Cortex Extract Research Articles

16p11.2 haploinsufficiency reduces mitochondrial biogenesis in brain endothelial cells and alters brain metabolism in adult mice

Neurovascular abnormalities in mouse models of 16p11.2 deletion autism syndrome are reminiscent of alterations reported in murine models of glucose transporter deficiency, including reduced brain angiogenesis and behavioral alterations. Yet, whether cerebrovascular alterations in 16p11.2df/+ mice affect brain metabolism is unknown. Here, we report that anesthetized 16p11.2df/+ mice display elevated brain glucose uptake, a phenomenon recapitulated in mice with endothelial-specific 16p11.2 haplodeficiency. Awake 16p11.2df/+ mice display attenuated relative fluctuations of extracellular brain glucose following systemic glucose administration. Targeted metabolomics on cerebral cortex extracts reveals enhanced metabolic responses to systemic glucose in 16p11.2df/+ mice that also display reduced mitochondria number in brain endothelial cells. This is not associated with changes in mitochondria fusion or fission proteins, but 16p11.2df/+ brain endothelial cells lack the splice variant NT-PGC-1α, suggesting defective mitochondrial biogenesis. We propose that altered brain metabolism in 16p11.2df/+ mice is compensatory to endothelial dysfunction, shedding light on previously unknown adaptative responses.

Synergistic Growth Inhibition of Herbal Plant Extract Combinations against Candida albicans

Many skin diseases are caused by microbial infections. Representative pathogenic fungus and bacterium that cause skin diseases are Candida albicans and Staphylococcus aureus, respectively. Malassezia pachydermatis is a fungus that causes animal skin diseases. In this study, we propose a method for removing pathogenic microorganisms from the skin using relatively safe edible herbal extracts. Herbal extracts were screened for skin health through the removal of pathogenic microorganisms, and combinations for effective utilization of the screened extracts were identified. In this study, among methanol extracts of 240 edible plants, C. albicans, S. aureus, and M. pachydermatis were killed by extracts of 10 plants: Acori Gramineri Rhizoma, Angelicae Tenuissimae Radix, Cinnamomi Cortex, Cinnamomi Ramulus, Impatientis Semen, Magnoliae Cortex, Moutan Cortex Radicis, Phellodendri Cortex, Scutellariae Radix, and Syzygii Flos. By evaluating the synergistic antifungal activities against C. albicans using all 45 possible combinations of these 10 extracts, five new synergistic antifungal combinations, Acori Gramineri Rhizoma with Magnoliae Cortex extracts, Acori Gramineri Rhizoma with Phellodendri Cortex extracts, Angelicae Tenuissimae Radix with Magnoliae Cortex extracts, Magnoliae Cortex with Phellodendri Cortex extracts, and Phellodendri Cortex with Syzygii Flos extracts, were identified. By utilizing the selected extracts and five combinations with synergistic antifungal effects, this work provides materials and methods to develop new and safe methods for treating candidiasis using natural products.

Identification of Differential Compositions of Aqueous Extracts of Cinnamomi Ramulus and Cinnamomi Cortex

Cinnamomi ramulus (CR) and Cinnamomi cortex (CC), both sourced from Cinnamomum cassia Presl, are commonly used Chinese medicines in the Chinese Pharmacopeia. However, while CR functions to dissipate cold and to resolve external problems of the body, CC functions to warm the internal organs. To clarify the material basis of these different functions and clinical effects, a simple and reliable UPLC-Orbitrap-Exploris-120-MS/MS method combined with multivariate statistical analyses was established in this study with the aim of exploring the difference in chemical compositions of aqueous extracts of CR and CC. As the results indicated, a total of 58 compounds was identified, including nine flavonoids, 23 phenylpropanoids and phenolic acids, two coumarins, four lignans, four terpenoids, 11 organic acids and five other components. Of these compounds, 26 significant differential compounds were identified statistically including six unique components in CR and four unique components in CC. Additionally, a robust HPLC method combined with hierarchical clustering analysis (HCA) was developed to simultaneously determine the concentrations and differentiating capacities of five major active ingredients in CR and CC: coumarin, cinnamyl alcohol, cinnamic acid, 2-methoxycinnamic acid and cinnamaldehyde. The HCA results showed that these five components could be used as markers for successfully distinguishing CR and CC. Finally, molecular docking analyses were conducted to obtain the affinities between each of the abovementioned 26 differential components, focusing on targets involved in diabetes peripheral neuropathy (DPN). The results indicated that the special and high-concentration components in CR showed high docking scores of affinities with targets such as HbA1c and proteins in the AMPK-PGC1-SIRT3 signaling pathway, suggesting that CR has greater potential than CC for treating DPN.

