Discovery and validation of COX2 as a target of flavonoids in Apocyni Veneti Folium: Implications for the treatment of liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Apocyni Veneti Folium (AVF), a popular traditional Chinese medicine (TCM), is known for its effects in soothing the liver and nerves and eliminating heat and water. It is relevant from an ethnopharmacological perspective. Pharmacological research has confirmed its benefits on antihypertension, antihyperlipidemia, antidepression, liver protection, immune system boosting, antiaging, and diabetic vascular lesions. Previous studies have shown that flavonoids, the active ingredients, have a hepatoprotective effect. However, the exact mechanism has not been clarified. AIM OF THE STUDY: This study aimed to identify the active flavonoids in AVF and their corresponding targets for liver injury. Multiple methods were introduced to confirm the targets. MATERIAL AND METHODS: AVF compounds were analyzed using liquid chromatography-mass spectrometry (LC-MS). Then, network pharmacology was utilized to screen potential hepatoprotection targets of the compounds. An enzyme activity assay was performed to determine the effect of the compounds on the targets. Biolayer interferometry (BLI) was applied to confirm the direct interaction between the compounds and the targets. RESULTS: A total of 71 compounds were identified by LC-MS and 19 compounds and 112 shared targets were screened using network pharmacology. These common targets were primarily involved in the TNF signaling pathway, cancer pathways, hepatitis B, drug responses, and negative regulation of the apoptotic process. Flavonoids were the primary pharmacological substance basis of AVF. The cyclooxygenase 2 (COX2) protein was one of the direct targets of flavonoids in AVF. The enzyme activity assay and BLI-based intermolecular interactions demonstrated that the compounds astragalin, isoquercitrin, and hyperoside exhibited stronger inhibition of enzyme activity and a higher affinity with COX2 compared to epigallocatechin, quercetin, and catechin. CONCLUSIONS: COX2 was preliminarily identified as a target of flavonoids, and the mechanism of the hepatoprotective effect of AVF might be linked to flavonoids inhibiting the activity of COX2. The findings can establish the foundation for future research on the traditional hepatoprotective effect of AVF on the liver and for clinical studies on liver disorders.

Melatonin ameliorates histone modification disorders in mammalian aged oocytes by neutralizing the alkylation of HDAC1.

Aging-associated histone modification changes in oocytes have been sporadically reported, but the underlying mechanisms remain elusive. Here, we systematically characterize multiple histone modifications in oocytes during aging. We find that maternal and postovulatory aging markedly alter the status of histone modifications, specifically H4K12ac and H3K4me3, in both mouse and porcine oocytes. Meanwhile, we identify a substantial reduction in HDAC1 (histone deacetylase 1) protein in aged oocytes, which contributes to the changes in H4K12ac and H3K4me3. Moreover, by employing methylglyoxal (MG) and site-directed mutagenesis, we demonstrate that the elevated reactive carbonyl species (RCS) level induces HDAC1 degradation, likely through attacking the cysteine residues, thereby influences histone modification state. Importantly, supplementation of melatonin not only prevents the loss of HDAC1 protein, but also partially corrects the H4K12ac and H3K4me3 status in aged oocytes. To sum up, this study established the link between redox disequilibrium and histone modification alterations during mammalian oocyte aging.

Agrimoniin is a dual inhibitor of AKT and ERK pathways that inhibit pancreatic cancer cell proliferation.

Molecular-targeted therapy has shown its effectiveness in pancreatic cancer, while single-targeted drug often cannot provide long-term benefit because of drug resistance. Fortunately, multitarget combination therapy can reverse drug resistance and achieve better efficacy. The typical treatment characteristics of traditional Chinese medicine monomer on tumor are multiple targets, with small side effects, low toxicity, and so forth. Agrimoniin has been reported to be effective on some cancers, while the mechanism still needs to be clarified. In this study, we used 5-ethynyl-2'-deoxyuridine, cell counting kit-8, flow cytometry, and western blot experiments to confirm that agrimoniin can significantly inhibit the proliferation of pancreatic cancer cell PANC-1 by inducing apoptosis and cell cycle arrest. In addition, by using SC79, LY294002 (the agonist or inhibitor of AKT pathway), and U0126 (the inhibitor of ERK pathway), we found that agrimoniin inhibited cell proliferation by simultaneously inhibiting AKT and ERK pathways. Moreover, agrimoniin could significantly increase the inhibitory effect of LY294002 and U0126 on pancreatic cancer cells. Meanwhile, in vivo experiments also supported the above results. In general, agrimoniin is a double-target inhibitor of AKT and ERK pathways in pancreatic cancer cells; it is expected to be used as a resistance reversal agent of targeted drugs or a synergistic drug of the inhibitor of AKT pathway or ERK pathway.

