Harnessing the benefits of glycine supplementation for improved pancreatic microcirculation in type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is predominantly managed using insulin replacement therapy, however, pancreatic microcirculatory disturbances play a critical role in T1DM pathogenesis, necessitating alternative therapies. This study aimed to investigate the protective effects of glycine supplementation on pancreatic microcirculation in T1DM. Streptozotocin-induced T1DM and glycine-supplemented mice (n = 6 per group) were used alongside control mice. Pancreatic microcirculatory profiles were determined using a laser Doppler blood perfusion monitoring system and wavelet transform spectral analysis. The T1DM group exhibited disorganized pancreatic microcirculatory oscillation. Glycine supplementation significantly restored regular biorhythmic contraction and relaxation, improving blood distribution patterns. Further-more, glycine reversed the lower amplitudes of endothelial oscillators in T1DM mice. Ultrastructural deterioration of islet microvascular endothelial cells (IMECs) and islet microvascular pericytes, including membrane and organelle damage, collagenous fiber proliferation, and reduced edema, was substantially reversed by glycine supplementation. Additionally, glycine supplementation inhibited the production of IL-6, TNF-α, IFN-γ, pro-MMP-9, and VEGF-A in T1DM, with no significant changes in energetic metabolism observed in glycine-supplemented IMECs. A statistically significant decrease in MDA levels accompanied by an increase in SOD levels was also observed with glycine supplementation. Notably, negative correlations emerged between inflammatory cytokines and microhemodynamic profiles. These findings suggest that glycine supplementation may offer a promising therapeutic approach for protecting against pancreatic microcirculatory dysfunction in T1DM.

Application Analysis of Multiacupoint Stimulation in Multimodal Labor Analgesia during the Whole Stage of Labor in Primipara.

Purpose: To analyze the application value of multimodal analgesia (MMA) regimen of patient-controlled epidural analgesia (PCEA) combined with multiacupoint stimulation analgesia during the whole stage of labor analgesia in primipara. Methods: 300 primiparas with natural delivery were selected. According to the different ways of labor analgesia, they were divided into the first stage of labor active period PCEA group (group A), the whole stage of labor PCEA group (group W), and the whole stage of labor PCEA combined with multiacupoint stimulation analgesia group (group WM). The effect of MMA during the whole-labor process on maternal and infant safety was evaluated. The specific observation indicators were as follows: visual analogue scale (VAS) scores before analgesia (T 0), at full opening of the uterus (T 1), at the end of the second stage of labor (T 2), and at the end of the third stage of labor (T 3); stress response indicators at T 0 and T 1: epinephrine (E), norepinephrine (NE), glucose (Glu), and ß-endorphin (ß-EP) levels; delivery time of each stage of labor; the Apgar score of newborns at 1 and 5 min after birth; indicators of umbilical artery blood gas analysis immediately after delivery: PH value, base excess (BE), partial pressure of oxygen (PaO2), and partial pressure of carbon dioxide (PaCO2); incidence of postpartum depression (PPD) at 6 weeks after delivery. Results: At T 1, T 2, and T 3, the VAS scores were lower in groups W and WM than in group A, and the VAS scores were lower in group WM than in group W (P < 0.05). At T 0, there was no significant difference in the comparison of E, NE, Glu, and ß-EP levels among the three groups (P > 0.05). At T 1, the levels of E, NE, Glu, and ß-EP were higher in the three groups than in the same group at T 0, the levels of E, NE, and Glu were lower, the levels of ß-EP were higher in groups W and WM than in group A, and the levels of ß-EP were higher in group WM than in group W (P < 0.05). Comparing the delivery time of the first stage of labor in the three groups, groups A and WM were shorter than group W (P < 0.05). Comparing the delivery time of the second and third stages of labor in the three groups, there was no significant difference (P > 0.05). Comparing the Apgar scores of the three groups of newborns at 1 and 5 min after birth, there was no significant difference (P > 0.05). Comparing the incidence of newborn asphyxia in the three groups, there was also no significant difference (P > 0.05). Comparing the PH, BE, PaO2, and PaCO2 of three groups of newborns after delivery, there were no significant differences (P > 0.05). At 6 weeks after delivery, the incidence of PPD was lower in groups W (10.00%) and WM (8.00%) than in group A (20.00%) (P < 0.05). Conclusion: The application of the MMA regimen of PCEA combined with multiacupoint stimulation for labor analgesia during the whole stage of labor in primipara can effectively reduce labor pain and stress response during the whole stage of labor and shorten the delivery time of the first stage of labor, the indicators of newborn Apgar score and umbilical artery blood gas analysis are not affected, and the incidence of PPD in patients is reduced, which can play a protective role for the safety of mother and infant.

