PMID: 

Case Rep Dent. 2020 ;2020:1675653. Epub 2020 Feb 13. PMID: 32123589

Abstract Title: 

Acemannan Induced Bone Regeneration in Lateral Sinus Augmentation Based on Cone Beam Computed Tomographic and Histopathological Evaluation.

Abstract: 

Acemannan, the major polysaccharide extracted from Aloe vera, is biomaterial that has demonstrated osteoinductive effectsandHowever, the effect of acemannan sponges on bone formation in open-type sinus augmentation has not evaluated. Here, we report a case study using radiographic and histological analyses to investigate the effect of acemannan on bone formation after lateral sinus lift surgery. The case was a 57-year-old female patient with an atrophic left posterior maxilla who underwent lateral sinus lift using an acemannan sponge using the two-stage procedure. In the first stage, an acemannan sponge was inserted through the bony window and placed between the antral floor and the elevated sinus membrane. Cone beam computed tomography (CBCT) images were taken immediately as baseline and 6-month postoperation for evaluation. A bone core specimen was also obtained for histological examination at the time of implant placement. The histological results revealed new bone formation, and the CBCT images demonstrated increased alveolar bone height at 6-month postoperation. Our findings suggest that an acemannan sponge could be a biomaterial for inducing bone formation in sinus lift surgery.

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PMID: 

Sci Total Environ. 2020 Mar 12 ;722:137887. Epub 2020 Mar 12. PMID: 32197165

Abstract Title: 

Prenatal bisphenol A exposure, fetal thyroid hormones and neurobehavioral development in children at 2 and 4 years: A prospective cohort study.

Abstract: 

Findings about the association between prenatal Bisphenol A (BPA) exposure and neurobehavioral development in children are still inconsistent. In addition, whether fetal thyroid hormones (THs) mediate the reported association remains unclear. The present study aimed to examine the association between prenatal BPA exposure and risks of child behavioral problems at 2 and 4 years of age and whether the association could be explained by alteration of fetal THs as measured in cord plasma. Using the Shanghai-Minhang Birth Cohort Study (S-MBCS), BPA concentration was measured in maternal urine samples collected at 12-16 weeks of gestation. Children's neurobehavioral development was assessed using the Child Behavior Checklist/1.5-5 (CBCL), at 2 and 4 years of age. Using generalized estimating equation (GEE) models, 745 mother-pairs were included to examine associations of BPA with CBCL scores, Using multiple linear regression models, 348 mother-pairs were includedto evaluate the association between maternal BPA and THs in cord plasma. A mediation analysis was conducted to explore the potential mediating role of THs. After adjusting for potential confounders, prenatal BPA level was associated with increased risks of Emotionally Reactive problem, Anxious/Depressed problem, having Somatic Complaints, exhibiting Aggressive Behavior, and Internalizing and Externalizing Problems: compared to the lowest tertile, the risks in the highest tertile and middle tertile, ranged between 1.55-fold (95% CI: 1.09, 2.21) and 2.59-fold (95% CI: 1.52, 4.42). The association was more pronounced among boys. None of the associations reached statistical significance among girls. An inverse association between prenatal BPA and fetal TH level was also observed. However, the observed neurotoxic effects of prenatal BPA exposure did not appear to be mediated by THs levels. The current findings suggest that prenatal exposure to BPA may disrupt fetal THs levels and may induce long-lasting behavioral alterations, especially in boys.

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PMID: 

Environ Res. 2020 Mar 16 ;184:109382. Epub 2020 Mar 16. PMID: 32192991

Abstract Title: 

Bisphenol A exposure in relation to altered lipid profile and dyslipidemia among Chinese adults: A repeated measures study.

