PMID: 

Rev Epidemiol Sante Publique. 1992 ;40 Suppl 1:S55-62. PMID: 1626106

Abstract Title: 

Electromagnetic fields and cancer risks.

Abstract: 

Cancer was first associated with exposure to electromagnetic fields (EMF) in 1979 when Wertheimer and Leeper reported that children dying from cancer resided more often in homes believed to be exposed to higher EMF than did healthy control children. The risks were as high as 2.23 (1.56-3.18) 3.09 (1.68-5.71) for all cancers, 2.98 (1.72-5.15) for leukemia and 2.40 (1.08-5.36) for brain cancers. Wire configuration around houses was used as a surrogate for direct EMF exposure measurements. Wertheimer's finding of an association between cancer and wire configuration around houses has been replicated in two recent studies. However, direct measurement of EMF fields in houses of cancer children have not yielded the same results as the wire configuration around houses, thereby jeopardizing the hypothesis of an association between EMF and cancer. To comprehend the putative association between residential exposure to EMF and childhood cancer, one would have to understand what is hidden behind the notion of 'wire configuration' around the house. In parallel with residential studies, scores of studies were conducted among workers occupationally exposed to EMF. What have we learned from these occupational studies? Hypotheses generating and case control studies have revealed the existence of an excess risk of leukemia among electrical workers. Pooled results have estimated the risk for all leukemia to be 1.18 (1.09-1.29) and for acute myeloid leukemia 1.46 (1.27-1.64). An increased risk of leukemia among electrical workers does not necessarily mean that EMF is a causal agent, other chemicals such as benzene, creosote, solvent, could possibly account for it but this has yet to be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

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Biomed Res Int. 2019 ;2019:4348973. Epub 2019 May 28. PMID: 31275971

Abstract Title: 

Carnosine Protects Mouse Podocytes from High Glucose Induced Apoptosis through PI3K/AKT and Nrf2 Pathways.

Abstract: 

Diabetic nephropathy is the complication of diabetes mellitus that can lead to chronic renal failure. Reactive oxygen species (ROS) production plays an important role in its pathological process. Previous studies showed that carnosine may reduce diabetic nephropathy by antioxidant effect. However, the molecular mechanism of its antioxidant was not fully understood. In the current study, we developed high glucose containing different concentrations of carnosine to reduce ROS levels and podocytes apoptosis, and Cell Counting Kit-8 test was used to observe the cell viability. Carnosine (5-20mM) was found to protect mouse podocytes (MPC5) cells from HG-induced injury. Quantitative real-time PCR, Western blotting, and immunofluorescence staining revealed that high glucose induced ROS levels and podocytes apoptosis were downregulated by PI3K/AKT and Nrf2 signaling pathways. The current findings suggest that carnosine may reduce ROS levels and MPC5 cells apoptosis by PI3K/AKT and Nrf2 signaling pathways activation.

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PMID: 

Curr Med Chem. 2019 Jul 30. Epub 2019 Jul 30. PMID: 31362685

Abstract Title: 

Carnosine and Kidney Diseases: What We Currently Know?

Abstract: 

Carnosine (beta-alanyl-L-histidine) is an endogenously synthesised dipeptide which is present in different human tissues e.g. in the kidney. Carnosine is degraded by enzyme serum carnosinase, encoding by CNDP1 gene. Carnosine is engaged in different metabolic pathways in the kidney. It reduces the level of proinflammatory and profibrotic cytokines, inhibits advanced glycation end products formation and moreover it decreases the mesangial cell proliferation. Carnosine may also serve as a scavenger of peroxyl and hydroxyl radicals and a natural angiotensin converting enzyme inhibitor. This review summarizes the results of experimental and human studies concerning the role of carnosine in kidney diseases, particularly in chronic kidney disease, ischemia/reperfusion induced acute renal failure, diabetic nephropathy and also drug-induced nephrotoxicity. The interplay between serum carnosine concentration and serum carnosinase activity and polymorphism in the CNDP1 gene is discussed. Carnosine has renoprotective properties. It has a promising potential for the treatment and prevention of different kidney diseases, particularly chronic kidney disease which is a global public health issue. Further studies of carnosine role in kidney may offer innovative and effective strategies for management of kidney diseases.