Moutan Cortex Extract Modulates Macrophage Activation via Lipopolysaccharide-Induced Calcium Signaling and ER Stress-CHOP Pathway.

Moutan Cortex, Paeonia suffruticosa root, has long been used as a medicine for the treatment of inflammatory diseases. The aim of this study was to evaluate the modulative properties of Moutan Cortex water extract (CP) on endoplasmic reticulum (ER) stress-related macrophage activation via the calcium-CHOP pathway. RAW 264.7 mouse macrophages were activated by lipopolysaccharide (LPS), and the levels of various inflammatory mediators from RAW 264.7 were evaluated. The multiplex cytokine assay was used to investigate both cytokines and growth factors, and RT-PCR was used to investigate the expressions of inflammation-related genes, such as CHOP. Data represent the levels of NO and cytosolic calcium in LPS-stimulated RAW 264.7 were significantly inhibited by CP as well as hydrogen peroxide (p < 0.05). Minutely, NO production in LPS-stimulated RAW 264.7 incubated with CP at concentrations of 25, 50, 100, and 200 µg/mL for 24 h was 97.32 ± 1.55%, 95.86 ± 2.26%, 94.64 ± 1.83%, and 92.69 ± 2.31% of the control value (LPS only), respectively (p < 0.05). Calcium release in LPS-stimulated RAW 264.7 incubated with CP at concentrations of 25, 50, 100, and 200 µg/mL for 18 h was 95.78 ± 1.64%, 95.41 ± 1.14%, 94.54 ± 2.76%, and 90.89 ± 3.34% of the control value, respectively (p < 0.05). Hydrogen peroxide production in LPS-stimulated RAW 264.7 incubated with CP at concentrations of 25, 50, 100, and 200 µg/mL for 24 h was 79.15 ± 7.16%, 63.83 ± 4.03%, 46.27 ± 4.38%, and 40.66 ± 4.03% of the control value, respectively (p < 0.05). It is interesting that the production of IL-6, TNF-α, G-CSF, MIP-1α, MIP-2, and M-CSF in LPS-stimulated RAW 264.7 were significantly inhibited by CP (p < 0.05), while the production of LIX, LIF, RANTES, and MIP-1β showed a meaningful decrease. CP at concentrations of 25, 50, 100, and 200 µg/mL significantly reduced the transcription of Chop, Camk2α, NOS, STAT1, STAT3, Ptgs2, Jak2, c-Jun, Fas, c-Fos, TLR3, and TLR9 in LPS-stimulated RAW 264.7 (p < 0.05). CP at concentrations of 25, 50, and 100 µg/mL significantly reduced the phosphorylation of STAT3, p38 MAPK, and IκB-α in LPS-stimulated RAW 264.7 (p < 0.05). These results suggest that CP might modulate macrophage activation via LPS-induced calcium signaling and the ER stress-CHOP pathway.

Moutan Cortex extract inhibited the proliferation and migration of endometrial stromal cells by inhibiting OPN-induced, MAPK-mediated MMP9 activation

Endometriosis is frequent in women of childbearing age with a morbidity rate of approximately 10%. Its clinical features mainly manifest as dysmenorrhea, chronic pelvic pain, and infertility. However, effective treatments are still lacking; hence, it is necessary to identify an effective and safe treatment strategy on endometriosis. Moutan Cortex extract (MCE) was prepared by decoction. Then, cell proliferation and apoptosis in human endometrial stromal cells (HESCs) were detected by cell counting kit-8, EdU cell proliferation assay, and flow cytometry. Wound-healing assay and transwell migration assay were performed to explore cell migration or invasion. The expression of indicators of downstream signaling pathways was determined by Western blot analysis or enzyme-linked-immunosorbent serologic assay. MCE treatment inhibited cell viability and proliferation in HESCs while promoting cell apoptosis. MCE reduced migration and invasion of HESCs. Furthermore, MCE inhibited osteopontin-induced, mitogen-activated, protein kinase (MAPK)-mediated matrix metallopeptidase 9 (MMP9) activation, and upregulation of OPN reversed the effect of MCE on HESCs. In this study, MCE inhibited the proliferation and migration of endometrial stromal cells by inhibiting OPN induced, MAPK-mediated MMP9 activation. MCE might be a novel treatment strategy on endometriosis.

