Maternal and Offspring Fatty Acid Desaturase Variants, Prenatal DHA Supplementation, and Dietary n-6:n-3 Fatty Acid Ratio in Relation to Cardiometabolic Health in Mexican Children.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in fatty acid desaturase (FADS) genes may modify dietary fatty acid requirements and influence cardiometabolic health (CMH). OBJECTIVES: We evaluated the role of selected variants in maternal and offspring FADS genes on offspring CMH at the age of 11 y and assessed interactions of genotype with diet quality and prenatal docosahexaenoic acid (DHA) supplementation. METHODS: We used data from offspring (n = 203) born to females who participated in a randomized controlled trial of DHA supplementation (400 mg/d) from midgestation to delivery. We generated a metabolic syndrome (MetS) score from body mass index, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and fasting glucose and identified 6 distinct haplotypes from 5 offspring FADS SNPs. Dietary n-6 (ω-6):n-3 fatty acid ratios were derived from 24-h recall data (n = 141). We used generalized linear models to test associations of offspring diet and FADS haplotypes with MetS score and interactions of maternal and offspring FADS SNP rs174602 with prenatal treatment group and dietary n-6:n-3 ratio on MetS score. RESULTS: Associations between FADS haplotypes and MetS score were null. Offspring SNP rs174602 did not modify the association of prenatal DHA supplementation with MetS score. Among children with TT or TC genotype for SNP rs174602 (n = 88), those in the highest n-6:n-3 ratio tertile (>8.61) had higher MetS score relative to the lowest tertile [<6.67) (Δ= 0.36; 95% confidence interval (CI): 0.03, 0.69]. Among children with CC genotype (n = 53), those in the highest n-6:n-3 ratio tertile had a lower MetS score relative to the lowest tertile (Δ= -0.23; 95% CI: -0.61, 0.16). CONCLUSIONS: There was evidence of an interaction of offspring FADS SNP rs174602 with current dietary polyunsaturated fatty acid intake, but not with prenatal DHA supplementation, on MetS score. Further studies may help to determine the utility of targeted supplementation strategies and dietary recommendations based on genetic profile.

Effects of prenatal docosahexaenoic acid supplementation on offspring cardiometabolic health at 11 years differs by maternal single nucleotide polymorphism rs174602: follow-up of a randomized controlled trial in Mexico.

BACKGROUND: There is limited evidence regarding long-term effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring cardiometabolic health (CMH). Inconsistent results may be attributable to variants of fatty acid desaturase (FADS) genes. OBJECTIVE: We aimed to evaluate the effect of prenatal DHA supplementation on offspring CMH and investigate effect modification by maternal FADS2 single nucleotide polymorphism (SNP) rs174602. METHODS: We used follow-up data from a double-blind, randomized controlled trial in Mexico in which pregnant females received 400 mg/d of algal DHA or placebo from midgestation until delivery. The study sample included 314 offspring with data at age 11 y and maternal FADS genetic data (DHA: n = 160; Placebo: n = 154). We derived a Metabolic Syndrome (MetS) score from body mass index, HDL, triglycerides, fasting glucose concentrations, and systolic blood pressure. Generalized linear models were used to evaluate the effect of the intervention on offspring MetS score and test interactions between treatment group and genotype, adjusting for maternal, offspring, and household factors. RESULTS: Offspring MetS score did not differ significantly by treatment group. We observed evidence of effect modification by maternal SNP rs174602 (P = 0.001); offspring of maternal TT genotype who received DHA had lower MetS score relative to the placebo group (DHA (mean ± standard error of the mean (SEM)): -0.21 ± 0.11, n = 21; Placebo: 0.05 ± 0.11, n = 23; Δ= -0.26 (95% CI: -0.55, 0.04), P = 0.09); among CC maternal genotype carriers, offspring of mothers who received DHA had higher MetS score (0.18 ± 0.06, n = 62) relative to the placebo group (-0.05 ± 0.06, n = 65, Δ=0.24 (0.06, 0.41), P < 0.01). CONCLUSION: The effect of prenatal DHA supplementation on offspring MetS score differed by maternal FADS SNP rs174602. These findings further support incorporating genetic analysis of FADS polymorphisms in DHA supplementation trials. CLINICAL TRIAL DETAILS: This trial was registered at clinicaltrials.gov as NCT00646360.

