Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

Protective Effect of Alkaline Mineral Water on Calcium Oxalate-Induced Kidney Injury in Mice.

Background: Kidney stone disease induces chronic renal insufficiency by crystal-induced renal tubular epithelial cell injury. It has been reported that the prevalence of kidney stone disease is increasing, accompanied by the high recurrence rate. Alkaline mineral water has been reported to possess beneficial effects to attenuate inflammation. Here, we explored the potential protective effects and underlying mechanisms of alkaline mineral water against calcium oxalate-induced kidney injury. Methods: We performed the mice kidney stone model by administering glyoxylate at 100 mg/kg once daily for 7 days. To assess the effects of alkaline mineral water on oxalate-induced kidney injury, mice drank different water (distilled water, natural mineral water at pH = 8.0, as well as natural mineral water at pH = 9.3) for 7 days, respectively, followed by glyoxylate exposure. After collection, crystal formation, kidney injury and cell apoptosis, fibrosis, oxidative stress, as well as inflammation were measured. Results: Our results showed that glyoxylate treatment led to kidney crystal formation and fibrosis, which can be attenuated by drinking alkaline mineral water. Furthermore, alkaline mineral water also reduced kidney injury and cell apoptosis, oxidative stress, and inflammation. Conclusion: Alkaline mineral water supplement prevents progression of glyoxylate-induced kidney stones through alleviating oxidative stress and inflammation.

Rhynchophylline inhibits methamphetamine dependence via modulating the miR-181a-5p/GABRA1 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (Miq.) Miq. ex Havil. is a plant species that is routinely devoted in traditional Chinese medicine to treat central nervous system disorders. Rhynchophylline (Rhy), a predominant alkaloid isolated from Uncaria rhynchophylla (Miq.) Miq. ex Havil., has been demonstrated to reverse methamphetamine-induced (METH-induced) conditioned place preference (CPP) effects in mice, rats and zebrafish. The precise mechanism is still poorly understood, thus further research is necessary. AIM OF STUDY: This study aimed to investigate the role of miRNAs in the inhibitory effect of Rhy on METH dependence. MATERIALS AND METHODS: A rat CPP paradigm and a PC12 cell addiction model were established. Microarray assays were used to screen and identify the candidate miRNA. Behavioral assessment, real-time PCR, dual-luciferase reporter assay, western blotting, stereotaxic injection of antagomir/agomir and cell transfection experiments were performed to elucidate the effect of the candidate miRNA and intervention mechanism of Rhy on METH dependence. RESULTS: Rhy successfully reversed METH-induced CPP effect and the upregulated miR-181a-5p expression in METH-dependent rat hippocampus and PC12 cells. Moreover, suppression of miR-181a-5p by antagomir 181a reversed METH-induced CPP effect. Meanwhile, overexpression of miR-181a-5p by agomir 181a in combination with low-dose METH (0.5 mg/kg) elicited a significant CPP effect, which was blocked by Rhy through inhibiting miR-181a-5p. Finally, the result demonstrated that miR-181a-5p exerted its regulatory role by targeting γ-aminobutyric acid A receptor α1 (GABRA1) both in vivo and in vitro. CONCLUSION: This finding reveals that Rhy inhibits METH dependence via modulating the miR-181a-5p/GABRA1 axis, which may be a promising target for treatment of METH dependence.

Treatment of endometriosis with dienogest in combination with traditional Chinese medicine: A systematic review and meta-analysis.

