The association of preconceptional folic acid supplementation with gestational age and preterm birth risk in twin pregnancies: a prospective cohort study in China.

PURPOSE: This study aims to explore the association of maternal preconceptional folic acid (FA) supplementation with gestational age and preterm birth in twin pregnancies, and whether the association varies by chorionicity or conception mode. METHODS: From November 2018 to December 2021, the information of FA supplementation and pregnancy outcomes were collected in twin pregnant women. The linear regression models and the logistic regression were used to test the association of preconceptional FA supplementation with gestational age at delivery and preterm birth and premature rupture of membranes (PROM). RESULTS: A total of 416 twin pregnancies were included. Compared with no use in twins, maternal preconceptional FA use was associated with a 0.385-week longer gestational age (95% CI 0.019-0.751) and lower risk of preterm birth < 36 weeks (adjusted OR 0.519; 95% CI 0.301-0.895) and PROM (adjusted OR 0.426; 95% CI 0.215-0.845). The protective effect on preterm birth < 36 weeks and PROM is similar whether taking FA supplements alone or multivitamins. However, the associations varied by chorionicity and conception mode of twins or compliance with supplementation. The positive associations between preconceptional FA use and gestational age only remained significant among twins via assisted reproductive technology or dichorionic diamniotic twins. Significant protective effects on preterm birth < 36 weeks and PROM were only found among women who took FA at least 4 times a week before conception. CONCLUSION: Maternal preconceptional FA supplementation was associated with longer gestation duration and lower risk of preterm birth < 36 weeks and PROM in twin pregnancies. To improve the success of their pregnancies, reproductive women should start taking FA supplements well before conception and with good compliance.

Changes in marker secondary metabolites revealed the medicinal parts, harvest time, and possible synthetic sites of Rubia cordifolia L.

Rubia cordifolia L. is a significant medicinal plant. To investigate the changes of marker metabolites of R. cordifolia, the purpurin, mollugin, carbon, nitrogen contents, and the expression of genes involved in anthraquinones synthesis were examined. The findings indicated that the two secondary metabolites were only detected in stems and roots. Root purpurin content was 5-26 times higher than in stems, and root mollugin content was 92 times higher than in stems in June. These findings suggest that the potential of the roots as a medicinal part. The roots were found to have highest purpurin content in October (2.406 mg g-1), whereas the mollugin content was highest in August (6.193 mg g-1). However, the purpurin content in August was only 0.029 mg g-1 lower than that in October, making August a suitable harvest period for R. cordifolia. The expression 1-deoxy-D-xylulose 5-phosphate synthase (dxs) and 1-deoxy-D-xylulose-5-phosphate reductorisomerase (dxr) genes in roots showed an upward trend. However, the expression level of dxr gene was significantly higher than dxs with the range of 60-518 times higher, indicating the important role of dxr gene. Through correlation and redundancy analyses, it was found that mollugin showed positive correlation with carbon contents and carbon-nitrogen ratio of aerial parts. Additionally, purpurin showed a positive correlation with the expression of both genes. As a result, mollugin is likely to be synthesized in the aerial parts and then stored in the roots, whereas purpurin might be synthesized in the stems and roots. These findings could provide cultivation guidelines for R. cordifolia.

[Qualitative and quantitative study of flavonoids in Notoginseng Radix et Rhizoma based on UPLC-Q-TOF-MS and HPLC-DAD].

The flavonoids in Panax notoginseng were qualitatively analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS), and the content of three main flavonoids in P. notoginseng of different specifications and grades collected from different habitats was determined by HPLC-DAD. Flavonoids and anthocyanins were analyzed by UPLC-Q-TOF-MS/MS in the positive and negative ion modes, respectively. Twelve flavonoid glycosides and one anthocyanin glycoside in P. notoginseng were identified, but no flavonoid aglycones were detected. Among them, 12 compounds were identified in the underground part of P. notoginseng for the first time and eight compounds were first reported in this plant. Moreover, six and four compounds were identified in the Panax genus and the Araliaceae family for the first time, respectively. A method for simultaneous determination of three flavonoids in P. notoginseng was established by HPLC-DAD. The content of flavonoids in 721 P. notoginseng samples of 124 specifications and grades collected from 20 different habitats was simultaneously determined. Among three flavonoids determined, the content of quercetin-3-O-(2″-ß-D-xylosyl)-ß-D-galactoside was the highest with the average content in the tested samples of 161.0 µg·g~(-1). The content of compounds quercetin-3-O-hexosyl-hexoside and kaempferol-3-O-pentosyl-hexoside was relatively low, with the average content of 18.5 µg·g~(-1)(calculated as quercetin-3-O-sophoroside) and 49.4 µg·g~(-1)(calculated as kaempferol-3-O-sangbu diglycoside). There were significant differences in flavonoids content of samples from different production area. The content of flavonoids in spring P. notoginseng was significantly lower than that in winter P. notoginseng when the other influencing factors such as production areas, germplasm resources, and cultivation conditions were fixed. As for P. notoginseng of different specifications, the flavonoid content in the part connecting the taproot and the aboveground stem was significantly higher than that in other parts. The results of large-scale data showed that the flavonoid content gradually increased with the increase in the number of heads. There were significant differences between the flavonoid content in most specifications and grades, especially the 20-head P. notoginseng and countless head P. notoginseng, whose content was significantly lower and significantly higher than that of other specifications and grades, respectively. This study provides a scientific basis for the study of the effective components and quality control of P. notoginseng from the perspective of flavonoids.

