Glutamine Supplementation as an Anticancer Strategy: A Potential Therapeutic Alternative to the Convention.

Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into the intricate dynamics surrounding both glutamine antagonism strategies and glutamine supplementation within the context of cancer treatment, emphasizing the critical role of glutamine metabolism in cancer progression and therapy. Glutamine antagonism, aiming to disrupt tumor growth by targeting critical metabolic pathways, is challenged by the adaptive nature of cancer cells and the complex metabolic microenvironment, potentially compromising its therapeutic efficacy. In contrast, glutamine supplementation supports immune function, improves gut integrity, alleviates treatment-related toxicities, and improves patient well-being. Moreover, recent studies highlighted its contributions to epigenetic regulation within cancer cells and its potential to bolster anti-cancer immune functions. However, glutamine implementation necessitates careful consideration of potential interactions with ongoing treatment regimens and the delicate equilibrium between supporting normal cellular function and promoting tumorigenesis. By critically assessing the implications of both glutamine antagonism strategies and glutamine supplementation, this review aims to offer comprehensive insights into potential therapeutic strategies targeting glutamine metabolism for effective cancer management.

Regulation of main ncRNAs by polyphenols: A novel anticancer therapeutic approach.

BACKGROUND: Plant polyphenols have shown promising applications in oncotherapy. Increasing evidence reveals that polyphenols possess the antitumor potential for multiple cancers. Non-coding RNAs (ncRNAs), mainly including small ncRNAs (microRNA) and long ncRNAs (lncRNAs), play critical roles in cancer initiation and progression. PURPOSE: To establish the modulation of ncRNAs by polyphenols as a novel and promising approach in anticancer treatment. STUDY DESIGN: The present research employed ncRNA, miRNA, lncRNA, and regulatory mechanism as keywords to retrieve the literature from PubMed, Web of Science, Science direct, and Google Scholar, in a 20-year period from 2003 to 2023. This study critically reviewed the current literature and presented the regulation of prominent ncRNAs by polyphenols. A comprehensive total of 169 papers were retrieved on polyphenols and their related ncRNAs in cancers. RESULTS: NcRNAs, mainly including miRNA and lncRNA, play critical roles in cancer initiation and progression, which are potential modulatory targets of bioactive polyphenols, such as resveratrol, genistein, curcumin, EGCG, quercetin, in cancer management. The mechanism involved in polyphenol-mediated ncRNA regulation includes epigenetic and transcriptional modification, and post-transcriptional processing. CONCLUSION: Regulatory ncRNAs are potential therapeutic targets of bioactive polyphenols, and these phytochemicals could modulate the level of these ncRNAs directly and indirectly. A better comprehension of the ncRNA regulation by polyphenols in cancers, their functional outcomes on tumor pathophysiology and regulatory molecular mechanisms, may be helpful to develop effective strategies to fight the devastating disease.

Combination L-Glutamine with Gemcitabine and Nab-Paclitaxel in Treatment-Naïve Advanced Pancreatic Cancer: The Phase I GlutaPanc Study Protocol.

Advanced pancreatic cancer is underscored by progressive therapeutic resistance and a dismal 5-year survival rate of 3%. Preclinical data demonstrated glutamine supplementation, not deprivation, elicited antitumor effects against pancreatic ductal adenocarcinoma (PDAC) alone and in combination with gemcitabine in a dose-dependent manner. The GlutaPanc phase I trial is a single-arm, open-label clinical trial investigating the safety of combination L-glutamine, gemcitabine, and nab-paclitaxel in subjects (n = 16) with untreated, locally advanced unresectable or metastatic pancreatic cancer. Following a 7-day lead-in phase with L-glutamine, the dose-finding phase via Bayesian design begins with treatment cycles lasting 28 days until disease progression, intolerance, or withdrawal. The primary objective is to establish the recommended phase II dose (RP2D) of combination L-glutamine, gemcitabine, and nab-paclitaxel. Secondary objectives include safety of the combination across all dose levels and preliminary evidence of antitumor activity. Exploratory objectives include evaluating changes in plasma metabolites across multiple time points and changes in the stool microbiome pre and post L-glutamine supplementation. If this phase I clinical trial demonstrates the feasibility of L-glutamine in combination with nab-paclitaxel and gemcitabine, we would advance the development of this combination as a first-line systemic option in subjects with metastatic pancreatic cancer, a high-risk subgroup desperately in need of additional therapies.