Determination of total phenol and six polyphenolic components in the polyphenol extract of Cinnamomi cortex by quantitative nuclear magnetic resonance spectroscopy.

A quantitative nuclear magnetic resonance spectroscopy (qNMR) method was established for determining the total phenol and six polyphenolic components in the polyphenol extract of Cinnamomi cortex. The qNMR approach utilized DMSO-d6 as the deuterated solvent and potassium hydrogen phthalate as the internal standard for quantifying the total phenolic content, expressed as epicatechin equivalence in the sample. Two complementary qNMR methods with DMSO-d6 or D2O as solvent were established to simultaneously determine 6 polyphenol components in the cinnamon polyphenol extract, including epigallocatechin gallate (EGCG), epicatechingallate (ECG), epicatechin (EC), epigallocatechin (EGC), gallocatechin gallate (GCG) and gallic acid (GA). Method validation demonstrated excellent precision with intraday relative standard deviation (RSD) below 1.08% and interday RSD below 1.48%. The linear correlation coefficient (r) exceeded 0.999, and the limits of detection (LOD) were from 0.01 to 0.14 mg mL-1, while the limits of quantification (LOQ) were from 0.07 to 0.69 mg mL-1. Recovery rates for this method fell within the range of 98.2% to 101.7%. Furthermore, the method has been successfully applied for determining the polyphenolic content in authentic cinnamon polyphenol extracts obtained from different sources.

Cinnamomi cortex extract mitigated monosodium urate-induced acute gouty arthritis in rats through nuclear factor-κB-NOD-like receptor thermal protein domain associated protein 3 signaling pathway.

Cinnamomi cortex was applied to mitigate joint injury since ancient China. However, the effect of Cinnamomi cortex on gouty arthritis (GA) was rarely reported. This study aimed to explore the effect of Cinnamomi cortex on monosodium urate (MSU)-induced acute GA (AGA) in rats, and clarify the underlying mechanism. The results showed that Cinnamomi cortex extract (CE) containing rich polyphenols and flavonoids alleviated joint swelling and inflammation by reducing programmed cell death in MSU-induced AGA rats. Network pharmacology analysis showed that CE's predictive inflammatory pathways included nuclear factor-κB (NF-κB) and necroptosis pathways. CE reduced expression of pyroptosis-related regulators including Gasdermin D and Caspase 1 via regulating NF-κB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway in AGA rats. In conclusion, this study provided a theoretical basis for Cinnamomi cortex applied as a new veterinary medicine to protect against GA.

Kukoamine B from Lycii Radicis Cortex Protects Human Keratinocyte HaCaT Cells through Covalent Modification by Trans-2-Nonenal

The unsaturated aldehyde trans-2-nonenal is known to be generated by lipid peroxidation at the surface of the skin in an aging-related manner and has harmful effects on keratinocytes in the skin. In this study, the protective effect of a Lycii Radicis Cortex (LRC) extract against trans-2-nonenal-induced cell damage on human keratinocyte cell lines (HaCaT) was investigated. Notably, treatment with the LRC extract resulted in an increase in cell survival, while trans-2-nonenal decreased the viability of HaCaT cells. For identification of interaction between the LRC extract and trans-2-nonenal, this mixture was incubated in simulated physiological conditions, showing a strong decrease in the amount of trans-2-nonenal by the LRC extract. Subsequent LC-ESI-MS analysis revealed that kukoamine B (KB) formed Schiff base-derived pyridinium adducts with trans-2-nonenal. Thus, these results suggest that KB could be a potential agent that may protect HaCaT cells by forming new products with trans-2-nonenal.