Polydopamine-guarded metal-organic frameworks as co-delivery systems for starvation-assisted chemo-photothermal therapy.

Cutting off glucose provision by glucose oxidase (GOx) to famish tumors can be an assistance with chemotherapy to eliminate cancer cells. Co-encapsulation of GOx and chemotherapeutics (doxorubicin) within pH-sensitive metal-organic frameworks (MOFs) could disorder metabolic pathways of cancer cells and generate excessive intracellular reactive oxygen species (ROS), together. To prevent premature leach of GOx from the porous channels of MOFs, polydopamine (PDA) was deposited on the surface of MOFs, which endowed the delivery system with photothermal conversion ability. Our nanoscaled co-delivery system (denoted as DGZPNs) remains stable with low amount of drug leakage under simulated physiological conditions in vitro and internal environment, while they are triggered to release doxorubicin (DOX) and GOx in acid tumor microenvironment and at high temperature for reinforced chemotherapy. NIR laser irradiation also activates superior photothermal conversion efficiency of PDA (36.9 %) to initiate hyperthermia to ablate tumor tissue. After being phagocytized by 4 T1 cells (breast cancer cells), the DGZPNs delivery system showed a superior therapeutic efficacy with a tumor growth inhibition of 88.9 ± 6.6 % under NIR irradiation, which indicated that the starvation-assisted chemo-photothermal therapy prompts the significant advance of synergistic therapy in a parallelly controlled mode.

Interrelation among one-carbon metabolic (OCM) pathway-related indicators and its impact on the occurence of pregnancy-induced hypertension disease in pregnant women supplemented with folate and vitamin B12: Real-world data analysis.

Background and objective: A considerable number of pregnant women who were supplemented with folate and vitamin B12 were selected as major participants in studying the one-carbon metabolic (OCM) pathway. Our study aimed to explore the effects of OCM-related indicators on pregnancy-induced hypertension (PIH) and preeclampsia (PE) in pregnant women with folate and vitamin B12 supplementation. Subjects and methods: A total of 1,178 pregnant women who took multivitamin tablets containing 800 µg folate and 4 µg vitamin B12 daily from 3 months before pregnancy to 3 months after pregnancy were enrolled in this study. These pregnant women were classified into three groups: the normotensive group (n = 1,006), the PIH group (n = 131), and the PE group (n = 41). The information on age, weight, body mass index (BMI), number of embryos, gravidity, parity, and OCM-related indicators (serum level of homocysteine, folate, and vitamin B12; MTHFR C677T genotype) was collected. Results: The accuracy of the prediction model based on the screened independent risk factors (hyperhomocysteine, OR = 1.170, 95% CI = 1.061-1.291; high folate status, OR = 1.018, 95% CI = 0.999-1.038; and high BMI, OR = 1.216, 95% CI = 1.140-1.297) for PIH in subjects with MTHFR CC genotype (AUC = 0.802) was obviously higher than that in subjects with MTHFR CT, TT genotype (AUC = 0.684,0.685, respectively) by receiver operating characteristic curve analysis. The homocysteine level of the PIH group was significantly higher than that of the normotensive group only in subjects with the MTHFR CC genotype (p = 0.005). A negative correlation between homocysteine and folate appeared in subjects with MTHFR CT + TT genotype (p = 0.005). A model including multiple embryos, nulliparas, and lower folate could predict the process from PIH to PE (AUC = 0.781, p < 0.0001). Conclusion: The prediction model composed of homocysteine, folate, and BMI for PIH was suitable for subjects with MTHFR CC genotype in pregnant women with supplementation of folate and vitamin B12. Lower folate levels could be an independent risk factor in developing the process from PIH to PE.

Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial / Efeito da pré‐ administração de flurbiprofeno axetil na CE50 do propofol durante anestesia em pacientes não estimulados: estudo clínico randomizado

Abstract Background and objectives Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol. Methods Ninety-six patients (ASA I or II, aged 18-65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg−1, 0.75 mg.kg−1 and 1 mg.kg−1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The "up-and-down" method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 µg.mL−1-lower (or -higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation and 15 minutes after intubation. Results The EC50 of propofol was lower in Group C (2.32 µg.mL−1, 95% Confidence Interval [95% CI] 1.85-2.75) and D (2.39 µg.mL−1, 95% CI 1.91-2.67) than in Group A (2.96 µg.mL−1, 95% CI 2.55-3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 µg.mL−1, 95% CI 2.33-2.71) and Group A (p > 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p < 0.01) and 15 minutes after intubation (61 ± 4 vs. 70 ± 8 bpm, p < 0.01). There were no significant differences among the four groups in Mean Arterial Pressure (MAP) at any time point. The MAP of the four groups was significantly lower after induction, after intubation, and 15 minutes after intubation than at baseline (p < 0.05). Conclusion High-dose FA (0.75 mg.kg−1 or 1 mg.kg−1) reduces the EC50 of propofol, and 1 mg.kg−1 FA reduces the HR for adequate anesthesia in unstimulated patients. Although this result should be investigated in cases of surgical stimulation, we suggest that FA pre-administration may reduce the propofol requirement when the depth of anesthesia is measured by BIS.

Resumo Justificativa e objetivos A administração pré‐operatória de Flurbiprofeno Axetil (FA) é amplamente usada para a modulação da analgesia. No entanto, a relação entre FA e fármacos sedativos permanece obscura. Neste estudo, nosso objetivo foi investigar os efeitos de diferentes doses de FA na Concentração Efetiva mediana (CE50) do propofol. Métodos Noventa e seis pacientes (ASA I ou II, com idades de 18-65 anos) foram alocados aleatoriamente em quatro grupos na proporção de 1:1:1:1. Dez minutos antes da indução, o Grupo A (grupo controle) recebeu 10 mL de Intralipid, enquanto os grupos B, C e D receberam FA na dose de 0,5 mg.kg‐1; 0,75 mg.kg‐1 e 1 mg.kg‐1, respectivamente. A profundidade da anestesia foi medida pelo Índice Bispectral (BIS). O método up‐and‐down foi usado para calcular a CE50 do propofol. Durante o período de equilíbrio, se o valor do BIS fosse ≤ 50 ou BIS > 50, o próximo paciente tinha a infusão de propofol ajustada para uma concentração alvo‐controlada 0,5 µg.mL‐1 inferior ou superior, respectivamente. Os dados hemodinâmicos foram registrados no início do estudo, 10 minutos após a administração de FA, após a indução, após a intubação e 15 minutos após a intubação. Resultados A CE50 do propofol foi menor no Grupo C (2,32 µg.mL‐1, Intervalo de Confiança de 95% [95% IC] 1,85-2,75) e D (2,39 µg.mL‐1, 95% IC 1,91-2,67) do que no Grupo A (2,96 µg.mL‐1; 95% IC 2,55-3,33) (p = 0,023, p = 0,048, respectivamente). Não houve diferenças significantes na CE50 entre o Grupo B (2,53 µg.mL‐1, 95% IC 2,33-2,71) e o Grupo A (p > 0,05). Não houve diferenças significantes na Frequência Cardíaca (FC) entre os grupos A, B e C. A FC foi significantemente menor no grupo D do que no grupo A após a intubação (66 ± 6 vs. 80 ± 10 bpm, p < 0,01) e 15 minutos após a intubação (61 ± 4 vs. 70 ± 8 bpm, p < 0,01). Não houve diferenças significantes entre os quatro grupos na Pressão Arterial Média (PAM) em qualquer momento. A PAM dos quatro grupos foi significantemente menor após a indução, após a intubação e 15 minutos após a intubação do que na linha de base (p < 0,05). Conclusão FA em altas doses (0,75 mg.kg‐1 ou 1 mg.kg‐1) reduz a CE50 do propofol, e 1 mg.kg‐1 de FA reduz a FC durante níveis adequados de anestesia em pacientes não estimulados. Embora esse resultado deva ser investigado na presença de estimulação cirúrgica, sugerimos que a pré‐administração de FA pode reduzir a necessidade de propofol durante anestesia cuja profundidade seja monitorada pelo BIS.

[Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial]. / Efeito da pré­administração de flurbiprofeno axetil na CE50 do propofol durante anestesia em pacientes não estimulados: estudo clínico randomizado.

BACKGROUND AND OBJECTIVES: Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol. METHODS: Ninety-six patients (ASA I or II, aged 18-65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg-1, 0.75 mg.kg-1 and 1 mg.kg-1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The "up-and-down" method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 µg.mL-1-lower (or-higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation, and 15 minutes after intubation. RESULTS: The EC50 of propofol was lower in Group C (2.32 µg.mL-1, 95% Confidence Interval [95% CI] 1.85-2.75) and D (2.39 µg.mL-1, 95% CI 1.91-2.67) than in Group A (2.96 µg.mL-1, 95% CI 2.55-3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 µg.mL-1, 95% CI 2.33-2.71) and Group A (p ˃ 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p < 0.01) and 15 minutes after intubation (61 ± 4 vs. 70 ± 8 bpm, p < 0.01). There were no significant differences among the four groups in Mean Arterial Pressure (MAP) at any time point. The MAP of the four groups was significantly lower after induction, after intubation, and 15 minutes after intubation than at baseline (p < 0.05). CONCLUSION: High-dose FA (0.75 mg.kg-1 or 1 mg.kg-1) reduces the EC50 of propofol, and 1 mg.kg-1 FA reduces the HR for adequate anesthesia in unstimulated patients. Although this result should be investigated in cases of surgical stimulation, we suggest that FA pre-administration may reduce the propofol requirement when the depth of anesthesia is measured by BIS.

Pyruvate Protects Against Intestinal Injury by Inhibiting the JAK/STAT Signaling Pathway in Rats With Hemorrhagic Shock.

BACKGROUND: This study aimed to investigate the role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in protection by peritoneal resuscitation (PR) using pyruvate-peritoneal dialysis solution (PY-PDS) against intestinal injury from hemorrhagic shock (HS) in rats. MATERIALS AND METHODS: Sixty-four rats were assigned to eight groups: group SHAM; group intravenous resuscitation (VR); groups NS, LA, and PY in which the rats were subjected to HS and PR with normal saline (NS), lactate-peritoneal dialysis solution (LA-PDS), and PY-PDS, respectively, combined with VR; and groups DMSO, RPM, and AG490 in which the rats were subjected to HS and VR with pretreatment of dimethyl sulfoxide (DMSO), rapamycin (RPM), and tyrphostin B42 (AG490). RESULTS: At 2 h after HS and resuscitation, the levels of diamine oxidase, 15-F2t-isoprostane, thromboxane B2, and endothelin-1, in the blood and the intestinal mucosal apoptotic index and caspase-3 were lower in groups PY, RPM, and AG490 than in groups VR, NS, LA, and DMSO. Group PY showed lower levels of malondialdehyde and myeloperoxidase and a higher level of superoxide dismutase than groups VR, NS, and LA. Phosphorylated JAK2 and phosphorylated STAT3 levels were lower in groups PY, RPM, AG490, and LA than in groups VR, NS, and DMSO. CONCLUSIONS: The protection mechanism of PR with PY-PDS combined with VR was related to the inhibition of the JAK/STAT signaling pathway during HS and resuscitation. The process might include suppression of oxidative stress, reduction of neutrophil infiltration, regulation of microcirculation, and inhibition of apoptosis.

Identification, characterization of selenoprotein W and its mRNA expression patterns in response to somatostatin 14, cysteamine hydrochloride, 17ß-estradiol and a binary mixture of 17ß-estradiol and cysteamine hydrochloride in topmouth culter (Erythroculter ilishaeformis).

