PMID: 

Zhonghua Liu Xing Bing Xue Za Zhi. 2004 Jan ;25(1):40-3. PMID: 15061945

Abstract Title: 

[A cross-sectional study on nonionizing radiation to male fertility].

Abstract: 

OBJECTIVE: To investigate the relationship between microwave radiation and male reproductivity.METHODS: After filling out questionnaire and body check, we carried out molecular epidemiological studies, using single cell gel electrophoresis (SCGE) and sperm automatic analysis among people working on radar.RESULTS: Quality of semen and semi-clinical injury of sperm among the people working on radar had changed when radar electromagnetic wave frequency distance, intensity, lasting time and protection shield were changing. Dose-response relationship was noticed and the increase of sperm dysmorphia played a principal role. The results between exposed group and control group showed significant difference (P

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PMID: 

Epidemiology. 2012 Mar ;23(2):301-7. PMID: 22249239

Abstract Title: 

Mobile phone use and incidence of glioma in the Nordic countries 1979-2008: consistency check.

Abstract: 

BACKGROUND: Some case-control studies have reported increased risks of glioma associated with mobile phone use. If true, this would ultimately affect the time trends for incidence rates (IRs). Correspondingly, lack of change in IRs would exclude certain magnitudes of risk. We investigated glioma IR trends in the Nordic countries, and compared the observed with expected incidence rates under various risk scenarios.METHODS: We analyzed annual age-standardized incidence rates in men and women aged 20 to 79 years during 1979-2008 using joinpoint regression (35,250 glioma cases). Probabilities of detecting various levels of relative risk were computed using simulations.RESULTS: For the period 1979 through 2008, the annual percent change in incidence rates was 0.4% (95% confidence interval = 0.1% to 0.6%) among men and 0.3% (0.1% to 0.5%) among women. Incidence rates have decreased in young men (20-39 years) since 1987, remained stable in middle-aged men (40-59 years) throughout the 30-year study period, and increased slightly in older men (60-79 years). In simulations, assumed relative risks for all users of 2.0 for an induction time of up to 15 years, 1.5 for up to 10 years, and 1.2 for up to 5 years were incompatible with observed incidence time trends. For heavy users of mobile phones, risks of 2.0 for up to 5 years' induction were also incompatible.CONCLUSION: No clear trend change in glioma incidence rates was observed. Several of the risk increases seen in case-control studies appear to be incompatible with the observed lack of incidence rate increase in middle-aged men. This suggests longer induction periods than currently investigated, lower risks than reported from some case-control studies, or the absence of any association.

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PMID: 

Biol Res. 2019 Jul 18 ;52(1):37. Epub 2019 Jul 18. PMID: 31319879

Abstract Title: 

Berberine in combination with cisplatin induces necroptosis and apoptosis in ovarian cancer cells.

Abstract: 

BACKGROUND: Berberine (BBR), a compound extracted from a variety of medicinal herbs, has been shown multiple pharmacological effects against cancer cells of different origins. Cisplatin (DDP) is known as an effective chemotherapeutic agent against cancer by inducing DNA damage and cell apoptosis. However, the effect of the combined used of BBR and DDP on cell necroptosis in ovarian cancer has not been reported.METHODS: OVCAR3 and three patient-derived primary ovarian cancer cell lines (POCCLs) were chosen as the experimental objects. To determine the potential anti-cancer activity of BBR and DDP in combination, we firstly treated OVCAR3 and POCCLs cells with BBR and/or DDP. The cell viability of OVCAR3 and POCCLs with treatment of BBR or DDP for different hours was measured by CCK-8 assay. Flow cytometry was used to analyze cell cycle distribution and changes in apoptotic cells after treatment with BBR and/or DDP. The morphological changes of OVCAR3 cells were observed by using Transmission electron microscopy (TEM) analysis. Proliferation, apoptosis and necroptosis related markers of OVCAR3 and POCCLs with treatment of BBR or DDP were measured by RT-qPCR, western blotting and immunofluorescence assay.RESULTS: Our results demonstrated that BBR significantly inhibited the proliferation of OVCAR3 and primary ovarian cancer cells in a dose- and time-dependent manner. The combination treatment of BBR and DDP had a prominent inhibitory effect on cancer cell growth and induced G0/G1 cell cycle arrest. TEM revealed that the majority of cells after BBR or DDP treatment had an increasing tendency of typical apoptotic and necrotic cell death morphology. Besides, BBR and DDP inhibited the expression of PCNA and Ki67 and enhanced the expression and activation of Caspase-3, Caspase-8, RIPK3 and MLKL.CONCLUSION: This study proposed that the combination therapy of BBR and DDP markedly enhanced more ovarian cancer cell death by inducing apoptosis and necroptosis, which may improve the anticancer effect of chemotherapy drugs. The apoptosis involved the caspase-dependent pathway, while the necroptosis involved the activation of the RIPK3-MLKL pathway. We hope our findings might provide a new insight for the potential of BBR as a therapeutic agent in the treatment of ovarian cancer.