Research note: effects of different anticoccidial regimens on the growth performance, hematological parameters, immune response, and intestinal coccidial lesion scores of yellow-feathered broilers.

Yellow-feathered broiler chickens generally have a longer growth cycle than white broilers and therefore face different coccidiosis challenges. General single vaccine and drug regimens struggle to prevent coccidiosis for yellow broilers. In this study, a single vaccine, and a combination of coccidiostat regimens was employed to explore the preventative and control effects of different pilot regimens on coccidiosis in yellow-feathered broilers. A total of 2,000 one day old Chinese Huang Youma female broilers were allocated into 4 experimental groups, each with 5 replicates. All birds were fed the same starter feed from Days 1 to 25, and all groups were inoculated with a vaccine on Day 4. After Day 26, the groups were then fed as follows: (1) Negative control group: basal diet + vaccine (NC); (2) NC + maduramycin (NCMD); (3) NC + narasin (NCNR); and (4) NC + salinomycin (NCSL). From Days 26 to 75, the NCNR group had a lower FCR than the other groups. The 75-d BW was higher in the NCNR group than in the NCSL group but was not significantly higher than that in the NC and NCMD groups. The growth performance followed the same trend during the whole experiment (Days 1-75). Compared to the NC group, the NCNR and NCSL groups had higher intestinal mucosa SIgA concentrations at Day 40 and Day 60 (P < 0.001); however the NCMD group had lower IgG levels at Day 40 and Day 60 (P = 0.036, P = 0.006 respectively). The combination groups had significantly reduced AKP levels and urine acid concentrations at Day 60 in comparison to those of the NC group (P = 0.004). The NCNR and NCMD groups had less severe intestinal coccidiosis lesion scores than the NC and NCSL groups in older birds. Thus, a single vaccine and/or combinations with different coccidiostats had different effects on broilers. The NCNR group showed comparatively better growth performance, blood biochemical indices, immune response, and coccidiosis lesion scores.

Exploring the Protective Effect and Mechanism of Buddlejae Flos on Sodium Selenite-Induced Cataract in Rats by Network Pharmacology, Molecular Docking, and Experimental Validation.

Objective: Buddlejae Flos has a long history of utilization by humans to treat ophthalmic diseases. Although in vitro study revealed that it can be used for treating cataract, the bioactive components and the mechanism of efficacy remained unclear. This study aims to discover the bioactive components and mode of efficacy of Buddlejae Flos in cataract treatment. Methods: Several databases were screened for bioactive components and corresponding targets, as well as cataract-related targets. Using the String database, common targets were determined and utilized to construct protein-protein interactions (PPI). The drug-component-target-disease network map was drawn using Cytoscape software. R language was utilized to execute Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analysis. Molecular docking was done through Schrödinger Maestro software utilization. Luteolin's (LUT) effect on cataract induced by sodium selenite in rat pups was evaluated. Results: Six bioactive components with 38 common targets were identified as being associated with cataract. TP53, AKT1, EGFR, CASP3, TNF, ESR1, INS, IL6, HIF1A, and VEGFA were identified as core targets in PPI analysis, and the binding energy of LUT with AKT was the lowest. LUT has been demonstrated to significantly lower MDA levels, raise glutathione (GSH) levels, and boost the activity of antioxidant enzymes like GST, SOD, GPx, and CAT. After LUT treatment, TNF-a, IL-2, and IL-6 levels were significantly lowered. Bcl-2 mRNA expression levels and p-PI3K and p-AKT protein expression were significantly elevated. In contrast, caspase-3 and Bax mRNA expression levels were significantly decreased. Conclusion: This study demonstrates that LUT is a possible bioactive component that may be utilized for cataract treatment. Its mode of action includes oxidative stress suppression, reducing inflammation, and inhibiting apoptosis via regulating the PI3K/AKT single pathway.

[Efficacy and safety of black tomato concentrate in the treatment of erectile dysfunction: A prospective randomized controlled open trial].