Background: Endometriosis is now considered to be a systemic disease rather than a disease that primarily affects the pelvis. Dienogest (DNG) has unique advantages in the treatment of endometriosis, but it also has side effects. Alternatively, Traditional Chinese Medicine (TCM) has been used for over 2000 years in the treatment and prevention of disease and growing numbers of Chinese scholars are experimenting with the combined use of Dienogest and TCM for endometriosis treatment. Objectives: This review evaluated the efficacy and safety of TCM in combination with Dienogest in the treatment of endometriosis through meta-analysis. Methods: MEDLINE, Embase, the Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure, Journal Integration Platform, and Wanfang were used in literature searches, with a deadline of May 31, 2022. Literature quality was assessed using the Cochrane Collaboration "risk of bias" (ROB2) tool, and the "meta" package of R software v.4.1 was used for meta-analysis. Dichotomous variables and continuous variables were assessed using the relative risk (RR) and 95% confidence intervals (95% CI); standard mean differences (MD) and 95% CI, respectively. Results: Twelve human randomized controlled trials (RCTs) and one retrospective study, all 13 written in the Chinese language, were included in the meta-analysis (720 experiments and 719 controls). The result indicated that TCM plus Dienogest was superior to Dienogest/TCM alone in increasing the cure rates (RR = 1.3780; 95% CI, 1.1058, 1.7172; P = 0.0043), remarkable effect rate (RR = 1.3389; 95% CI, 1.1829, 1.5154; P < 0.0001), invalid rate (RR = 0.2299; 95% CI, 0.1591, 0.3322; P < 0.0001), and rate of adverse effects (RR = 0.6177; 95% CI, 0.4288, 0.8899; P = 0.0097). The same conclusion was drawn from the subgroup analysis. Conclusion: Results suggest that TCM combined with Dienogest is superior to Dienogest or TCM alone and can be used as a complementary treatment for endometriosis. TCMs have potential to improve clinical efficacy and reduce the side effects of Dienogest. This study was financially supported by Annual Science and Technology Steering Plan Project of Zhuzhou. PROSPERO has registered our meta-analysis as CRD42022339518 (https://www.crd.york.ac.uk/prospero/record_email.php).

Relationships between urinary metals concentrations and cognitive performance among U.S. older people in NHANES 2011-2014.

Background: Epidemiological evidence on Urine metals and cognitive impairment in older individuals is sparse and limited. The goal of this study was to analyze if there was a link between urinary metal levels and cognitive performance in U.S. people aged 60 and up. Methods: The National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 were utilized in this cross-sectional analysis. Memory function was quantified using the following methods: Established Consortium for Word Learning in Alzheimer's Disease (CERAD-WL) (immediate learning and recall and delayed recall), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). An inductively coupled plasma mass spectrometry (ICP-MS) was used to estimate urine metal concentrations. The connection of Urine metals level with cognitive function was investigated employing binary logistic regression and restricted cubic spline models. Results: A total of 840 participants aged 60 years and over were enrolled in this study. After controlling for confounders, the association between cadmium, barium, cobalt, cesium, manganese, and thallium and poor cognitive performance showed significance in multiple logistic regression compared to the lowest quartile of metals. In the DSST test, the weighted multivariate adjusted ORs (95% CI) for cadmium in the highest quartile, barium and cesium in the third quartile were 2.444 (1.310-4.560), 0.412 (0.180-0.942) and 0.440 (0.198-0.979), respectively. There were L-shaped associations between urine cesium, barium, or manganese and low cognitive performance in DSST. Urine lead, molybdenum and uranium did not show any significant relationships with cognitive impairment, respectively, compared to the respective lowest quartile concentrations. Conclusion: The levels of barium (Ba), cobalt (Co), cesium (Cs), manganese (Mn), and thallium (Tl) in urine were found to be negatively related to the prevalence of impaired cognitive performance in our cross-sectional investigation. Higher cadmium (Cd) levels were associated with cognitive impairment.

Vitamin D supplementation in pregnant women or infants for preventing allergic diseases: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: It is still unclear if and to what extent antenatal or infant or childhood vitamin D supplementation would affect the development of allergy diseases later in life. This study aimed to review the efficacy of vitamin D supplementation in pregnant women, infants, or children for the prevention of allergies. METHODS: MEDLINE (PubMed), EMBASE (OVID), and the Cochrane Central Register of Controlled Trials were searched up to March 1, 2020. We included only randomized controlled trials (RCTs). We performed a systematic review and meta-analysis for vitamin D supplementation in primary allergy prevention. These trials were assessed for risk of bias using the Cochrane Collaboration domains and the consensus was reached via discussion with the full study group. We descriptively summarized and quantitatively synthesized original data to evaluate vitamin D supplementation in primary allergy prevention by using Review Manager software for meta-analysis. RESULTS: The search yielded 1251 studies. Seven RCTs were included in this analysis. A meta-analysis revealed that vitamin D supplementation for pregnant women or infants may not decrease the risk of developing allergic diseases, such as asthma or wheezing (supplementation for pregnant women, risk ratio [RR]: 1.01, 95% confidence interval [CI]: 0.81-1.26, P = 0.90, I2 = 47%; supplementation for infants, RR: 1.00, 95% CI: 0.70-1.43, P = 0.99, I2 = 0%; supplementation for pregnant women and infants, RR: 0.35, 95% CI: 0.10-1.25, P = 0.11), eczema (supplementation for pregnant women, RR: 0.95, 95% CI: 0.80-1.13, P = 0.77, I2 = 0%; supplementation for infants, RR: 0.84, 95% CI: 0.64-1.11, P = 0.19, I2 = 42%), allergic rhinitis (supplementation for pregnant women, RR: 0.93, 95% CI: 0.78-1.11, P = 0.15, I2 = 47%), lower respiratory tract infection (LRTI) (supplementation for pregnant women, RR: 0.97, 95% CI: 0.85-1.11, P = 0.59, I2 = 0%), or food allergy. CONCLUSIONS: Supplementation of vitamin D in pregnant women or infants does not have an effect on the primary prevention of allergic diseases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42020167747).