Mapping global zoonotic niche and interregional transmission risk of monkeypox: a retrospective observational study.

BACKGROUND: Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. METHODS: We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 - 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. RESULTS: As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89-6.71), Brazil (3.45, 95% CI: 1.62-7.00) and the United States (2.44, 95% CI: 1.62-3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. CONCLUSIONS: The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.

Clustering of cardiometabolic risk factors in Mexican pre-adolescents.

OBJECTIVE: To examine clustering of cardiometabolic markers in Mexican children at age 11 years and compare a metabolic syndrome (MetS) score to an exploratory cardiometabolic health (CMH) score. METHODS: We used data from children enrolled in the POSGRAD birth cohort with cardiometabolic data available (n = 413). We used principal component analysis (PCA) to derive a Metabolic Syndrome (MetS) score and an exploratory cardiometabolic health (CMH) score, which additionally included adipokines, lipids, inflammatory markers, and adiposity. We assessed reliability of individual cardiometabolic risk as defined by MetS and CMH by calculating % agreement and Cohen's kappa statistic. RESULTS: At least one cardiometabolic risk factor was present in 42 % of study participants; the most common risk factors were low High-Density Lipoprotein (HDL) cholesterol (31.9 %) and elevated triglycerides (18.2 %). Measures of adiposity and lipids explained the most variation in cardiometabolic measures for both MetS and CMH scores. Two-thirds of individuals were categorized in the same risk category by both MetS and CMH scores (κ = 0.42). CONCLUSIONS: MetS and CMH scores capture a similar amount of variation. Additional follow-up studies comparing predictive abilities of MetS and CMH scores may enable improved identification of children at risk for cardiometabolic disease.

Genotype-specific features reduce the susceptibility of South American yellow fever virus strains to vaccine-induced antibodies.

The resurgence of yellow fever in South America has prompted vaccination against the etiologic agent, yellow fever virus (YFV). Current vaccines are based on a live-attenuated YF-17D virus derived from a virulent African isolate. The capacity of these vaccines to induce neutralizing antibodies against the vaccine strain is used as a surrogate for protection. However, the sensitivity of genetically distinct South American strains to vaccine-induced antibodies is unknown. We show that antiviral potency of the polyclonal antibody response in vaccinees is attenuated against an emergent Brazilian strain. This reduction was attributable to amino acid changes at two sites in central domain II of the glycoprotein E, including multiple changes at the domain I-domain II hinge, which are unique to and shared among most South American YFV strains. Our findings call for a reevaluation of current approaches to YFV immunological surveillance in South America and suggest approaches for updating vaccines.

Metabolomic Profiling Demonstrates Postprandial Changes in Fatty Acids and Glycerophospholipids Are Associated with Fasting Inflammation in Guatemalan Adults.

BACKGROUND: Metabolic flexibility is the responsiveness to heterogeneous physiological conditions, such as food ingestion. A key unresolved question is how inflammation affects metabolic flexibility. OBJECTIVES: Our study objective was to compare metabolic flexibility, specifically the metabolomic response to a standardized meal, by fasting inflammation status. METHODS: Participants in Guatemala (n = 302, median age 44 y, 43.7% men) received a standardized, mixed-macronutrient liquid meal. Plasma samples (fasting, 2 h postmeal) were assayed by dual-column LC [reverse phase (C18) and hydrophilic interaction LC (HILIC)] with ultra-high-resolution MS, for concentrations of 6 inflammation biomarkers: high-sensitivity C-reactive protein (hsCRP), leptin, resistin, IL-10, adiponectin, and soluble TNF receptor II (TNFsR). We summed the individual inflammation biomarker z-scores, after reverse-coding of anti-inflammation biomarkers. We identified features with peak areas that differed between fasting and postmeal (false discovery rate-adjusted q <0.05) and compared median log2 postprandial/fasting peak area ratios by inflammation indicators. RESULTS: We found 1397 C18 and 974 HILIC features with significant postprandial/fasting feature ratios (q <0.05). Overall inflammation z-score was directly associated with the postprandial/fasting feature ratios of arachidic acid, and inversely associated with the feature ratio of lysophosphatidic acid (LPA), adjusting for age and sex (all P < 0.05). The postprandial/fasting ratio of arachidic acid was negatively correlated with resistin, IL-10, adiponectin, and TNFsR concentrations (all P < 0.05). Feature ratios of several fatty acids-myristic acid [m/z 227.2018, retention time (RT) 229], heptadecanoic acid (m/z 269.2491, RT 276), linoleic acid (m/z 280.2358, RT 236)-were negatively correlated with fasting plasma concentrations of leptin (nanograms per milliliter) and adiponectin (micrograms per milliliter), respectively (all P < 0.05). The postprandial/fasting ratio of LPA was positively correlated with IL-10 and adiponectin (both P < 0.05); and the ratio of phosphatidylinositol was positively correlated with hsCRP (P < 0.05). CONCLUSIONS: Postprandial responses of fatty acids and glycerophospholipids are associated with fasting inflammation status in adults in Guatemala.