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Naunyn Schmiedebergs Arch Pharmacol. 2019 Oct 22. Epub 2019 Oct 22. PMID: 31641819

Abstract Title: 

Carnosine and L-arginine attenuate the downregulation of brain monoamines and gamma aminobutyric acid; reverse apoptosis and upregulate the expression of angiogenic factors in a model of hemic hypoxia in rats.

Abstract: 

PURPOSE: The purpose of the present study was to investigate the preventive effect of L-arginine (ARG) and carnosine (CAR) on hypoxia-induced neurotoxicity in rats. The impact on neuro-inflammation, apoptosis, angiogenesis, and the brain levels of monoamines and GABA were investigated.METHODS: Rats were divided into the following: normal control, hypoxia model induced by sodium nitrite (75 mg/kg s.c), and hypoxic rats pre-treated with CAR (250 mg/kg), ARG (200 mg/kg), and their combination.RESULTS: Data revealed that hypoxia induced significant elevation of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and its receptor reflecting the stimulation of angiogenesis. Hypoxia also resulted in increased inflammatory mediators-including nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). In addition, hypoxia initiates cerebral apoptosis as revealed by increased caspase-3 and BAX with reduced Bcl-2. These changes were associated with reduced brain levels of GABA and monoamines including noradrenaline (NADR), dopamine (DOP), and serotonin (SER). Pre-treatment with ARG and/or CAR significantly mitigated the neural changes induced by hypoxia and attenuated the elevated levels of NF-κB, TNF-α, IL-6, caspase-3, and BAX, while ameliorated the reduced levels of Bcl-2, NADR, DOP, SER, and GABA, with the best improvement observed with the combination. Further elevation of the angiogenic markers was observed indicating their role in boosting oxygen delivery to brain.CONCLUSION: CAR, ARG, and, importantly, their combination could effectively protect against hypoxia-induced neurotoxicity, via their angiogenic, anti-inflammatory, and anti-apoptotic properties in addition to reversing the effect on GABA and monoamines.

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PMID: 

Oxid Med Cell Longev. 2019 ;2019:5958043. Epub 2019 Jun 24. PMID: 31341531

Abstract Title: 

Carnosol Improved Lifespan and Healthspan by Promoting Antioxidant Capacity in.

Abstract: 

Carnosol, a phenolic diterpene, is one of the main constituents of. It is known to possess a range of bioactivities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Nevertheless, the antiaging effects of carnosol have received little attention. This study first indicated that carnosol increased the healthspan of(). First, compared with the control condition, carnosol treatment effectively decreased ROS accumulation under normal or oxidative stress condition, significantly increased several key antioxidant enzyme activities, and significantly decreased MDA content. Second, carnosol effectively prolonged lifespan under normal and stress conditions and slowed aging-related declines, including mobility, age pigmentation, and neurodegenerative disease, but had no effect on fertility and fat deposition. Finally, carnosol-mediated longevity required the upregulated expression of,,,, andand was dependent on thegene. Increased DAF-16 translocation was observed, butwas independent of the effects on lifespan induced by carnosol. These results suggested that carnosol might serve as a good source of natural antioxidants, and in particular, carnosol could be explored as a potential dietary supplement to slow aging.

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PMID: 

Front Oncol. 2019 ;9:743. Epub 2019 Aug 8. PMID: 31456939

Abstract Title: 

Carnosol, a Natural Polyphenol, Inhibits Migration, Metastasis, and Tumor Growth of Breast Cancer via a ROS-Dependent Proteasome Degradation of STAT3.

Abstract: 