The Effect of Yijinjing on the Cognitive Function of Patients With Chronic Schizophrenia.

Background: Patients with chronic schizophrenia present cognitive impairment, which affects their social function and prevents them from reintegrating into society. Yijinjing is a traditional Chinese aerobic exercise that has a putative psychosomatic effect on improving cognitive function. Methods: From January to May 2021, 40 patients with chronic schizophrenia were recruited and randomly divided into a control group and a Yijinjing group. In the 12-week intervention, the patients in the control group received conventional treatment, whereas patients in the Yijinjing group performed Yijinjing exercise (40 min/session, twice a week) in addition to receiving conventional treatment. The Positive and Negative Syndrome Scale (PANSS), the Insight and Treatment Attitude Questionnaire (ITAQ), the Rosenberg Self-esteem Scale (SES), and the Mini Mental State Examination (MMSE) were used to measure clinical symptoms and cognitive function at 0, 6, and 12 weeks. Results: The demographic information was not significantly different between groups. At baseline, the scores of all the scales were not statistically different between groups. After 12 weeks of intervention, compared to those at baseline, the scores of the negative scale (t = 19.00, p < 0.0001), general psychopathology scale (t = 15.98, p < 0.0001), and total score (t = 15.47, p < 0.0001) of the PANSS and SES (t = 5.378, p < 0.0001) had significantly decreased, and the scores of the ITAQ (t = 7.984, p < 0.0001) and MMSE (t = 6.750, p < 0.0001) had significantly increased in Yijinjing group; the score of the MMSE increased in the control group as well (t = 2.491, p = 0.0222). Compared to the respective scores in the control group, the negative scale score (t = 2.953, p = 0.0054) significantly decreased, and the ITAQ (t = 3.043, p = 0.0042) and MMSE (t = 2.2.68, p = 0.0291) scores significantly increased in the Yijinjing group after 12 weeks of intervention. Conclusion: These results provide a preliminary indication that Yijinjing exercise had the potential to improve cognitive function and negative symptoms in patients with chronic schizophrenia. A larger-scale study to determine the trajectory of change in the longer term should be undertaken.

Network pharmacology-based exploration of therapeutic mechanism of Liu-Yu-Tang in atypical antipsychotic drug-induced metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is prevalent in patients receiving atypical antipsychotic drugs (AADs), but there are few effective interventions. The Traditional Chinese herbal decoction Liu-Yu-Tang (LYT) has achieved clinical improvement for AAD-induced MetS, but its pharmacological mechanism remains unclear. METHOD: A network pharmacology-based method was utilized in this study. First, the TCMSP and SwissTargetPrediction database were used to acquire plasma-absorbed components and putative targets of LYT, respectively. Second, an interaction network between shared targets of LYT and MetS was constructed using STRING online tool. Topological analyses were performed to extract hub gene targets. Finally, we did a pathway analysis of gene targets using the Kyoto Encyclopedia of Genes and Genomes (KEGG) to find biological pathways of LYT. RESULTS: We obtained 655 putative targets of LYT, 434 known targets of AADs, and 1577 MetS-related gene targets. There are 232 shared targets between LYT and MetS. Interaction network construction and topological analysis yielded 60 hub targets, of which 18 were major hub targets, among which IL-6, IL-8, TNF, PI3K, MAPK, and NF-κB (RELA) are the most important in LYT's treatment of AAD-induced MetS. Pathway enrichment analysis revealed a statistically high significance of the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis and the insulin resistance pathway. CONCLUSIONS: LYT may control activities of the pro-inflammatory cytokines IL-6, IL-8, TNF and the important signal transduction molecules PI3K, MAPKs, and NF-κB (RELA), regulating metabolic disturbance-related pathways like the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis, and the insulin resistance pathway, generating therapeutic effects for AAD-induced MetS.