Effect of fatigue load on internal mechanical properties of the intervertebral disc / Efecto de la carga de fatiga en las propiedades mecánicas internas del disco intervertebral

SUMMARY: Lumbar disc herniation is considered to be the main pathological factor for the common clinical disease of low back pain. Biomechanical factor is an important cause of lumbar disc herniation, so it is urgent to analyze the stress/strain behavior of intervertebral disc under different loading condition. Slow repetitive loading is considered to be an important factor of spine and disc injuries, and the effect of fatigue load on internal displacement in the intervertebral disc was investigated by applying the optimized digital image correlation technique in this study. The first finding was that fatigue load had a significant effect on the displacement distribution in the intervertebral disc under compression. Superficial AF exhibited the largest axial displacements before fatigue load, while it exhibited the smallest axial displacements after fatigue load. Inner AF exhibited slightly smaller radial displacements than outer AF before fatigue load, while it exhibited significantly greater radial displacements than outer AF displacements after fatigue load. The second finding was that fatigue load had a certain effect on the internal displacement distribution in the flexed intervertebral disc under compression. Middle AF exhibited the smallest axial displacements before fatigue load, while deep AF exhibited the smallest axial displacements after fatigue load. The radial displacement distribution did not change before and after fatigue load, as the radial displacement in outer AF was the smallest, while the radial displacement in inner AF was the largest. The third finding was that with the increase in fatigue time and amplitude, the Young's modulus of the intervertebral disc increased significantly. This study can provide the basis for clinical intervertebral disc disease prevention and treatment? and is important for mechanical function evaluation of artificial intervertebral disc as well.

RESUMEN: La hernia de disco lumbar se considera el principal factor patológico para la enfermedad clínica común del dolor lumbar. El factor biomecánico es una causa importante de hernia de disco lumbar, por lo que es urgente analizar el comportamiento de esfuerzo / tensión del disco intervertebral bajo diferentes condiciones de carga. La carga repetitiva lenta se considera un factor importante de lesiones de columna y disco, y en este estudio el efecto de la carga de fatiga sobre el desplazamiento interno en el disco intervertebral se investigó mediante la aplicación de la técnica de correlación de imagen digital optimizada. El primer hallazgo fue que la carga de fatiga tuvo un efecto significativo en la distribución del desplazamiento en el disco intervertebral bajo compresión. El AF superficial exhibió los desplazamientos axiales más grandes antes de la carga de fatiga, mientras que exhibió los desplazamientos axiales más pequeños después de la carga de fatiga. El AF interno exhibió desplazamientos radiales ligeramente más pequeños que el AF externo antes de la carga de fatiga, mientras que exhibió desplazamientos radiales significativamente mayores que los desplazamientos AF externos después de la carga de fatiga. El segundo hallazgo fue que la carga de fatiga tenía un cierto efecto sobre la distribución del desplazamiento interno en el disco intervertebral flexionado bajo compresión. El AF medio exhibió los desplazamientos axiales más pequeños antes de la carga de fatiga, mientras que el AF profundo exhibió los desplazamientos axiales más pequeños después de la carga de fatiga. La distribución del desplazamiento radial no cambió antes ni después de la carga de fatiga, ya que el desplazamiento radial en la FA externa fue el más pequeño, mientras que el desplazamiento radial en la FA interna fue el más grande. El tercer hallazgo fue que con el aumento del tiempo de fatiga y la amplitud, el módulo de Young del disco intervertebral aumentó significativamente. Este estudio puede proporcionar la base para la prevención y el tratamiento clínico de la enfermedad del disco intervertebral, y también es importante para la evaluación de la función mecánica del disco intervertebral artificial.

