Effects of Saffron Extract (Affron®) with 100 mg/kg and 200 mg/kg on Hypothalamic-Pituitary-Adrenal Axis and Stress Resilience in Chronic Mild Stress-Induced Depression in Wistar Rats.

Stress-related symptoms are a global concern, impacting millions of individuals, yet effective and safe treatments remain scarce. Although multiple studies have highlighted the stress- alleviating properties of saffron extract, the underlying mechanisms remain unclear. This study employs the unpredictable chronic mild stress (CMS) animal model to investigate the impact of a standardized saffron extract, Affron® (AFN), on hypothalamic-pituitary-adrenal (HPA) axis regulation and neuroplasticity in Wistar rats following repeated oral administration. The research evaluates AFN's effects on various stress-related parameters, including hypothalamic gene expression, stress hormone levels, and the sucrose preference test. In animals subjected to continuous unpredictable CMS, repetitive administration of AFN at doses of 100 mg/kg and 200 mg/kg effectively normalized HPA axis dysregulation and enhanced neuroplasticity. Increased concentrations of AFN demonstrated greater efficacy. Following AFN oral administration, adrenocorticotropic and corticosterone hormone levels exhibited significant or nearly significant reductions in comparison to subjects exposed to stress only. These changes align with the alleviation of stress and the normalization of the HPA axis. These findings elucidate AFN's role in stress mitigation, affirm its health benefits, validate its potential as a treatment for stress-related symptoms, confirm its physiological effectiveness, and emphasize its therapeutic promise.

Associations of hiatus hernia with CT-based interstitial lung changes: the MESA Lung Study.

BACKGROUND: Hiatus hernia (HH) is prevalent in adults with pulmonary fibrosis. We hypothesised that HH would be associated with markers of lung inflammation and fibrosis among community-dwelling adults and stronger among MUC5B (rs35705950) risk allele carriers. METHODS: In the Multi-Ethnic Study of Atherosclerosis, HH was assessed from cardiac and full-lung computed tomography (CT) scans performed at Exam 1 (2000-2002, n=3342) and Exam 5 (2010-2012, n=3091), respectively. Percentage of high attenuation areas (HAAs; percentage of voxels with attenuation between -600 and -250 HU) was measured from cardiac and lung scans. Interstitial lung abnormalities (ILAs) were examined from Exam 5 scans (n=2380). Regression models were used to examine the associations of HH with HAAs, ILAs and serum matrix metalloproteinase-7 (MMP-7), and adjusted for age, sex, race/ethnicity, educational attainment, smoking, height, weight and scanner parameters for HAA analysis. RESULTS: HH detected from Exam 5 scans was associated with a mean percentage difference in HAAs of 2.23% (95% CI 0.57-3.93%) and an increase of 0.48% (95% CI 0.07-0.89%) per year, particularly in MUC5B risk allele carriers (p-value for interaction=0.02). HH was associated with ILAs among those <80 years of age (OR for ILAs 1.78, 95% CI 1.14-2.80) and higher serum MMP-7 level among smokers (p-value for smoking interaction=0.04). CONCLUSIONS: HH was associated with more HAAs over time, particularly among MUC5B risk allele carriers, and ILAs in younger adults, and may be a risk factor in the early stages of interstitial lung disease.

Pulmonary Embolism in Hospitalized Patients with COVID-19: A Multicenter Study.