Abstract: 

Animal experiments suggest that bisphenol A (BPA) could potentially induce lipid abnormalities. However, whether BPA exposure associates with altered lipid metabolism in humans has not been fully elucidated. We thus comprehensively investigated the relationship of BPA exposure and its change with lipid profile and development of incident dyslipidemia among Chinese adults. We initially included 1872 participants aged 40 years or older who were free of dyslipidemia at baseline in 2009, and followed them for 4 years. Urinary BPA and serum lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined at baseline and follow-up. Linear mixed models were used for repeated measures analyses and linear and logistic regression models were used to evaluate longitudinal changes in lipid profile and risk of incident dyslipidemia. In repeated measures analyses, per doubling of urinary BPA concentrations was associated with higher serum levels of LDL-C, non-HDL-C, TC to HDL-C ratio, and lower levels of HDL-C and TG. In longitudinal change analyses, participants with high BPA at both baseline and follow-up showed an additional 2.94% increase in LDL-C (95% CI: 0.02%, 5.95%) and 6.12% increase in TG (95% CI: 0.74%, 11.8%), as compared with those who maintained low BPA. Furthermore, participants with sustained high BPA at two time points had increased odds of developing hyper-LDL cholesterolemia (odds ratio = 1.93, 95% CI: 1.02, 3.66). Our results suggested that high BPA exposure, especially maintained a long time period apart, was associated with deterioration of lipid profiles among middle-aged and elderly adults, supporting a detrimental role of BPA in lipid metabolism.

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PMID: 

Environ Res. 2020 Mar 18 ;184:109381. Epub 2020 Mar 18. PMID: 32199324

Abstract Title: 

Perinatal exposure to bisphenol A increases in the adulthood of the offspring the susceptibility to the human parasite Toxocara canis.

Abstract: 

Bisphenol A, a very widespread environmental pollutant and endocrine disruptor compound, can interact with several steroid receptors, particularly with estrogen ones. In different studies, it has observed that the endocrine disruption during critical periods of development can trigger alterations in the immune response during the adult life. Male Wistar rats were exposed indirectly to BPA at a dose of 250 μg/kg day during the perinatal period (from day 5 of pregnancy until day 21 postnatal), At the 60 days of age, the adulthood, animals were infected with larvated eggs of the Toxocara canis, and were sacrificed at 7 days post-infection. Parasitic loads in the lung and in the liver were analyzed byartificial digestion. Furthermore, immune cell subpopulations (macrophages, NK cells, Tγδ, total T cells, T helper, T cytotoxic, and B lymphocytes) present in spleen, peripheral and mesenteric lymph nodes were analyzed by flow cytometry. The expression of Th1 and Th2 cytokines at the splenic level was determined by real-time quantitative PCR. Finally, the titers of specific antibodies against to the parasite were analyzed by ELISA. The BPA treatment administrated in the perinatally stage favors a significant increase of the percentage of Toxocara canis larvae in the lungs and liver in the adulthood. Additionally, the exposure to this compound caused a dramatically decrease in the production of specific antibodies against to this parasite, downregulating together Th2 cytokines (IL-4, IL-5 and IL-13), meanwhile upregulated Th1 cytokines (IFN-γ and TNF-α). Perinatal exposure to BPA affects the performance of the immune response during adult life, modifying both cytokines and antibodies production by these cells, which favors the susceptibility to infections, specifically toxocariosis.

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PMID: 

Med Hypotheses. 2020 Mar 11 ;140:109675. Epub 2020 Mar 11. PMID: 32200183

Abstract Title: 

The effect of BPA exposure on insulin resistance and type 2 diabetes – The impact of muscle contraction.

Abstract: 

Type 2 diabetes (T2D) is considered one of the leading causes of death worldwide. In addition to physical inactivity and obesity, established risk factors for T2D, chemical contaminants consumed in industrialized food such as BPA might also be a contributor to the development of T2D. Epidemiological studies have shown that BPA concentrations are higher in human specimens of T2D when compared to healthy subjects, while experimental studies suggested that bisphenol A (BPA) impairs the pathway by which insulin stimulates glucose uptake. In skeletal muscle and adipocytes, insulin resistance is developed by the impairment of the insulin pathway to stimulate the translocation of glucose transporter, GLUT4, to the cell membrane. Recent results demonstrated that BPA impairs several components of insulin-induced glucose uptake pathway and affect the expression of GLUT4. Regular physical exercise delays or inhibits the development of T2D due to the physiologic processes taking place during muscle contraction, and the fact that skeletal muscle is the site for almost 80% of the glucose transported under insulin stimulation. In fact, the mechanism by which contraction induces glucose uptake in skeletal muscle is partially independent of the insulin pathway, therefore, the effect of BPA on this mechanism is unknown. We hypothesize that during the development of insulin resistance, BPA contributes to the impairment of the molecular pathway by which insulin induces glucose uptake while contraction-induced glucose uptake is not impaired. At the late stages of T2D, BPA may affect GLUT4 expression that will decrease the ability of muscle contraction to induce glucose uptake.