Polyvinyl alcohol/chitosan composite hydrogels with sustained release of traditional Tibetan medicine for promoting chronic diabetic wound healing.

The Tibetan eighteen flavor dangshen pills (TEP) are composed of 18 traditional Tibetan medicines, which are commonly used in the treatment of skin diseases in the Tibetan medical system. They have anti-inflammatory and analgesic effects, and healing properties. However, TEP contain large doses and have strong side effects and low bioavailability. To improve the utilization rate of TEP in skin treatment, we prepared TEP powder and then introduced it into polyvinyl alcohol/chitosan (PVA/CS) hydrogels to treat diabetic wounds by slowly releasing the active ingredients of TEP. In vitro studies showed that TEP-loaded hydrogels can effectively and continuously release the active ingredients of TEP and have antibacterial and antioxidant properties. In addition, the hydrogel system was not cytotoxic to L929 cells, and significantly promoted the proliferation of HUVECs. Moreover, when the TEP-loaded hydrogel was applied to diabetic wounds in rats, it reduced the inflammatory response and improved collagen deposition, which in turn promoted skin healing. Our results indicate that TEP-loaded hydrogels may be a new formulation for the application of traditional Tibetan medicines for the treatment of chronic wounds.

Altered anxiety and social behaviors in a mouse model of Fragile X syndrome treated with hyperbaric oxygen therapy.

Fragile X syndrome (FXS) is a common mental retardation syndrome. Anxiety and abnormal social behaviors are prominent features of FXS in humans. To better understand the effects of hyperbaric oxygen therapy (HBOT) on these behaviors, we analyzed anxiety-related and social behaviors in Fmr1 knockout mice treated by HBOT. In the open field test, HBOT group mice preferred the periphery to central areas and tended to run or walk along the wall. The results suggested that thigmotaxis was significantly increased in the HBOT group compared with the control group. In the elevated plus maze test, the percentage of distance traveled was significantly increased in the open arm and significantly decreased in the closed arm for HBOT group mice compared with control group mice. These results suggested that HBOT group mice displayed enhanced motor activity in the open arm and exhibited fewer anxiety-related behaviors. In the three-chambered social approach test, the HBOT group mice made more approaches to the wire cup containing an acquaintance mouse than control group mice in the sociability test and made more approaches to the wire cup containing a stranger mouse than control group mice in the social novelty preference test. The results suggested that HBOT group mice showed increased levels of social interaction and decreased "social anxiety" than the control group to partner mice in this test. Our findings indicated that HBOT resulted in altered anxiety and social behavior in Fmr1 knockout mice and could possibly be used as a treatment for FXS.

Comparison of anti-inflammatory effects of berberine, and its natural oxidative and reduced derivatives from Rhizoma Coptidis in vitro and in vivo.