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PMID: 

Int J Crit Illn Inj Sci. 2019 Apr-Jun;9(2):69-74. PMID: 31334048

Abstract Title: 

Synergistic effect of berberine and pentoxifylline in attenuation of acute kidney injury.

Abstract: 

Objective: To evaluate the renoprotective effects of berberine and/or pentoxifylline in reduction of diclofenac-induced acute kidney injury (AKI) in rats.Material and Methods: Fifty male Sprague-Dawley rats were allocated into five groups, Group 1: Rats treated with distilled water plus normal saline for 12 days. Group 2: Rats treated with distilled water plus diclofenac for 12 days. Group 3: Rats treated with berberine plus diclofenac for 12 days. Group 4: Rats treated with pentoxifylline plus diclofenac for 12 days. Group 5: Rats treated with berberine + pentoxifylline plus diclofenac 15 mg/kg for 12 days. Blood urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecules (KIM-1), and cystatin-c were used to measure the severity of AKI.Results: Diclofenac led to significant AKI by significant elevation of blood urea, serum creatinine, KIM-1, and NGAL. Treatment with berberine showed no significant effect on all biomarkers level compared to diclofenac group except on serum KIM-1 level which also seen in the pentoxifylline group whereas combination of berberine and pentoxifylline led to more significant effect in the reduction of all renal biomarkers.Conclusion: Combination of berberine with pentoxifylline illustrated a synergistic effect in attenuation of diclofenac-induced AKI.

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PMID: 

J Diabetes Investig. 2019 Jul 23. Epub 2019 Jul 23. PMID: 31336024

Abstract Title: 

Berberine ameliorates renal impairment and inhibits podocyte dysfunction by targeting the PI3K/Akt pathway in diabetic rat.

Abstract: 

AIMS: Amelioration of renal impairment is the key to diabetic nephropathy (DN) therapy. The progression of DN is closely related to podocyte dysfunction, but the detailed mechanism has not yet been clarified. This study aims to explore the renal impairment amelioration effect of berberine and related mechanism targeting podocyte dysfunction under diabetic state.MATERIALS AND METHODS: Streptozotocin (35 mg·kg) were used to built DN rat model together with high glucose/lipid diet. Renal functional parameters and glomerular ultrastructure changes have been recorded. The alterations of PI3K, Akt and p-Akt in kidney cortex were determined by western blot. Meantime, podocyte dysfunction was induced and treated with berberine and LY294002. After that, podocyte adhesion functional parameters, protein biomarker as well as the alterations of PI3K/Akt pathway were detected.RESULTS: Berberine declines the increased levels of biochemical indicators and significantly improves the abnormal expression of PI3K, Akt and p-Akt in model rat kidney. In vitro, co-stimulating factor could obviously reduce the podocyte adhesion activity, including the decreases expression of nephrin, podocin and adhesion moleculeα3β1 levels, to induce the podocyte dysfunction, and the trends were markedly reversed by the therapy of berberine and LY294002. Moreover, reduction of PI3K and p-Akt levels were observed in the berberine (30 and 60 μM) and LY294002 (40 μM) treatment group, but the Akt protein expression showedlittle change.CONCLUSIONS: Berberine could ameliorate the renal impairment and inhibit the podocyte dysfunction in diabetic rat, and the underlying molecular mechanisms may be involved in the regulation of PI3K/Akt signaling pathway. This article is protected by copyright. All rights reserved.

