PMID: 

Biol Pharm Bull. 2019 Jul 30. Epub 2019 Jul 30. PMID: 31366853

Abstract Title: 

Caffeic Acid Phenethyl Ester Inhibits the Proliferation of HEp2 Cells by Regulating Stat3/Plk1 Pathway and Inducing S Phase Arrest.

Abstract: 

Caffeic acid phenethyl ester (CAPE), an active polyphenolic component of honeybee propolis, has been demonstrated to have many medicinal properties. However, the antitumor effect and mechanism of CAPE on laryngeal carcinoma cells have not been examined. In this study, we treated HEp2 cells with various concentration of CAPE, and the results showed that CAPE can reduce the viability of HEp2 cells with ICvalues of 23.8± 0.7 μM for 72 h. Meanwhile, CAPE significantly inhibited activation of Stat3 in a concentration dependent manner in HEp2 cells and regulated the expression and transcription of Plk1. AG490, a specific Stat3 inhibitor, not only inhibited the activation and expression of Stat3, but also inhibitedthe expression of Plk1 in HEp2 cells, so Stat3 was probably involved in the regulation of Plk1 in HEp2 cells. In addition, treatment of CAPE leaded to a blockage of cell cycle in S phase in HEp2 cells. Therefore, CAPE inhibited the proliferation of HEp2 Cells probably by regulating Stat3/Plk1 pathway and inducing S phase arrest.

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PMID: 

J Pharm Pract. 2019 Jun 27:897190019857851. Epub 2019 Jun 27. PMID: 31248326

Abstract Title: 

Statin-Associated Bilateral Foot Myopathy.

Abstract: 

OBJECTIVE: To report a case of statin-induced bilateral foot myopathy that resulted from 2 different statins.CASE SUMMARY: A 44-year-old Caucasian male with a history of ventricular fibrillation cardiac arrest, hyperlipidemia, and coronary artery disease experienced bilateral foot pain, weakness, and soreness while taking atorvastatin 20 mg daily. The pain subsided within weeks of discontinuing atorvastatin but returned years later after the initiation of rosuvastatin. The Naranjo probability scale indicates that this is a definite association between bilateral foot myopathy and statin use.DISCUSSION: There is an association with statin use and lowering cardiovascular risk in patients with dyslipidemia and cardiovascular disease. However, statin metabolites can accumulate in the myocytes of muscle groups to cause a common side effect of myopathy. Statin myopathy typically occurs in large, bilateral, or proximal muscle groups, such as the thighs, back, calves, or buttocks. This patient was unusual in that his muscle symptoms only occurred in his feet and was severe enough to affect his ambulation.CONCLUSION: Stain-associated muscle symptoms have been reported to lessen medication adherence. There is also a risk with muscle symptoms that the patient could develop rhabdomyolysis, a rare but serious condition. Recognizing statin-associated muscle symptoms even in uncommon locations is important, so that alternative lipid-lowering strategies can be implemented to lower cardiovascular risk.

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PMID: 

J Clin Endocrinol Metab. 2019 Jul 31. Epub 2019 Jul 31. PMID: 31365088

Abstract Title: 

Medications affecting the biochemical conversion to type 2 diabetes: A systematic review and meta-analysis.

Abstract: 

BACKGROUND: The extent to which some pharmacological interventions reduce or increase the risk of biochemical conversion to T2DM in at-risk individuals is unclear.METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus through August 24, 2017, for randomized controlled trials evaluating the effect of drugs suspected to modify the risk of biochemical conversion to T2DM.RESULTS: We included 43 trials with 192,156 subjects (mean age 60 years; 56% men; mean BMI 30.4 kg/m2). Alpha-glucosidase inhibitors, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, metformin, orlistat, phentermine-topiramate and pioglitazone significantly reduced the risk of biochemical conversion to T2DM, whereas statins and nateglinide increased the risk. There was insufficient direct evidence regarding the effects of sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter-2 inhibitors. Most trials were brief and evaluated this outcome during treatment without a withdrawal or washout period.CONCLUSIONS: Several drugs modify the risk of biochemical conversation to T2DM, although whether this effect is persistent and clinically relevant is unclear. Future studies need to focus on cardiovascular disease prevention, mortality and patient-important outcomes instead of biochemical conversion to T2DM.