BACKGROUND: Berberine (BBR) is the most abundant and major active constituent of Rhizoma Coptidis (RC), which has been widely used to treat inflammatory diseases in traditional oriental medicine. Despite BBR has been found to exhibit pronounced anti-inflammatory effect, the anti-inflammatory activities of its natural derivatives were sparsely dissected out. PURPOSE: To comparatively investigate the anti-inflammatory potential of BBR, and its natural oxoderivative (oxyberberine, OBB) and reduced derivative (dihydroberberine, DHBB) in vitro and in vivo, and delineate the possible underlying mechanism. METHODS: LC-MS/MS was used to identify the natural derivatives of BBR in RC. The potential anti-inflammatory properties of BBR and its natural derivatives were comparatively evaluated in vitro by lipopolysaccharide (LPS)-induced RAW264.7 macrophages cells, and in vivo via three typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by ELISA, qRT-PCR and Western blotting. RESULTS: LC-MS/MS led to the identification of BBR, OBB and DHBB in RC ethyl acetate extract. The in vitro assay indicated that BBR, OBB and DHBB (1.25, 2.5 and 5 µM) pretreatment significantly decreased the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and nitricoxide (NO), and inhibited the mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitricoxide synthase (iNOS) in a dose-dependent manner, with relative efficiency of OBB > BBR > DHBB. Furthermore, OBB, BBR and DHBB remarkably inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 and inhibitory kappa Bα (IκBα). In vivo, BBR (20 mg/kg) and OBB (5, 10, and 20 mg/kg) pretreatment significantly ameliorated the xylene-induced ear edema, carrageenan-stimulated paw edema, and acetic acid-elicited vascular permeability in mice in a dose-dependent manner, with OBB exhibiting superior anti-inflammatory effect at the same dose (20 mg/kg). Histopathological analysis indicated that OBB and BBR could markedly attenuate the inflammatory deterioration and decrease the cellular infiltration in paw tissues. Additionally, the carrageenan-induced increases in TNF-α, IL-6, IL-1ß, PGE2 and NO productions, and COX-2 and iNOS mRNA expressions were effectually and concentration-dependently suppressed by OBB and BBR pretreatment. CONCLUSION: The anti-inflammatory activity of BBR and its natural derivatives was in the order of OBB > BBR > DHBB. OBB was for the first time found to be endowed with pronounced anti-inflammatory property, which was probably associated with suppressing the activation of NF-κB signaling pathway, and the subsequent gene expressions and productions of pro-inflammatory mediators. The results might contribute to illuminating the pharmacodynamic underpinnings of RC and provide evidence for developing OBB as a safe and promising natural lead compound in inflammation treatment.

Are personalized tongxie formula based on diagnostic analyses more effective in reducing IBS symptoms?-A randomized controlled trial.

OBJECTIVES: To examine the efficacy and safety ofpersonalized tongxie formulas; to decrease type II errors to minimum. METHODS: Patients were randomized (1:1:1) into three groups given tongxie, placebo, or pinaverium 3 times daily for 4 weeks. Patients in the tongxie group were treated with personalized formulas based on TCM differential diagnosis, i.e., basic type of IBS, IBS due to liver depression and qi stagnation, excess heat in the liver, deficient spleen function, deficient kidney function, and others (groups 1-6). Primary endpoints were significantly greater reductions in abdominal pain and Bristol stool score. Secondary endpoints were reductions in pain and stool frequencies and abdominal discomfort and its frequency. RESULTS: There were significantly more patients whose stool consistencies were improved than pains were relieved in the entire population (p < 0.001), but there was no significantly difference in subpopulation group 3 (p > 0.05). There were significantly more patients whose stool frequencies were reduced than pain frequencies were reduced in the entire population (p < 0.001), but there were no significantly difference in the subpopulation Groups 1, 3, 4, and 6 (p > 0.05). Multiple active ingredients and their mechanisms of actions to relieve IBS symptoms were identified. CONCLUSION: The outcomes in subpopulations may be different from those of the entire population, indicating that personalized formulas are important to achieve optimal outcomes; the active ingredients and innovative mechanisms identified in this study can be the candidates for developing new IBS drugs, and used to manage IBS, respectively. TRIAL REGISTRATION: NCT01641224 (www.ClinicalTrials.gov).

Expression of miRNAs in Serum Exosomes versus Hippocampus in Methamphetamine-Induced Rats and Intervention of Rhynchophylline.

OBJECTIVE: To compare the expressions of miRNAs (microRNAs) in serum exosomes and in hippocampus and to provide insights into the miRNA-mediated relationship between peripheral and central nervous systems in the presence of methamphetamine. METHODS: Published results on conditioned place preference (CPP) in rats conditioned by methamphetamine were replicated. The expressions of miRNAs in serum exosomes and hippocampus were determined by gene-chip sequencing. We then predicted the potential target genes of selected, differentially expressed (DE) miRNAs and then carried out functional analysis of these target genes. We also verified our results by RT-qPCR. RESULTS: Methamphetamine reward could greatly increase the activity time and distance in the intrinsically nonpreferred side of the behavioral apparatus compared with control rats (P < 0.01). Rhynchophylline treatment significantly counteracted these changes (P < 0.01). Methamphetamine-induced CPP upregulated 23 miRNAs (log2 fold change [FC] > 1, P < 0.01) in serum exosomes, whereas rhynchophylline treatment could downregulate these miRNAs (log2 FC < -1, P < 0.01). Analysis of hippocampal miRNAs profiles found 22 DE miRNAs (log2 FC > 1 or <-1, P < 0.01). When methamphetamine induced CPP, 11 of those miRNAs were upregulated, whereas rhynchophylline treatment could downregulate these miRNAs. The other 11 miRNAs behaved in the opposite way. We selected six DE miRNAs from each of serum exosomes and hippocampus for target gene prediction and functional analysis. We found that, in both, the DE miRNAs and their target genes may be related to neuronal information transmission and synaptic transmission. CONCLUSIONS: Rhynchophylline blocked the alteration of behavior and the expression of some DE miRNAs induced by methamphetamine. The biological functions of these DE miRNAs target genes are correlated between serum exosomes and hippocampus. As to these biological processes and pathways which are involved in the development of addiction at multiple stages, we speculate that these DE miRNAs in serum exosomes and hippocampus are closely related to methamphetamine addiction.