Associations Between Mild Cognitive Impairment and Whole Blood Zinc and Selenium in the Elderly Cohort.

Some studies have shown that an imbalance in trace element homeostasis can lead to cognitive dysfunction, but data are lacking. The purpose of this study was to investigate the association between whole blood zinc (Zn), selenium (Se), copper-zinc ratio (Cu/Zn), copper-selenium ratio (Cu/Se), and zinc-selenium ratio (Zn/Se) and mild cognitive impairment (MCI) in elderly Chinese individuals. The study was based on the Elderly Health and Controlled Environmental Factors Cohort in Lu'an, Anhui Province, China, from June to September 2016. The cognitive function of the elderly was determined by the Mini-Mental State Examination (MMSE) and activities of daily living (ADL) scales. The concentrations of Zn, Cu, and Se in the whole blood were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Binary logistic regression was used to analyze the associations between trace elements and MCI. A total of 1006 participants with an average age of 71.70 years old were included in this study. Compared with healthy people, MCI patients had higher whole blood Zn levels and lower Se levels, and Cu/Zn, Cu/Se, and Zn/Se were also significantly different. Binary logistic regression analysis showed that Zn, Cu/Se, and Zn/Se exposure in the third tertile was associated with an increased risk of MCI, while Se exposure in the third tertile was associated with a reduced risk of MCI. After adjustment for sex, age, marital status, BMI, and living status, whole blood Zn, Se, Cu/Zn, Cu/Se, and Zn/Se were significantly associated with MCI risk, especially in elderly women.

ccTCM: A quantitative component and compound platform for promoting the research of traditional Chinese medicine.

Traditional Chinese medicine (TCM) databases play a vital role in bridging the gap between TCM and modern medicine, as well as in promoting the popularity of TCM. Elucidating the bioactive ingredients of Chinese medicinal materials is key to TCM modernization and new drug discovery. However, one drawback of current TCM databases is the lack of quantitative data on the constituents of Chinese medicinal materials. Herein, we present ccTCM, a web-based platform designed to provide a component and compound-content-based resource on TCM and analysis services for medical experts. In terms of design features, ccTCM combines resource distribution, similarity analysis, and molecular-mechanism analysis to accelerate the discovery of bioactive ingredients in TCM. ccTCM contains 273 Chinese medicinal materials commonly used in clinical settings, covering 29 functional classifications. By searching and comparing, we finally adopted 2043 studies, from which we collected the compounds contained in each TCM with content greater than 0.001 %, and a total of 1449 were extracted. Subsequently, we collected 40,767 compound-target pairs by integrating multiple databases. Taken together, ccTCM is a versatile platform that can be used by TCM scientists to perform scientific and clinical TCM studies based on quantified ingredients of Chinese medicinal materials. ccTCM is freely accessible at http://www.cctcm.org.cn.

Integrated Medical Care and the Continuous 4C Nursing Model to Improve Nursing Quality and Clinical Treatment of Patients with Acute Stroke: Based on a Retrospective Case-Control Study.

Objective: This research paper is based on a retrospective case-control study for exploring the effects of medical nursing integration and the continuous 4C nursing model to improve the clinical treatment and nursing quality of patients with acute stroke. Method: For this purpose, a total of 313 patients with acute stroke, treated in our hospital from February 2020 to April 2021, were enrolled. They were divided into control and study groups with an even number of patients. The control group received integrated medical care number (N = 156), while the study group received integrated medical care and a continuous 4C nursing model (N = 157). In integrated medical care, the general data, self-nursing ability, degree of neurological impairment, Fugl-Meyer Assessment (FMA) score, Barthel index score, and quality of life score were compared between the two groups. Result: The self-nursing concept, self-nursing responsibility, self-nursing skills, health knowledge, and total score of the patients in the study group were higher than those in the control group (P < 0.05). The neurological function scores of the study group were lower than those of the control group at 1, 3, and 6 months after discharge (P < 0.05). The scores of the study group were higher than those of the control group at 1, 3, and 6 months after discharge (P < 0.05). The Barthel index score of the study group was higher than that of the control group at 1, 3, and 6 months after discharge. The scores of physical function, psychological function, social function, and health self-cognition in the study group were lower than those in the control group (P < 0.05). Conclusion: The application of integrated medical care and the continuous 4C nursing model for patients with acute stroke is beneficial to enhance the degree of neurological impairment of stroke patients, improve activities of daily life and motor function, and facilitate patients' quality of life. It is helpful to strengthen the attitude and feeling of cooperation between doctors and nurses, promote cooperation between doctors and nurses, reduce the defects of nursing work, heighten the quality of nursing, and achieve the requirement and goal of effectively promoting high-quality nursing.

