Analysis of Clinical Characteristics and Prognostic Factors Related to EMs Correlation in Ovarian Cancer Patients.

Objective: To investigate the clinical characteristics and prognostic factors in patients with endometriosis-associated ovarian cancer. Methods: In this study, we retrospectively analyzed the medical records of 135 ovarian cancer patients admitted to our hospital from January 2016 to January 2018. Based on the presence of concomitant endometriosis (EMs), the patients were divided into two groups: the Endometriosis-Associated Ovarian Cancer (EAOC) group (n=64) and the non-EAOC (NEAOC) group (n=71). We compared the clinical characteristics of the two groups. Additionally, in the EAOC group, we followed up with patients for 5 years, categorized them into the survival group (n=40) and the deceased group (n=24) based on their prognosis, and conducted univariate and multivariate logistic regression analyses to identify influencing factors. Results: In comparison to the NEAOC group, patients in the EAOC group exhibited higher rates of menopause occurrence, pathological stages I-II, vaginal bleeding, and history of cesarean section, with statistical significance (P < .05). They also had a lower incidence of dysmenorrhea, lymph node metastasis, and abdominal distension, as well as an earlier age of onset, all of which were statistically significant (P < .05). There were no statistically significant differences (P > .05) between the two groups in terms of parity, gravidity, tumor diameter, abdominal pain incidence, and body mass index. Based on prognosis, the patients were categorized into a survival group (n=40) and a deceased group (n=24). Comparison between the two groups showed statistically significant differences (P < .05) in terms of postoperative residue, epithelial-mesenchymal transition, and lymph node metastasis. In contrast, there were no statistically significant differences (P > .05) in terms of tumor laterality, histological type, tumor stage, differentiation degree, and vaginal bleeding. The variables with P < .05 were assigned as independent variables, with the prognosis of death as the dependent variable. Multivariate logistic regression analysis revealed that epithelial-mesenchymal transition and lymph node metastasis were independent risk factors for mortality in EAOC patients (P < .05). Conclusion: Clinical characteristics of EAOC patients show significant differences, with epithelial-mesenchymal transition and lymph node metastasis being identified as independent adverse prognostic factors associated with poor outcomes in EAOC patients. However, this study has limitations such as a relatively small sample size, and further research is therefore necessary.

Optimization and characterization of pectin extracted from hawthorn by deep eutectic solvent.

In this study, hawthorn pectin was extracted from dried hawthorn with deep eutectic solvent(DES) and compared with the traditional extraction methods such as acid extraction (AE) and ultrasonic-assisted extraction (UAE). Under optimal conditions, with a molar ratio of choline chloride to urea at 1:3, a water content of 30 %, a liquid-to-solid ratio of 30:1 (mL/g), an extraction temperature of 80 °C, an extraction time of 60 min, and a pH of 1, the yield of hawthorn pectin was 4.33 % ± 0.02 %. The measured results were consistent with the prediction. In addition, compared with AE and UAE, the experimental results showed that DES had a higher yield, a lower degree of esterification, and a slightly different monosaccharide composition from other extraction methods. The results of infrared spectroscopy and scanning electron microscopy showed that DES had a fine microstructure and coarser surface, and the main chemical structure of DES didn't change. The rheological analysis showed that DES had lower apparent viscosity than AE and UAE. These results represent a green source for pectin extraction with high pectin yield and good performance. In conclusion, the deep eutectic solvent has good application prospects in extracting hawthorn pectin.

Correlation of Serum ß2-MG, HGF, Lp-PLA2 with Carotid Atherosclerosis in Patients with Hypertension Combined with Cerebral Infarction and their Prognostic Value.