Preparative separation of gallocatechin gallate from Camellia ptilophylla using macroporous resins followed by sephadex LH-20 column chromatography.

Gallocatechin gallate (GCG) possesses multiple potential biological activities. However, the content of GCG in traditional green tea is too low which limits its in-depth pharmacological research and application. In the present study, a simple, efficient and environment-friendly chromatographic separation method was developed for preparative enrichment and separation of GCG from cocoa tea (Camellia ptilophylla) which contains high content of GCG. In the first step, the adsorption properties of selected resins were evaluated, and XAD-7HP resin was chosen by its adsorption and desorption properties for GCG. In order to maximize column efficiency for GCG collection, the operating parameters (e.g., flow rate, ethanol concentration, and bed height) were optimized. We found that the best combination was the feed concentration at 20mg/mL, flow rate at 0.75 BV/h and the ratio of diameter to bed heights as 1:12. Under these conditions, the purity of GCG was 45% with a recovery of 89%. In order to obtain pure target, a second step was established using column chromatography with sephadex LH-20 gel and 55% ethanol-water solution as eluent. After this step, the purity of the GCG was 91% with a recovery of 68% finally.

[Application of high performance liquid-ion trap mass spectrometry in analyzing saponins in sodium aescinate].

Sodium aescinate, which is produced from saponins of Chinese Buckeye Seed, is a prescription drug for treatment of brain edema and all kinds of swellings caused by surgery. In this article, high-performance liquid chromatography/ion trap (HPLC-IT) mass spectrometry was applied to study the characteristic ions of ten reference substances, namely escin Ⅰa, escin Ⅰb, isoescin Ⅰa, isoescin Ⅰb, aesculiside A, aesculiside B, aesculuside A, escin Ⅳc, escinⅡa and escin Ⅴ, which were isolated from aescinate. Furthermore, 19 saponin compounds were predicted in sodium aescinate, besides the above mentioned reference substances. The study showed that sapogenins in sodium aescinate had two structural types, namely protoaescigenin and barringenol C, and the substituent acetyl, tigloyl or angeloyl was usually located at C-21, C-22 or C-28 position. Among these predicted saponins, their sugar chains were all located at C-3 position consisting of glucose and glucuronide. This study provides experimental data for chemical constituents in sodium aescinate and scientific basis for quality and safety evaluation.

Inhibitory effects of cocoa tea (Camellia ptilophylla) in human hepatocellular carcinoma HepG2 in vitro and in vivo through apoptosis.

Cocoa tea (Camellia ptilophylla), a naturally decaffeinated tea commonly consumed as a healthy beverage in southern China, has been recently found to be a potential candidate for the treatment of different diseases, including obesity and cancers. The present study aimed to evaluate the anti-liver cancer activities of green cocoa tea infusion (GCTI) in vitro and in vivo using human hepatocarcinoma cell line HepG2 cells and nude mice xenograft model. The apoptotic activities of GCTI were assessed using flow cytometry, Western blotting and immunohistochemical analysis. Our results showed that GCTI significantly inhibited the proliferation of HepG2 cells in a dose-dependent manner (IC50 values=292 µg/ml at 72 h). GCTI induced HepG2 cells to undergo apoptosis, which was demonstrated by cell cycle analysis and annexin-V and propidium iodide staining. The caspase cascade was activated as shown by significant proteolytic cleavage of caspase-3 and PARP in GCTI-treated cells in a dose- and time-dependent manner. In addition, GCTI increased the expression of cell cycle inhibitory proteins (p21, p27 and p53) and the Bax-to-Bcl-2 ratio to induce apoptosis. The antiproliferative effect of GCTI was confirmed in HepG2 xenograft nude mice. The tumor growth was effectively inhibited by GCTI in a dose-dependent manner as indicated by the decrease in tumor volume and tumor weight after 4 weeks of treatment. Administration of GCTI increased terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and caspase-3-positive cells in the tumor section. In conclusion, these results revealed that GCTI may be a potential and promising agent of natural resource to treat liver cancer.