OBJECTIVE: To evaluate the efficacy and safety of black tomato concentrate (BTC), which is rich in polyphenols, in the treatment of ED. METHODS: We conducted a prospective randomized open clinical study of 150 ED patients from December 2018 to February 2020, and treated the them with placebo (n = 50), BTC (n = 50) and Compound Xuanju Capsules (CXC) (n = 50), respectively, all for 8 weeks. Before and at 4 and 8 weeks after treatment, we obtained the scores of the patients on IIEF-5, Erection Hardness Score (EHS), Sexual Encounter Profile (SEP-2,3) and General Assessment Questionnaire (GAQ-1,2), related biochemical indexes and the T level, followed by comparison among the three groups. RESULTS: Totally, 120 of the patients completed the clinical trial, 37 in the placebo, 43 in the BTC and 40 in the CXC group. There were no statistically significant differences among the placebo, BTC and CXC groups in the baseline scores on IIEF-5 (12.03 �� 3.50 vs 11.70 �� 3.80 vs 11.42 �� 3.82), EHS, and SEP-2,3 (P > 0.05). At 8 weeks after treatment, the patients in the BTC group showed significant improvement in IIEF-5 (15.67 �� 3.63), EHS, SEP-2,3 and GAQ-1 positive response compared with those in the placebo group (P < 0.05) and similar improvement to that in the CXC group in IIEF-5 (15.67 �� 3.63 vs 15.65 �� 3.87), EHS, SEP-2,3 and GAQ-1,2 (P > 0.05). No statistically significant differences were observed in the incidence of adverse reactions among the placebo, BTC and CXC groups (4.7% vs 2.7% vs 5.0%, P > 0.05), and the symptoms were significantly relieved in the BTC group after change of the administration time to after meal. CONCLUSION: Black tomato concentrate is comparable to Compound Xuanju Capsules and better than placebo (P < 0.05) in improving the IIEF-5, EHS and SEP-2,3 scores of ED patients. And, with a high safety, it can be used as an alternative treatment of ED.

Orbital coupling of hetero-diatomic nickel-iron site for bifunctional electrocatalysis of CO2 reduction and oxygen evolution.

While inheriting the exceptional merits of single atom catalysts, diatomic site catalysts (DASCs) utilize two adjacent atomic metal species for their complementary functionalities and synergistic actions. Herein, a DASC consisting of nickel-iron hetero-diatomic pairs anchored on nitrogen-doped graphene is synthesized. It exhibits extraordinary electrocatalytic activities and stability for both CO2 reduction reaction (CO2RR) and oxygen evolution reaction (OER). Furthermore, the rechargeable Zn-CO2 battery equipped with such bifunctional catalyst shows high Faradaic efficiency and outstanding rechargeability. The in-depth experimental and theoretical analyses reveal the orbital coupling between the catalytic iron center and the adjacent nickel atom, which leads to alteration in orbital energy level, unique electronic states, higher oxidation state of iron, and weakened binding strength to the reaction intermediates, thus boosted CO2RR and OER performance. This work provides critical insights to rational design, working mechanism, and application of hetero-DASCs.

[Clinical application of common botanical preparations in the treatment of benign prostatic hyperplasia].

With the increasing incidence of BPH, lower urinary tract symptoms (LUTS) it induces seriously affect the quality of life of middle-aged and elderly patients. Botanical preparations have the advantages of easy availability, reliable efficacy and less adverse reactions for the treatment of BPH. Botanical preparations commonly used for this purpose include lycopene, saw palmetto fruit extract, Pygeumafricanum extract, urtica extract, and so on. This article reviews the action mechanisms and the latest clinical application of the above four botanical preparations in the treatment of BPH, aiming to provide some more evidence for the selection of botanical therapies for BPH and a wider clinical application of botanical preparations.

Wolbachia supplement biotin and riboflavin to enhance reproduction in planthoppers.