Background Pulmonary embolism (PE) commonly complicates SARS-CoV-2 infection, but incidence and mortality reported in single-center studies, along with risk factors, vary. Purpose To determine the incidence of PE in patients with COVID-19 and its associations with clinical and laboratory parameters. Materials and Methods In this HIPAA-compliant study, electronic medical records were searched retrospectively for demographic, clinical, and laboratory data and outcomes among patients with COVID-19 admitted at four hospitals from March through June 2020. PE found at CT pulmonary angiography and perfusion scintigraphy was correlated with clinical and laboratory parameters. The d-dimer level was used to predict PE, and the obtained threshold was externally validated among 85 hospitalized patients with COVID-19 at a fifth hospital. The association between right-sided heart strain and embolic burden was evaluated in patients with PE undergoing echocardiography. Results A total of 413 patients with COVID-19 (mean age, 60 years ± 16 [standard deviation]; age range, 20-98 years; 230 men) were evaluated. PE was diagnosed in 102 (25%; 95% CI: 21, 29) of 413 hospitalized patients with COVID-19 who underwent CT pulmonary angiography or perfusion scintigraphy. PE was observed in 21 (29%; 95% CI: 19, 41) of 73 patients in the intensive care unit (ICU) versus 81 (24%; 95% CI: 20, 29) of 340 patients who were not in the ICU (P = .37). PE was associated with male sex (odds ratio [OR], 1.74; 95% CI: 1.1, 2.8; P = .02); smoking (OR, 1.86; 95% CI: 1.0, 3.4; P = .04); and increased d-dimer (P < .001), lactate dehydrogenase (P < .001), ferritin (P = .001), and interleukin-6 (P = .02) levels. Mortality in hospitalized patients was similar between patients with PE and those without PE (14% [13 of 102]; 95% CI: 8, 22] vs 13% [40 of 311]; 95% CI: 9, 17; P = .98), suggesting that diagnosis and treatment of PE were not associated with excess mortality. The d-dimer levels greater than 1600 ng/mL [8.761 nmol/L] helped predict PE with 100% sensitivity and 62% specificity in an external validation cohort. Embolic burden was higher in patients with right-sided heart strain among the patients with PE undergoing echocardiography (P = .03). Conclusion Pulmonary embolism (PE) incidence was 25% in patients hospitalized with COVID-19 suspected of having PE. A d-dimer level greater than 1600 ng/mL [8.761 nmol/L] was sensitive for identification of patients who needed CT pulmonary angiography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Ketai in this issue.

Hiatal hernia prevalence and natural history on non-contrast CT in the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVE: To determine the prevalence, risk factors and natural history of hiatal hernia (HH) on CT in the general population. MATERIALS AND METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) acquired full-lung CT on 3200 subjects, aged 53-94 years. Three blinded observers independently determined presence/absence and type (I-IV) of HH. Associations between HH and participant characteristics were assessed via unadjusted and multivariable-adjusted relative risk regression. HH natural history was assessed compared with prior MESA CT. RESULTS: Excellent interobserver agreement was found for presence (κ=0.86) and type of HH (κ=0.97). Among 316 HH identified (prevalence=9.9%), 223 (71%) were type I and 93 (29%) were type III. HH prevalence increased with age, from 2.4% in 6th decade to 16.6% in 9th decade (unadjusted prevalence ratio (PR)=1.1 (95% CI 1.04 to 1.1)). HH prevalence was greater in women (12.7%) than men (7.0%) (unadjusted PR=1.8 (95% CI 1.5 to 2.3)) and associated with proton pump inhibitor use (p<0.001). In 75 participants with HH with 10-year follow-up, median HH area increased from 9.9 cm2 to 17.9 cm2 (p=0.02) with a higher mean body mass index (BMI) in subjects with increasing HH size compared with HH decreasing in size: mean BMI=30.2±6.2 vs 26.8±7.2 (p=0.02). CONCLUSION: HH on non-contrast CT is prevalent in the general population, increasing with age, female gender and BMI. Its association with proton pump inhibitor use confirms a role in gastro-oesophageal reflux disease and HH progression is associated with increased BMI. TRIAL REGISTRATION NUMBER: NCT00005487.

Lancemaside A from Codonopsis lanceolata prevents hypertension by inhibiting NADPH oxidase 2-mediated MAPK signalling and improving NO bioavailability in rats.

OBJECTIVES: This study investigated whether lancemaside A (LMA) can prevent hypertension and assessed the mechanisms of action of LMA in rats. METHODS: Hypertension was induced by chronic immobilization stress and nicotine administration. Hypertensive vehicle rats were treated with LMA (1, 20, or 40 mg/kg) or nifedipine (10 mg/kg) as a positive control daily for 3 weeks. KEY FINDINGS: In hypertensive vehicle rats, LMA dose-dependently reduced systolic blood pressure. LMA doses of 20 and 40 mg/kg reduced the aortic expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)2 (both P < 0.01), and 40 mg/kg LMA reduced serum malondialdehyde (P < 0.01). Serum nitrite levels were significantly higher in LMA treated rats than in hypertensive vehicle rats, with LMA doses of 20 and 40 mg/kg reducing the expression of endothelial nitric oxide synthase in rat aortas (P < 0.001 and P < 0.01, respectively). LMA also reduced the aortic levels of nuclear factor kappa B and the activation of the three isoforms of mitogen-activated protein kinase (MAPK). CONCLUSIONS: Lancemaside A prevents hypertension in rats by inhibiting the activation of MAPK signalling and the impairment in nitric oxide bioavailability due to NOX2-mediated oxidative stress. Thus, LMA may act as a preventive agent for hypertension.