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PMID: 

Environ Toxicol Pharmacol. 2020 Mar 19 ;77:103373. Epub 2020 Mar 19. PMID: 32200274

Abstract Title: 

Bisphenol A-induced metabolic disorders: From exposure to mechanism of action.

Abstract: 

Bisphenol A (BPA) is considered as ubiquitous xenooestrogen and an endocrine disrupting chemical which has deleterious effects on endocrine functions. Human populations are continuously exposed to BPA as it is abundant in daily life. It has been found to be associated with wide range of metabolic disorders notably type 2 diabetes mellitus (DM). Numerous epidemiological studies have been conducted to find its role in development of DM. Experimental studies have found that BPA exposure is associated with pathogenesis of DM and also considered as a risk factor for gestational diabetes. Being a lipophilic compound, BPA is preferably accumulated in adipose tissues where it alters the production of adipokines that play important roles in insulin resistance. BPA induces apoptosis by caspase activation after mitochondrial damage and it impairs insulin signaling pathways by altering associated ion channel activity especially potassium channels. Perinatal exposure of BPA makes offspring more susceptible to develop DM in early years. Epigenetic modifications are the key mechanisms for BPA-induced metabolic re-programming, where BPA alters the expression of DNA methyltransferases involved in methylation of various genes. In this way, DNA methyltransferase controls the expression of numerous genes including genes important for insulin secretion and signaling. Furthermore, BPA induces histone modifications and alters miRNA expression. In this article, we have briefly described the sources of BPA exposure to human being and summarized the evidence from epidemiological studies linking DM with BPA exposure. Additionally, we have also highlighted the potential molecular pathways for BPA-induced DM.

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PMID: 

J Neuroimmune Pharmacol. 2020 Jan 6. Epub 2020 Jan 6. PMID: 31909440

Abstract Title: 

Anti-Inflammation Associated Protective Mechanism of Berberine and its Derivatives on Attenuating Pentylenetetrazole-Induced Seizures in Zebrafish.

Abstract: 

Epileptic seizures are characterized by synchronized discharges of neurons, leading to the activation of inflammatory responses that in turn contributes to seizure progression. Berberine (BBR), a bioactive constituent extracted from berberis, has been known to relieve seizures in rodent models. In this study, we synthesized two derivatives of berberine (BBR-D1 and BBR-D2) to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. We found a structure-activity relationship between hydrophilic/hydrophobic composition of the derivatives and their anticonvulsant activity. We also investigated the underlying mechanism related to their anti-inflammatory effect during seizures. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures. The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives. Our results suggest that BBR and its derivatives attenuate PTZ-induced seizures and modulate anti-inflammatory effect to potentially protect zebrafish from the occurrence of further seizures. From the tested compounds, BBR-D1 (the hydrophilic berberrubine) showed the strongest seizure reducing effect. Graphical Abstract Two derivatives of berberine (BBR-D1 and BBR-D2) were synthesized to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures.The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives.

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PMID: 

Drug Deliv. 2020 Dec ;27(1):283-291. PMID: 32013620

Abstract Title: 

Autologous erythrocytes delivery of berberine hydrochloride with long-acting effect for hypolipidemia treatment.

Abstract: 

Discovery of novel pharmacological effects of berberine hydrochloride (BH) has made its clinical application valuable. However, further development and applications of BH are hampered by its short half-life and the side effects associated with its intravenous (iv) injection. To improve the hypolipidemia efficacy and reduce side effects, we encapsulated BH into biocompatible red blood cells (RBCs) to explore its sustained-release effect by hypotonic pre-swelling method. Fromevaluation, BH loaded RBCs (BH-RBCs) presented similar morphology and osmotic fragility to native RBCs (NRBCs). After the loading process, the BH-RBCs maintained around 69% of Na/K-ATPase activity of NRBCs and phosphatidylserine externalization value of BH-RBCs was about 26.1 ± 2.9%. The survival test showed that the loaded cells could circulate in plasma for over 9 d. Forevaluation, a series of tests including pharmacokinetics study and hypolipidemic effect were carried out to examine the long-acting effect of BH-RBCs. The results showed that the release of BH in the loaded cells could last for about 5 d and the hypolipidemic effect can still be observed on 5 d after injection. BH-loaded autologous erythrocytes seem to be a promising sustained releasing delivery system with long hypolipidemic effect.