Symbiont-mediated nutritional mutualisms can contribute to the host fitness of insects, especially for those that feed exclusively on nutritionally unbalanced diets. Here, we elucidate the importance of B group vitamins in the association of endosymbiotic bacteria Wolbachia with two plant-sap feeding insects, the small brown planthopper, Laodelphax striatellus (Fallén), and the brown planthopper, Nilaparvata lugens (Stål). Infected planthoppers of both species laid more eggs than uninfected planthoppers, while the experimental transfer of Wolbachia into uninfected lines of one planthopper species rescued this fecundity deficit. The genomic analysis showed that Wolbachia strains from the two planthopper species encoded complete biosynthesis operons for biotin and riboflavin, while a metabolic analysis revealed that Wolbachia-infected planthoppers of both species had higher titers of biotin and riboflavin. Furthermore, experimental supplementation of food with a mixture of biotin and riboflavin recovered the fecundity deficit of Wolbachia-uninfected planthoppers. In addition, comparative genomic analysis suggested that the riboflavin synthesis genes are conserved among Wolbachia supergroups. Biotin operons are rare in Wolbachia, and those described share a recent ancestor that may have been horizontally transferred from Cardinium bacteria. Our research demonstrates a type of mutualism that involves a facultative interaction between Wolbachia and plant-sap feeding insects involving vitamin Bs.

Functional Connectivity of the Corticobasal Ganglia-Thalamocortical Network in Parkinson Disease: A Systematic Review and Meta-Analysis with Cross-Validation.

Purpose To quantitatively summarize the functional connectivity (FC) feature of the corticobasal ganglia-thalamocortical (CBTC) network in patients with Parkinson disease (PD) by means of a meta-analysis with cross-validation. Materials and Methods For this prospective study, a systematic literature search in the PubMed and EMBASE databases was performed for resting-state functional magnetic resonance (MR) imaging studies of PD published between January 2000 and May 2017. Then, a coordinate-based meta-analysis was conducted by Effect Size-Signed Differential Mapping. A cross-validation analysis was performed by using an independent resting-state functional MR imaging data set that contained 25 patients with PD and 19 age-, sex-, and education-matched healthy control participants. Two-sample t test was performed on FC maps between PD and control groups. Results Thirty studies with 854 patients with PD and 831 control participants were included in this meta-analysis. The main meta-analysis found increased FC in the left pre- and postcentral gyrus in patients with PD compared with healthy control participants (z = 2.6; P < .001). The abnormality of the postcentral gyrus was further confirmed by subgroup meta-analyses on medication-naive (n = 25; z = 2.2; P < .001) and medication-off (n = 11; z = 1.5; P < .001) experiments, which suggested that the finding was unaffected by medication. The abnormality of the postcentral gyrus was cross-validated by the independent data set (t = 5.0; P < .05), which suggested a high reproducibility and generalizability. Conclusion This meta-analysis emphasizes the left postcentral gyrus as a critical region in PD, which may become a potential target for clinical intervention. © RSNA, 2018 Online supplemental material is available for this article.

VCPA, a novel synthetic derivative of α-tocopheryl succinate, sensitizes human gastric cancer to doxorubicin-induced apoptosis via ROS-dependent mitochondrial dysfunction.

Gastric carcinoma is a common malignant disease worldwide and has a dismal prognosis. Doxorubicin (DOX), one of the most widely used chemotherapeutic agents, has limited use because of its side effects and the development of tumor-cell resistance. Combinations of doxorubicin and non-cross-resistant agents have been required for adjuvant chemotherapy of gastric cancer. Here, we report that VCPA, a novel synthetic derivative of α-Tocopheryl Succinate, induced apoptosis via production of reactive oxygen species (ROS). When used in combination with doxorubicin, lower doses of VCPA sensitized human gastric cancer cells to DOX-induced apoptosis. The DOX/VCPA combination treatment caused an imbalance in the ratio of Bcl-2 to Bax and induced a lethal mitochondrial dysfunction. MAPKs were also activated in response to the DOX/VCPA treatment but played a protective role in DOX-induced cell death. In vivo studies further confirmed the sensitizing effect of VCPA. Combining DOX with VCPA markedly inhibited tumor growth in a tumor xenograft model of human gastric cancer. Taken together, our study revealed that VCPA, through increased ROS production, could synergize with DOX and circumvent DOX resistance in human gastric cancer cells.

D2-resected stage IIIc gastric cancer patients benefit from adjuvant chemoradiotherapy.

