanced, poorly differentiated NSCLC (highly expressing programmed death ligand-1 [PD-L1]) that progressed despite multiple lines of chemotherapy but then spontaneously remitted.CASE PRESENTATION: The patient presented with hemoptysis and was diagnosed with stage IIIA poorly differentiated NSCLC via bronchoscopic biopsy. She had an unremarkable medical history and moderate performance status. The initial treatment plan was surgery after neoadjuvant chemotherapy. Despite conventional chemotherapy, follow-up chest computed tomography (CT) showed gradual tumor progression and she decided against further treatment after fifth-line chemotherapy. However, the size of lung mass was markedly decreased on follow-up chest CT one year after ceasing chemotherapy. Also, follow-up positron emission tomography images showed decreased metabolic activity in the lung mass and a percutaneous biopsy specimen from the diminished lung mass revealed no viable tumor cells. A diagnosis of SR of NSCLC was confirmed, and the patient was without tumor progression on follow-up nine months later. Later, PD-L1 immunostaining revealed high positivity (> 99%) in initial tumor cells.CONCLUSION: Our case showing SR of poorly advanced NSCLC refractory to multiple lines of chemotherapy suggested the association between immunity and tumor regression.

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PMID: 

Anticancer Res. 2019 Oct ;39(10):5597-5604. PMID: 31570455

Abstract Title: 

Bilateral Asynchronous Renal Cell Carcinoma With Lung Metastases: A Case Report of a Patient Treated Solely With High-dose Intravenous and SubcutaneousExtract for a Second Renal Lesion.

Abstract: 

BACKGROUND: Bilateral asynchronous renal cell carcinoma (RCC) is infrequent. Immunotherapy is the first-line treatment for advanced RCC not controlled by locoregional therapy. Viscum album extracts (VAE) have been shown to improve quality of life as well as immunological and antineoplastic properties in different types of cancers.CASE REPORT: A 67-year-old man was diagnosed with Fuhrman grade 3/4 RCC, stage pT1bN0M0 in the right kidney. During the subsequent 6 years, he underwent a right nephrectomy and two metastasectomies (lung). Then an RCC lesion of the left kidney was detected. The patient refused a second nephrectomy and was treated solely with high-dose intravenous and subsequent subcutaneous VAE. A central necrotic area and a peritumoral halo were seen on an ultrasound follow-up from month 7. The patient showed no further progression of RCC during the next 2.5 years.CONCLUSION: As far as we are aware of, this is the first report of a patient with metastatic RCC with an RCC lesion of the second kidney treated solely with high-dose intravenous and subcutaneous VAE, associated with 2.5 years of progression-free survival and a good quality of life. The use of VAE in RCC should be carefully documented and published to determine future research.

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PMID: 

Arch Pharm Res. 2010 Mar ;33(3):463-8. Epub 2010 Mar 30. PMID: 20361313

Abstract Title: 

The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze.

Abstract: 

Functional consequences of hypothyroidism include impaired learning and memory and inability to produce long-term potentiation (LTP) in hippocampus. Olibanum has been used for variety of therapeutic purposes. In traditional medicine, oilbanum is used to enhance learning and memory. In the present study the effect of olibanum on memory deficit in hypothyroid rats was investigated. Male wistar rats were divided into four groups and treated for 180 days. Group 1 received tap drinking water while in group 2, 0.03% methimazol was added to drinking water. Group 3 and 4 were treated with 0.03% methimazole as well as 100 and 500 mg/kg olibanum respectively. The animals were tested in Morris water maze. The swimming speed was significantly lower and the distance and time latency were higher in group 2 compared with group 1. In groups 3 and 4 the swimming speed was significantly higher while, the length of the swim path and time latency were significantly lower in comparison with group 2. It is concluded that methimazole-induced hypothyroidism impairs learning and memory in adult rats which could be prevented by using olibanum.

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PMID: 

Biochem Pharmacol. 2012 Jan 1 ;83(1):115-21. Epub 2011 Oct 5. PMID: 22001311

Abstract Title: 

Boswellic acids from frankincense inhibit lipopolysaccharide functionality through direct molecular interference.

Abstract: 

Lipophilic extracts of gum resins of Boswellia species (BSE) are used in folk medicine to treat various inflammatory disorders and infections. The molecular background of the beneficial pharmacological effects of such extracts is still unclear. Various boswellic acids (BAs) have been identified as abundant bioactive ingredients of BSE. Here we report the identification of defined BAs as direct inhibitors of lipopolysaccharide (LPS) functionality and LPS-induced cellular responses. In pull-down experiments, LPS could be precipitated using an immobilized BA, implying direct molecular interactions. Binding of BAs to LPS leads to an inhibition of LPS activity which was observed in vitro using a modified limulus amoebocyte lysate assay. Analysis of different BAs revealed clear structure-activity relationships with the classicalβ-BA as most potent derivative (IC(50)=1.8 μM). In RAW264.7 cells, LPS-induced expression of inducible nitric oxide synthase (iNOS, EC 1.14.13.39) was selectively inhibited by those BAs that interfered with LPS activity. In contrast, interferon-γ-induced iNOS induction was not affected by BAs. Weconclude that structurally defined BAs are LPS inhibiting agents and we suggest that β-BA may contribute to the observed anti-inflammatory effects of BSE during infections by suppressing LPS activity.

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