Cerebral infarction is characterized by a high morbidity, disability, and fatality rate. This study explored the relationship between serum ß2 microglobulin (ß2-MG), HGF, lipoprotein-associated phospholipase A2 (Lp-PLA2) and carotid atherosclerosis in patients with hypertension combined with cerebral infarction and their prognostic value. A total of 320 patients with cerebral infarction complicated with hypertension who were hospitalized from January 2015 to January 2020 were collected. HGF, Lp-PLA2 and ß2-MG levels were detected. Plaque score (Crouse score) was the patient's cumulative plaque thickness measurements. Additionally, the maximum plaque thickness and the number of plaques were measured.. The correlation was found between high ß2-MG levels and the poor prognosis (HR: 1.29, 95% CI: 1.03-1.52, P = .022). Patients who had elevated levels of HGF were also less likely to have a positive outcome (HR: 1.38, 95% CI: 1.26-1.56, P = .015). High Lp-PLA2 levels were associated with a worse prognosis than low levels (HR: 1.74, 95% CI: 1.29-2.32, P = .015). In conclusion, the levels of ß2-MG, HGF, and Lp-PLA2 in patients with hypertension combined with cerebral infarction were substantially linked with carotid plaques.

[Determination of 101 pesticide residues in Platycodonis radix and extracts of Angelica sinensis by gel permeation chromatography-gas chromatography-ion trap mass spectrometry].

With the growing global popularity of traditional medicine and natural drugs， especially in Southeast Asia， the quality of traditional Chinese medicines （TCMs） has attracted the attention of regulators. China's major TCM export destinations， such as South Korea， Japan， and Europe， have formulated strict maximum residue limits （MRLs） of pesticides in TCMs. Therefore， a sensitive and high-throughput method for the simultaneous determination of 101 pesticide residues in Platycodonis radix and extracts of Angelica sinensis was established， involving gel permeation chromatography （GPC） coupled with gas chromatography-ion trap mass spectrometry （GC-ITMS）. In this method， the samples were first ground into fine powder and extracted twice with 20 mL acetonitrile in an ultrasonic cleaner for 30 min. After centrifugation for 10 min at 6000 r/min， the supernatants were combined and dried at 40 ℃ using a rotary vacuum evaporator. The residue was re-dissolved in 2 mL ethyl acetate-cyclohexane （1∶1， v/v） and purified by gel permeation chromatography using a 40 cm×20 mm column. The eluent collecting time was optimized as 17-30 min to ensure both the recovery of target compounds and the removal of interferences such as pigments and lipids from the target compounds. The eluent was then dried and re-dissolved with 1 mL toluene for analysis. The 101 pesticide residues were separated using the DB-5MS capillary column and analyzed by ion trap mass spectrometry. The pretreatment conditions and ion trap mass spectrometry parameters were optimized to effectively reduce the interference of complex TCM matrices and greatly improve the quantitative accuracy of the analysis and recovery of the target pesticides. Three spiked levels of 101 pesticides were tested. The average recovery range was 58.3%-108.9% and the relative standard deviations （RSDs） at the three spiked levels （n=10） ranged from 0.4% to 16.5%. The limits of detection （LODs， S/N=3） of the 101 pesticide compounds ranged from 0.2 to 40.0 µg/kg， while the limits of quantification （LOQs， S/N=10） ranged from 0.6 to 120.0 µg/kg， which met the maximum residue limits of China's main TCM export countries and organizations. This rapid analysis method was easy to operate and high throughput， with strong sensitivity and good repeatability. The employment of gel permeation chromatography overcame the drawback of inadequate cleanup of the solid phase extraction column during TCM analysis. The application of ion trap technology further eliminated the interference of matrix impurities and increased the accuracy of the quantitative and qualitative analyses. This method fills the knowledge gap in multiple pesticide residue determination in TCMs using gas chromatography-ion trap mass spectrometry and is a useful and beneficial alternative to current analytical methods of TCMs.

Improvement Effect of PERMA Model-Based Nursing Intervention plus Music Therapy on Patients with Acute Liver Failure Undergoing Plasma Exchange Therapy.