A newly designed intensive caregiver education program reduces cognitive impairment, anxiety, and depression in patients with acute ischemic stroke.

This study aimed to evaluate the effect of a newly designed intensive caregiver education program (ICEP) on reducing cognitive impairment, anxiety, and depression in acute ischemic stroke (AIS) patients. One hundred and ninety-six AIS patients were divided into ICEP group and Control group in a 1:1 ratio using blocked randomization method. In the ICEP group, the caregivers received ICEP, while in the Control group caregivers received usual education and guidance. All patients received conventional rehabilitation treatment. Cognitive impairment (assessed by Mini Mental State Examination (MMSE) score and Montreal Cognitive Assessment (MoCA) score), anxiety (assessed by Hospital Anxiety and Depression Scale (HADS)-A score and Self-rating Anxiety Scale (SAS) score), and depression (assessed by HADS-D score and Self-rating Depression Scale (SDS) score) were assessed at baseline (M0), 3 months (M3), 6 months (M6), and 12 months (M12). Cognitive impairment score at M12 and cognitive impairment score change (M12-M0) were increased, while cognitive impairment rate at M12 was reduced in the ICEP group compared with the Control group. Anxiety score change (M12-M0), anxiety score at M12, and anxiety rate at M12 were decreased in the ICEP group compared with the Control group. Depression score change (M12-M0), depression score at M12, and depression rate at M12 were lower in the ICEP group compared with the Control group. Further subgroup analysis based on baseline features also provided similar results. In conclusion, ICEP effectively reduced cognitive impairment, anxiety, and depression in AIS patients.

A newly designed intensive caregiver education program reduces cognitive impairment, anxiety, and depression in patients with acute ischemic stroke

This study aimed to evaluate the effect of a newly designed intensive caregiver education program (ICEP) on reducing cognitive impairment, anxiety, and depression in acute ischemic stroke (AIS) patients. One hundred and ninety-six AIS patients were divided into ICEP group and Control group in a 1:1 ratio using blocked randomization method. In the ICEP group, the caregivers received ICEP, while in the Control group caregivers received usual education and guidance. All patients received conventional rehabilitation treatment. Cognitive impairment (assessed by Mini Mental State Examination (MMSE) score and Montreal Cognitive Assessment (MoCA) score), anxiety (assessed by Hospital Anxiety and Depression Scale (HADS)-A score and Self-rating Anxiety Scale (SAS) score), and depression (assessed by HADS-D score and Self-rating Depression Scale (SDS) score) were assessed at baseline (M0), 3 months (M3), 6 months (M6), and 12 months (M12). Cognitive impairment score at M12 and cognitive impairment score change (M12-M0) were increased, while cognitive impairment rate at M12 was reduced in the ICEP group compared with the Control group. Anxiety score change (M12-M0), anxiety score at M12, and anxiety rate at M12 were decreased in the ICEP group compared with the Control group. Depression score change (M12-M0), depression score at M12, and depression rate at M12 were lower in the ICEP group compared with the Control group. Further subgroup analysis based on baseline features also provided similar results. In conclusion, ICEP effectively reduced cognitive impairment, anxiety, and depression in AIS patients.

Identification of key genes and miRNAs markers of papillary thyroid cancer.