Ophiopogonin B alleviates cisplatin resistance of lung cancer cells by inducing Caspase-1/GSDMD dependent pyroptosis.

Drug resistance has become the main reason for the failure of tumor chemotherapy. Radix Ophiopogon Japonicus has long been used as traditional Chinese medicine to treat pulmonary disease, and Ophiopogonin B (OP-B) as a bioactive component of it has also been verified to inhibit cell proliferation of various non-small cell lung cancer (NSCLC) cells in vivo and in vitro. Therefore, we wonder whether OP-B is also effective to drug resistant lung cancer cells. Firstly, Cell Counting Kit-8 (CCK8) assay was used to compare the sensitivity of OP-B on NCI-H460, A549, cisplatin resistant A549 (A549/DDP) and paclitaxel resistant A549 (A549/PTX) cells, and A549/DDP cells were shown to be more sensitive to OP-B than other three cell lines, the results were further verified in orthotopic tumor nude mice model and zebrafish tumor model. Moreover, observation of cell morphological feature, mitochondrial membrane potential, LDH release rate, and production of IL-1ß all suggested that OP-B induced pyroptosis in A549/DDP cells more significantly than that in A549 cells. Meanwhile, transcriptomic sequencing results between OP-B treated and the Mock A549/DDP group also suggested that OP-B induced more significant Caspase-1/GSDMD dependent pyroptosis in A549/DDP group, which was further verified by VX-765, the inhibitor of Caspase-1. Together, the experimental results suggested that OP-B alleviated DDP resistance of A549 cells through inducing more significant Caspase-1/GSDMD-dependent pyroptosis.

NAMPT reduction-induced NAD+ insufficiency contributes to the compromised oocyte quality from obese mice.

Maternal obesity is associated with multiple adverse reproductive outcomes, whereas the underlying molecular mechanisms are still not fully understood. Here, we found the reduced nicotinamide phosphoribosyl transferase (NAMPT) expression and lowered nicotinamide adenine dinucleotide (NAD+ ) content in oocytes from obese mice. Next, by performing morpholino knockdown assay and pharmacological inhibition, we revealed that NAMPT deficiency not only severely disrupts maturational progression and meiotic apparatus, but also induces the metabolic dysfunction in oocytes. Furthermore, overexpression analysis demonstrated that NAMPT insufficiency induced NAD+ loss contributes to the compromised developmental potential of oocytes and early embryos from obese mice. Importantly, in vitro supplement and in vivo administration of nicotinic acid (NA) was able to ameliorate the obesity-associated meiotic defects and oxidative stress in oocytes. Our results indicate a role of NAMPT in modulating oocyte meiosis and metabolism, and uncover the beneficial effects of NA treatment on oocyte quality from obese mice.

Ophiopogonin B inhibits migration and invasion in non-small cell lung cancer cells through enhancing the interaction between Axin and ß-catenin.

