Oxygen vacancy engineering of TiO2 nanosheets for enhanced photothermal therapy against cervical cancer in the second near-infrared window.

Cervical cancer is the most common and deadly female cancer on the worldwide scale. Considering that the conventional surgery treatment and chemotherapy would cause certain side effects, photothermal therapy (PTT) possesses desired therapeutic efficiency and insignificant side effects against cervical cancer. However, the lack of efficient and safe photothermal agents that operate in the second near-infrared (NIR-II) window is a main obstacle hindering the clinical transformation of PTT. Titanium dioxide (TiO2)-based nanomaterials are commonly applied in the biomedicine field, but the weak absorption and low photothermal conversion efficiency (PCE) of TiO2 in the NIR region limit their applications in PTT. Herein, we report the oxygen vacancy engineering that is a robust strategy to regulate the electronic structures of TiO2 for photothermal conversion properties optimizing. The obtained oxygen vacancy-doped TiO2-x nanosheets exhibit strong NIR-II absorption and high PCE owing to their decreased bandgap. Specifically, the PCE of TiO2-x nanosheets is determined to be 69.5 % in the efficient NIR-II window, which is much higher than that of widely reported PTT agents. Complete tumor recession without recurrence or pulmonary metastasis is realized by enhanced NIR-II PTT via TiO2-x nanosheets at an ultralow and safe laser exposure (0.6 W/cm2). Our findings suggest that oxygen vacancy engineering of nanomaterials could regulate their photothermal conversion performances, promoting the further application of TiO2-based nanomaterials in the biomedical.

Nootkatone alleviates rotenone-induced Parkinson's disease symptoms through activation of the PI3K/Akt signaling pathway.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Nootkatone (NKT) has been shown to have neuroprotective, anti-inflammatory, and antioxidant effects and in this study, we systematically studied the efficacy and mechanism of action of NKT in rotenone (ROT)-induced PD rats. Firstly, through behavioral experiments and brain tissue staining, we found that NKT alleviated behavioral dysfunction and protected dopaminergic neurons associated with ROT-induced PD rats. Next, target prediction, protein-protein interaction (PPI), Gene Ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of NKT for the potential treatment of PD. Furthermore, we also applied molecular docking to predict the binding capacity of NKT and related targets. Additionally, in vivo experiments confirmed that NKT could inhibit the expression of Mitogen-activated protein kinase 3 (MAPK3) by activating the PI3K/Akt signaling pathway, reducing neuroinflammation, and ultimately ameliorating ROT-induced PD symptoms. Taken together, the results of the study provide a clear explanation for the remission of PD symptoms by NKT, suggesting that it may be a promising candidate for the treatment of PD.

[Spectrum-effect relationship of the blood-activating efficacy of Notoginseng Radix et Rhizoma].

This study aims to establish the high-performance liquid chromatography(HPLC) fingerprints of different batches of Notoginseng Radix et Rhizoma, determine their pharmacodynamic indexes of promoting blood circulation, and explore the spectrum-effect relationship between the chemical components of Notoginseng Radix et Rhizoma and the efficacy of promoting blood circulation. Firstly, the HPLC fingerprints of different batches of Notoginseng Radix et Rhizoma were established. Then, the pharmacodynamic indexes were determined after the capillary coagulation experiment and the cerebral ischemia-reperfusion in rats, including capillary coagulation time, percentage of cerebral ischemic area, cerebral water loss rate, and brain-body index. Afterward, the partial least-squares method was used to explore the spectrum-effect relationship between the chemical components of Notoginseng Radix et Rhizoma and the pharmacodynamic indexes. The results showed that this study successfully established the HPLC fingerprints of different batches of Notoginseng Radix et Rhizoma, found 23 common peaks, and identified 12 of them, all of which were saponins. The method was proved stable and reliable. Both the capillary coagulation experiment and the middle cerebral artery occlusion(MCAO)-induced cerebral ischemia-reperfusion experiment on rats revealed that there were obvious differences in the pharmacodynamic indexes of different batches of Notoginseng Radix et Rhizoma. The relationships between 23 common components of Notoginseng Radix et Rhizoma in different batches and the pharmacodynamic indexes were discussed by means of spectrum-effect correlation analysis, of which 17 components had positive effects while 6 components had negative effects on the pharmacodynamic indexes. This study provides a certain reference basis for the clinical rational use and quality control of Notoginseng Radix et Rhizoma.

