Target and Mechanism of the Xihuang Pill Based on Network Pharmacology for Lung Squamous Cell Carcinoma.

Context: Lung squamous cell carcinoma (LUSC) accounts for 30% of non-small-cell lung cancers (NSCLC), and an effective pharmacological treatment for LUSC isn't yet available. The Xihuang Pill is a potent Chinese medicinal preparation widely prescribed for the management of LUSC. Objective: The study intended to use the network-pharmacology method to ascertain the effective active ingredients, targets of action, and cellular-signal transduction involved in the prevention and treatment of LUSC when using the Xihuang Pill and to identify the mechanism of action of the pills against LUSC, to provide a more adequate scientific basis for subsequent studies. Design: The research team performed a genetic study. Setting: The study took place at Shanghai. Outcome Measures: The research team: (1) created the feature sets, for both the LUSC and normal features, using the Cancer Genome Atlas' (TCGA's) LUSC dataset; (2) performed a weighted correlation network analysis (WGCNA) of the differentially expressed genes (DEGs) using the R package WGCNA; (3) searched for the chemical components of the Xihuang Pill using the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP) and the Herb Group Identification Platform, and (4) selected the novel the Matthews correlation coefficient (MCC) algorithm to screen the hub genes. Results: The study found 8713 DEGs between the LUSC and normal groups. The top ten, important, downregulated genes included: (1) advanced glycosylation end product (AGER), (2) chitinase, acidic pseudogene 2 (CHIAP2), (3) CD300 molecule like family member G (CD300LG), (4) solute carrier family 6 member 4 (SLC6A4), (5) carboxypeptidase B2 (CPB2), (6) claudin 18 (CLDN18), (7) gamma-glutamyltransferase light chain 1 (GGTLC1), (8) gastrokine 2 (GKN2), (9) progastricsin (PGC), and (10) pulmonary surfactant-associated protein C (SFTPC). The top 10 upregulated genes included: (1) cancer susceptibility 9 (CASC9), (2) homeobox C13 (HOXC13), (3) keratin 6a (KRT6A), (4) desmoglein 3 (DSG3), (5) keratin 16 (KRT16), (6) forkhead box E1 (FOXE1), (7) preferentially expressed antigen in melanoma (PRAME), (8) calmodulin-like protein 3 (CALML3), (9) KRT68, and (10) aldo-keto reductase family 1 member B10 (AKR1B10). The study found 41 active ingredients and 843 targets for the Xihuang Pill. The PPI network included 10 hub genes, including cyclin dependent kinase 1 (CDK1), cyclin B1 (CCNB1), cyclin B2 (CCNB2), polo-like kinase 1 (PLK1), aurora kinase B (AURKB), baculoviral IAP repeat containing 5 (BIRC5), cyclin A2 (CCNA2), aurora kinase A (AURKA), centrosome-associated protein E (CENPE), and threonine tyrosine kinase (TTK), which were the principal target genes at the core of the gene-pathway network for the drug compound to central-target relationship. The enrichment analyses used the overlapping genes and the 10 hub genes and found 390 biological processes (BPs), 25 molecular functions (MFs), 43 cellular components (CCs), and 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The main enrichment occurred in the regulation of protein serine-threonine kinase activity, mitotic nuclear division, progesterone-mediated oocyte maturation, and the cell cycle. Conclusions: The study found the targets and relevant pathways of the hub genes of Xihuang Pill using biological analysis and molecular docking and demonstrated the interactions of critical chemical compounds with the hub's targeted genes were. More research is necessary to further determine whether the Xihuang Pill can improve LUSC patients' survival rate by regulation of those genes.

Aloe polymeric acemannan inhibits the cytokine storm in mouse pneumonia models by modulating macrophage metabolism.