Although adjuvant chemoradiotherapy has been an important part in the treatment of gastric cancer, whether or not adjuvant radiation can benefit patients undergoing resection with D2 lymph node dissection remains controversial. This retrospective study aimed to evaluate the role of adjuvant chemoradiotherapy on patients with D2-resected gastric cancer. A total of 337 patients with resected gastric cancer treated at Zhongnan Hospital of Wuhan University from 2004 to 2012 were retrospectively analyzed. Eligible patients were divided into the adjuvant chemoradiotherapy group (CRT; n = 124) and the adjuvant chemotherapy group (CT; n = 213). The primary endpoints were disease-free survival (DFS) and overall survival (OS), with toxicity as the secondary endpoint. A subgroup analysis was performed based on clinical staging. The two groups were comparable in baseline characteristic, except for the number of lymph nodes dissected. The median OSs in the CRT and CT groups were 51.0 months and 48.6 months, respectively (P = 0.251), and the median DFSs were 40.7 months and 31.2 months, respectively (P = 0.112). Subgroup analysis revealed that the median OSs in patients at stage IIIc in the CRT group and CT group were 29.0 and 23.0 months, respectively (P = 0.049), and those of the median DFSs were 21.2 and 15.1 months, respectively (P = 0.015). There was no significant difference in main adverse events between two groups. Collectively, adjuvant chemoradiotherapy in gastric cancer patients with D2 resection was well tolerated. For Stage IIIc patients, the addition of adjuvant chemoradiotherapy was associated with a significant benefit in both OS and DFS.

[Acupuncture combined with medication for blood-stasis in unstable angina patients with different thrombolysis in myocardial infarction risk stratification].

OBJECTIVE: To observe the intervention effects of acupuncture combined with standardized treatment of western medicine on blood-stasis syndrome in unstable angina (UA) patients with different thrombolysis in myo-cardial infarction (TIMI) risk stratification. METHODS: According to TIMI risk score, a total of 72 UA patients were included, 24 cases in low-risk (0 to 2 points) group, 24 cases in moderate-risk (3 to 4 points) group and 24 cases in high-risk (5 to 7 points) group. Based on routine standardized treatment of western medicine, acupuncture was applied at Xinshu (BL 15), Xuehai (SP 10), Geshu (BL 17), Danzhong (CV 17), Jueyinshu (BL 14), Ximen (PC 4) and Neiguan (PC 6) in three groups. Acupuncture was given once a day, 14 days as a session. After one session, each symptom score and total score of blood stasis syndrome were observed. RESULTS: One patient dropped out respectively, and 23 patients in each group were included in the analysis. After treatment, the score of angina symptom and total score of blood stasis syndrome were significantly improved in three groups (all P<0.01). The improvements of each score and total score of blood stasis syndrome in the high-risk group were superior to those in the low-risk group and moderate-risk group (P<0.05, P<0.01). CONCLUSIONS: With the higher TIMI scores, the blood stasis syndrome is aggravated accordingly. Acupuncture combined with standardized treatment of western medicine could effectively intervene blood stasis syndrome, especially for the score of blood stasis syndrome of patients in high-risk group.

Connectome Reorganization Associated With Surgical Outcome in Temporal Lobe Epilepsy.

To identify the distinct pattern of anatomical network reorganization in surgically refractory mesial temporal lobe epilepsy (MTLE) patients using a longitudinal design. We collected longitudinal diffusion-weighted images of 19 MTLE patients before and after anterior temporal lobectomy. Patients were classified as seizure-free (SF) or nonseizure-free (NSF) at least 1 year after surgery. We constructed whole-brain anatomical networks derived from white matter tractography and evaluated network connectivity measures by graph theoretical analysis. The reorganization trajectories of network measures in SF and NSF patients were investigated by two-way mixed analysis of variance, with factors "group" (SF vs NSF) and "treatment" (presurgery vs postsurgery). Widespread brain structures showed opposite reorganization trajectories in FS and NSF groups (interaction effect). Most of them showed group difference before surgery and then converge after surgery, suggesting that surgery remodeled these structures into a similar status. Conversly, contralateral amygdala-planum-temporale and thalamic-parietal tracts showed higher connectivity strength in NSF than in SF patients after surgery, indicating maladaptive neuroplastic responses to surgery in NSF patients. Our findings suggest that surgical outcomes are associated not only with the preoperative pattern of anatomical connectivity, but also with connectome reconfiguration following surgery. The reorganization of contralateral temporal lobe and corticothalamic tracts may be particularly important for seizure control in MTLE.