OBJECTIVE: In this study, crucial genes and microRNAs (miRNAs) associated with the progression, staging, and prognosis of papillary thyroid cancer (PTC) were identified. METHODS: Four PTC datasets, including our own mRNA-sequencing (mRNA-seq) dataset and three public datasets downloaded from Gene Expression Omnibus and The Cancer Genome Atlas, were used to analyze differentially expressed genes (DEGs) and miRNAs (DEMs) between PTC tumor tissues and paired normal tissues (control). Gene ontology (GO) terms and pathways associated with these DEGs were identified, and protein-protein interactions (PPIs) were analyzed. Additionally, an miRNA-mRNA regulatory network was constructed and the functions of DEMs were explored. Finally, miRNAs/mRNAs associated with tumor staging and prognosis were identified. The expression levels of several key genes and miRNAs were validated by qRT-PCR. RESULTS: Numerous DEGs and DEMs were identified between tumor and control groups in four datasets. The DEGs were significantly enriched in cell adhesion and cancer-related GO terms and pathways. In the constructed PPI network, ITGA2, FN1, ICAM1, TIMP1 and CDH2 were hub proteins. In the miRNA-mRNA negative regulatory networks, miR-204-5p regulated the largest number of target genes, such as TNFRSF12A. miR-146b, miR-204, miR-7-2, and FN1 were associated with tumor stage in PTC, and TNFRSF12A and CLDN1 were related to prognosis. CONCLUSIONS: Our results suggested the important roles of ITGA2, FN1, ICAM1, TIMP1 and CDH2 in the progression of PTC. miR-204-5p, miR-7-2, and miR-146b are potential biomarkers for PTC staging and FN1, CLDN1, and TNFRSF12A may serve as markers of prognosis in PTC.

Cytochrome c is important in apoptosis of labial glands in primary Sjogren's syndrome.

The present study aimed to investigate the expression and effect of cytochrome c (Cytc) in patients with primary Sjogren's syndrome (pSS). In total, 35 newly diagnosed pSS patients and 35 healthy subjects were enrolled in the present study. The mRNA expression levels of Cytc were detected using reverse transcription­polymerase chain reaction and RT­quantitative PCR. The expression of the Cytc protein in labial salivary glands was detected by immunohistochemistry and was associated with the integral optical density (IOD) of clinical and laboratory variables. In addition, the content of Cytc in the cytoplasm and mitochondria were examined. The mRNA and protein expression levels of Cytc, and the content of Cytc in the cytoplasm of the pSS patients was increased significantly compared with the healthy controls (P<0.05). The content of Cytc in the mitochondria was significantly decreased compared with the healthy controls (P<0.05). The IOD of Cytc protein levels was positively correlated with immunoglobin G (r=0.8142, P<0.05) and erythrocyte sedimentation rate (r=0.7512, P<0.05). Cytc was upregulated in the pSS patients, indicating the potential role of Cytc in the pathogenesis and development of pSS. Further studies may facilitate the development of targeting this molecular pathway for the treatment of pSS.

Identification of key genes and miRNAs markers of papillary thyroid cancer

OBJECTIVE: In this study, crucial genes and microRNAs (miRNAs) associated with the progression, staging, and prognosis of papillary thyroid cancer (PTC) were identified. METHODS: Four PTC datasets, including our own mRNA-sequencing (mRNA-seq) dataset and three public datasets downloaded from Gene Expression Omnibus and The Cancer Genome Atlas, were used to analyze differentially expressed genes (DEGs) and miRNAs (DEMs) between PTC tumor tissues and paired normal tissues (control). Gene ontology (GO) terms and pathways associated with these DEGs were identified, and protein-protein interactions (PPIs) were analyzed. Additionally, an miRNA-mRNA regulatory network was constructed and the functions of DEMs were explored. Finally, miRNAs/mRNAs associated with tumor staging and prognosis were identified. The expression levels of several key genes and miRNAs were validated by qRT-PCR. RESULTS: Numerous DEGs and DEMs were identified between tumor and control groups in four datasets. The DEGs were significantly enriched in cell adhesion and cancer-related GO terms and pathways. In the constructed PPI network, ITGA2, FN1, ICAM1, TIMP1 and CDH2 were hub proteins. In the miRNA-mRNA negative regulatory networks, miR-204-5p regulated the largest number of target genes, such as TNFRSF12A. miR-146b, miR-204, miR-7-2, and FN1 were associated with tumor stage in PTC, and TNFRSF12A and CLDN1 were related to prognosis. CONCLUSIONS: Our results suggested the important roles of ITGA2, FN1, ICAM1, TIMP1 and CDH2 in the progression of PTC. miR-204-5p, miR-7-2, and miR-146b are potential biomarkers for PTC staging and FN1, CLDN1, and TNFRSF12A may serve as markers of prognosis in PTC.

Brazilin Inhibits Prostatic Acidic Phosphatase Fibrillogenesis and Decreases its Cytotoxicity.