The cytokine storm is highly associated with inflammatory-type disease severity and patients' survival. Plant polysaccharides, the main natural phytomedicine source, have a great potential to be an effective drug to treat cytokine storm. Herein we found that a polymeric acemannan (ABPA1) isolated from Aloe Vera Barbadensis extract C (AVBEC) exerted prominent inhibitory effects on inflammation-induced cytokine storm. The results displayed that ABPA1 effectively suppressed LPS-induced proinflammatory cytokines release in vitro. Moreover, ABPA1 treatment alleviated the cytokine storm and tissue damage in LPS- and IAV-induced mouse pneumonia models, and altered the phenotypic balance of macrophages in lung tissues. Functionally, ABPA1 enhanced macrophage M2 polarization and phagocytosis in RAW264.7 cells and inhibited LPS-induced M1 polarization. Mechanistically, ABPA1 enhanced mitochondrial metabolism and OXPHOS through activated PI3K/Akt/GSK-3ß signalling pathway. Overall, our findings suggest that ABPA1 may modulate macrophage activation and mitochondrial metabolism by targeting PI3K/Akt/GSK-3ß signalling pathway, thereby alleviating cytokine storm and inflammation.

Efficacy of Moxibustion in the Treatment of Parkinson's Disease Based on Meta-Analysis under Intelligent Medical Treatment.

Dementia in Parkinson's disease (PD) has become a major factor affecting the quality of life of patients with Parkinson's disease. Early detection and timely prevention can delay the progression of dementia, improve the quality of life of patients, and reduce the burden on society. This article is aimed at studying how to analyze the efficacy of moxibustion in the treatment of Parkinson's disease through meta-analysis on the basis of smart medicine. This article puts forward the related conceptual knowledge of smart medicine and meta-analysis and moxibustion treatment and proposes a deep learning method based on smart medicine to analyze the effects of moxibustion treatment on patients. The experiment in this article can be seen from the data in one of the figures that the highest curative effect of using a single moxibustion to treat Parkinson's disease is about 46%, while the curative effect of using a combination of moxibustion and Western medicine has reached 90%. It can be seen that a single moxibustion is not as effective as a combination of the two for Parkinson's disease. From the data in one of the tables, it can be seen that the proportion of Parkinson's disease in 2016 was 15%, showing an increase of 5%. By 2020, the proportion of Parkinson's disease was as high as 38%, and the growth rate reached 9%. It can be seen that the prevalence of this disease is getting higher and higher. Parkinson's disease has caused many undesirable effects on patients, such as slow movement, mental disorders, and a decline in mental state. Therefore, it is urgent to study the treatment of Parkinson's disease. Moxibustion can improve the patient's blood circulation and help the patient's local limbs to recover more easily and can help improve the patient's motor function.

Taohong Siwu decoction promotes the process of fracture healing by activating the VEGF-FAK signal pathway and systemically regulating the gut microbiota.

AIMS: This study aimed to explore the effect of Taohong Siwu Decoction (THSWD) on bone marrow mesenchymal stem cells (BMSCs) at the cellular level and the possible mechanism of systemic regulation of gut microbiota on fracture recovery. METHODS AND RESULTS: Cell Counting Kit-8 (CCK-8) experiments show that THSWD effectively promotes the proliferation of BMSCs. Transwell and wound healing assays show that THSWD effectively promotes the invasion and migration of BMSCs. Alizarin red staining showed that the THSWD model enhanced the osteogenic differentiation of BMSCs. Moreover, the effect of THSWD on BMSCs is time- and concentration-dependent. RT-qPCR and western blot results showed that THSWD treatment up-regulated the expression of vascular endothelial growth factor (VEGF) and focal adhesion kinase (FAK) at mRNA and protein levels, respectively. Haematoxylin-eosin and crocin O-quick green staining showed that after 14 days of THSWD treatment, the area of callus and cartilage regeneration at the fracture site increased significantly in rats with right femoral shaft fractures. Gut microbiota was changed in fractured rats, such as the abundance of Bacteroidetes and Firmicutes was increased. THSWD showed positive regulation of both to a certain extent. CONCLUSION: THSWD up-regulates VEGF and activates the FAK signalling pathway to enhance the development and differentiation of BMSCs, and systematically regulates the gut microbiota to promote fracture healing. SIGNIFICANCE AND IMPACT OF STUDY: This study provides new insights on the cellular and systemic level to understand the mechanism of THSWD in the treatment of fractures.

A Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer's Disease.

Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer's disease (AD). Mounting evidence suggests the emerging important role of circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute to both T2DM and AD. Here, we review the relationship among circadian rhythm disruption, T2DM and AD, and suggest that the occurrence and progression of T2DM and AD may in part be associated with circadian disruption. Then, we summarize the promising therapeutic strategies targeting circadian dysfunction for T2DM and AD, including pharmacological treatment such as melatonin, orexin, and circadian molecules, as well as non-pharmacological treatments like light therapy, feeding behavior, and exercise.