Intrinsic brain activity as a diagnostic biomarker in children with benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is often associated with neural circuit dysfunction, particularly during the transient active state characterized by interictal epileptiform discharges (IEDs). Little is known, however, about the functional neural circuit abnormalities in BECTS without IEDs, or if such abnormalities could be used to differentiate BECTS patients without IEDs from healthy controls (HCs) for early diagnosis. To this end, we conducted resting-state functional magnetic resonance imaging (RS-fMRI) and simultaneous Electroencephalogram (EEG) in children with BECTS (n = 43) and age-matched HC (n = 28). The simultaneous EEG recordings distinguished BECTS with IEDs (n = 20) from without IEDs (n = 23). Intrinsic brain activity was measured in all three groups using the amplitude of low frequency fluctuation at rest. Compared to HC, BECTS patients with IEDs exhibited an intrinsic activity abnormality in the thalamus, suggesting that thalamic dysfunction could contribute to IED emergence while patients without IEDs exhibited intrinsic activity abnormalities in middle frontal gyrus and superior parietal gyrus. Using multivariate pattern classification analysis, we were able to differentiate BECTS without IEDs from HCs with 88.23% accuracy. BECTS without epileptic transients can be distinguished from HC and BECTS with IEDs by unique regional abnormalities in resting brain activity. Both transient abnormalities as reflected by IEDs and chronic abnormalities as reflected by RS-fMRI may contribute to BECTS development and expression. Intrinsic brain activity and multivariate pattern classification techniques are promising tools to diagnose and differentiate BECTS syndromes. Hum Brain Mapp 36:3878-3889, 2015. © 2015 Wiley Periodicals, Inc.

Adnectin-targeted inhibitors: rationale and results.

Adnectins are a family of binding proteins derived from the 10th type III domain of human fibronectin (10Fn3), which is part of the immunoglobulin superfamily and normally binds integrin. The 10Fn3 has the potential for broad therapeutic applications given its structural stability, ability to be manipulated, and its abundance in the human body. The most commonly studied adnectin is CT-322, which is an inhibitor of vascular endothelial growth factor receptor-2. A bispecific adnectin, El-Tandem, has also been developed and binds to epidermal growth factor receptor and insulin-like growth factor-1 receptor simultaneously. Pre-clinical studies have shown promising results in relation to reducing tumor growth, decreasing microvessel density, and promoting normalization of tumor architecture. The phase I trial with CT-322 demonstrates relatively low toxicities. However, the phase II study done with CT-322 in recurrent glioblastoma does not reveal as promising results.

Salvianolic acid Y: a new protector of PC12 cells against hydrogen peroxide-induced injury from Salvia officinalis.

Salvianolic acid Y (TSL 1), a new phenolic acid with the same planar structure as salvianolic acid B, was isolated from Salvia officinalis. The structural elucidation and stereochemistry determination were achieved by spectroscopic and chemical methods, including 1D, 2D-NMR (1H-1H COSY, HMQC and HMBC) and circular dichroism (CD) experiments. The biosynthesis pathway of salvianolic acid B and salvianolic acid Y (TSL 1) was proposed based on structural analysis. The protection of PC12 cells from injury induced by H2O2 was assessed in vitro using a cell viability assay. Salvianolic acid Y (TSL 1) protected cells from injury by 54.2%, which was significantly higher than salvianolic acid B (35.2%).

Glycogen synthase kinase 3 inhibitor attenuates endotoxin-induced liver injury.