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PMID: 

Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419866379. PMID: 31337260

Abstract Title: 

Berberine reduces neuroglia activation and inflammation in streptozotocin-induced diabetic mice.

Abstract: 

We aimed to analyze the action of berberine on the neuropathic pain and neuroglia activation in experimental diabetes mellitus (DM) model. Diabetes in mice was induced by intraperitoneal injection of streptozotocin (STZ) followed by the administration of berberine. Mechanical allodynia and thermal hyperalgesia and activations of microglia and astrocytes were evaluated. The levels of pro-inflammatory cytokines and protein expressions of inflammatory proteins were assessed by enzyme-linked immunosorbent assay (ELISA) and western blot, respectively. Our results revealed the anti-nociceptive effects of berberine in DM mice, supported by the improved mechanical threshold and thermal latency. In addition, berberine suppressed the activations of microglia and astrocytes in the spinal cords of diabetic mice. Berberine inhibited the expression of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and interleukin-1β (IL-1β), along with inflammatory proteins including iNOS and COX-2. Berberine suppressed neuropathic pain in STZ-induced diabetic mice, and this effect is related to the reduction on the neuroglia activation and inflammation associated with DM.

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PMID: 

J Pharmacopuncture. 2019 Jun ;22(2):90-94. Epub 2019 Jun 30. PMID: 31338248

Abstract Title: 

Berberine Alleviates Paclitaxel-Induced Neuropathy.

Abstract: 

Objectives: Paclitaxel (PTX) as an anticancer drug used against solid cancers, possesses adverse reactions such as neuropathic pain which has confined its use. PTX-induced neuropathic pain is mediated via activation of oxidative stress. Berberine (BER), an isoquinoline phytochemical found in several plants, exerts strong antioxidant and painkilling properties. In the current study, we aimed to evaluate pain-relieving effect of BER in a mouse model of PTX-induced neuropathic pain.Methods: This study was done using 42 male albino mice that were randomly divided into 6 groups (n = 7) as follow: Sham-operated (not treated with PTX), negative control group (PTX-treated mice receiving normal saline), BER 5, 10, and 20 mg/kg (PTX-treated mice receiving BER) and positive control group (PTX-treated mice receiving imipramine 10 mg/kg). Neuropathic pain was induced by intraperitoneal administration of four doses of PTX (2 mg/kg/day) on days 1, 3, 5 and 7. Then, on day 7, hot plate test was done to assess latency to heat to measure possible anti-neuropathic pain effect of BER.Results: Four doses of PTX 2 mg/kg/day induced neuropathy that was reduced by BER at all time-points (i.e. 0, 30, 60, 90 and 120 min) after injection (P

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PMID: 

J Cell Mol Med. 2019 Jul 23. Epub 2019 Jul 23. PMID: 31338966

Abstract Title: 

Berberine attenuates XRCC1-mediated base excision repair and sensitizes breast cancer cells to the chemotherapeutic drugs.

Abstract: 

Berberine (BBR) is a natural isoquinoline alkaloid, which is used in traditional medicine for its anti-microbial, anti-protozoal, anti-diarrhoeal activities. Berberine interacts with DNA and displays anti-cancer activities, yet its effects on cellular DNA repair and on synthetic treatments with chemotherapeutic drugs remain unclear. In this study, we investigated the effects of BBR on DNA repair and on sensitization of breast cancer cells to different types of DNA damage anti-tumoural drugs. We found BBR arrested cells in the cell cycle S phase and induced DNA breaks. Cell growth analysis showed BBR sensitized MDA-MB-231 cells to cisplatin, camptothecin and methyl methanesulfonate; however, BBR had no synergistic effects with hydroxurea and olaparib. These results suggest BBR only affects specific DNA repair pathways. Western blot showed BBR down-regulated XRCC1 expressions, and the rescued XRCC1 recovered the resistance of cancer cells to BBR. Therefore, we conclude that BBR interferes with XRCC1-mediated base excision repair to sensitize cancer cells to chemotherapeutic drugs. These finding can contribute to understanding the effects of BBR on cellular DNA repair and the clinical employment of BBR in treatment of breast cancer.