Objective: To explore the improvement effect of PERMA model-based nursing intervention plus music therapy (MT) on patients with acute liver failure (AHF) undergoing plasma exchange therapy (PET). Methods: This research included 100 AHF patients treated with PET in our hospital, between January 2020 and December 2021, including 54 cases receiving PERMA model-based nursing intervention plus MT (observation group, OG) and 46 cases receiving routine nursing (control group, CG). Clinical efficacy and liver function (LF) were compared between the groups. Prenursing and postnursing psychology, treatment compliance, sleep, pain, and quality of life were assessed, and patient satisfaction was investigated at discharge. Results: The postnursing overall efficacy showed no evident difference between the groups (P > 0.05). The clinical efficacy was mainly markedly significant (50.00%) in OG and effective (43.48%) in CG. The overall response rate was not statistically different between groups (χ 2 = 1.392, P > 0.05). OG presented better LF, treatment compliance, and sleep quality after nursing, with milder negative emotions and pain than CG (P < 0.05). A higher patient satisfaction rate was also determined in OG at discharge (P < 0.05). Conclusions: PERMA model-based nursing intervention plus MT can effectively improve the psychological state, treatment compliance, and quality of life of AHF patients with PET and reduce pain sensation, which has promising clinical application value in the future.

Combined effect of tetracycline and copper ion on catalase activity of microorganisms during the biological phosphorus removal.

Microbial catalase is a key enzyme that affects the activities of microorganisms, and the catalase activity is affected by pollutants in wastewater. However, the effects of mixed pollutants on catalase activity are rather complex. To reveal the effect of the mixed pollutants on catalase activity of microorganisms, the present study investigated tetracycline and copper ion as pollutants during the biological phosphorus removal. Three concentration ratios of tetracycline and copper ion and 27 different concentration gradients were designed through the direct equipartition ray and the dilution factor method. The effects of mixed pollutants on the catalase activity of microorganisms were analyzed by the nonlinear regression equation and concentration-addition model. The results showed that, with the increase of actuation duration and the pollutant concentration, the inhibitory effects on the catalase activity of microorganisms obviously increased, which indicated that the inhibitory effects are concentration-dependent and time-dependent. The concentration-addition model suggested that when the ratio was 0.297, the combined effect of mixed pollutants on the activity of microbial catalase was mainly antagonism. When the ratio is 0.894, the combined effect was mainly additivity. When the ratio was 2.676, the combined effect transformed from synergism to additivity and antagonism. The study of the combined effects of tetracycline and copper ion on the catalase activity is helpful to further study their ecotoxicological mechanisms in wastewater treatment.

Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway.

Glioblastoma multiforme (GBM) in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it. Studies of sinomenine, an alkaloid from the Chinese medicinal plant, Sinomenium acutum, showed that it had inhibitory effects on several kinds of cancer. Here, we synthesized a sinomenine derivative, sino-wcj-33 (SW33), tested it for antitumor activity on GBM and explored the underlying mechanism. SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells. It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis. Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body. SW33 also induced autophagy through the PI3K/AKT/mTOR and AMPK/mTOR pathways. Thus, SW33 appears to be a promising drug for treating GBM effectively and safely.

Effect of Psychological Care Combined with Traditional Chinese Medicine on Postoperative Psychological Stress Response in Patients with Advanced Cervical Cancer.