Efficacy of sequential therapies with sorafenib-sunitinib versus sunitinib-sorafenib in metastatic renal cell carcinoma: A systematic review and meta-analysis.

The most efficient sequence of targeted agents for metastatic renal cell carcinoma patients has yet to be identified. Whether the sequence of sorafenib and sunitinib really matters is controversial and not answered clearly until now. This meta-analysis aims to estimate the efficacy of receptor tyrosine kinase inhibitors sorafenib-sunitinib and sunitinib-sorafenib for metastatic renal cell carcinoma, on the outcome of first-line progression-free survival, second-line progression-free survival, total progression-free survival and overall survival.We searched PubMed, Embase, Cochrane Library and ClinicalTrails.gov for eligible studies. Data were analyzed using random or fixed effects model depending on the heterogeneity of the eligible studies. Heterogeneity across studies were analyzed using Q and I2 statistics.Of 902 identified studies, ten were qualified in our analysis (N = 1732 patients). Sorafenib-sunitinib yielded no statistically significant benefit in first-line progression-free survival (fixed effects; HR = 0.95; 95%CI 0.75-1.21; p = 0.702), total progression-free survival (random effects; HR = 0.92; 95%CI 0.71-1.19; p = 0.531) and overall survival (fixed effects; HR = 0.89; 95%CI 0.72-1.09; p = 0.257), compared with sunitinib-sorafenib. Second-line progression-free survival was longer for sorafenib-sunitinib than sunitinib-sorafenib (fixed effects; HR = 0.55; 95%CI 0.44-0.68; p = 0.000).Sequential therapies with sorafenib and sunitinib is well tolerated and efficient in mRCC. However, there are no evidence supported that sorafenib-sunitinib has the superiority to sunitinib-sorafenib in sequence. The ideal sequence of targeted agents requires further elucidation.

Point application with Angong Niuhuang sticker protects hippocampal and cortical neurons in rats with cerebral ischemia.

Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological functions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris and Realgar), we used transdermal enhancers to deliver Angong Niuhuang pill by modern technology, which expanded the safe dose range and clinical indications. In this study, Angong Niuhuang stickers administered at different point application doses (1.35, 2.7, and 5.4 g/kg) were administered to the Dazhui (DU14), Qihai (RN6) and Mingmen (DU4) of rats with chronic cerebral ischemia, for 4 weeks. The Morris water maze was used to determine the learning and memory ability of rats. Hematoxylin-eosin staining and Nissl staining were used to observe neuronal damage of the cortex and hippocampal CA1 region in rats with chronic cerebral ischemia. The middle- and high-dose point application of Angong Niuhuang stickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efficacy similar to interventions by electroacupuncture at Dazhui (DU14), Qihai (RN6) and Mingmen (DU4). Our experimental findings indicate that point application with Angong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efficacy to acupuncture.

Effect of rhynchophylline on the expression of p-CREB and sc-Fos in triatum and hippocampal CA1 area of methamphetamine-induced conditioned place preference rats.

To explore the effect of rhynchophylline (Rhy) on the expression of p-CREB and c-Fos in the striatum and hippocampal CA1 area of methamphetamine-induced conditioned place preference (CPP) rat, methamphetamine (2 mg/kg) was injected to rats and the conditioned place preference was observed in these rats treated with or without Rhy. An immunohistochemistry assay was used to determine the expression of p-CREB and c-Fos in the striatum and hippocampal CA1 area. Methamphetamine induced significant behavior alteration in CPP, while after pretreatment with rhynchophylline or ketamine, the time of staying in methamphetamine-paired compartment of rats was significantly reduced. Methamphetamine also increased the number of p-CREB positive cells in the striatum and hippocampal CA1 zone, as well as p-Fos positive cells. However, the compound Rhy could attenuate the effect. These findings show that Rhy can suppress the acquisition of CPP in rats induced by methamphetamine and the action may be related with the reduced expression of p-CREB and p-Fos in the striatum and hippocampus.