"Evaluation of the effect of Cassia fistula L. extracts on the muscle contraction intensity using an ex vivo model"

Cassia fistula L. is a peculiar Fabaceae representative that has long been used in traditional medicine. The purpose of this study is to evaluate the effect of Cassia fistula L. herbal extracts in the form of solutions of a certain concentration on the smooth muscles of the intestine. The design of the experiment involved the identification of raw materials, their drying, grinding, extraction of soluble fractions, purification of aqueous, ethereal (diethyl ether) and ethanol extracts and their testing on the tissues of the ileum of the domestic chicken (Gallus gallus domesticus L.) extracted ex vivo. It was shown that the ethereal, ethanol and aqueous extracts of Cassia fistula L. fruits showed a generally high relaxation activity in comparison with the control relaxation stimulants, leaf extracts showed a more modest relaxation activity, a similar situation was observed during testing of extracts of young shoots, and aqueous extracts showed more modest results, while the alcoholic and ethanol extracts of young shoots performed better than the corresponding leaf extracts, and the most modest results in terms of a dose sufficient for a physiological response were demonstrated by root extracts. The initial assessment of the activity of Cassia fistula L. extracts makes it possible to identify as the most promising for further chemical study the pools of substances concentrated in the ethanol extract of fruits, which exhibit the minimum effective dose, in the ether extracts of fruits and bark, which demonstrate the shortest reaction time, and in aqueous extracts of young shoots and cortex showing the highest percentage increase in activity in comparison with the control.

Applying antagonistic activation pattern to the single-trial classification of mental arithmetic

BackgroundAt present, the application of fNIRS in the field of brain-computer interface (BCI) is being a hot topic. By fNIRS-BCI, the brain realizes the control of external devices. A state-of-the-art BCI system has five steps which are cerebral cortex signal acquisition, data pre-processing, feature selection and extraction, feature classification and application interface. Proper feature selection and extraction are crucial to the final fNIRS-BCI effect. This paper proposes a feature selection and extraction method for the mental arithmetic task. Specifically, we modified the antagonistic activation pattern approach and used the combination of antagonistic activation patterns to extract features for enhancement of the classification accuracy with low calculation costs. MethodsExperiments are conducted on an open-acquisition dataset including fNIRS signals of eight healthy subjects of mental arithmetic (MA) tasks and rest tasks. First, the signals are filtered using band-pass filters to remove noise. Second, channels are selected by prior knowledge about antagonistic activation patterns. We used cerebral blood volume (CBV) and cerebral oxygen exchange (COE) of selected each channel to build novel attributes. Finally, we proposed three groups of attributes which are CBV, COE and CBV + COE. Based on attributes generated by the proposed method, we calculated temporal statistical measures (average, variance, maximum, minimum and slope). Any two of five statistical measures were combined as feature sets. Main resultsWith the LDA, QDA, and SVM classifiers, the proposed method obtained higher classification accuracies the basic control method. The maximum classification accuracies achieved by the proposed method are 67.45 ± 14.56% with LDA classifier, 89.73 ± 5.71% with QDA classifier, and 87.04 ± 6.88% with SVM classifier. The novel method reduced the running time by 3.75 times compared with the method incorporating all channels into the feature set. Therefore, the novel method reduces the computational costs while maintaining high classification accuracy. The results are validated by another open-access dataset including MA and rest tasks of 29 healthy subjects.

Tau seeding activity in various regions of down syndrome brain assessed by two novel assays

Propagation of tau pathology via the seeding of naive tau aggregation underlies the progression of Alzheimer’s disease (AD) and related tauopathies. Individuals with Down syndrome (DS) develop tau pathology at the fourth decade of life, but tau seeding activity in DS brain has not yet been determined. To measure tau seeding activity, we developed capture assay and seeded-tau aggregation assay with truncated tau151-391. By using brain extracts from AD and related tauopathies, we validated these two methods and found that the brain extracts from AD and related tauopathies, but not from controls and the diseases in which tau was not hyperphosphorylated, captured in vitro and seeded 3R-tau151-391 and 4R-tau151-391 to aggregate in cultured cells similarly. Captured tau151-391 levels were strongly correlated with the seeded-tau151-391 aggregation. Employing these two newly developed assays, we analyzed tau seeding activity in the temporal (TC), frontal (FC), and occipital cortex (OC); corpus callosum (CC); and cerebellar cortex (CBC) of DS and control brains. We found that the extracts of TC, FC, or OC, but not the CC or CBC of DS or the corresponding brain regions of control cases, captured tau151-391. Levels of the captured tau151-391 by brain extracts were positively correlated with their levels of phosphorylated tau. Extracts of cerebral cortex and CC, but not CBC of DS with a similar tau level, induced more tau151-391 aggregation than did the corresponding samples from the control cases. Thus, higher tau seeding activity associated with tau hyperphosphorylation was found in the TC, FC, and OC of DS compared with the corresponding control regions as well as with the CBC and CC of DS. Of note, these two assays are sensitive, specific, and repeatable at a low cost and provide a platform for measuring tau seeding activity and for drug screening that targets tau propagation.

Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models.

The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer's disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term FMD cycles reduce hippocampal Aβ load and hyperphosphorylated tau, enhance genesis of neural stem cells, decrease microglia number, and reduce expression of neuroinflammatory genes, including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin also display improved cognition and reduced microglia activation compared with controls. Clinical data indicate that FMD cycles are feasible and generally safe in a small group of AD patients. These results indicate that FMD cycles delay cognitive decline in AD models in part by reducing neuroinflammation and/or superoxide production in the brain.

Anti-inflammatory effects of hydrophobic constituents in the extract of the root cortex of Paeonia suffruticosa

Background: The root cortex of Paeonia suffruticosa Andrews (Paeoniaceae), which is also called moutan bark, is known as Botanpi in Japan. This crude drug has been used in several Kampo formulas, such as Daiobotanpito, to treat menstrual disturbance and constipation by improving blood stasis and suppressing inflammation. However, the anti-inflammatory effect has not been well studied.Objective: To clarify the anti-inflammatory effects of moutan bark, we isolated its constituents and investigated their activity.Methods: Moutan bark was extracted and successively fractionated with ethyl acetate (EtOAc) and n-butanol. The constituents were analyzed using HPLC. The production of nitric oxide (NO), an inflammatory mediator, was measured in interleukin (IL)-1β-treated rat hepatocytes to identify active fractions or constituents.Results: The EtOAc-soluble fraction of moutan bark extract significantly inhibited NO production. Three hydrophobic constituents were isolated from this fraction and identified as paeonol (1), 1,2,3,4,6-pentagalloyl-β-D-glucose (β-PGG; 2), and methyl gallate (3). Paeonol and paeoniflorin (4) were abundantly present in the EtOAc-soluble fraction and n-butanol-soluble fraction, respectively. The hydrophobic constituents suppressed NO production without exerting cytotoxicity and reduced the protein and mRNA levels of inducible nitric oxide synthase in IL-1β-treated hepatocytes; β-PGG showed the highest potency. Furthermore, β-PGG, methyl gallate, and paeonol decreased the mRNA levels of tumor necrosis factor α and IL-1 receptor type 1, which are involved in inflammation.Conclusion: These results suggest that hydrophobic constituents of moutan bark, such as β-PGG, methyl gallate, and paeonol, are involved in the anti-inflammatory effects of moutan bark.Keywords: Galloylglucose, tannin, nitric oxide, Kampo medicine, cytokine.

Localization of Thioredoxin-Interacting Protein in Aging and Alzheimer's Disease Brains.

Thioredoxin-Interacting Protein (TXNIP) has been shown to have significant pathogenic roles in many human diseases, particularly those associated with diabetes and hyperglycemia. Its main mode of action is to sequester thioredoxins, resulting in enhanced oxidative stress. The aim of this study was to identify if cellular expression of TXNIP in human aged and Alzheimer's disease (AD) brains correlated with pathological structures. This study employed fixed tissue sections and protein extracts of temporal cortex from AD and aged control brains. Studies employed light and fluorescent immunohistochemical techniques using the monoclonal antibody JY2 to TXNIP to identify cellular structures. Immunoblots were used to quantify relative amounts of TXNIP in brain protein extracts. The major finding was the identification of TXNIP immunoreactivity in selective neuronal populations and structures, particularly in non-AD brains. In AD brains, less neuronal TXNIP but increased numbers of TXNIP-positive plaque-associated microglia were observed. Immunoblot analyses showed no significant increase in levels of TXNIP protein in the AD samples tested. In conclusion, this study identified altered patterns of expression of TXNIP in human brains with progression of AD pathology.