Lancemaside A, a major triterpene saponin of Codonopsis lanceolata enhances regulation of nitric oxide synthesis via eNOS activation.

BACKGROUND: Many studies on the effect of saponin-rich Codonopsis lanceolata as a bioactive source for improving physical health have been performed. C. lanceolata contains triterpenoid saponins, including lancemasides. These saponins are known to be particularly involved in the regulation of blood pressure or hypertension. This study investigated whether lancemaside A (LA), a major triterpenoid saponin from C. lanceolata, regulates nitric oxide (NO) production via the activation of endothelial NO synthase (eNOS) in human umbilical vein endothelial cells. METHODS: Upon separation with petroleum ether, ethyl acetate, and n-butanol, LA was found to be abundant in the n-butanol-soluble portion. For further purification of LA, HPLC was performed to collect fraction, and LA was identified using analysis of LC/MSMS and 13C-NMR values. In in vitro, the effects of LA on NO release mechanism in HUVECs were investigated by Griess assay, quantitative real-time reverse-transcription PCR, and Western blotting. RESULTS: Our results showed that NO production was efficiently improved by treatment with LA in a dose-dependent manner. In addition, the LA treatment resulted in extensive recovery of the NO production suppressed by the eNOS inhibitor, L-NAME, compared with that in the control group. Additionally, the level of eNOS mRNA was increased by this treatment in a dose-dependent manner. These results suggested that LA is an inducer of NO synthesis via eNOS mRNA expression. Also, the study indicated that LA is involved in activating the PI3K/Akt/eNOS signaling pathway. CONCLUSION: These results suggested that LA is an inducer of NO synthesis via eNOS mRNA expression. Also, the study indicated that LA is involved in activating the PI3K/Akt/eNOS signaling pathway. These findings suggest the value of using LA as a component of functional foods and natural pharmaceuticals.

Comparing levels of perfluorinated compounds in processed marine products.

Perfluorinated compounds (PFCs) are widely distributed in nature and have many applications due to their unique chemical and physicochemical properties. While, PFCs are present in soil, water, and air, their pathway for entry into the human body is circumstantially via contaminated food. The demand for seafood has been increasing. In this study, we investigated via LC-MS/MS, the content of 19 different types of PFCs in 302 samples belonging to five different categories of the typical South Korean seafood. The highest levels of PFOA, PFTrDA, PFOS, and PFPeA were found in dried seafood, canned and salted seafood, processed fish food, and seasoned laver, respectively. The levels of PFOA and PFOS were compared on the basis of various criteria including the nomenclature, biological classification, and habitat of the source of seafood. High levels of PFOA and PFOS were detected in anchovy, sea squirt, and mackerel based on the nomenclature of raw seafood, in crustaceans based on the biological classification, and in demersal organisms based on the habitat. The human intake values of PFOA and PFOS from the processed marine products in South Korea were lower than the tolerable daily intake, indicating that the consumption of these processed seafood poses no immediate harm.

Assessment of the effect of cooking on speciation and bioaccessibility/cellular uptake of arsenic in rice, using in vitro digestion and Caco-2 and PSI cells as model.

In vitro digestion/Caco-2 or pig small intestinal epithelium cell line (PSI) uptake models were used to study the bioaccessibility and cellular uptake of arsenic (As) in cooked white rice and brown rice. The arsenite(AsIII), was the predominant species in cooked rice and in its bioaccessible fractions. The percentage of total As bioaccessibility in white rice (75%) was slightly higher (p=0.061) than that in brown rice(66%). However, there was no difference in the inorganic As (iAs) bioaccessibility between white rice (95%) and brown rice (96%). In Caco-2 cell monolayer, total As retention was 7-31%, transport was 4-25%, and uptake (sum of retention and transport) was 16-38%. In PSI cell model, the retention, transport, and uptake of tAs were 10-28%, 14-31%, and 29-50%, respectively. In both cells, the cellular uptake of tAs in brown rice was 1.4-1.5 folds lower (p<0.05) than that of white rice. These results indicate that the cellular uptake of As can be affected by nutritional compositions. These in vitro screening methods can serve as preliminary screens to predict the relative impact in rice matrix having different As species and processing conditions, although more research efforts should be applied to validating the existing in vitro methods.