OBJECTIVE: To study the effects of psychological care combined with traditional Chinese medicine treatment on the postoperative psychological stress response and the expression levels of serum C-reactive protein (CRP) and interferon-γ (IFN-γ) in patients with advanced cervical cancer. METHOD: 232 postoperative advanced cervical cancer patients treated in our hospital from December 2015 to December 2018 were selected as study objects and divided into the control group and study group using the random number table method. The control group was given basic care combined with traditional Chinese medicine treatment, while the study group was given psychological care treatment on the basis of the control group to compare the treatment effect, psychological stress response, pain level, quality of life, and long-term efficacy of the two groups. The serum CRP and IFN-γ levels and their correlation with different psychological stress responses were compared between the two groups before and after treatment. RESULT: Comparing the clinical efficacy of the two groups, the total effective rate of the study group was higher than that of the control group. VAS scores in the study group were significantly lower than those in the control group 30 and 60 days after treatment. The SCL-90 scores of the study group after treatment were lower than those of the control group. After treatment, the differences between the two groups were statistically significant in the scores of emotional function, social function, and role function. The two-year cumulative survival rate in the study group (82.76%) was significantly increased compared to that in the control group (55.17%). The serum CRP and IFN-γ expression levels in the two groups were significantly decreased after treatment compared to those before treatment, and the serum CRP and IFN-γ expression levels in the study group were significantly decreased compared to those in the control group. CONCLUSION: Psychological care combined with traditional Chinese medicine in the treatment of advanced cervical cancer patients after surgery was effective in improving patients' psychological status, reducing their pain level, relieving postoperative negative emotions, increasing compliance, improving the quality of life, helping to prolong survival time, and controlling serum indexes back to normal, which was worth promoting in clinical practice.

Comparative study of structural properties and biological activities of polysaccharides extracted from Chroogomphus rutilus by four different approaches.

Extraction processes significantly alter the structural and functional properties of polysaccharides. In this study, we extracted polysaccharides from Chroogomphis rutilus fruiting bodies (designated as CRP) using four methods, including hot water, ultrasound, microwave and sequential ultrasound-microwave, and designated these polysaccharides as CRP-H, CRP-M, CRP-U and CRP-UM, respectively. All CRPs were heteropolysaccharides with semblable monosaccharide types of glucose, mannose and galactose, mainly constituted of α-d-glucopyranosyl-(1 â†’ 4). The extraction processes significantly affected the molecular weights, monosaccharide proportions, glycosidic bond ratios, branching degrees, triple-helix conformation and surface morphology of the CRPs. Among them, CRP-UM showed the highest yield and most potent antioxidative capacity in vitro and in HL-7702 cells, but the weakest activation of immunostimulatory response in RAW264.7 cells. In contrast, CRP-H exhibited the lowest yield but strongest immunostimulatory activity. Overall, microwave extraction could be utilized as a general and practical CRP extraction approach, based on its relatively high yield and bioactivities.

Xiaoxuming Decoction Regulates Vascular Function by Modulating G Protein-Coupled Receptors: A Molecular Docking Study.

Xiaoxuming decoction (XXMD) is a traditional Chinese herbal medicine (CHM) that is used for the treatment of stroke in China. Stroke injury damages the cerebral vasculature and disrupts the autoregulation of vasoconstriction and vasodilatation, which is crucial for maintaining constant cerebral blood flow (CBF). It has been reported that XXMD exerts a positive effect on cerebral circulation in animal models of stroke. However, the mechanisms underlying the regulatory effect of XXMD on vascular tone, and the interactions among the multiple components of XXMD, remain unclear. In this study, XXMD was found to induce relaxation of the basilar artery rings of rats precontracted by 5-hydroxytryptamine (5-HT) in vitro, in a dose-dependent manner. The modulation of vascular tone and the process of cerebral ischemia are mediated via the interactions between G protein-coupled receptors (GPCRs) and their ligands, including 5-HT, angiotensin II (Ang II), and urotensin II (UII). Thus, the potential synergistic effects of the different components of XXMD on the regulation of vasoconstriction and vasodilation were further investigated by molecular docking based on network pharmacology. We constructed and analyzed a database comprising 963 compounds of XXMD and studied the interactions between five vascular GPCRs (5-HT1A receptor (5-HT1AR), 5-HT1B receptor (5-HT1BR), Ang II type 1 receptor (AT1R), beta 2-adrenergic receptor (ß2-AR), and UII receptor (UTR)) and the various herbal constituents of XXMD using molecular docking. By constructing and analyzing the compound-target networks of XXMD, we found that Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, and Paeoniae Radix Alba were the three major herbs that contained a large number of compounds with high docking scores. We additionally observed that several constituents of XXMD, including gallotannin, liquiritin apioside, nariutin, 1,2,3,4,6-pentagalloylglucose, folic acid, and ginsenoside Rb1, targeted multiple vascular GPCRs. Moreover, the interactions between the components of XXMD and the targets related to vascular tone constituted the comprehensive cerebrovascular regulatory function of XXMD and provided a material basis of the vasoregulatory function of XXMD. The study reports the contributions of various components of XXMD to the regulatory effects on vascular tone and provides scientific evidence for the multicomponent and multitargeting characteristics of XXMD.