Role and mechanism of Cortex Moutan components in inhibiting production of toxic advanced glycation end products (AGEs)

Advanced glycation end products(AGEs) can lead to many diseases such as diabetes and its complications. In this study, an in vitro non-enzymatic glycosylation reaction model-bovine serum albumin/methylglyoxal(BSA/MGO) reaction system was constructed and incubated with Cortex Moutan extract. High performance liquid chromatography(HPLC) and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) were used to detect and identify the active components that inhibited the formation of AGEs in the co-incubation solution of Cortex Moutan extract and MGO, and differential components such as salvianan, paeoniside, benzoylpaeoniflorin, mudanpioside J, galloyloxypaeoniflorin, benzoyloxy-paeoniflorin, 5-hydroxy-3 s-hydroxymethyl-6-methyl-2,3-dihydro benzofuran, and galloylpaeoniflorin were screened out, which were inferred to be the potential active components of Cortex Moutan extract to capture MGO. In addition, BSA-glucose reaction system was performed to investigate the influence of different concentrations of Cortex Moutan extract(decoction concentrations: 40, 80, 120, 160, and 200 mg·mL~(-1)) on inhibiting the production of AGEs in vitro. The inhibitory effects of Cortex Moutan extract and the differential components galloylpaeoniflorin and benzoyl paeoniflorin on the production of AGEs in human umbilical vein endothelial cells(HUVECs) induced by high glucose was further evaluated. Cell apoptosis was observed by acridine orange and ethidium bromide(AO/EB) double fluorescence staining. The results showed that Cortex Moutan Cortex extract and its differential components had certain inhibitory effects on the formation of AGEs, and could reduce cell apoptosis. This study provided reference for the treatment of diabetic vascular complications by Cortex Moutan inhibiting the toxic AGEs.

Rates of pyruvate carboxylase, glutamate and GABA neurotransmitter cycling, and glucose oxidation in multiple brain regions of the awake rat using a combination of [2-13C]/[1-13C]glucose infusion and 1H-[13C]NMR ex vivo

Anaplerosis occurs predominately in astroglia through the action of pyruvate carboxylase (PC). The rate of PC (Vpc) has been reported for cerebral cortex (or whole brain) of awake humans and anesthetized rodents, but regional brain rates remain largely unknown and, hence, were subjected to investigation in the current study. Awake male rats were infused with either [2-13C]glucose or [1-13C]glucose (n = 27/30) for 8, 15, 30, 60 or 120 min, followed by rapid euthanasia with focused-beam microwave irradiation to the brain. Blood plasma and extracts of cerebellum, hippocampus, striatum, and cerebral cortex were analyzed by 1H-[13C]-NMR to establish 13C-enrichment time courses for glutamate-C4,C3,C2, glutamine-C4,C3, GABA-C2,C3,C4 and aspartate-C2,C3. Metabolic rates were determined by fitting a three-compartment metabolic model (glutamatergic and GABAergic neurons and astroglia) to the eighteen time courses. Vpc varied by 44% across brain regions, being lowest in the cerebellum (0.087 ± 0.004 µmol/g/min) and highest in striatum (0.125 ± 0.009) with intermediate values in cerebral cortex (0.106 ± 0.005) and hippocampus (0.114 ± 0.005). Vpc constituted 13–19% of the oxidative glucose consumption rate. Combination of cerebral cortical data with literature values revealed a positive correlation between Vpc and the rates of glutamate/glutamine-cycling and oxidative glucose consumption, respectively, consistent with earlier observations.

The Role of Structure MRI in Diagnosing Autism.

This study proposes a Computer-Aided Diagnostic (CAD) system to diagnose subjects with autism spectrum disorder (ASD). The CAD system identifies morphological anomalies within the brain regions of ASD subjects. Cortical features are scored according to their contribution in diagnosing a subject to be ASD or typically developed (TD) based on a trained machine-learning (ML) model. This approach opens the hope for developing a new CAD system for early personalized diagnosis of ASD. We propose a framework to extract the cerebral cortex from structural MRI as well as identifying the altered areas in the cerebral cortex. This framework consists of the following five main steps: (i) extraction of cerebral cortex from structural MRI; (ii) cortical parcellation to a standard atlas; (iii) identifying ASD associated cortical markers; (iv) adjusting feature values according to sex and age; (v) building tailored neuro-atlases to identify ASD; and (vi) artificial neural networks (NN) are trained to classify ASD. The system is tested on the Autism Brain Imaging Data Exchange (ABIDE I) sites achieving an average balanced accuracy score of . This paper demonstrates the ability to develop an objective CAD system using structure MRI and tailored neuro-atlases describing specific developmental patterns of the brain in autism.