Ophiopogonin B (OP-B), a kind of saponin compound that exists in Radix Ophiopogonis is frequently adopted for the treatment of lung disease as traditional Chinese medicine. The present work aimed to explore the anti-tumor activity of OP-B on non-small cell lung carcinoma (NSCLC) and its possible mechanism. We found that OP-B-treated cells suppressed the viability and proliferation of cells depending on its concentration, as assayed by MTT and Alamar Blue (IC50 were 14.22 ± 1.94, 12.14 ± 2.01, and 16.11 ± 1.83 µM in A549, NCI-H1299, and NCI-H460 cells, respectively). Then, the suppressive effect of OP-B on the invasion and migration of NSCLC was observed through wound healing and Transwell assays, and the epithelial-mesenchymal transition (EMT) markers was detected by immunofluorescence and western blotting. In addition, a dose-dependent reduction of ß-catenin both within cytoplasm and nucleus was observed, and the downstream proteins cyclin D1 and c-Myc of Wnt/ß-catenin pathway were also reduced. We further constructed ß-catenin-overexpression cell models to reveal the underlying mechanism. The results showed that 10 µM of OP-B notably reduced ß-catenin protein levels, as well as cell migration and invasion. In spite of the increasement of ß-catenin, activation of Wnt pathway and EMT progression, knockdown of Axin leaded to de-function of OP-B on cell metastasis. Taken together, OP-B reduced NSCLC migration and invasion by strengthening the Axin/ß-catenin interaction and reducing ß-catenin protein translocation.

A strategy for quality evaluation of salt-treated Apocyni Veneti Folium and discovery of efficacy-associated markers by fingerprint-activity relationship modeling.

In this study, a fingerprint-activity relationship between chemical fingerprints and hepatoprotective activity was established to evaluate the quality of salt-treated Apocyni Veneti Folium (AVF). Characteristic fingerprints of AVF samples exposed to different concentrations of salt were generated by ultrafast liquid chromatography tandem triple time-of-flight mass/mass spectrometry (UFLC-Triple TOF-MS/MS), and a similarity analysis was performed based on common characteristic peaks by hierarchical clustering analysis (HCA). Then, the hepatoprotective activity of AVF against CCl4-induced acute liver damage in mice was investigated by assessing biochemical markers and histopathology, which showed that a high dose of AVF exposed to low levels of salt stress produced a marked amelioration of hepatic damage compared with the other salt-treated AVF. Finally, fingerprint-activity relationship modeling, which was capable of discovering the bioactive markers used in the quality evaluation, was investigated by the chemical fingerprints and the hepatoprotective activities utilizing multivariate statistical analysis, gray correlation analysis (GCA) and bivariate correlation analysis (BCA). The results showed that the accumulation of polyphenols, such as flavonoids and phenolic acids, in AVF subjected to low levels of salt stress could result in the effective scavenging of free radicals. Therefore, the present study may provide a powerful strategy to holistically evaluate the quality of salt-treated AVF in combination with chemical fingerprint and bioactivity evaluation.

Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axis.

BACKGROUND: As most lung cancer patients present with invasive, metastatic disease, it is vital to investigate anti-metastatic treatments for non-small cell lung cancer (NSCLC). Houttuynia cordata is commonly used as a Chinese anticancer medicine in the clinic, and sodium new houttuyfonate (SNH), a main compound of this herb, has long been found to have antibiotic effects, although its anticancer effects have not been investigated. Here, we tried to address this lack of research from the perspective of the competing endogenous RNA (ceRNA) theory. METHODS: The effects of SNH on NSCLC cells were analysed with Cell Counting Kit-8 assays and colony formation assays. In addition, transwell assays and wound healing assays were used to determine the effects of SNH on migration and invasion in NSCLC cells. The levels of key genes and proteins were examined by quantitative real-time PCR, western blotting, immunofluorescence staining and IHC staining. Through transcriptome screening and digital gene expression profiling, Linc00668 was identified to be regulated by SNH. Dual-luciferase reporter assays and RNA immunoprecipitation assays verified the binding efficiency between miR-147a and Linc00668 or Slug. RESULTS: In the present study, SNH regulated NSCLC cells in multiple ways, the most prominent of which was suppressing the expression of Linc00668, which was indicated to promote migration and invasion in NSCLC cells. Functional studies demonstrated that Linc00668 acted as a ceRNA by sponging miR-147a to further regulate Slug mRNA levels, thereby influencing the progression of the epithelial-mesenchymal transition. Consistently, the results of in vivo animal models showed that SNH depressed Linc00668 and suppressed the metastasis of NSCLC. CONCLUSIONS: SNH suppressed metastasis of NSCLC cells and the mechanism may involve with the Linc00668/miR-147a/Slug axis.

Qualitative detection of ginsenosides in brain tissues after oral administration of high-purity ginseng total saponins by using polyclonal antibody against ginsenosides.