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PMID: 

Int Immunopharmacol. 2020 Feb 9 ;81:106205. Epub 2020 Feb 9. PMID: 32050154

Abstract Title: 

Berberine combined with cyclosporine A alleviates acute graft-versus-host disease in murine models.

Abstract: 

Graft-versus-host disease (GVHD) causes significant mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Berberine (BBR) is primarily used to alleviate inflammation caused by autoimmune disorders. Herein the effect of BBR and cyclosporine A (CsA) on GVHD prevention in murine models is explored. Acute GVHD was induced by total body irradiation and tail vein injection with the mixture of bone marrow cells and spleen lymphocytes. Then models were treated with BBR (10 mg/kg), CsA (5 mg/kg) or the combination of BBR and CsA (10 mg/kg and 5 mg/kg) once a day for 10 days. The survival rate, weight loss and GVHD index were monitored. Then the histological changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, apoptosis and thelevels of inflammatory cytokines, oxidative stress and nuclear factor-κB (NF-κB) signaling in liver and intestine were analyzed. Moreover, the levels of inflammatory cytokines and oxidative stress, and the count of T helper 1 (Th1) cells and Th17 cells in peripheral blood were determined. The results showed that BBR reduced GVHD-induced weight loss and GVHD index scores, attenuated liver and intestinal injury, and inhibited ALT and AST activities, inflammation, oxidative stress and NF-κB activation in liver and intestine. Additionally, BBR inhibited inflammation and reduced Th1 cell countsbut had no effect on Th17 cell counts. Interestingly, the concomitant therapy of BBR and CsA was more potent than either BBR or CsA and effectively elevated the survival rate of GVHD models. This present study provides a new therapeutic strategy for alleviation of acute GVHD.

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PMID: 

Life Sci. 2020 Apr 15 ;247:117442. Epub 2020 Feb 17. PMID: 32081663

Abstract Title: 

Berberine attenuated olanzapine-induced metabolic alterations in mice: Targeting transient receptor potential vanilloid type 1 and 3 channels.

Abstract: 

Transient receptor potential vanilloid type 1 (TRPV1) channels are emerging therapeutic targets for metabolic disorders. Berberine, which is a modulator of TRPV1, has proven antiobesity and antidiabetic potentials. The present study was aimed to investigate the protective effects of berberine in olanzapine-induced alterations in hypothalamic appetite control, inflammation and metabolic aberrations in mice targeting TRPV1 channels. Female BALB/c mice (18-23 g) were treated with olanzapine (6 mg/kg, p.o.) for six weeks to induce metabolic alterations, while berberine (100 and 200 mg/kg, p.o.) and metformin (100 mg/kg, p.o) were used as test and standard interventions respectively. Weekly assessment of feed-water intake, body temperature and body weight was done, while locomotion was measured at the end of week 1 and 6. Serum glucose and lipid profile were assessed by biochemical methods, while other serum biomarkers were assessed by ELISA. qPCR was used to quantify the mRNA expression in the hypothalamus. Olanzapine treatment significantly increased the feed intake, weight gain, adiposity index, while reduced body temperature and locomotor activity which were reversed by berberine treatment. Berberine treatment reduced serum ghrelin and leptin levels as well decrease in hypothalamic mRNA expression of orexigenic neuropeptides, inflammatory markers and ghrelin receptor in olanzapine-treated mice. Olanzapine treatment increased expression of TRPV1/TRPV3 in the hypothalamus which was significantly decreased by berberine treatment. Our results suggest that berberine, by TRPV1/TRPV3 modulation, attenuated the olanzapine-induced metabolic alterations in mice. Hence berberine supplementation in psychiatric patients could be a preventive approach to reduce the metabolic adverse effects of antipsychotics.

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