A 39-amino acid peptide fragment that is derived from prostatic acidic phosphatase (PAP), PAP248-286 , is secreted in large amounts in human semen and forms amyloid fibrils. These fibrils can capture HIV virions and increase the attachment of virions to target cells; as such, they are called a "semen-derived enhancer of virus infection" (SEVI). Therefore, the inhibition of the formation of PAP248-286 amyloid fibrils is of great significance. Herein, we demonstrate that brazilin effectively inhibits PAP248-286 aggregation. The inhibitory effect increases with increasing brazilin concentration. Thioflavin T fluorescence assays and TEM observations confirmed that a few fibrils formed when brazilin was present with PAP248-286 in an equimolar concentration. Circular dichroism spectroscopy indicated that brazilin inhibited the secondary structural transitions from α-helices and random coils into ß-sheets. Cytotoxicity assays showed that brazilin significantly decreased the cytotoxicity of the fibrils at 0.01 mmol L-1 . Isothermal titration calorimetry revealed that hydrophobic interactions were the main driving force for the binding of brazilin to the PAP248-286 monomer (dissociation constant, 4.03 µmol L-1 ), and that the binding affinity of brazilin for the fibrils was at least three orders of magnitude lower than that for the monomer. These results indicate that brazilin holds great potential as a small-molecule agent against SEVIs.

Anxiolytic Effects of Royal Sun Medicinal Mushroom, Agaricus brasiliensis (Higher Basidiomycetes) on Ischemia-Induced Anxiety in Rats.

We investigated the anxiolytic effects Agaricus brasiliensis extract (AbSE) on ischemia-induced anxiety using the plus-maze test and the social interaction test. The animals were treated orally with AbSE (4, 8, and 10 mg/kg/d, respectively) for 30 d, followed by middle cerebral artery occlusion-induced cerebral ischemia. Levels of noradrenaline, dopamine, and serotonin in the cerebral cortex of rats, as well as oxidative stress and plasma corticosterone levels were analyzed, respectively. The rota-rod test was carried out to exclude any false positive results in experimental procedures related to anxiety disorders, and the catalepsy test was carried out to investigate whether AbSE induces catalepsy. Our results demonstrate that oral administration of AbSE presented anxiolytic-like effects in the elevated plus-maze test and the social interaction test. Furthermore, AbSE did not induce extrapyramidal symptoms in the catalepsy test. The mechanism underlying the anxiolytic effect of AbSE might be increased brain monoamine levels and plasma corticosterone levels and decreased oxidative stress in cerebral ischemia/reperfusion rats.

Brazilin inhibits amyloid ß-protein fibrillogenesis, remodels amyloid fibrils and reduces amyloid cytotoxicity.

Soluble amyloid ß-protein (Aß) oligomers, the main neurotoxic species, are predominantly formed from monomers through a fibril-catalyzed secondary nucleation. Herein, we virtually screened an in-house library of natural compounds and discovered brazilin as a dual functional compound in both Aß42 fibrillogenesis inhibition and mature fibril remodeling, leading to significant reduction in Aß42 cytotoxicity. The potent inhibitory effect of brazilin was proven by an IC50 of 1.5 ± 0.3 µM, which was smaller than that of (-)-epigallocatechin gallate in Phase III clinical trials and about one order of magnitude smaller than those of curcumin and resveratrol. Most importantly, it was found that brazilin redirected Aß42 monomers and its mature fibrils into unstructured Aß aggregates with some ß-sheet structures, which could prevent both the primary nucleation and the fibril-catalyzed secondary nucleation. Molecular simulations demonstrated that brazilin inhibited Aß42 fibrillogenesis by directly binding to Aß42 species via hydrophobic interactions and hydrogen bonding and remodeled mature fibrils by disrupting the intermolecular salt bridge Asp23-Lys28 via hydrogen bonding. Both experimental and computational studies revealed a different working mechanism of brazilin from that of known inhibitors. These findings indicate that brazilin is of great potential as a neuroprotective and therapeutic agent for Alzheimer's disease.

The agaricoglyceride of royal sun medicinal mushroom, Agaricus brasiliensis (higher basidiomycetes) is anti-inflammatory and reverses diabetic glycemia in the liver of mice.