We have previously demonstrated that carnosol, a naturally occurring diterpene, inhibitedcell viability and colony growth, as well as induced cell cycle arrest, autophagy and apoptosis in human triple negative breast cancer (TNBC) cells. In the present study, we evaluated the ability of carnosol to inhibit tumor growth and metastasis. We found that non-cytotoxic concentrations of carnosol inhibited the migration and invasion of MDA-MB-231 cells in wound healing and matrigel invasion assays. Furthermore, gelatin zymography, ELISA, and RT-PCR assays revealed that carnosol inhibited the activity and downregulation the expression of MMP-9. Mechanistically, we demonstrated that carnosol suppressed the activation of STAT3 signaling pathway through a ROS-dependent targeting of STAT3 to proteasome-degradation in breast cancer cells (MDA-MB-231, Hs578T, MCF-7, and T47D). We show that blockade of proteasome activity, by MG-132 and bortezomib, or ROS accumulation, by N-acetylcysteine (NAC), restored the level of STAT3 protein. In addition, using chick embryo tumor growth assay, we showed that carnosol significantly and markedly suppressed tumor growth and metastasis of breast cancer xenografts. To the best of our knowledge, this is the first report which shows that carnosol specifically targets signal transducer and activator of transcription 3 (STAT3) for proteasome degradation in breast cancer. Our study further provide evidence that carnosol may represent a promising therapeutic candidate that canmodulate breast cancer growth and metastasis.

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Eur J Pharm Sci. 2019 Sep 1 ;137:104988. Epub 2019 Jul 7. PMID: 31291598

Abstract Title: 

Piperine-loaded nanoparticles with enhanced dissolution and oral bioavailability for epilepsy control.

Abstract: 

Piperine, an alkaloid from black pepper, has demonstrated beneficial effects in central nervous system, especially in epilepsy control. However, its therapeutic application remains limited due to the low aqueous solubility of piperine. Thus, the present study aimed to formulate piperine into a more solubilized form to enhance its oral bioavailability and facilitate its development as a potential anti-epileptic treatment. The nanoprecipitation method was applied to prepare piperine nanoparticles, which were then examined under transmission electron microscopy. A spherical nanosized particle was obtained with small particle size (average particle size 130.20 ± 1.57 nm), narrow size distribution (polydispersity index 0.195 ± 0.002) and efficient entrapment (entrapment efficiency 92.2 ± 2.5%). Compared with the unformulated piperine, nanosized piperine had a much faster dissolution rate with 3 times higher accumulated drug release after24 h. After oral administration at 3.5 mg/kg in rats, the nanosized piperine formulations could improve its oral bioavailability by 2.7-fold with 16 times higher concentrations in brain at 10 h postdosing. Moreover, the piperine nanoparticles exhibited effective protection against pentylenetetrazol-induced seizures in both zebrafish and mice. In summary, the present study provided a simple formulation strategy for oral administration of piperine to overcome its limitation in water solubility. The developed formulations could effectively enhance oral bioavailability of piperine with promising anti-epileptic effect, which could be applied as a potential therapy in epilepsy control.

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PMID: 

Zhonghua Xin Xue Guan Bing Za Zhi. 2019 Jul 24 ;47(7):554-560. PMID: 31365997

Abstract Title: 

[Piperine inhibits the transformation of endothelial cells into fibroblasts].

Abstract: 

To investigate the role of piperine on the transformation of endothelial cells into fibroblasts.Cultured human umbilical vein endothelial cells (HUVECs, 4-6 passage) were used for the main experiments. The transformation models of endothelial cells into fibroblasts were induced by transforming growth factorβ (TGF-β) stimulation. HUVECs were divided into 6 groups: control group, TGF-β group and 4 groups treated with various concentrations of piperine (1, 5, 10, 20 μmol/L). CKK-8 was used to detect cell proliferation. The CD31/α-smooth muscle actin (α-SMA) expression level was detected by fluorescent staining. The vascular endothelial cadherin (VE-cadherin)/vimentin expression was detected by immunofluorescence staining. RT-PCR was used detect the mRNA expressions of transformation markers. Western blot was used to detect the protein expression of snail and twist.TGF-β increased HUVECs proliferation (0.05), which could be significantly inhibited by 10 and 20μmol/L of piperine, but not by 1 and 5 μmol/L of piperine. Immunofluorescence results demonstrated that TGF-β increased HUVECs transformation to fibroblasts as shown by downregulated expression of endothelial markers CD31, VE-cadherin, and upregulated expression of α-SMA and vimentin, again, these effects could be attenuated by 10 and 20 μmol/L piperine. The expression levels of collagen type Ⅰ and type Ⅲ were significantly higher in TGF-β group than in control group (0.05), significantly lower in TGF-β+10 μmol/L piperine group and TGF-β+20 μmol/L piperine group than in TGF-β group (0.05).In addition, RT-PCR results showed that TGF-β increased mRNA expression of transformation markers (snail1, snail2, twist1, twist2), while 10 and 20 μmol/L of piperine could significantly downregulated the mRNA expressions of these markers. The protein expression levels of snail and twist were significantly higher in TGF-β group than in control group (both0.05), which was significantly lower in TGF-β+20 μmol/L piperine group than in TGF-β group (both0.05).Piperine can inhibit the transformation of endothelial cells into fibroblasts. This effect might be viewed as one of the potential mechanisms of reduced myocardial fibrosis post piperine treatment.