Given the limited studies and conflicting findings, the transport character of ginsenosides crossing the blood-brain barrier (BBB) remains unclear. The present study was designed to qualitatively determine the distribution of ginsenosides in brain tissues after oral administration of ginseng total saponins, using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with immunohistochemistry. In brain tissue homogenates, ginsenoside Rg1 was detectable and no other ginsenosides or their metabolites were found. No ginsenosides were detected in cerebrospinal fluid. Immunohistochemistry staining of brain tissue sections by using anti-ginsenoside polyclonal antibodies revealed the localization of ginsenosides in brain tissues. Furthermore, immunofluorescence double staining revealed that ginsenosides widely existed in vascular endotheliocytes and astrocytes, and in few neurons. These results indicated that Rg1 was the main component that entered the brain after oral administration of ginseng total saponins and that ginsenosides could cross the BBB, although the transport capability of ginsenosides through the BBB may be poor.

Extraction of Fenugreek (Trigonella foenum-graceum L.) Seed Oil Using Subcritical Butane: Characterization and Process Optimization.

In this study, the subcritical butane extraction process of fenugreek seed oil was optimized using response surface methodology with a Box-Behnken design. The optimum conditions for extracted oil from fenugreek seed was as follows: extraction temperature of 43.24 °C , extraction time of 32.80 min, and particle size of 0.26 mm. No significant differences were found between the experimental and predicted values. The physical and chemical properties of the oil showed that the oil could be used as edible oil. Fatty acid composition of oils obtained by subcritical butane under the optimum conditions and by accelerated solvent extraction showed negligible difference. The oils were rich in linoleic acid (42.71%-42.80%), linolenic acid (26.03%-26.15%), and oleic acid (14.24%-14.40%). The results revealed that the proposed method was feasible, and this essay shows the way to exploit fenugreek seeds by subcritical butane extraction under the scope of edible oils.

Process optimization and characterization of fragrant oil from red pepper (Capsicum annuum L.) seed extracted by subcritical butane extraction.

BACKGROUND: Red pepper seeds account for 450-500 g kg-1 of the total pepper weight and are often discarded as waste. In this study, process optimization and characterization of fragrant oil from roasted red pepper seed extracted by subcritical butane extraction were carried out. RESULTS: The optimal conditions of extraction were a temperature of 74.61 °C, a time of 68.65 min and a liquid/solid ratio of 30.24:1. The oil had a refractive index (25 °C) of 1.471, a relative density of 0.900, an acid value of 1.421 mg g-1 oil, an iodine value of 127.035 g per 100 g, a saponification value of 184.060 mg KOH g-1 , an unsaponifiable matter content of 12.400 g kg-1 , a peroxide value of 2.465 meq. O2 kg-1 and a viscosity of 52.094 cP. The main fatty acids in the oil were linoleic acid (72.95%) followed by palmitic acid (11.43%) and oleic acid (10.00%). The oil showed desirable thermal and oxidative stability. A total of 19 volatile compounds, mostly aldehydes and alkenes, were identified from the oil. CONCLUSION: The results indicated that the method is appropriate for the preparation of fragrant red pepper seed oil, and the oil is suitable for used as edible oil. © 2016 Society of Chemical Industry.

Antioxidant, anticancer and apoptotic effects of the Bupleurum chinense root extract in HO-8910 ovarian cancer cells.

PURPOSE: The purpose of this study was to evaluate the anticancer, apoptotic and antioxidant properties of Bupleurum chinense (B.C) root extract against human epithelial ovarian cancer cells (HO-8910) in vitro. METHODS: MTT assay was used to evaluate the cell viability of HO-8910 cells after treatment with different B.C extract doses. Apoptotic and morphological effects induced by the extract were demonstrated by inverted phase contrast microscopy and fluorescence microscopy. The percentage of apoptotic cells was quantified by Annexin V/PI double staining assay. Flow cytometry using rhodamine-123 dye was used to measure disruption of mitochondrial membrane potential (Δψm). Gel electrophoresis was used to study the effects of the extract on DNA fragmentation. The antioxidant activity of the extract using 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazolin-6-sulphonic acid) (ABTS) radical scavenging assays was also evaluated. RESULTS: The results showed that B.C extract could induce potent and dose-dependent cytotoxic effects on the HO-8910 cells as demonstrated by MTT assay. The extract also induced cell shrinkage, chromatin condensation and membrane blebbing which are the hallmark of apoptosis. The average proportion of Annexin V-staining positive cells (total apoptotic cells) significantly increased from 9.4% in control cells to 18.5, 28.2 and 50.5% in 20, 80 and 120 µg/ml B.C extract-treated cells respectively. Different doses of the extract (20, 80 and 120 µg/ml) after 48 hrs exposure led to a substantial increase in DNA fragmentation.The number of cells with disrupted Δψm increased from 6.6% in untreated (control cells) to 14.2, 42.1 and 73.4% in 20, 80 and 120 µg/ml in extract-treated cells, respectively CONCLUSION: The anticancer effects of Bupleurum chinense extract were mediated through the induction of apoptosis, DNA fragmentation and disruption of mitochondrial membrane potential.