The comprehensive study on the therapeutic effects of baicalein for the treatment of COVID-19 in vivo and in vitro.

Baicalein is the main active compound of Scutellaria baicalensis Georgi, a medicinal herb with multiple pharmacological activities, including the broad anti-virus effects. In this paper, the preclinical study of baicalein on the treatment of COVID-19 was performed. Results showed that baicalein inhibited cell damage induced by SARS-CoV-2 and improved the morphology of Vero E6 cells at a concentration of 0.1 µM and above. The effective concentration could be reached after oral administration of 200 mg/kg crystal form ß of baicalein in rats. Furthermore, baicalein significantly inhibited the body weight loss, the replication of the virus, and relieved the lesions of lung tissue in hACE2 transgenic mice infected with SARS-CoV-2. In LPS-induced acute lung injury of mice, baicalein improved the respiratory function, inhibited inflammatory cell infiltration in the lung, and decreased the levels of IL-1ß and TNF-α in serum. In conclusion, oral administration of crystal form ß of baicalein could reach its effective concentration against SARS-CoV-2. Baicalein could inhibit SARS-CoV-2-induced injury both in vitro and in vivo. Therefore, baicalein might be a promising therapeutic drug for the treatment of COVID-19.

Fish oil supplementation attenuates cognitive impairment by inhibiting neuroinflammation in STZ-induced diabetic rats.

Type 2 diabetes mellitus (T2DM) markedly impairs human health. During T2DM development, some patients experience cognitive dysfunction and behavioral deficits, which are characterized by neuronal injury and memory loss. It has been reported that the incidence of dementia in middle-aged and elderly patients with diabetes is significantly higher than that in normal elderly patients. Currently, the pathogenesis of cognitive dysfunction in diabetes remains unknown, and there is no standard or specific method to diagnose the disease in clinical practice. Evidence has shown that fish oil (FO) can alleviate depressive-like behaviors by attenuating neuroinflammation in a rat model, and improve cognitive dysfunction by inhibiting apoptosis. Therefore, it is reasonable to speculate that FO may reduce cognitive impairment by attenuating neuroinflammation in diabetic rats. In the present study, we investigated the effects of FO supplementation on cognitive dysfunction in a streptozotocin-induced diabetic rat model. FO administration for 10 weeks improved spatial learning and memory as evaluated by performance in the Morris water maze (MWM). Besides, FO significantly improved the morphology of neurons in the hippocampus and cortex of diabetic rats and reduced the neuronal nuclear condensation. Moreover, FO decreased the mRNA expression of IL-1ß, IL -6, and TNF-α and increased the mRNA expression of IL-4 and IL-10 in the cortex and hippocampus. FO also attenuated the brain inflammatory cascade and simultaneously reduced diabetes-induced oxidative stress. In addition, FO increased the protein expression of Nrf2 and HO-1 in cortex and hippocampus of diabetic rats. These results provide a novel horizon for the study of neuroprotective effect of FO and further clarify the connections among inflammation, oxidative stress and diabetes-induced cognitive impairment.

Ethno-medicinal study of Artemisia ordosica Krasch. (traditional Chinese/Mongolian medicine) extracts for the treatment of allergic rhinitis and nasosinusitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. AIM: To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. MATERIALS AND METHODS: Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. RESULTS: In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. CONCLUSIONS: Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.

Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor α (ERα) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC50 values ranging from 4.83 to 10.22 µM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD.

Dexmedetomidine inhibits neuronal apoptosis by inducing Sigma-1 receptor signaling in cerebral ischemia-reperfusion injury.