[Spectrum-effect relationship of hemostatic effects of Notoginseng Radix et Rhizoma with different commodity specifications].

This article aims to establish the fingerprints, determine the hemostatic pharmacodynamic indicators, and explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in 12 different specifications. Firstly, HPLC and liquid chromatography-mass spectrometry(LC-MS) were employed to establish the fingerprints of Notoginseng Radix et Rhizoma. The rat plasma recalcification experiment and the rat gastric bleeding experiment were conducted to determine the pharmacodynamic indicators, including plasma recalcification time(PRT), thrombin time(TT), prothrombin time(PT), and activated partial thromboplastin time(APTT). Afterwards, the partial least squares method was employed to explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in different specifications. Twenty-six common peaks were detected in the HPLC fingerprints of different specifications of Notoginseng Radix et Rhizoma, and 11 out of the 26 common peaks represented saponins. The content of dencichine was determined by LC-MS. The rat experiments showed that the pharmacodynamic indicators were significantly different among different specifications of Notoginseng Radix et Rhizoma. The spectrum-effect relationship was explored between 27 common components and pharmacodynamic indicators. Among them, 16 components had positive effects on the pharmacodynamic indicators of Notoginseng Radix et Rhizoma, and 11 exerted negative effects. This study provides a basis for the precision medication and quality control of Notoginseng Radix et Rhizoma.

Anthocyanins in Lycium ruthenicum Murray reduce nicotine withdrawal-induced anxiety and craving in mice.

Lycium ruthenicum Murray is widely used in traditional Chinese medicine and is believed to have antimicrobial, antioxidant, and anti-fatigue effects. Anthocyanins are considered to be one of the main active components. The previous work by our research team found that the anthocyanins in Lycium ruthenicum extract (ALRM) produce a stable anti-anxiety effect. The mechanisms of action include reducing the level of corticotropin-releasing factor (CRF) as well as regulating extracellular signal-regulated kinase/mitogen activation, protein kinase (ERK/MAPK) pathways, and others, all of which are related to the mechanisms of nicotine addiction. To investigate the effects of ALRM on anxiety and craving behavior after nicotine withdrawal, the components of ALRM were analyzed using the UPLC-Orbitrap MS method. The effects of ALRM on anxiety behavior induced by nicotine withdrawal were investigated in mice using the elevated plus maze (EPM) and light-dark box (LDB) tests. The effects of ALRM on craving behavior after nicotine withdrawal were further investigated using the conditional place preference (CPP) test. The EPM and LDB tests demonstrated that ALRM could alleviate the anxiety behavior induced by nicotine withdrawal and reduce nicotine craving in mice. Based on the identified ALRM components, the network pharmacology method was used to predict the mechanism of ALRM alleviating anxiety after nicotine withdrawal in mice. It was speculated that ALRM was involved in the production and transmission of dopamine, choline, and other nervous system functions and exhibited a potential role in treating nicotine addiction.

Nardosinone Alleviates Parkinson's Disease Symptoms in Mice by Regulating Dopamine D2 Receptor.

Nardostachyos Radix et Rhizoma (nardostachys) is the root and rhizome of Nardostachys jatamansi DC. Recent studies have shown that nardostachys may exert an anti-PD effect. In this study, the UHPLC-LTQ-Orbitrap-MS method was used to analyze the brain components of nardostachys in rats. Based on the results of UHPLC-LTQ-Orbitrap-MS analysis, nardosinone was identified to be the most effective anti-PD compound in nardostachys. To further verify this inference, a mouse PD model was established and the effect of nardosinone on PD mice was determined using classic behavioral tests. The results showed that nardosinone was indeed effective for relieving PD symptoms in mice. Moreover, network pharmacology analysis was used to elucidate the mechanism underlying the anti-PD effect of nardosinone. Dopamine receptor D2 (DRD2) was identified as the key target of nardosinone-PD interaction network, which was further verified by molecular docking and Western blotting. The results demonstrated that nardosinone and DRD2 could interact with each other. Furthermore, the expression level of DRD2 was decreased in the brain tissue of PD mice, and nardosinone could restore its expression to a certain extent. In conclusion, our findings suggest that nardosinone may reduce the motor and cognitive symptoms in the animal PD model by regulating DRD2 expression.