Torrefaction, temperature, and heating rate dependencies of pyrolysis of coffee grounds: Its performances, bio-oils, and emissions.

The torrefaction pretreatment is of great significance to the efficient conversion of biomass residues into bioenergy. In this study, the effects of the three torrefaction temperatures (200, 250, and 300 °C) on the pyrolysis performance and products of coffee grounds (CG) were quantified. The torrefaction treatment increased the initial devolatilization and maximum peak temperatures of the CG pyrolysis. Activation energy of CG250 was lower than that of CG and more conducive to the pyrolysis. Torrefaction altered the distributions of the pyrolytic products and promoted the generation of C=C. Torrefaction changed the composition ratio of the pyrolytic bio-oils although cyanoacetic acid and 2-butene still dominated the bio-oils. The joint optimization pointed to pyrolysis temperature > 600 °C and torrefaction temperature ≤ 270 °C as the optimal conditions. Our experimental results also verified that torrefaction of CG may be more suitable at 200 and 250 °C than 300 °C.

Aloe vera gel extract: Safety evaluation for acute and chronic oral administration in Sprague-Dawley rats and anticancer activity in breast and lung cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera (L.) Burm. f. is a typical traditional Chinese medicine (TCM) collected in the Pharmacopoeia of the People's Republic of China (version 2015). It has been traditionally used for the treatment of constipation, and its potential therapeutic activities have been widely evaluated, including anti-tumor, anti-inflammatory and immune regulatory effects. The wide application of Aloe vera in food and therapy has raised safety issues and there are multiple safety assessments with a diverse toxicity and adverse effects from clinics and animals. AIM OF THE STUDY: This study aimed to investigate the safety of Aloe vera barbadensis extract C (AVBEC) in rats and analyze its anticancer activity in cell lines. MATERIALS AND METHODS: We administrated AVBEC orally in an acute toxicity study and a 6-month chronic toxicity study to observe and confirm its safety in Sprague-Dawley (SD) rats. Additionally, we explored the cytotoxicity of AVBEC in cancer cells and non-cancer cells. We further investigated the anti-tumor activity of AVBEC, and in the meantime, probed the function of component from AVBEC. RESULTS: No deaths or substance-relative toxicity were observed in the acute toxicity study or the 6-month chronic toxicity study with doses of 44.8 g·kg-1 and 4.48 g·kg-1, respectively. In the chronic toxicity study, AVBEC did not cause organ toxicity, including crucial organ structure and chemical function, and peripheral and central immune system damage. Additionally, we found that AVBEC could induce cancer cell apoptosis with a relatively higher apoptotic ratio than in non-cancer cells by decreasing adenosine triphosphate (ATP) concentration and enhancing reactive oxygen species (ROS) production. We also identified components in AVBEC using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) and probed the function of malic acid. This demonstrated that under the same circumstances, malic acid induced cell necrosis in cancer cells and non-cancer cells, while AVBEC did not. CONCLUSIONS: These results reveal a novel mechanism of aloe gel extract in regulating cancer cell apoptosis via modulating the mitochondrial metabolism and imply a possible application of AVBEC for the treatment of malignant cancer with the safety evaluation from rats and anticancer investigation from cancer cells and non-cancer cells.

Effect of plant extracts and citric acid on phytoremediation of metal-contaminated soil.