Preparative separation of spirobisnaphthalenes from endophytic fungus Berkleasmium sp. Dzf12 by high-speed counter-current chromatography.

High-speed counter-current chromatography (HSCCC) was applied for the first time for the preparative separation of spirobisnaphthalenes from a crude extract of the endophytic fungus Berkleasmium sp. Dzf12, associated with the medicinal plant Dioscorea zingiberensis. Six spirobisnaphthalenes were successfully separated by HSCCC with a two-phase solvent system composed of n-hexane-chloroform-methanol-water (1.5:3.0:2.5:2.0, v/v). About 18.0 mg of diepoxin κ (1), 245.7 mg of palmarumycin C13 (2), 42.4 mg of palmarumycin C16 (3), 42.2 mg of palmarumycin C15 (4), 32.6 mg of diepoxin δ (5), and 22.3 mg of diepoxin γ (6) with purities of 56.82, 71.39, 76.57, 75.86, 91.01 and 82.48%, respectively, as determined by high-performance liquid chromatography (HPLC), were obtained from 500 mg of the crude extract in a one-step elution within 7 h of separation procedure by HSCCC. The purified spirobisnaphthalenes were further structurally characterized by means of physicochemical and spectrometric analysis.

Phenolic compounds from Halimodendron halodendron (Pall.) voss and their antimicrobial and antioxidant activities.

Halimodendron halodendron has been used as forage in northwestern China for a long time. Its young leaves and flowers are edible and favored by indigenous people. In this study, eleven phenolic compounds were bioassay-guided and isolated from the aerial parts of H. halodendron for the first time. They were identified by means of physicochemical and spectrometric analysis as quercetin (1), 3,5,7,8,4'-pentahydroxy-3'-methoxy flavone (2), 3-O-methylquercetin (3), 3,3'-di-O-methylquercetin (4), 3,3'-di-O-methylquercetin-7-O-ß-d-glucopyranoside (5), isorhamentin-3-O-ß-d-rutinoside (6), 8-O-methylretusin (7), 8-O-methylretusin-7-O-ß-d-glucopyranoside (8), salicylic acid (9), p-hydroxybenzoic acid (ferulic acid) (10), and 4-hydroxy-3-methoxy cinnamic acid (11). They were sorted as flavonols (1-6), soflavones (7 and 8), and phenolic acids (9-11). Among the compounds, flanools 1-4 revealed a strong antibacterial activity with minimum inhibitory concentration (MIC) values of 50-150 µg/mL, and median inhibitory concentration (IC(50)) values of 26.8-125.1 µg/mL. The two isoflavones (7 and 8) showed moderate inhibitory activity on the test bacteria. Three phenolic acids (9, 10 and 11) showed strong antibacterial activity with IC(50) values of 28.1-149.7 µg/mL. Antifungal activities of the compounds were similar to their antibacterial activities. All these phenolic compounds showed significant antimicrobial activity with a broad spectrum as well as antioxidant activity based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and ß-carotene-linoleic acid bleaching assays. In general, the flavonol aglycones with relatively low polarity exhibited stronger activities than the glycosides. The results suggest the potential of this plant as a source of functional food ingredients and provide support data for its utilization as forage as well.

[Study on chemical constituents of the ethyl acetate extract from Blumea aromatica].

OBJECTIVE: To study the chemical constituents of the ethyl acetate extract from Blumea aromatica. METHODS: Column chromatographic techniques were used for the isolation and purification. Spectroscopic techniques were used for the identification of structures. RESULTS: Seven compounds were isolated from the ethyl acetate extract of 80% alcohol extract of the whole plant, and their structures were identified as xanthoxylin(1), dibutyl phthalate(2), luteolin-3',4',7-trimethyl ether(3), rubiadin(4), eriodictyol(5), kaempherol(6), luteolin 7,3'-dimethyl ether(7). CONCLUSION: All the compounds are isolated from this plant for the first time. Among them, compounds 2,4 and 7 are isolated from this genus for the first time.