Effects of modified Haizao Yuhu Decoction in experimental autoimmune thyroiditis rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Haizao Yuhu Decoction (MHYD), based on clinical experience, has been used for approximately 500 years and famous for its efficiency in treating thyroid-related diseases. AIM OF THE STUDY: To investigate therapeutic effects of MHYD on thyroid-related autoantibodies and thyroid hormone in experimental autoimmune thyroiditis (EAT) rats, and to provide evidence for the immunomodulatory potential during antigenmediated immunostimulation. MATERIALS AND METHODS: The effect of MHYD was investigated in EAT rats induced by subcutaneous injection of porcine thyroglobulin with Freund's adjuvant (complete and incomplete, CFA and IFA). MHYD was fed to EAT rats daily at a dose of 100mg/kg for 10 weeks. The presence of mononuclear cell infiltration in thyroid tissues were examined to assess the severity of EAT. The levels of serum T3, T4, TgAb and TPOAb were determined by radioimmunoassay and protein expressions of TRAIL were detected by immunohistochemistry. RESULTS: MHYD exhibited a significant protective effects by reversing serum T3, T4, TgAb and TPOAb levels, histopathological changes and TRAIL protein expression of thyroid in EAT model rats. Sargassum fusiforme and Radix Glycyrrhiza in the formulation could be responsible for the immunomodulatory effects of MHYD. CONCLUSIONS: These results showed MHYD playing a role as an immunomodulator and TRAIL inhibitor during antigenmediated immunostimulation, may warrant further evaluation as a possible agent for the treatment of Hashimoto's thyroiditis.

Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities.

The anti-inflammatory and analgesic effects of theacrine (1, 3, 7, 9-tetramethyluric acid), a purine alkaloid which is abundantly present in Camellia kucha, were investigated. Xylene-induced ear edema, acetic acid-induced vascular permeability and lambda-carrageenan-induced paw edema were used to investigate anti-inflammatory activity, and acetic acid-induced writhing and hot-plate tests were used to determine analgesic effect. Oral administration of theacrine (8-32 mg/kg) induced dose-related anti-inflammatory and analgesic effects. On the other hand, oral caffeine administration (8-32 mg/kg) did not show an inhibitory effect on the inhibition of inflammatory response or cause analgesia. Additionally, the result of the acute toxicity test showed that the LD(50) of theacrine was 810.6 mg/kg (769.5-858.0mg/kg). The data obtained suggest theacrine possessed analgesic and anti-inflammatory activities.

[Relationships between constitutional types of traditional Chinese medicine and hypertension].

OBJECTIVE: To investigate the relationships between constitutional types of traditional Chinese medicine (TCM) and hypertension so as to provide epidemiological evidence for the theory of correlation between constitution and disease. METHODS: A cross-sectional survey of TCM constitution data from a population of 7 782 from Beijng and 8 provinces of China (Jiangsu, Anhui, Gansu, Qinghai, Fujian, Jilin, Jiangxi, and Henan) was made in the study. The survey of TCM constitutions was performed by standardized TCM Constitution Questionnaire. Discriminatory analysis was used to judge the individual constitutional types including normal constitution, and qi deficiency, yang deficiency, yin deficiency, phlegm-dampness, damp-heat, blood stasis, qi stagnation and special constitutions. A multiple stepwise logistic regression analysis was applied to explore the significantly influential constitutional factors of hypertension. RESULTS: After controlling several factors like gender, age, marital status, occupation, and educational background, three TCM constitutional factors according to different degrees of relative risks were entered into the multiple stepwise logistic regression model. The three factors were phlegm-dampness, yin deficiency and qi deficiency constitutions, and the odds ratio (OR) and 95% confidence interval (CI) were 2.00 [1.58, 2.55], 1.66 [1.33, 2.08] and 1.37 [1.13, 1.66] respectively. The main constitutional influential factors of hypertension in male patients were phlegm-dampness and yin deficiency constitutions, with OR and 95% CI of 1.61 [1.22, 2.14] and 1.60 [1.17, 2.19]. Phlegm-dampness, yin deficiency and qi deficiency constitutions were the main constitutional influential factors of hypertension in female patients. The OR and 95% CI were 2.80 [1.79, 4.39], 1.55 [1.13, 2.14] and 1.39 [1.05, 1.84] respectively. Phlegm-dampness constitution had more influence on hypertension in female patients than other constitution types. CONCLUSION: Phlegm-dampness, yin deficiency, and qi deficiency constitutions are the main influential factors of hypertension. Hypertensive patients with different gender have different constitutional influential factors.

Study on the pharmacokinetics drug-drug interaction potential of Glycyrrhiza uralensis, a traditional Chinese medicine, with lidocaine in rats.