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PMID: 

Front Pharmacol. 2019 ;10:786. Epub 2019 Jul 11. PMID: 31354497

Abstract Title: 

Berberine Protects Mice Against Dextran Sulfate Sodium-Induced Colitis by Activating mTORC1 Pathway.

Abstract: 

Berberine is a plant alkaloid that can be extracted from many Chinese herbs. It has been reported that berberine could protect mice from ulcerative colitis, but the mechanism remains unclear. The current study's aim was to determine the potential mechanism by which berberine exhibits its anti-inflammatory function. Mice with colitis induced by dextran sulfate sodium (DSS) were administered with berberine at 50 mg/kg by gavage. Berberine significantly increased the proportion of regulatory T cells (Treg cells). The targeted metabolomics analysis was then performed to find that glutamine and glutamate metabolism played an important role in the process of regulating immune response. mTORC1 pathway was reported to closely relate with glutamine metabolism. As a result, the relative expression levels of downstream effector genes of mTORC were further determined, and data obtained showed that berberine could significantly increase the relative expression levels of S6K1 and 4EBP1. In addition, rapamycin was used to inhibit mTORC1 signaling, and it was found that colon length, disease associated index (DAI), and proportion of Treg cells of mice in the rapamycin-DSS group were not different from those of mice in the rapamycin/berberine-DSS group. Together, these results suggest that berberine exhibits significant protective effects against DSS colitis by activating the mTORC1 pathway to increase the proportion of Treg cells.

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PMID: 

Dose Response. 2019 Jul-Sep;17(3):1559325819862449. Epub 2019 Jul 16. PMID: 31360147

Abstract Title: 

Ameliorative Effect of Berberine on Neonatally Induced Type 2 Diabetic Neuropathy via Modulation of BDNF, IGF-1, PPAR-γ, and AMPK Expressions.

Abstract: 

Neonatal-streptozotocin (n-STZ)-induced diabetes mimics most of the clinicopathological symptoms of type 2 diabetes mellitus (T2DM) peripheral neuropathy. Berberine, a plant alkaloid, is reported to have antidiabetic, antioxidant, anti-inflammatory, and neuroprotective potential. The aim of the present study was to investigate the potential of berberine against n-STZ-induced painful diabetic peripheral polyneuropathy by assessing various biochemical, electrophysiological, morphological, and ultrastructural studies. Type 2 diabetes mellitus was produced neonatal at the age of 2 days (10-12 g) by STZ (90 mg/kg intraperitoneal). After confirmation of neuropathy at 6 weeks, rats were treated with berberine (10, 20, and 40 mg/kg). Administration of n-STZ resulted in T2DM-induced neuropathic pain reflected by a significant alterations (.05) in hyperalgesia, allodynia, and motor as well as sensory nerve conduction velocities whereas berberine (20 and 40 mg/kg) treatment significantly attenuated (.05) these alterations. Berberine treatment significantly inhibited (.05) STZ-induced alterations in aldose reductase, glycated hemoglobin, serum insulin, hepatic cholesterol, and triglyceride levels. The elevated oxido-nitrosative stress and decreased Na-K-ATPase and pulse Ox levels were significantly attenuated (.05) by berberine. It also significantly downregulated (.05) neural tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 messenger RNA (mRNA), and protein expressions both. Streptozotocin-induced downregulated mRNA expressions of brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), and peroxisome proliferator-activated receptors-γ (PPAR-γ) in sciatic nerve were significantly upregulated (.05) by berberine. Western blot analysis revealed that STZ-induced alterations in adenosine monophosphate protein kinase (AMPK; Thr-172) and protein phosphatase 2C-α protein expressions in dorsal root ganglia were inhibited by berberine. It also attenuated histological and ultrastructural alterations induced in sciatic nerve by STZ. In conclusion, berberine exerts its neuroprotective effect against n-STZ-induced diabetic peripheral neuropathy via modulation of pro-inflammatory cytokines (TNF α, IL-1β, and IL-6), oxido-nitrosative stress, BDNF, IGF-1, PPAR-γ, and AMPK expression to ameliorate impaired allodynia, hyperalgesia, and nerve conduction velocity during T2DM.

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