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PMID: 

Heliyon. 2019 Aug ;5(8):e02180. Epub 2019 Aug 13. PMID: 31463384

Abstract Title: 

Piperine pretreatment attenuates renal ischemia-reperfusion induced liver injury.

Abstract: 

Background: Remote organ injury is one of the complications which are developed following ischemia-reperfusion induced acute kidney injury (AKI), dramatically increasing its mortality rate. The aim of the present study was to investigate the effect of piperine pretreatment on liver dysfunction following ischemia-reperfusion induced AKI.Materials and methods: Acute kidney injury was induced by 30 min-bilateral renal ischemia followed by 24 h of reperfusion. To investigate liver damages, the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) enzymes were measured in plasma. In order to study oxidative stress, malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP) levels were measured. Furthermore, the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA along with infiltration of leukocytes in the liver tissue was measured for inflammation assessment. Histopathological damages were studied through measuring the extent of cellular fibrosis, sinusoidal dilatation, and vascular congestion in liver tissue.Results: Following acute kidney injury, AST, ALT, and ALP levels in plasma, MDA level and ICAM-1 expression in the liver tissue, infiltration of leukocytes into the interstitium, and hepatic histopathologic damages increased significantly, while FRAP decreased. Pretreatment with piperine at 10 and 20 mg/kg body weight was able to improve these damages, such that some of them reached its value in the sham group, though piperine in the 20 mg/kg was more effective.Conclusions: The results of this study suggest that ischemia-reperfusion induced AKI result in hepatic damages, and pretreatment with piperine can prevent development of these damages through its antioxidant and anti-inflammatory properties.

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PMID: 

Mol Med Rep. 2019 Oct ;20(4):3709-3718. Epub 2019 Sep 2. PMID: 31485676

Abstract Title: 

Piperine ameliorates the severity of fibrosis via inhibition of TGF‑β/SMAD signaling in a mouse model of chronic pancreatitis.

Abstract: 

Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation and fibrosis. Currently, there are no drugs for the treatment of pancreatic fibrosis associated with CP. Piperine, a natural alkaloid found in black pepper, has been reported to show anti‑inflammatory, anti‑oxidative, and antitumor activities. Although piperine exhibits numerous properties in regards to the regulation of diverse diseases, the effects of piperine on CP have not been established. To investigate the effects of piperine on CP in vivo, we induced CP in mice throughthe repetitive administration of cerulein (50 µg/kg) six times at 1‑h intervals, 5 times per week, for a total of 3 weeks. In the pre‑treatment groups, piperine (1, 5, or 10 mg/kg) or corn oil were administrated orally at 1 h before the first cerulein injection, once a day, 5 times aweek, for a total of 3 weeks. In the post‑treatment groups, piperine (10 mg/kg) or corn oil was administered orally at 1 or 2 week after the first cerulein injection. Pancreases were collected for histological analysis. In addition, pancreatic stellate cells (PSCs) were isolated to examinethe anti‑fibrogenic effects and regulatory mechanisms of piperine. Piperine treatment significantly inhibited histological damage in the pancreas, increased the pancreatic acinar cell survival, reduced collagen deposition and reduced pro‑inflammatory cytokines and chemokines. In addition, piperine treatment reduced the expression of fibrotic mediators, such as α‑smooth muscle actin (α‑SMA), collagen, and fibronectin 1 in the pancreas and PSCs. Moreover, piperine treatment reduced the production of transforming growth factor (TGF)‑β in the pancreas and PSCs. Furthermore, piperinetreatment inhibited TGF‑β‑induced pSMAD2/3 activation but not pSMAD1/5 in the PSCs. These findings suggest that piperine treatment ameliorates pancreatic fibrosis by inhibiting TGF‑β/SMAD2/3 signaling during CP.

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