Pain inhibition by optogenetic activation of specific anterior cingulate cortical neurons.

Cumulative evidence from both humans and animals suggests that the anterior cingulate cortex (ACC) is important for pain-related perception, and thus a likely target for pain relief therapy. However, use of existing electrode based ACC stimulation has not significantly reduced pain, at least in part due to the lack of specificity and likely co-activation of both excitatory and inhibitory neurons. Herein, we report a dramatic reduction of pain behavior in transgenic mice by optogenetic stimulation of the inhibitory neural circuitry of the ACC expressing channelrhodopsin-2. Electrophysiological measurements confirmed that stimulation of ACC inhibitory neurons is associated with decreased neural activity in the ACC. Further, a distinct optogenetic stimulation intensity and frequency-dependent inhibition of spiking activity in the ACC was observed. Moreover, we confirmed specific electrophysiological responses from different neuronal units in the thalamus, in response to particular types of painful stimuli (i,e., formalin injection, pinch), which we found to be modulated by optogenetic control of the ACC inhibitory neurons. These results underscore the inhibition of the ACC as a clinical alternative in inhibiting chronic pain, and leads to a better understanding of the pain processing circuitry of the cingulate cortex.

An evidence-based update on the pharmacological activities and possible molecular targets of Lycium barbarum polysaccharides.

Lycium barbarum berries, also named wolfberry, Fructus lycii, and Goji berries, have been used in the People's Republic of China and other Asian countries for more than 2,000 years as a traditional medicinal herb and food supplement. L. barbarum polysaccharides (LBPs) are the primary active components of L. barbarum berries and have been reported to possess a wide array of pharmacological activities. Herein, we update our knowledge on the main pharmacological activities and possible molecular targets of LBPs. Several clinical studies in healthy subjects show that consumption of wolfberry juice improves general wellbeing and immune functions. LBPs are reported to have antioxidative and antiaging properties in different models. LBPs show antitumor activities against various types of cancer cells and inhibit tumor growth in nude mice through induction of apoptosis and cell cycle arrest. LBPs may potentiate the efficacy of lymphokine activated killer/interleukin-2 combination therapy in cancer patients. LBPs exhibit significant hypoglycemic effects and insulin-sensitizing activity by increasing glucose metabolism and insulin secretion and promoting pancreatic ß-cell proliferation. They protect retinal ganglion cells in experimental models of glaucoma. LBPs protect the liver from injuries due to exposure to toxic chemicals or other insults. They also show potent immunoenhancing activities in vitro and in vivo. Furthermore, LBPs protect against neuronal injury and loss induced by ß-amyloid peptide, glutamate excitotoxicity, ischemic/reperfusion, and other neurotoxic insults. LBPs ameliorate the symptoms of mice with Alzheimer's disease and enhance neurogenesis in the hippocampus and subventricular zone, improving learning and memory abilities. They reduce irradiation- or chemotherapy-induced organ toxicities. LBPs are beneficial to male reproduction by increasing the quality, quantity, and motility of sperm, improving sexual performance, and protecting the testis against toxic insults. Moreover, LBPs exhibit hypolipidemic, cardioprotective, antiviral, and antiinflammatory activities. There is increasing evidence from preclinical and clinical studies supporting the therapeutic and health-promoting effects of LBPs, but further mechanistic and clinical studies are warranted to establish the dose-response relationships and safety profiles of LBPs.

Effects of Zuogui Pill () and Yougui Pill () on the expression of brain-derived neurotrophic factor and cyclic adenosine monophosphate/protein kinase A signaling transduction pathways of axonal regeneration in model rats with experimental autoimmune encephalomyelitis.