Application of activating agents can significantly improve efficiency of plants for remediation of soils contaminated by heavy metals, however, damage to soil and plants limits application of traditional activating agents. The aim of our experiments is to select an efficient,green and low-cost activating agent to improve efficiency of plant extraction technology. In this study, contaminated soil was remediated by Sedum alfredii. The effects of two plant extracts (i.e., Oxalis corniculata,OX and Medicago sativaextract, ME) in addition to citric acid (CA) were studied in oscillatory activation experiment and pot experiment. The oscillation activation experiment revealed that extraction quantity of heavy metals in the soil was enhanced significantly with concentration of plant extract. The extraction quantity of Zn from 100% OX extract and ME extract were significantly higher than 10 mmol/L CA (54.04% and 33.09%, respectively). The 10 mmol/L CA has best extraction efficiency for Cd, up to 41.36 µg/kg, which is significantly higher than CK (control) (p < 0.05). The pot experiment exhibited that application of CA has significantly reduced soil pH and organic matter content by 8.63% and 28.21%, respectively, however the two extracts have no significant effect on soil properties. The study indicated that application of CA has negative effects on root morphological parameters and chlorophyll fluorescence parameters of Sedum alfredii.The addition of extracts of two plants have not caused any harm to Sedum alfredii. The application of three activating agents was beneficial for purification of Cd and Zn in soils, and its repairing efficiency was improved by 3.92, 3.37, 3.33 times and 0.44, 0.20, 0.86 times, respectively. The combination of plant extracts and hyperaccumulators can effectively remove heavy metals from contaminated soils, which provided a theoretical basis for mitigation of pollution in soils.

Multidisciplinary and Comprehensive Chinese Medicine for Advanced Non-Small Cell Lung Cancer Patients: A Retrospective Study of 855 Cases.

OBJECTIVE: To investigate the effects of multidisciplinary and comprehensive Chinese medicine (CM) treatments on progression-free survival (PFS) and median survival time (MST) in patients with advanced non-small cell lung cancer (NSCLC) and identify factors that influence progression and prognosis. METHODS: Clinical data of 855 patients with advanced NSCLC who received multidisciplinary and comprehensive CM treatments at Longhua Hospital from January 2009 to December 2018 were retrospectively analyzed. Univariate analysis was performed by the Kaplan-Meier method and log-rank sequential inspection. Multivariate analysis of significant variables from the univariate analysis was performed with Cox regression modeling. Key factors correlated to progression and prognosis were screened out, and a Cox proportional hazard model was established to calculate the prognostic index. RESULTS: The PFS and MST of 855 advanced NSCLC patients were 9.0 and 26.0 months, respectively. The 1-, 2-, 3-, and 5-year survival rates were 79.2%, 54%, 36.2%, and 17.1%, respectively. Gender, pathologic type, and clinical stage were independent prognostic risk factors; surgical history, radiotherapy, treatment course of Chinese patent medicine, intravenous drip of Chinese herbal preparation, duration of oral administration of Chinese herbal decoction (CHD), and intervention measures were independent prognostic protective factors. Gender was an independent risk factor for progression, while operation history and oral CHD administration duration were independent protective factors (all P<0.05). Women with stage IIIb-IIIc lung adenocarcinoma had the best outcomes. CONCLUSIONS: Female patients have lower progression risk and better prognoses than male patients, younger patients have higher progression risk but better long-term prognoses than the elderlys, and patients with lower performance status scores are at lower risk for progression and have better prognoses. Comprehensive CM treatments could significantly reduce progression risk, improve prognosis, and prolong survival time for patients with advanced NSCLC. This treatment mode offers additional advantages over supportive care alone.

Association between antidiabetic agents use and leukocyte telomere shortening rates in patients with type 2 diabetes.

Telomere length and telomere shortening rate (TSR) are accepted indicators of aging in cross-sectional population studies. This study aimed to investigate the potential influence of common antidiabetic agents on telomere length and TSR in patients with type 2 diabetes mellitus (T2DM). Leukocyte telomere length was measured through terminal restriction fragment analysis, and TSR was calculated in 388 T2DM patients. Depending on whether or not they received antidiabetic medication, patients were first divided into a treatment group and a nontreatment group. Treated patients were further subdivided into an acarbose-free group (patients taking antidiabetic agents without acarbose) and an acarbose group (patients using acarbose for more than 3 months). Results showed that untreated patients had higher TSRs than patients on antidiabetic drugs. Interestingly, patients in the acarbose group had significantly higher TSRs than patients in the acarbose-free group. Compared to the nontreatment group, the acarbose group showed better glycemic control of HbA1c, but the TSR was also higher. Our results suggest that antidiabetic treatments without acarbose can slow aging. By contrast, acarbose may accelerate biological aging in patients with T2DM, independently of glycemic control.

Simultaneous determination of kaempferol, quercetin, mangiferin, gallic acid, p-hydroxybenzoic acid and chlorpheniramine maleate in rat plasma after oral administration of Mang-Guo-Zhi-Ke tablets by UHPLC-MS/MS and its application to pharmacokinetics.