Viscoelastic properties of epithelial cells

Epithelial cells form tight barriers that line both the outer and inner surfaces of organs and cavities and therefore face diverse environmental challenges. The response to these challenges relies on the cells' dynamic viscoelastic properties, playing a pivotal role in many biological processes such as adhesion, growth, differentiation, and motility. Therefore, the cells usually adapt their viscoelastic properties to mirror the environment that determines their fate and vitality. Albeit not a high-throughput method, atomic force microscopy is still among the dominating methods to study the mechanical properties of adherent cells since it offers a broad range of forces from Piconewtons to Micronewtons at biologically significant time scales. Here, some recent work of deformation studies on epithelial cells is reviewed with a focus on viscoelastic models suitable to describe force cycle measurements congruent with the architecture of the actin cytoskeleton. The prominent role of the cortex in the cell's response to external forces is discussed also in the context of isolated cortex extracts on porous surfaces.

Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin.

Nephrotoxicity is a major complication of cisplatin-based chemotherapy, leading to acute kidney injury in ca. 30% of patients, with no preventive intervention or treatment available for clinical use. Cilastatin has proved to exert a nephroprotective effect for cisplatin therapies in in vitro and in vivo models, having recently entered clinical trials. A deeper understanding at the molecular level of cisplatin-induced renal damage and the effect of potential protective agents could be key to develop successful nephroprotective therapies and to establish new biomarkers of renal damage and nephroprotection. A targeted lipidomics approach, using LC-MS/MS, was employed for the quantification of 108 lipid species (comprising phospholipids, sphingolipids, and free and esterified cholesterol) in kidney cortex and medulla extracts from rats treated with cisplatin and/or cilastatin. Up to 56 and 63 lipid species were found to be altered in the cortex and medulla, respectively, after cisplatin treatment. Co-treatment with cilastatin attenuated many of these lipid changes, either totally or partially with respect to control levels. Multivariate analysis revealed that lipid species can be used to discriminate renal damage and nephroprotection, with cholesterol esters being the most discriminating species, along with sulfatides and phospholipids. Potential diagnostic biomarkers of cisplatin-induced renal damage and cilastatin nephroprotection were also found.

Drug-Drug Interaction Potential, Cytotoxicity, and Reactive Oxygen Species Production of Salix Cortex Extracts Using Human Hepatocyte-Like HepaRG Cells.

Herbal preparations of willow bark (Salix cortex) are available in many countries as non-prescription medicines for pain and inflammation, and also as dietary supplements. Currently only little information on toxicity and drug interaction potential of the extracts is available. This study now evaluated the effects of two Salix cortex extracts on human hepatocyte-like HepaRG cells, in view of clinically relevant CYP450 enzyme activity modulation, cytotoxicity and production of reactive oxygen species (ROS). Drug metabolism via the CYP450 enzyme system is considered an important parameter for the occurrence of drug-drug interactions, which can lead to toxicity, decreased pharmacological activity, and adverse drug reactions. We evaluated two different bark extracts standardized to 10 mg/ml phenolic content. Herein, extract S6 (S. pentandra, containing 8.15 mg/ml total salicylates and 0.08 mg/ml salicin) and extract B (industrial reference, containing 5.35 mg/ml total salicylates and 2.26 mg/ml salicin) were tested. Both Salix cortex extracts showed no relevant reduction in cell viability or increase in ROS production in hepatocyte-like HepaRG cells. However, they reduced CYP1A2 and CYP3A4 enzyme activity after 48 h at ≥25 μg/ml, this was statistically significant only for S6. CYP2C19 activity inhibition (0.5 h) was also observed at ≥25 μg/ml, mRNA expression inhibition by 48 h treatment with S6 at 25 μg/ml. In conclusion, at higher concentrations, the tested Salix cortex extracts showed a drug interaction potential, but with different potency. Given the high prevalence of polypharmacy, particularly in the elderly with chronic pain, further systematic studies of Salix species of medical interest should be conducted in the future to more accurately determine the risk of potential drug interactions.