BACKGROUND/AIMS: Endotoxin (lipopolysaccharide, LPS)-induced acute liver injury was attenuated by endotoxin tolerance (ET), which is characterized by phosphatidylinositol 3-kinase pathway/Akt signaling. Glycogen synthase kinase 3 (GSK-3) acts downstream of phosphatidylinositol 3-kinase pathway/Akt and GSK-3 inhibitor protects against organic injury. This study evaluates the hypothesis that ET attenuated LPS-induced liver injury through inhibiting GSK-3 functional activity and downstream signaling. METHODS: Sprague-Dawley rats with or without low-dose LPS pretreatment were challenged with or without large dose of LPS and subsequently received studies. Serum tumor necrosis factor-alpha, interleukin-10, alanine aminotransferase, lactate dehydrogenase, and total bilirubin levels were analyzed, morphology of liver tissue was performed, glycogen content, myeloperoxidase content, phagocytosis activity of Kupffer cells, and the expression and inhibitory phosphorylation as well as kinase activity of GSK-3 were examined. Survival after LPS administration was also determined. RESULTS: LPS induced significant increases of serum TNF-α, alanine aminotransferase, lactate dehydrogenase, and total bilirubin (P < 0.05), which were companied by obvious alterations in liver: the injury of liver tissue, the decrease of glycogen, the infiltration of neutrophils, and the enhancement of phagocytosis of Kupffer cells (P < 0.05). LPS pretreatment significantly attenuated these alterations, promoted the inhibitory phosphorylation of GSK-3 and inhibited its kinase activity, and improved the survival rate (P < 0.05). CONCLUSIONS: ET attenuated LPS-induced acute liver injury through inhibiting GSK-3 functional activity and its downstream signaling.

Synthesis, DNA binding, photo-induced DNA cleavage, cytotoxicity and apoptosis studies of copper(II) complexes.

Two new Cu(II) complexes, [Cu(acac)(dpq)Cl] (1) and [Cu(acac)(dppz)Cl] (2) (acac = acetylacetonate, dpq = dipyrido[3,2-d:20,30-f]quinoxaline, dppz = dipyrido[3,2-a:20,30-c] phenazine), have been synthesized and their DNA binding, photo-induced DNA cleavage activity and cell cytotoxicity are studied. The complexes show good binding propensity to calf thymus DNA in the order: 2(dppz) >1(dpq). Furthermore, two complexes exhibit efficient DNA cleavage activity on natural light or UV-A (365 nm) irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The photo-induced DNA cleavage activity of the dppz complex 2 is found to be more efficient than its dpq analogue. In vitro study of the photocytotoxicity of two complexes on HeLa cells indicate that both of them have the potential to act as effective anticancer drugs, with IC(50) values of 5.25±0.83 µM (1) and 4.40±0.52 µM (2) in the natural light, and 2.57±0.92 µM (1) and 2.18±0.52 µM (2) in UV-A light. In addition, to detect an apoptotic HeLa body, cells were stained with Hoechst 33342 dye.

Cytotoxic activities of extracts and compounds from Viscum coloratum and its transformation products by Rhodobacter sphaeroides.

The bioassay-oriented fractionation of mistletoe crude extracts (MCEE) using 75% ethanol and culture products of mistletoe transformed by Rhodobacter sphaeroides, a photosynthetic bacterium (PSBT), revealed that the high cytotoxic activities were due to the petroleum ether extracts (PEs) and the acid-precipitated proteins from the aqueous extracts (AQs) of MCEE and PSBT. The isolated triterpenes may account for the activities of the PEs of MCEE and PSBT, respectively. Extraction of MCEE using petroleum ether led to the isolation of 3-epi-betulinic acid (1), betulonic acid (2), oleanolic acid (3), and beta-amyrin acetate (4), while petroleum ether extraction of PSBT led to the isolation of 1,3,4,betulinic acid (5), erythrodiol (6), and (3beta)-olean-12-ene-3,23-diol (7). The PE of PSBT exerted higher cytotoxicity than the PE of MCEE, which was due to the different triterpene contents of these two extracts. The cytotoxic activities of all compounds were tested, and the results revealed that compounds 1, 2, 3, 5, 6, and 7 contributed significantly to the cytotoxicities of both PEs. The AQ of the PSBT exerted almost the same cytotoxic activity and lower toxicity compared to the AQ of the MCEE. These findings indicate that mistletoe products biotransformed by R. sphaeroides could be used to treat cancers, since they have lower toxicities and higher antitumor activities compared to standard treatments.