Mang-Guo-Zhi-Ke tablets (MGZKTs) is an effective Chinese patent medicine. It contains mango leaf extract as the main raw material and the antihistamine drug, chlorpheniramine maleate is included in the formulation. However, its pharmacokinetic effect is rarely reported. A highly sensitive, reliable and rapid high-throughput method using ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was used to simultaneously determine kaempferol, quercetin, mangiferin, p-hydroxybenzoic acid, gallic acid and chlorpheniramine maleate in rat plasma after oral administration of MGZKTs. The method was successfully developed and fully validated to investigate the pharmacokinetics of MGZKTs. Chloramphenicol and clarithromycin were used as internal standards (IS). A practicable protein precipitation procedure with methanol was adopted for sample preparation. The samples were separated on an Acquity UHPLC Syncronis C18 column (100 × 2.1 mm, 1.7 µm) using 0.1% formic acid-acetonitrile as the mobile phase. The flow rate was set at 0.4 mL/min. The obtained calibration curves were linear in the concentration range of ~1-1000 ng/mL for plasma (r > 0.99). Method validation results met the criteria reported in the US Food and Drug Administration guidelines. Quercetin, p-hydroxybenzoic acid and kaempferol were absorbed rapidly and reached the peak concentration between 0.16 and 0.25 h. This validated that the UHPLC-MS/MS method was successfully applied to study the pharmacokinetic parameters of the six compounds in rat plasma after oral administration of MGZKTs. This evidence will be useful for the clinical rational use of Mang-Guo-Zhi-Ke tablets.

Glycemic index, glycemic load, and glycemic response to pomelo in patients with type 2 diabetes.

Food intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D). Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study. The dose of insulin for each patient was adjusted on the first 3 days. A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days. Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34±1.88 and 72.15±1.95 respectively. The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation. It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients. These results may mean more varieties of food choices for T2D patients.

Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus.

Exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus. In this study, we examined the potential neural mechanisms by which these effects occur. Male Sprague Dawley rats were implanted with a cannula in the third ventricle of the brain through which an inhibitor of phosphatidylinositol-3 kinase (PI3K) (wortmannin) was administered, and EX-4 or vehicle was administered via intraperitoneal (IP) injection. The activity of PI3K/protein kinase B (AKT) and insulin receptor substrate-1 (IRS-1) in the hypothalamic arcuate was determined. We found that EX-4 treatment significantly decreased food intake and body weight. However, there were almost no changes in food intake and body weight when wortmannin injection (into the third ventricle) occurred prior to EX-4 IP injection. EX-4 not only increased the activity of PI3K/AKT, but it also increased IRS-1 activity. These results show that EX-4 likely suppresses food intake due to its ability to enhance insulin signaling.

Comparative analysis of 15 chemical constituents in Scutellaria baicalensis stem-leaf from different regions in China by ultra-high performance liquid chromatography with triple quadrupole tandem mass spectrometry.

Scutellaria baicalensis is a traditional Chinese herbal medicine containing multiple components, which has been extensively used in clinics to treat epidemic febrile disease and hyperactivity cough. To get a deeper understanding about Scutellaria baicalensis stem-leaf resources, we analyzed 15 chemical constituents in 35 batches of Scutellaria baicalensis stem-leaf from eight regions in China. A rapid, simple, and sensitive method using ultra-high performance liquid chromatography coupled with triple quadrupole electrospray tandem mass spectrometry has been developed for the first time to simultaneously determine 15 chemical constituents (including phenolic acids and flavonoids) in Scutellaria baicalensis stem-leaf. Sufficient separation of 15 target constituents was achieved on a Waters Acquity UPLC BEH C18 (2.1 mm × 100 mm, 1.7 µm) column within 14 min under the optimized chromatographic conditions. The established method was validated and showed good linearity, precision, repeatability, stability, and recovery and was successfully applied for the simultaneous determination of the 15 chemical constituents in these samples. Hierarchical clustering analysis and principal components analysis were performed to estimate and classify these samples based on the contents of the 15 chemical constituents. This study provided theoretical basis and scientific evidence for the development and utilization of Scutellaria baicalensis stem-leaf resources.