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PMID: 

Am Surg. 2018 Nov 1 ;84(11):1727-1733. PMID: 30747624

Abstract Title: 

Serotonin-Modulating Antidepressants and Risk of Bleeding after Trauma.

Abstract: 

Serotonin-modulating antidepressants have been associated with increased risk of gastrointestinal bleeding and increased blood loss during elective surgery. This study sought to investigate the effect of preinjury selective-serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) use on transfusion requirements after trauma, and to evaluate whether resumption of SSRI/SNRI after trauma may worsen bleeding risk. This was a retrospective matched-cohort study evaluating patients with solid organ injury. Preinjury SSRI/SNRI users were matched to non-SSRI/SNRI users based on age, preinjury aspirin use, Injury Severity Score, and abdominal Abbreviated Injury Severity Score. The primary endpoint was transfusion requirement during hospitalization. The absolute need for transfusion was higher in SSRI/SNRI users throughout hospitalization (50.9%37.3%,= 0.02). After logistic multivariate analysis, SSRI/SNRI users were more likely to require transfusion at 24 hours (odds ratio (95% confidence interval): 2.73 (1.41, 5.29),= 0.003), but this difference did not persist for overall hospitalization (odds ratio (95% confidence interval): 1.32 (0.74, 2.36),= 0.35). Fewer patients restarted on SSRI/SNRI therapy within 72 hours required packed red blood cell transfusion compared with those who were restarted later or not at all (43.2%60.3%;= 0.04). Preinjury use of serotonin-modulating antidepressants led to an increased requirement of blood transfusions after solid organ injury. Although clinicians should weigh bleeding risk before reinitiation of SSRI/SNRI, the results of this study indicate that reasonable efforts to restart these medications after stabilization do not result in further risk for transfusion.

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PMID: 

J Biomed Phys Eng. 2015 Sep ;5(3):151-4. Epub 2015 Sep 1. PMID: 26396971

Abstract Title: 

A Challenging Issue in the Etiology of Speech Problems: The Effect of Maternal Exposure to Electromagnetic Fields on Speech Problems in the Offspring.

Abstract: 

BACKGROUND: Nowadays, mothers are continuously exposed to different sources of electromagnetic fields before and even during pregnancy.  It has recently been shown that exposure to mobile phone radiation during pregnancy may lead to adverse effects on the brain development in offspring and cause hyperactivity. Researchers have shown that behavioral problems in laboratory animals which have a similar appearance to ADHD are caused by intrauterine exposure to mobile phones.OBJECTIVE: The purpose of this study was to investigate whether the maternal exposure to different sources of electromagnetic fields affect on the rate and severity of speech problems in their offspring.METHODS: In this study, mothers of 35 healthy 3-5 year old children (control group) and 77 children and diagnosed with speech problems who had been referred to a speech treatment center in Shiraz, Iran were interviewed. These mothers were asked whether they had exposure to different sources of electromagnetic fields such as mobile phones, mobile base stations, Wi-Fi, cordless phones, laptops and power lines.RESULTS: We found a significant association between either the call time (P=0.002) or history of mobile phone use (months used) and speech problems in the offspring (P=0.003). However, other exposures had no effect on the occurrence of speech problems. To the best of our knowledge, this is the first study to investigate a possible association between maternal exposure to electromagnetic field and speech problems in the offspring. Although a major limitation in our study is the relatively small sample size, this study indicates that the maternal exposure to common sources of electromagnetic fields such as mobile phones can affect the occurrence of speech problems in the offspring.

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PMID: 

J Sci Food Agric. 2019 Jun 17. Epub 2019 Jun 17. PMID: 31206687

Abstract Title: 

Anti-inflammatory activity ofβ-caryophyllene combined with docosahexaenoic acid in a model of sepsis induced by Staphylococcus aureus in mice.