Discovery and proteomics analysis of effective compounds in Valeriana jatamansi jones for the treatment of anxiety.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhizhu Xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. However, there have been few investigations to clarify the compounds in ZZX for the treatment of anxiety. AIM OF THE STUDY: Our previous study has identified five anti-anxiety components, including hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C and chlorogenic acid, from extract of ZZX. In order to find the optimal combination and the underlying mechanism of these five components in the treatment of anxiety disorder, researches were designed based on uniform design method and proteomic technology. MATERIALS AND METHODS: The samples with different proportion and content of the five active components were arranged by uniform design method. Then a mathematical model was formulated using partial least square method and stepwise regression analysis. Moreover, the empty bottle stress-induced anxiety rat model was established, and the anti-anxiety effect was recorded by the unconditioned reflex elevated maze test and the open field test. In addition, the isobaric tags for relative and absolute quantitation (iTRAQ) technique, along with the multidimensional liquid chromatography and high-resolution mass spectrometry were applied in proteomic study. At last, the result of proteomic analysis was further confirmed by Western blot. RESULTS: The optimal combination of the components from the extract of ZZX was 1.153 mg/kg hesperidin, 2.197 mg/kg Isochlorogenic acid A, 0.699 mg/kg Isochlorogenic acid B and 1.249 mg/kg Chlorogenic acid. Total 6818 proteins were identified using proteomic analysis and 80 differentially expressed proteins were used for further bioinformatic analysis. These proteins were involved in the neuroactive ligand-receptor interaction, protein digestion and absorption, cholesterol metabolism, Chagas disease, and AGE/RAGE signaling pathway. CONCLUSIONS: The composition and proportion of anti-anxiety components in extract of ZZX was disclosed, and there was an anti-anxiety effect for the combined components of flavonoids and phenolic acids. Through proteomic analysis and Western blot, it was found that the effective components of extract of ZZX can exert synergistic anti-anxiety effects via the regulation of multi-signaling pathways. These findings could provide a preliminary research basis for the development of new low-toxic, efficient, stable and controllable anti-anxiety drugs.

Anxiolytic Effect of Alcohol-Water Extracted Suanzaoren-Wuweizi Herb-Pair by Regulating ECS-BDNF-ERK Signaling Pathway Expression in Acute Restraint Stress Male Rats.

Herb-pairs are the basic units of composition in Chinese herbal formulae, where the bridge linking Chinese medicine and prescription consists of two Chinese medicine herbs. The Suanzaoren-Wuweizi herb-pair (SWHP) is commonly used as a sedative or tranquilizer. SWHP has been demonstrated to exert an antianxiety effect in animal models of anxiety. However, little information about its mechanism is available and the effects of SWHP have not been investigated. This study examined the effects of SWHP on ameliorating anxiety-like behaviors by regulating endocannabinoids system (ECS)-brain-derived neurotrophic factor (BDNF)-extracellular regulated protein kinases (ERK) signaling pathway expression, induced by restraint stress (RS) procedures. The antianxiety effects of SWHP on RS rats were then examined through the open-field test (OF) and the elevated plus maze test (EPM). The concentration of BNDF, ERK1/2, p-ERK1/2, cAMP-response element binding protein (CREB), and p-CREB expression in the prefrontal cortex and hippocampus of the rats was then measured by western blot. The number of positive cells of CB1 and CB2 in the rats' hippocampus CA1 region was measured by immunohistochemistry. These results gave compelling evidence that SWHP could modify anxiety-like behaviors of RS rats through regulation of the ECS-BDNF-ERK signaling pathway. Our study demonstrated that SWHP improved anxiety-like behaviors in RS rat models by regulating the ECS-BDNF-ERK signaling pathway. The findings indicate that SWHP may have a therapeutic application in the RS model of anxiety disorder, which proposes a potential new direction for research into anxiety disorders regarding mechanisms and the development of novel antianxiety drugs.

[Effect of Lanthanum on accumulation of active constituent and key enzymes expression of Salvia miltiorrhiza hairy root].

The effect of Lanthanum on the accumulation of active constituent and key enzymes expression of Salvia miltiorrhiza hairy root were studied and furthermore signaling molecules mediating the synthesis of secondary metabolism was also defined in order to provide references for the reveal of synthesis mechanism of active constituent of S. miltiorrhiza hairy root inducing by Lanthanum. The content of active constituents were detected by HPLC. RNA was extracted with RNA prep Pure RNA purification kit (Tiangen). The results shows that LaCl3 processing promoted the accumulation of tanshinones and phenolic acids in S. miltiorrhiza hairy root. The accumulation of phenolic acids reached the highest at 9 d after treatment, and tanshinones accumulation continued to increase in 15 days. Accumulation of active substance in S. miltiorrhiza may relate with FPPS, TAT, HPPR several key enzyme activation.

