Summary Background Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic ...activity predicts risk of subsequent cardiovascular events. Methods Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent18 F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses. Findings 293 patients (median age 55 years IQR 45·0–65·5) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7–4·8). Amygdalar activity was associated with increased bone-marrow activity ( r =0·47; p<0·0001), arterial inflammation ( r =0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27–1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation ( r =0·70; p=0·0083). Perceived stress was associated with amygdalar activity ( r =0·56; p=0·0485), arterial inflammation ( r =0·59; p=0·0345), and C-reactive protein ( r =0·83; p=0·0210). Interpretation In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings. Funding None.
Epirubicin’s (EPI) efficacy as a chemotherapeutic agent against breast cancer is limited by EPI’s neurotoxicity associated with increased oxidative and inflammatory stressors. 3-Indolepropionic acid ...(3-IPA) derived from in vivo metabolism of tryptophan is reported to possess antioxidative properties devoid of pro-oxidant activity. In this regard, we investigated the effect of 3-IPA on EPI-mediated neurotoxicity in forty female rats (180–200 g; five cohorts (n = 6) treated as follows:
Untreated control
;
EPI alone
(2.5 mg/Kg);
3-IPA alone
(40 mg/Kg body weight);
EPI
(2.5 mg/Kg
)
+
3-IPA
(20 mg/Kg) and
EPI
(2.5 mg/Kg
) + 3-IPA
(40 mg/Kg) for 28 days. Experimental rats were treated with EPI
via
intraperitoneal injection thrice weekly or co-treated with 3-IPA daily by
gavage
. Subsequently, the rat’s locomotor activities were measured as endpoints of neurobehavioural status. After sacrifice, inflammation, oxidative stress and DNA damage biomarkers were assessed in rats’ cerebrum and cerebellum alongside histopathology. Our results demonstrated that locomotor and exploratory deficits were pronounced in EPI-alone treated rats and improved in the presence of 3-IPA co-treatment. EPI-mediated decreases in tissue antioxidant status, increases in reactive oxygen and nitrogen species (RONS), as well as in lipid peroxidation (LPO) and xanthine oxidase (XO) were lessened in the cerebrum and cerebellum of 3-IPA co-treated rats. Increases in nitric oxide (NO) and 8-hydroxydeguanosin (8-OHdG) levels and myeloperoxidase MPO activity were also abated by 3-IPA. Light microscopic examination of the cerebrum and cerebellum revealed EPI-precipitated histopathological lesions were subsequently alleviated in rats co-treated with 3-IPA. Our findings demonstrate that supplementing endogenously derived 3-IPA from tryptophan metabolism enhances tissue antioxidant status, protects against EPI-mediated neuronal toxicity, and improves neurobehavioural and cognitive levels in experimental rats. These findings may benefit breast cancer patients undergoing Epirubicin chemotherapy.
The present study investigated the individual and combined impact of organophosphorus pesticide chlorpyrifos (CPF) and manganese (Mn), a naturally occurring trace metal, on hepatorenal function in ...adult rats. The four experimental groups namely control, CPF alone (5 mg/kg), Mn alone (10 mg/kg) and the co-exposure group consisted of eight rats which were orally gavage for 14 consecutive days. Following sacrifice, the biomarkers of hepatorenal damage, antioxidant enzyme activities, myeloperoxidase (MPO) activity as well as levels of nitric oxide, reactive oxygen and nitrogen (RONS) species and lipid peroxidation (LPO) were analysed spectrophotometrically. Further, the concentration of tumour necrosis factor alpha (TNF-α), interleukin-1 β (IL-1β) and caspase-3 activity were assessed using ELISA. Results showed that the CPF-induced increase in biomarkers of hepatorenal toxicity were significantly (p < 0.05) alleviated in rats co-expose to CPF and Mn. Moreover, the decrease in antioxidant status as well as the elevation in RONS and LPO were significantly assuaged in rats co-treated with CPF and Mn. In addition, CPF mediated increase in TNF-α, IL-1β and caspase-3 activity were significantly diminished in the liver and kidney of rats co-exposed to CPF and Mn. Light microscopic examination evidenced that the severity of histopathological lesions induced by CPF were alleviated in rats co-exposed to CPF and Mn. In conclusion, the results highlight that co-exposure to CPF and Mn in rats assuaged CPF-induced oxidative stress, inflammation and caspase-3 activation in the liver and kidney of the rats.