[Treatment of Radical Resected NSCLC by Chinese Medicine Combined with Adjuvant Chemother- apy: a Clinical Study].

OBJECTIVE: To evaluate the efficacy of Chinese medicine (CM) combined adjuvant chemotherapy in postponing relapse and metastasis of radical resected Ib-IIIa stage non-small cell lung cancer (NSCLC) patients, and to explore its effect in improving their quality of life (QOL) and clinical symptoms. METHODS: We designed a cohort study of 336 radical resected Ib-IIIa NSCLC patients by analyzing disease free survival (DFS) using Log-rank test. They were randomly assigned to the control group (155 cases, treated by adjuvant chemotherapy group) and the test group (181 cases, treated by adjuvant chemotherapy combined CM). By using controlled method, 60 radical resected NSCLC patients undergoing NP/NC program in 2012 (vinorelbine 25 mg/m2, combined with cisplatin 75 mg/m2 on day 1 and day 8/on day 1 or on day 1, 2, and 3; or carboplatin AUC = 5 on day 1) were assigned to the control group (29 cases) and the test group (31 cases). QOL scores (using EORTC QLQ-LC43 questionnaire) and TCM symptoms scores were compared between the two groups before chemotherapy, peri-chemotherapy (one day before the 2nd course of chemotherapy) , and after chemotherapy (20 days after ending the 4th course of chemotherapy). RESULTS: (1) The median DFS was longer in the test group than in the control group, but with no statistical difference between the two groups (42.73 months vs 35.57 months , P = 0.179). In the subgroup analysis, there was statistical difference in IIIa stage DFS. The median IIIa stage DFS of was longer in the test group than in the control group with statistical difference (27.87 months vs 19. 93 months, P = 0.047). (2) In the control study, repeated measured data indicated there was significant difference in physical functions between the two groups (P < 0.05). Total scores for health states decreased more in the test group than in the control group, but with no statistical difference (P > 0.05). Scores for constipation and CM syndrome scores were higher in the test group than in the control group (P < 0.05). CONCLUSIONS: CM had advantages in postponing DFS of radical resected NSCLC patients, especially in IIIa stage. CM could improve their QOL and clinical symptoms during adjuvant chemotherapy.

Capsaicin ameliorates stress-induced Alzheimer's disease-like pathological and cognitive impairments in rats.

Hyperphosphorylated tau aggregated into neurofibrillary tangles is a hallmark lesion of Alzheimer's disease (AD) and is linked to synaptic and cognitive impairments. In animal models, cold water stress (CWS) can cause cognitive disorder and tau hyperphosphorylation. Capsaicin (CAP), a specific TRPV1 agonist, is neuroprotective against stress-induced impairment, but the detailed mechanisms are still elusive. Here, we investigated whether CAP mitigates CWS-induced cognitive and AD-like pathological alterations in rats. The animals were administered CAP (10 mg/kg in 0.2 ml, 0.1% ethanol) or a control (0.2 ml normal saline, 0.1% ethanol) by intragastric infusion 1 h before CWS treatment. Our results showed that CAP significantly attenuated CWS-induced spatial memory impairment and suppression of PP-DG long-term potentiation; CAP abolished CWS-induced dendritic regression and enhanced several memory-associated proteins decreased by CWS, such as synapsin I and PSD93; CAP also prevented CWS-induced tau hyperphosphorylation by abolishing inhibition of protein phosphatase 2A. Taken together, this study demonstrated that activation of TRPV1 can mitigate CWS-induced AD-like neuropathological alterations and cognitive impairment and may be a promising target for therapeutic intervention in AD.

An acidic method of zein extraction from DDGS.

Zein with a higher intrinsic viscosity and phosphorus content, similar protein content, lower yellowness, and at potentially much lower cost than commercially available zein was obtained from distillers dried grains with solubles (DDGS). A novel extraction method using acidic conditions in the presence of a reducing agent has been used to obtain about 10% aqueous ethanol soluble zein from DDGS. The optimum pH, time, temperature, and amount of reducing agent that can produce zein with high quality and yield have been developed. In addition to the zein, about 17% oil based on the dry weight of DDGS has also been obtained during zein extraction. The zein obtained from this research is expected to be suitable for use as fibers, films, and binders and in paints.