Dexmedetomidine is known to alleviate cerebral ischemia-reperfusion injury (CIRI). We established a rat model of CIRI, which exhibited higher neurological deficit scores and a greater number of apoptotic cells in the cerebral ischemic penumbra than controls. Dexmedetomidine reversed the neuronal apoptosis and improved neurological function in this model. We then examined Sigma-1 receptor (Sig-1R) expression on the endoplasmic reticulum (ER) in brain tissues at different reperfusion time points. Sig-1R expression increased with CIRI and decreased with increasing reperfusion times. After 24 hours of reperfusion, dexmedetomidine upregulated Sig-1R expression, and ER stress proteins (GRP78, CHOP, JNK and Caspase-3) were detected in brain tissues with Western blotting. Moreover, GRP78 expression followed a pattern similar to Sig-1R. Dexmedetomidine induced GRP78 expression but inhibited CHOP, Caspase-3 and phosphorylated-JNK expression in brain tissues. A Sig-1R-specific inhibitor reduced GRP78 expression and partially inhibited the upregulation of GRP78 by dexmedetomidine. The inhibitor also increased CHOP and Caspase-3 expression and partially reversed the inhibitory effects of dexmedetomidine on these pro-apoptotic ER stress proteins. These results suggest that dexmedetomidine at least partially inhibits ER stress-induced apoptosis by activating Sig-1R, thereby attenuating brain damage after 24 hours of ischemia-reperfusion.

Application of Rice Grain Husk Derived Biochar in Ameliorating Toxicity Impacts of Cu and Zn on Growth, Physiology and Enzymatic Functioning of Wheat Seedlings.

Livestock and poultry manure containing high levels of copper and zinc have led to contamination of farmland and products which could have an impact on human health. Biochar is an inexpensive and efficient heavy metal absorbent. In the present study, we have used biochar to mitigate the effects of heavy metals on the growth of wheat seedlings. The study showed that the effects of heavy metals on wheat seedlings growth were mitigated by increasing exposure to biochar. Compared to the control group, the germination potential, germination rate, germination index and vigor index of wheat seedlings with supplemented biochar increased significantly. Moreover, the specific activity of catalase, peroxidase, superoxide dismutase decreased and chlorophyll contents increased, which promote wheat growth and suggests that the addition of biochar could reduce the effects of heavy metals on wheat seedlings.

Taurine Supplementation Ameliorates Arsenic-Induced Hepatotoxicity and Oxidative Stress in Mouse.

We previously reported that taurine treatment inhibited arsenic (As)-induced apoptosis in the liver of mice. This study was designed to explore the effect of taurine on liver function and its underlying mechanism in As-exposed mice. Mice were randomly divided into 3 groups, ten mice in each group. Group 1, control group, only orally received drinking water alone. Group 2, As intoxication group, was exposed to 4 mg/L As2O3 via drinking water for 60 days. Group 3, taurine protection group, was treated with 4 mg/L As2O3 and 150 mg/kg both. Taurine administration significantly revered the increases of alanine transaminase (ALT) and aspartate transaminase (AST) activities in serum. The decrease of glutathione (GSH) was inhibited with taurine treatment in the liver of As-exposed mice. At the same time, taurine significantly inhihibited As-induced enhancement of malondialdehyde (MDA) in the liver. Here we show that taurine protective effect on liver function in As-exposed mice maybe involve lipid peroxidation.

Network pharmacology study of traditional Chinese medicines for stroke treatment and effective constituents screening.