Encouraging knowledge flow between mutually relevant disciplines is a worthy aim of research policy makers. Yet, it is less clear what types of research promote cross-disciplinary knowledge flow and ...whether such research generates particularly influential knowledge. Empirical questions remain as to how to identify knowledge-flow mediating research and how to provide support for this research. This study contributes to addressing these gaps by proposing a new way to identify knowledge-flow mediating research at the individual research article level, instead of at more aggregated levels. We identify journal articles that link two mutually relevant disciplines in three ways-aggregating, bridging, and diffusing. We then examine the likelihood that these papers receive subsequent citations or have funding acknowledgments. Our case study of cognitive science and educational research knowledge flow suggests that articles that aggregate knowledge from multiple disciplines are cited significantly more often than are those whose references are drawn primarily from a single discipline. Interestingly, the articles that meet the criteria for being considered knowledge-flow mediators are less likely to reflect funding, based on reported acknowledgements, than were those that did not meet these criteria. Based on these findings, we draw implications for research policymakers.
The features that stabilize the structures of membrane proteins remain poorly understood. Polar interactions contribute modestly, and the hydrophobic effect contributes little to the energetics of ...apolar side-chain packing in membranes. Disruption of steric packing can destabilize the native folds of membrane proteins, but is packing alone sufficient to drive folding in lipids? If so, then membrane proteins stabilized by this feature should be readily designed and structurally characterized-yet this has not been achieved. Through simulation of the natural protein phospholamban and redesign of variants, we define a steric packing code underlying its assembly. Synthetic membrane proteins designed using this code and stabilized entirely by apolar side chains conform to the intended fold. Although highly stable, the steric complementarity required for their folding is surprisingly stringent. Structural informatics shows that the designed packing motif recurs across the proteome, emphasizing a prominent role for precise apolar packing in membrane protein folding, stabilization, and evolution.
The idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity ...has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30-100 Hz) and slow theta (3-8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, gamma power rises as that region desynchronizes with gamma activity elsewhere in the brain, establishing gamma as a largely asynchronous phenomenon. The abundant phenomenon of theta synchrony is positively correlated with a brain region's gamma power, suggesting a predominant low-frequency mechanism for inter-regional communication.
Aflatoxicosis can induce largescale toxicities in predisposed populations. Food fortification with adequate antioxidant sources may reduce the toxic burden from aflatoxicosis. We examined the ...individual and combined effect of Caffeic acid (CA) on the aflatoxin B1 (AFB1)-induced hepatic and renal injury in male rats. Five experimental rat cohort (n = 6) consisting of the control (2 mL/kg corn oil), AFB1 alone (50 μg/kg), CA alone (40 mg/kg), AFB1+CA1 (50 μg/kg + 20 mg/kg) and AFB1+CA2 (50 μg/kg + 40 mg/kg) were so treated for 28 consecutive days. Upon sacrifices, diagnostic markers of hepatorenal functions, oxidative stress, inflammation, oxidative deoxyribonucleic acid -DNA-damage and apoptosis were analysed. Our results showed that CA reduced AFB1-induced toxicities in rats' liver and kidneys by significantly increasing (p < 0.05) endogenous antioxidant and the anti-inflammatory IL-10 level. Caffeic acid simultaneously reduced hepatic and renal dysfunction biomarkers in the serum, oxidative stress, and lipid peroxidation levels. Besides, CA diminished reactive oxygen and nitrogen species, inflammatory nitric oxide levels, interleukin-1 β and the activities of xanthine oxidase and myeloperoxidase. Additionally, CA reduced DNA damage and caspase-mediated apoptotic responses and preserved the cytoarchitecture of rats' liver and kidneys treated with AFB1. These data suggest that CA can be used as a food additive to mitigate AFB1-induced toxicity in the examined organs.
•Fortification with antioxidant rich food including caffeic acid may reduce aflatoxicosis burden.•Caffeic acid reduced experimental rat liver and kidney dysfunction, biomarkers of oxidative stress and lipid peroxidation.•Caffeic acid improved rats' endogenous antioxidant, anti-inflammatory response and reduced aflatoxin B1 toxicities.•Caffeic acid reduced reactive oxygen and nitrogen species, nitric oxide, myeloperoxidase, and interleukin-1 β levels.•Caffeic acid reduced deoxyribonucleic acid damage, caspases activities and preserve organs cytoarchitecture treated rat.