[Study on Commercial Specification of Lonicerae Japonicae Flos].

OBJECTIVE: To provide the basis data for the institute of commercial specification standard of Lonicerae Japonicae Flos. METHODS: 39 samples of Lonicerae Japonicae Flos commercial of different grades in market were collected, and vernier caliper and electronic balance were used to measure the numbers of flower bud and blooming rate per 0. 5 g, contamination content, browning degree, milden and rot, length, upside diameter, middle diameter and bottom diameter of Lonicerae Japonicae Flos. The content of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, galuteolin,3,5-icaffeoylquinic acid and 4,5-dicaffeoylquinic acid were detected by HPLC. Correlation analysis, principal component analysis and cluster analysis were used by SPSS to analyze all index data,and the correlation of appearance characteristics and intrinsic active constituents was discussed. RESULTS: The numbers of flower bud and blooming rate per 0. 5 g, contamination content and browning degree were principal component indexes. The length of flower bud showed a significant correlation with galuteolin content, and the browning degree and upside diameter showed a significant correlation with chlorogenic acid content. CONCLUSION: Lonicerae Japonicae Flos commercial should be divided into four specification grades by sieved indexes.

[Effect of smoke water and distillation liquid on the seed germination and seedling growth of Trichosathes kirilowii].

Smoke water and distillation liquid were used to treat the seeds of Trichosathes kirilowii and to study the effects of smoke water and distillation liquid on the seed germination and seedling growth of T. kirilowii. The results showed that germination rate, germination index and germination vigor of T. kirilowii all were significantly improved with the treatment of SW and DL treatment. The activity of α-amylase were significantly increased with the treatment of SW and DL at 1:2,000. SW and DL treatment showed no significant effects on the activity of SOD. The activity of POD were markedly enhanced under the treatment of SW (1:000) and DL (1:2,000). CAT activity were increased with the treatment of SW and DL at 1:2,000 while were inhibited by SW and DL at 1:500. Seedling height and root length were increased with the treatment of SW and DL (1:1,000, 1:2,000). SW and DL treaments improved the content of chlorophyll, and moreover with the concentration of SW and DL, the stimulatory were also increased. This work demonstrated that smoke water and diatillation liquid at 1:2,000 could stimulate the seed germination and seedling growth of T. kirilowii, and it provided the references for the study of seed germination technology.

[Comparison on surface ultrastructure characteristic and drought resistance of different Trichosanthes kirilowii strains].

Trichosanthes kirilowii has been widely cultivated as its medicinal use, health care and food value. Drought resistance of seedlings is an important feature in breeding. Seeds of two T. kirilowii strains were used to research the difference of surface ultrastructure characteristic and drought resistance. Scanning electron microscope was used to identify the surface ultrastructure characteristic of seeds and PEG was used to simulate drought stress. The seeds germination rate, MDA content, chlorophyll content and the antioxidant enzymes activity were measured under the drought stress. The results showed that the seed surface colour of KXY-001 was lighter than that of KXY-005. The testa cobwebbing of KXY-001 was more intensive than that of KXY-005. The germination rate of KXY-001 was higher than that of KXY-005 under drought stress. The MDA content was increased and the chlorophyll content was decreased with the increasing of drought degree. The SOD activity of KXY-001 was higher than that of KXY-005, while the activity of POD and CAT was also increased firstly and decreased later. Surface reticulate of seeds and hilar traits can be used as identification points to identify the investigated strains. SOD and POD are activated to resist drought in T. kirilowii seedlings and the drought resistance of KXY-001 is superior than that of KXY-005.

[Influence of Lepidium meyemii walp on lipid and bone mass in ovariectomized rats].