The agaricoglyceride is a new fungal secondary metabolite that constitutes esters of chlorinated 4-hydroxy benzoic acid and glycerol. The objective of this study was to explore whether the administration of agaricoglyceride could correct hepatic glycemic metabolism dysfunction by attenuating inflammation in the liver. The effects of agaricoglycerides on tumor necrosis factor-α, interleukin-1ß, vascular endothelial growth factor-α, interleukin-17, insulin secretion, adiponectin, leptin, hepatic glycogen, nuclear factor-κB activation, and total antioxidant activity were studied respectively. We demonstrated that administration of agaricoglycerides alleviated glycemic metabolism dysfunction, inflammation, and oxidative stress in mice. These data indicate that agaricoglyceride supplementation could restrain metabolic dysfunction through suppressing the nuclear factor-κB pathway as well as decreasing the levels of inflammatory cytokines and total antioxidant activities.

Coronary heart disease mortality in China: age, gender, and urban—rural gaps during epidemiological transition / Mortalidad por cardiopatía coronaria en China: edad, sexo y brechas entre la población urbana y la rural durante la transición epidemiológica

Objetivo. Examinar y describir la mortalidad por cardiopatía coronaria y su patrón de cambio (tendencia) por sexo, edad y zona de residencia (urbana frente a rural) en Tianjín, China, en el contexto de la transición epidemiológica, y compararla con lastendencias actuales en las Américas y Europa. Métodos. Se analizaron 104 393 casos de muertes debidas a cardiopatía coronaria ocurridas en Tianjín entre 1999 y 2008. Se codificó la mortalidad debida a cardiopatíacoronaria según la Clasificación Internacional de Enfermedades (novena y décima revisiones). Se analizaron las tasas estandarizadas de mortalidad por cardiopatía coronaria y sus tendencias por edad, sexo y residencia urbana frente a rural. Resultados. Durante el período de estudio, de 10 años, la proporción de la mortalidad total debida a cardiopatía coronaria registrada en Tianjín aumentó significativamente(de 16% a 24%) y la mortalidad por cardiopatía coronaria estandarizadapor edad aumentó levemente (sin significación estadística), en contraposición con las tendencias de mortalidad por cardiopatía coronaria observadas en diversos países delas Américas y Europa, que están descendiendo. No se encontraron diferencias en la tendencia de la mortalidad por cardiopatía coronaria por sexo en Tianjín. La mortalidadgeneral por cardiopatía coronaria fue sistemáticamente más elevada en los grupos de mayor edad, los varones y los residentes de zonas urbanas. La proporción de muertes debidas a cardiopatía coronaria que ocurrieron fuera de los hospitales fue de 55,81%, con una tendencia decreciente en el período de estudio. Esta proporción fuemayor en las zonas rurales que en las urbanas, pero no se encontró diferencia entre los distintos grupos de edad.Conclusiones. Desde 1999 hasta el 2008, la mortalidad por cardiopatía coronaria en Tianjín varió según el sexo, la edad y la residencia urbana frente a la rural...

Objective. To examine and describe coronary heart disease (CHD) mortality and its pattern of change (trend) by sex, age, and area of residence (urban versus rural) in Tianjin, China, within the context of epidemiological transition, and compare it with current trends in the Americas and Europe.Methods. A total of 104 393 cases of CHD death in Tianjin occurring between 1999 and 2008 were monitored. Death due to CHD was coded using International Classification of Diseases (ICD) standards (ninth and tenth revisions). Standardized CHD mortality rates and their trends were analyzed by age, sex, and urban versus rural residence. Results. During the 10-year study period, the proportion of total deaths due to CHD in Tianjin increased significantly (from 16% to 24%) and age-standardized CHD mortalityincreased slightly (with no statistical differences), in contrast to CHD mortality trends in various countries in the Americas and Europe, which are declining. No difference was found inTianjin’s CHD mortality trend by sex. Overall CHD mortality was consistently higher among older age groups, males, and residents of urban areas. The proportion of CHD deaths occurringoutside hospitals was 55.81%, with a declining trend over the study period. Rural areas had a higher proportion of outside-hospital CHD mortality than urban areas, but no difference wasfound across age groups. Conclusions. From 1999 to 2008, CHD mortality in Tianjin varied by sex, age, and urbanversus rural area of residence. Future research to identify CHD risk factors and the populations most vulnerable to the disease is recommended to help strengthen CHD prevention. Strategiesfor CHD control similar to those used in various developed countries in the Americas and Europe should be developed to reduce the CHD burden in China.