OBJECTIVE: To study the effects of Zuogui Pill (, ZGP) and Yougui Pill (, YGP) on the expressions of brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling of axonal regeneration in the Lewis rats with experimental autoimmune encephalomyelitis (EAE), in order to explore the possible mechanism of ZGP and YGP on promoting axonal regeneration. METHODS: The rats were randomly divided into normal control (NC), model (MO), prednisone acetate (PA), ZGP and YGP groups. The EAE model of rat was established by injecting antigen containing myelin basic protein (MBP)68-86. The brain and spinal cord were harvested on the 14th and 28th day post-immunization (PI), the protein and mRNA expression of BDNF and PKA in the brain and spinal cord of rats were detected by Western blot analysis and real-time quantitative polymerase chain reaction (PCR), and the cAMP levels were detected by using enzyme-immunoassay method. RESULTS: (1) On the 28th day PI, the mRNA expression of BDNF in brain white matter and spinal cord of rats in ZGP and YGP groups were up-regulated, especially in YGP group (P<0.05 or P<0.01). (2) On the 14th day PI, the cAMP levels in brain white matters significantly increased in PA and YGP groups compared with MO group (P<0.05 or P<0.01), and the cAMP level in YGP group was higher than that in ZGP group (P<0.05). The cAMP level in spinal cord also significantly increased in YGP group compared with MO, PA and ZGP groups, respectively (P<0.01). (3) On the 14th day PI, the PKA expression in spinal cord of rats in ZGP group was significantly decreased compared with MO and YGP groups, respectively (P<0.05). (4) On the 28th day PI, there was a positive correlation between cAMP and PKA expression in the brain white matter of YGP rats. CONCLUSIONS: The results suggest that ZGP and YGP may promote axonal regeneration by modulating cAMP/PKA signal transduction pathway, but the targets of molecular mechanism of ZGP may be different from those of YGP.

Magnetic-field-assisted photothermal therapy of cancer cells using Fe-doped carbon nanoparticles.

Photothermal therapy with assistance of nanoparticles offers a solution for the destruction of cancer cells without significant collateral damage to otherwise healthy cells. However, minimizing the required number of injected nanoparticles is a major challenge. Here, we introduce the use of magnetic carbon nanoparticles (MCNPs), localizing them in a desired region by applying an external magnetic-field, and irradiating the targeted cancer cells with a near-infrared laser beam. The MCNPs were prepared in benzene, using an electric plasma discharge, generated in the cavitation field of an ultrasonic horn. The CNPs were made ferromagnetic by use of Fe-electrodes to dope the CNPs, as confirmed by magnetometry. Transmission electron microscopy measurements showed the size distribution of these MCNPs to be in the range of 5 to 10 nm. For photothermal irradiation, a tunable continuous wave Ti: Sapphire laser beam was weakly focused on to the cell monolayer under an inverted fluorescence microscope. The response of different cell types to photothermal irradiation was investigated. Cell death in the presence of both MCNPs and laser beam was confirmed by morphological changes and propidium iodide fluorescence inclusion assay. The results of our study suggest that MCNP based photothermal therapy is a promising approach to remotely guide photothermal therapy.

Puerarin inhibits acid-sensing ion channels and protects against neuron death induced by acidosis.

Puerarin, the main isoflavone found in the root of the wild leguminous creeper Pueraria lobata (Willd.) Ohwi, is known to protect the brain from ischemia-induced injuries. However, its effect on acidosis, a byproduct of brain ischemia and one factor promoting cell death, remains unknown. The purpose of this study was to investigate the effects of puerarin on acid-sensing ion channels (ASICs), which are reported to be activated by extracellular acidosis. Using the MTT assay and Hoechst/PI staining, we showed that puerarin could prevent hippocampal cell death during extracellular low pH. Data from whole-cell patch clamp recordings demonstrated that puerarin decreased the amplitude of ASIC currents and accelerated the desensitization of ASICs. Puerarin also reduced the amplitude of homomeric ASIC1a channels in CHO cells expressing pECFP-ASIC1a. Collectively, our study demonstrated that puerarin prevented hippocampal cells from acidosis-induced death via ASIC blockage, providing a mechanical insight into the neuroprotective effects of puerarin during brain ischemia.