OBJECTIVE: To observe the potential effects of Lepidium meyemii Waip (MACA) on body fat, sexual hormone, bone metabolism in post-ovariectomized rats. METHOD: Healthy Sprague-Dawley rats were randomly divided into 6 groups: sham operated group, ovariectomized model group (OVX), OVX + estrogen treated group (0.3 g/kg), OVX + Maca low dose treated group (0.3 g/kg), OVX + Maca middle dose treated group (0.6 g/kg) and OVX + Maca high dose treated group (1.8 g/kg). After 7 weeks treated the rats were sacrificed, the body weight, uterus and adrenal gland weight were measured, the blood lipids, sexual hormone, bone metabolism were analyzed. RESULTS: In ovariectomized model group (GYX) the level of estrogen, progesterone, testosterone and the weigh of uterine and adrenal were decreased, the body weight gain, serum lipid and the activities of alkaline phosphatase (ALP) were increased (compared with sham operated group, P < 0.01), though the change of femoral bone density and mineral content was not observed. The blood estrogen and BPG level were increased in OVX + MACA high dose treated group, and had less uterine weight loss and body weight gain, while, the triglyceride, LDL-C and ALP level were similar to sham operated group. CONCLUSION: Dietary supplementation with Maca may have potential effects on prevention from poatmenopausal lipid abnormality and bone metabolism via a different mechanism from estrogen.

Effects of yogurt supplementation on the growth of preschool children in Beijing suburbs.

OBJECTIVE: To investigate the effect of yogurt supplementation on the growth of preschool children in Beijing suburbs. METHODS: Four hundred and two preschool children (217 males, 185 females), aged 3-5 years, whose height for age and/or weight for age were less than the reference level, were selected as subjects from 7 kindergartens in Beijing Fangshan District. The subjects were divided randomly into control group (CG, 201) and yogurt supplemented group (YG, 201). Each subject in YG was given one serving of yogurt (125 g) for 5 days a week from March to December in 2001, while nothing additional was provided to CG. All subjects kept their usual diet during the study. Anthropometry (body height and weight and upper-arm circumference) and the bone mineral density (BMD) of forearm were measured every 3 months. Disease status and dietary intake were also recorded and assessed. RESULTS: The intake of calcium, zinc, and vitamin B2 in YG was significantly higher than that in CG. The incidence and duration of upper-respiratory infection and diarrhea of children in YG were significantly less than those in CG. The height gain of children in YG was significantly higher than that in CG after yogurt was supplemented for 3, 6, and 9 months (P<0.05) (1.90+/-0.49 cm vs 1.77+/-0.54 cm, 3.83+/-0.57 cm vs 3.64+/-0.66 cm and 5.43+/-0.69 cm vs 5.24+/-0.76 cm, respectively). The weight gain of children in YG was significantly higher than that in CG after yogurt was supplemented for 3, 6, and 9 months (P<0.05) (0.70+/-0.43 kg vs 0.49+/-0.35 kg, 0.98+/-0.62 kg vs 0.80+/-0.60 kg and 1.42+/-0.76 kg vs 1.20+/-0.67 kg, respectively). The BMD of children in YG was significantly higher than that in CG after yogurt was supplemented for 9 months (P<0.05) (0.415+/-0.058 g/cm2 vs 0.400+/-0.065 g/cm2). CONCLUSION: Yogurt is beneficial to the improvement of calcium, zinc, and vitamin B2 intake, the decreasing of the incidence and duration of upper-respiratory infection and diarrhea, and the promotion of the health and the growth and development of preschool children.

Effect of micronutrient supplementation on the growth of preschool children in China.

OBJECTIVE: To study the relationship between micronutrient supplementation and children growth. METHODS: A double-blind, placebo-controlled trial was conducted in 156 growth retarded preschool children. They were randomly assigned to five groups: supplemental control (S-control, n = 28), zinc supplementation (+Zn, 3.5 mg Zn/day, n = 34), zinc and calcium supplementation (+ZnCa, 3.5 mg Zn + 250 mg Ca/day, n = 37), zinc and calcium and vitamin A supplementation (+ZnCaVA, 3.5 mg Zn + 250 mg Ca + 200 g VA/day, n = 28), Calcium, and vitamin A supplementation (+CaVA, 250 mg Ca + 200 g VA/day, n = 29). Another 34 children with normal height were selected as normal control (N-control). Supplementation continued for twelve months. RESULTS: The height gain in +Zn group (7.84 cm per year) and +ZnCa group (7.70 cm per year) was significantly higher than that in S-control group (6.74 cm per year, P < 0.05); The weight gain in +ZnCaVA group (2.55 kg per year) and +CaVA group (2.57 kg per year) was also significantly higher than that in S-control group (2.19 kg per year, P < 0.05); The average days of illness in each supplementation group were lower than that in S-control (13 days per year compared with 23 days per year). No significant difference was observed on bone age. CONCLUSION: Zinc and Zinc + Calcium supplementation can improve the height gain, and vitamin A can improve weight gain in growth retarded preschool children, but do not affect the maturity of bone. Micronutrient supplementation can lower the morbidity of these children.