Abstract: 

BACKGROUND: Sepsis is a set of serious organic manifestations caused by an infection, whose progression culminates in exacerbated inflammation and oxidative stress, poor prognosis, and high hospital costs. Antioxidants used against sepsis have been evaluated, including essential oils such asβ-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The aim of this study was to evaluate the anti-inflammatory activity of the association of these two compounds.RESULTS: Treatment with BCP-DHA, at a dose of 200 μL/animal, significantly inhibited the migration of neutrophils in a Cg-induced peritonitis model. After Staphylococcus aureus infection, in the groups treated with BCP-DHA there was a significant decrease in the total and differential count of leukocytes, increased expression of cytokines TNF-αand IFN-γ in treated groups, an increase of IL-4 and IL-5 in B/D and B/D + SA groups, and an augmentation of IL-6 and IL-12 groups in B/D + SA groups. Histological and bacterial analysis revealed lower neutrophil migration and lower bacterial load in the infected and treated groups.CONCLUSION: In general, the BCP-DHA association presented anti-inflammatory activity against two different models of acute inflammation and infection, showing promising potential as a therapeutic adjuvant in sepsis.© 2019 Society of Chemical Industry.

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PMID: 

Electromagn Biol Med. 2015 Sep ;34(3):238-43. PMID: 26444199

Abstract Title: 

Body mass index as a risk prediction and prevention factor for professional mixed low-intensity EMF burden.

Abstract: 

The exposure conditions in the physiotherapy are characterized with various sources emitting electromagnetic fields (EMF) in different frequency ranges. Very little is known about the exposure modalities' influence on the operators. In this article, we present the effects of EMF on personnel morbidity profile dependent on the body mass index (BMI) increase. By cross-tabulation, the role of higher BMI on enhancing the EMF vulnerability potential is confirmed. The correlation of the higher BMI with some serious diseases and conditions' development has been evidenced statistically significant.Вy the whole-studied group, a general tendency for allergy, cardiovascular diseases, sleep disruption and age-shortened menopause, as well as allergy and leiomyoma in the expositional criteria subgroups (ESG), formed for the purposes of this study, is evidenced. The three ESGs are formed on work residence duration in the electrolight therapy section. The first – up to four working hour daily, the second – the entire working day (7 h) and the third group is not residenced in the electrolight therapy section. We hypothesize two signaling ways of interaction of the chronically low-intensity EMFand the higher BMI as the most likely: hormonal – by melatonin levels decrease due to estrogen levels increasing and endocrine – mast-cells auto replication and degranulation stimulation. Based on the results of the study, the BMI increase as an observed control factor in the prediction of the professional risk can be recommended.

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PMID: 

Environ Int. 2015 Dec ;85:343-51. Epub 2015 Oct 30. PMID: 26474271

Abstract Title: 

Memory performance, wireless communication and exposure to radiofrequency electromagnetic fields: A prospective cohort study in adolescents.

Abstract: 

BACKGROUND: The aim of this study is to investigate whether memory performance in adolescents is affected by radiofrequency electromagnetic fields (RF-EMF) from wireless device use or by the wireless device use itself due to non-radiation related factors in that context.METHODS: We conducted a prospective cohort study with 439 adolescents. Verbal and figural memory tasks at baseline and after one year were completed using a standardized, computerized cognitive test battery. Use of wireless devices was inquired by questionnaire and operator recorded mobile phone use data was obtained for a subgroup of 234 adolescents. RF-EMF dose measures considering various factors affecting RF-EMF exposure were computed for the brain and the whole body. Data were analysed using a longitudinal approach, to investigate whether cumulative exposure over one year was related to changes in memory performance. All analyses were adjusted for relevant confounders.RESULTS: The kappa coefficients between cumulative mobile phone call duration and RF-EMF brain and whole body dose were 0.62 and 0.67, respectively for the whole sample and 0.48 and 0.28, respectively for the sample with operator data. In linear exposure-response models an interquartile increase in cumulative operator recorded mobile phone call duration was associated with a decrease in figural memory performance score by -0.15 (95% CI: -0.33, 0.03) units. For cumulative RF-EMF brain and whole body dose corresponding decreases in figural memory scores were -0.26 (95% CI: -0.42, -0.10) and -0.40 (95% CI: -0.79, -0.01), respectively. No exposure-response associations were observed for sending text messages and duration of gaming, which produces tiny RF-EMF emissions.CONCLUSIONS: A change in memory performance over one year was negatively associated with cumulative duration of wireless phone use and more strongly with RF-EMF dose. This may indicate that RF-EMF exposure affects memory performance.