Drug-drug interaction potentials of an herbal medicine named Glycyrrhiza uralensis was investigated in rats via in vitro and in vivo pharmacokinetic studies. P(450) levels and the metabolic rate of lidocaine in the liver microsomes prepared from different treatment groups were measured. In a separate in vivo pharmacokinetic study, the pharmacokinetic parameters of lidocaine in plasma and urine were estimated. P(450) levels in the rats pretreated by Glycyrrhiza uralensis were significant higher than that in the non-treatment control. The increase in P(450) levels was dose-dependent. Glycyrrhiza uralensis (1 and 3 g/kg) increased P(450) levels by 62% and 91%, respectively, compared with the non-treatment control (0.695 nmol/mg protein). The metabolic rate of lidocaine in the liver microsomes was significantly higher in the herb pretreated rats. The pharmacokinetic profile of lidocaine was significantly modified in the rats with the herbal pretreatment. Elimination half-lives were shortened by 39%, and total clearances were increased by 59% with the pretreatment of Glycyrrhiza uralensis. In conclusion, Glycyrrhiza uralensis showed induction effect on P(450) isozymes. Efficacy and safety profiles of a drug may be affected when the herbal products or herbal prescriptions containing the plant medicine were concomitantly used.

Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes.

Rhein, an active ingredient extensively found in plants such as Aloe, Cassitora L., rhubarb and so on, has been used for a long time in China. Pharmacological tests revealed that rhein not only had a strong antibacterial action, but also may be useful in cancer chemotherapy as a biochemical modulator. Its therapeutic action and toxicity is still the subject of considerable research. With microsome incubation assays in vitro and HPLC methods, the inhibition of rat liver CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A enzymes by rhein were studied kinetically. The results showed the most inhibition of CYP2E1 by rhein (K(i) = 10 microm, mixed); CYP3A and CYP2C9 were also inhibited by rhein, K(i) = 30 microm (mixed) and K(i) = 38 microm (mixed), respectively; rhein revealed some inhibition of CYP1A2 (K(i) = 62 microm, uncompetitive) and CYP2D6 (K(i) = 74 microm, mixed). Drug-drug interactions, especially cytochrome P450 (CYP)-mediated interactions, cause an enhancement or attenuation in the efficacy of co-administered drugs. Inhibition of the five major CYP enzymes observed for rhein suggested that changes in pharmacokinetics of co-administered drugs were likely to occur. Therefore, caution should be paid to the possible drug interaction of medicinal plants containing rhein and CYP substrates.

Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins.

Overexpression of prosurvival proteins such as Bcl-2 and Bcl-X L has been correlated with tumorigenesis and resistance to chemotherapy, and thus, the development of antagonists of these proteins may provide a novel means for the treatment of cancer. We recently described the discovery of 1 (ABT-737), which binds Bcl-2, Bcl-X L, and Bcl-w with high affinity, shows robust antitumor activity in murine tumor xenograft models, but is not orally bioavailable. Herein, we report that targeted modifications at three key positions of 1 resulted in a 20-fold improvement in the pharmacokinetic/pharmacodynamic relationship (PK/PD) between oral exposure (AUC) and in vitro efficacy in human tumor cell lines (EC 50). The resulting compound, 2 (ABT-263), is orally efficacious in an established xenograft model of human small cell lung cancer, inducing complete tumor regressions in all animals. Compound 2 is currently in multiple phase 1 clinical trials in patients with small cell lung cancer and hematological malignancies.

[DNA fingerprinting structure of plankton community and its relations to environmental physical-chemical factors in Donghu Lake].

By the method of RAPD fingerprinting, this paper studied the DNA fingerprinting structure of plankton community and its relations to the main environmental physical-chemical factors at five sites in Donghu Lake. From the screened 9 random primers, a total of 210 observable bands with a length of 150-2 000 bp were amplified, 93.3% of which were polymorphic. At the five sites, the average number of amplified bands was 42, with the maximum (53) at site IV and the minimum (35) at site V. The PO4(3-)-P and TP contents were the highest at site I, NH4(+)-N, TN and NO2(-)-N contents were the highest at site V, while the values of all test physical-chemical parameters were the lowest at site IV. No obvious differences in COD, alkalinity, rigidity, and calcium content were observed among the study sites. Similarity clustering analysis showed that the DNA fingerprinting of plankton community based on RAPD marker could cluster the five sites into two groups, i. e., sites I, II and III could be clustered into one group, while sites IV and V could be clustered into another group, which was consistent with the clustering analysis based on the main environmental physical-chemical factors. In conclusion, there was a close relation between the DNA fingerprinting structure of plankton community and the main environmental physical-chemical factors in Donghu Lake.