Interest in cross-disciplinary research knowledge interchange runs high. Review processes at funding agencies, such as the U.S. National Science Foundation, consider plans to disseminate research ...across disciplinary bounds. Publication in the leading multidisciplinary journals, Nature and Science, may signify the epitome of successful interdisciplinary integration of research knowledge and cross-disciplinary dissemination of findings. But how interdisciplinary are they? The journals are multidisciplinary, but do the individual articles themselves draw upon multiple fields of knowledge and does their influence span disciplines? This research compares articles in three fields (Cell Biology, Physical Chemistry, and Cognitive Science) published in a leading disciplinary journal in each field to those published in Nature and Science. We find comparable degrees of interdisciplinary integration and only modest differences in cross-disciplinary diffusion. That said, though the rate of out-of-field diffusion might be comparable, the sheer reach of Nature and Science, indicated by their potent Journal Impact Factors, means that the diffusion of knowledge therein can far exceed that of leading disciplinary journals in some fields (such as Physical Chemistry and Cognitive Science in our samples).
We investigated the impact of Coartem™ (COA) and aflatoxin B1 (AFB
) on rats' hypothalamus, epididymis, and testis. Male rats were randomly grouped (n = 5 rats) and treated: control group (corn oil), ...AFB
(70 µg/kg), COA (5 mg/kg), COA + AFB
(5 + 0.035 mg/kg) and COA + AFB
(5 + 0.07 mg/kg) for 28 days. Blood samples were collected for serum prolactin, testosterone, follicle-stimulating and luteinising hormones (FSH and LH) assay upon sacrifice. The semen, hypothalamus, epididymis, and testes were harvested for morphological, biochemical, and histopathology determination of oxidative, inflammation stress, genomic integrity, and pathological alterations. Exposure to the COA and AFB
caused the cauda epididymal spermatozoa to display low motility, viability, and volume, with increased abnormalities. Hormonal disruption ensued in animals exposed to COA and AFB
alone or together, exemplified by increased prolactin, and decreased testosterone, FSH and LH levels. Treatment-related reduction in biomarkers of testicular metabolism-acid and alkaline phosphatases, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase-were observed. Also, COA and AFB
treatment caused reductions in antioxidant (Glutathione and total thiols) levels and antioxidant enzyme (Catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase) activities in the examined organs. At the same time, treatment-related increases in DNA damage (p53), oxidative stress (xanthine oxidase, reactive oxygen and nitrogen species and lipid peroxidation), inflammation (nitric oxide and tumour necrosis factor-alpha), and apoptosis (caspase-9, and -3) were observed. Chronic exposure to COA and AFB1 led to oxidative stress, inflammation, and DNA damage in male rats' hypothalamic-reproductive axis, which might potentiate infertility if not contained.
•Protocatechuic acid (PCA), a dietary polyphenol, elicits beneficial effects on male reproductive system.•PCA alleviated furan-mediated declines in sperm quality and serum reproductive hormones.•PCA ...attenuated furan-induced reduction in antioxidant enzyme activities and testicular function marker enzymes.•PCA effectively alleviated furan-mediated increases in myeloperoxidase activity, reactive oxygen and nitrogen species, nitric oxide, TNF-α, and IL-1β.•PCA increased anti-inflammatory cytokine IL-10, suppressed caspase-9 and caspase-3 activities and ameliorated injury in the testes, epididymis and hypothalamus of furan treated rats.
The reproductive toxicity associated with furan exposure in both animals and humans has been documented. Protocatechuic acid (PCA), a dietary polyphenolic chemical, reportedly elicits beneficial effects on the male reproductive system. However, the influence of PCA on the reproductive toxicity related to furan exposure is unavailable in the literature. The current study evaluated the effects of PCA on the dysfunctional reproductive axis caused by furan exposure in rats. Experimental animals were exposed to furan (8 mg/kg) or co-treated with furan (8 mg/kg) and PCA (25 or 50 mg/kg) for twenty-eight successive days. Results revealed that PCA treatment significantly alleviated furan-mediated declines in sperm production and characteristic qualities as well as in serum levels of prolactin, luteinizing hormone, follicle-stimulating hormone, and testosterone. Further, PCA attenuated furan-induced reduction in antioxidant enzyme activities and testicular function marker enzymes, namely lactate dehydrogenase, glucose-6-phosphate dehydrogenase, acid phosphatase, and alkaline phosphatase. PCA effectively mitigated furan-mediated increases in myeloperoxidase activity, levels of reactive oxygen and nitrogen species, nitric oxide, tumour necrosis factor-alpha, and interleukin-1β in testes, epididymis, and hypothalamus of rats. Moreover, PCA increased anti-inflammatory cytokine interleukin-10 but suppressed caspase-9 and caspase-3 activities and ameliorated injuries in the testes, epididymis, and hypothalamus of furan-treated rats. In conclusion, PCA ameliorated deficits in the hypothalamic-pituitary-gonadal axis function in furan-exposed rats by suppressing oxido-inflammatory stress and apoptosis.
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