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PMID: 

Eur J Pharmacol. 2019 Sep 5 ;858:172467. Epub 2019 Jun 16. PMID: 31216443

Abstract Title: 

β-caryophyllene, a dietary phytocannabinoid attenuates oxidative stress, inflammation, apoptosis and prevents structural alterations of the myocardium against doxorubicin-induced acute cardiotoxicity in rats: An in vitro and in vivo study.

Abstract: 

The present study investigates the cardioprotective effect ofβ-caryophyllene against doxorubicin-induced acute cardiotoxicity in rats. Doxorubicin (12.5 mg/kg) and β-caryophyllene (25, 50 or 100 mg/kg) were administered intraperitoneally to male albino Wistar rats. Doxorubicin-treated rats showed elevated levels of creatine kinase-MB in serum and oxidative stress in the myocardium as evidenced by decreased superoxide dismutase, catalase and glutathione with a concomitant rise in malondialdehyde levels. Doxorubicin also induced pro-inflammatory cytokines release following activation of the nuclear factor kappa-B and elevated expressions of inducible nitric oxide synthase and cyclooxygenase-2 in the myocardium. Additionally, doxorubicin also increased expression of γ-H2AX, a marker of DNA damage as well as increased expression of proapoptotic (Bax, p53, and active caspase-3) proteins along with the decreased expression of anti-apoptotic protein, Bcl2 in the myocardium. The histological and ultrastructural studies further revealed edema, inflammation and structural degeneration of cardiomyocytes following doxorubicin injection. However, treatment with β-caryophyllene showed significant cardioprotective effects as evidenced by favorableimprovement of biochemical and molecular parameters along with remarkable preservation of cardiomyocytes in histological and ultrastructural studies. Results of the present study demonstrate that β-caryophyllene has potential to protect heart against doxorubicin-induced acute cardiotoxicity in rats. Moreover, the antioxidant and free radical scavenging properties of β-caryophyllene was confirmed by in vitro assays. Provided the anticancer and chemosensitizing properties of β-caryophyllene, the cardioprotective effects of β-caryophyllene are suggestive of its multiple properties that provides an additional basis of its possible therapeutic application in chemotherapy-associated cardiotoxicity.

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PMID: 

Toxicol Ind Health. 2018 Jan ;34(1):23-35. Epub 2017 Nov 22. PMID: 29166827

Abstract Title: 

Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice.

Abstract: 

The exploding popularity of mobile phones and their close proximity to the brain when in use has raised public concern regarding possible adverse effects from exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Numerous studies have suggested that RF-EMF emitted by mobile phones can influence neuronal functions in the brain. Currently, there is still very limited information on what biological mechanisms influence neuronal cells of the brain. In the present study, we explored whether autophagy is triggered in the hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835 MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks; afterward, the hippocampus and brain stem of mice were dissected and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that several autophagic genes, which play key roles in autophagy regulation, were significantly upregulated only in the hippocampus and not in the brain stem. Expression levels of LC3B-II protein and p62, crucial autophagic regulatory proteins, were significantly changed only in the hippocampus. In parallel, transmission electron microscopy (TEM) revealed an increase in the number of autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed mice. The present study revealed that autophagy was induced in the hippocampus, not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks. These results could suggest that among the various adaptation processes to the RF-EMF exposure environment, autophagic degradation is one possible mechanism in specific brain regions.

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