ETHNOPHARMACOLOGICAL RELEVANCE: Stroke is one of the most frequent causes of death and disability. So far there are no effective preventives or treatments. The therapeutic system of traditional Chinese medicines (TCMs) has been in use for several thousand years and still affords a valuable resource for today's clinicians in preserving health. MATERIALS AND METHODS: We had collected the Chinese medicinal formulae and then commonly used single herbs or drug combinations were analyzed through data mining. The ingredients from the top 30 frequently used herbs which have good druggability and blood-brain barrier permeability were collected as a natural product library. Targets of the related ingredients were predicted using various databases and analyzed by GO and KEGG pathway mapping. The potential stroke targets were validated in the market or from clinical trials, and used to establish molecular docking, HipHop and SBP models to screen new compounds for multi-target activity. Lastly, in vitro experiments with models for oxygen and glucose deprivation and reperfusion (OGDR) were conducted to test the activities of compounds identified by screening. RESULTS: A total of 1679 Chinese medicinal formulas were selected and their prescription rules were analyzed. 4277 compounds were from the top 30 herbs and 3560 molecules were filtered to build the natural product library. The ingredient-target network, target-disease network and target-target interaction network were established to explain the characteristics and mechanisms of the TCMs. Thirty-one molecules were selected to have multi-target activity on targets of stroke via virtual screening. Five of these had already been reported to have therapeutic effects on stroke. Three of the eight compounds which have been examined showed protective effects on OGDR model. CONCLUSIONS: This paper details a novel strategy for exploring the characteristics and mechanisms of herbal medicines from a systematic standpoint in an attempt to identify those affecting specific target pathways related to stroke. Using this methodology on our natural products library, we found a number of lead candidates with multi-target activity.

Inhibition of FOXO3a/BIM signaling pathway contributes to the protective effect of salvianolic acid A against cerebral ischemia/reperfusion injury.

Salvianolic acid A (SalA) is an effective compound extracted from traditional Chinese medicine Salvia miltiorrhiza Bunge. The Forkhead box O3a (FOXO3a) signaling pathway plays crucial roles in the modulation of ischemia-induced cell apoptosis. However, no information about the regulatory effect of SalA on FoxO3a is available. To explore the anti-cerebral ischemia effect and clarify the therapeutic mechanism of SalA, SH-SY5Y cells and Sprague-Dawley rats were applied, which were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively. The involved pathway was identified using the specific inhibitor LY294002. Results showed that SalA concentration-dependently inhibited OGD/R injury triggered cell viability loss. SalA reduced cerebral infarction, lowered brain edema, improved neurological function, and inhibited neuron apoptosis in MCAO/R rats, which were attenuated by the treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) specific inhibitor LY294002. SalA time- and concentration-dependently upregulated the phosphorylation levels of protein kinase B (AKT) and its downstream protein FOXO3a. Moreover, the nuclear translocation of FOXO3a was inhibited by SalA both in vivo and in vitro, which was also reversed by LY294002. The above results indicated that SalA fought against ischemia/reperfusion damage at least partially via the AKT/FOXO3a/BIM pathway.

Indirubin suppresses ovarian cancer cell viabilities through the STAT3 signaling pathway.

BACKGROUND: Indirubin is the active component of Danggui Longhui Wan, a traditional Chinese medicine formulation. Due to its anti-inflammation and anti-tumor effects, indirubin has been widely used for the treatment of inflammation, cancer, and other chronic disease. Herein, we aimed to investigate the role and mechanism of indirubin in human ovarian cancer cell proliferation. MATERIALS AND METHODS: The cell viability was determined by Cell Counting Kit-8 and colony formation assays by treatment with different dosages of indirubin over 72 hours. Apoptosis was examined by flow cytometry with fluorescein isothiocyanate Annexin V Apoptosis Detection Kit. Western blot assay was finally applied to analyze the expression of cancer-related STAT3 pathway and its downstream proteins. RESULTS: Indirubin was found to significantly inhibit cell viability and induce apoptosis in 2 human ovarian cancer cell lines. Mechanistic studies revealed that indirubin treatment led to reduced levels of phosphorylated-STAT3, thus repressing the downstream pro-survival proteins and elevating pro-apoptosis ones. CONCLUSION: Our study provided the evidence for anti-survival activity of indirubin by inhibiting cell viability and inducing apoptosis in human ovarian cancer cells, which involved impaired STAT3 signaling pathway. Our findings further support indirubin as a potential drug candidate against human ovarian cancer.