In this study, a selenoprotein W cDNA was cloned from topmouth culter (Erythroculter ilishaeformis), and it was designated as EISelW. The EISelW open reading frame was composed of 261 base pairs (bp), encoding 86-amino-acid protein. The 5' untranslated region (UTR) consisted of 104 bp, and the 3'-UTR was composed of 365 bp. A selenocysteine insertion sequence (SECIS) element was found in the 3'-UTR of EISelW mRNA. The SECIS element was classified as form II because of a small additional apical loop presented in SECIS element of EISelW mRNA. Bioinformatic approaches showed that the secondary structure of EISelW was a ß1-α1-ß2-ß3-ß4-α2 pattern from amino-terminal to carboxy-terminal. Real-time PCR analysis of EISelW mRNAs expression in 17 tissues showed that the EISelW mRNA was predominantly expressed in liver, ovary, pituitary, various regions of the brain, spinal cord and head kidney. Study of intraperitoneal injection showed that the levels of EISelW mRNA in brain, liver, ovary and spleen were regulated by somatostatin 14 (SS14), 17ß-estradiol (E2), cysteamine hydrochloride (CSH) and a binary mixture of E2 and CSH, dependent on the dosage. These results suggest that E2, SS14 and CSH status may affect tissues of selenium metabolism by regulating the expression of SelW mRNA, as SelW plays a central role in selenium metabolism.

The effect of electroacupuncture at ST36 on severe thermal injury-induced remote acute lung injury in rats.

OBJECTIVE: Acupuncture at ST36 can produce anti-inflammatory effects, which might be associated with vagus nerve activity. This study explored the effects of electroacupuncture (EA) at ST36 on severe thermal injury-induced remote acute lung injury in rats. INTERVENTIONS: Forty male Sprague-Dawley (SD) rats were randomly divided into five groups: (1) the sham (S) group, (2) the thermal injury (TEM) group subjected to 30% total body surface area (30% TBSA) third-degree scald, (3) the EA at ST36 group subjected to EA stimulation at ST36 (3V, 2ms, and 3Hz) after 30% TBSA scald, (4) the EA at non-acupoint group subjected to EA stimulation at non-acupoint after 30% TBSA scald, and (5) the α-bungarotoxin (α7 nicotinic acetylcholine receptor subunit antagonist) group administered 1.0 µg kg(-1) α-bungarotoxin before EA at ST36. MEASUREMENTS AND MAIN RESULTS: Thermal injury of 30% TBSA induced leukocytosis in the alveolar space, interstitial edema, and the pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, and high-mobility group box 1 (HMGB-1); the expression of both HMGB-1 messenger RNA (mRNA) and protein in lung tissue was significantly enhanced. EA at ST36 significantly downregulated the levels of inflammatory cytokines and improved lung tissue injury. However, pretreatment with α-bungarotoxin reversed the effects of electrical stimulation of ST36. CONCLUSIONS: EA at ST36 might have a potential protective effect on severe thermal injury-induced remote acute lung injury via limitation of inflammatory responses in rats.

Smac is another pathway in the anti-tumour activity of Trichosanthin and reverses Trichosanthin resistance in CaSki cervical cancer cells.

Trichosanthin (TCS), or Tin Hua Fen, is a renowned traditional Chinese medicine and is still used in Chinese clinics for midterm abortion and the treatment of choriocarcinoma. Many studies have demonstrated that TCS has anti-tumour action as a type I ribosome-inactivating protein. We hypothesized that there is another pathway of the anti-tumour activity of TCS. cDNA array analysis was applied to profile changes in gene expression of human CaSki in response to TCS stimulation. Smac, a mitochondrial protein, was identified as the highly upregulated protein in response to TCS treatment. The mRNA and protein levels of Smac were determined by real-time RT-PCR and Western blotting respectively. We analysed the methylation status of Smac using methylation-specific PCR (MSP) and indicates that TCS promotes Smac demethylation and increases its expression in cervical CaSki cells. Tumour cells develop resistance to TCS during prolonged treatment, as with other classic chemotherapeutic agents. Smac expression was downregulated and Twist was upregulated in TCS-resistant cells. These results indicate that TCS has demethylating activity and that Smac is involved in both TCS response and TCS resistance.

Protection against intestinal injury from hemorrhagic shock by direct peritoneal resuscitation with pyruvate in rats.

OBJECTIVE: We explored the effects of direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution (PDS) following intravenous resuscitation (VR) on intestinal ischemia-reperfusion injury in rats with hemorrhagic shock (HS). METHODS: Fifty rats were randomly assigned equally to five groups. In group sham, a surgical operation was performed on rats without shock or resuscitation. In group VR, rats were subjected only to VR. In groups NS, LA, and PY, direct peritoneal resuscitation was performed with normal saline (NS), lactate-based PDS (Lac-PDS), and pyruvate-based PDS (Pyr-PDS), respectively, after VR. Mean arterial pressure was monitored in the right common carotid artery. Two hours after resuscitation, the lactate level in arterial blood and the wet weight/dry weight ratio of the intestine were determined. The intestinal mucosal damage index was estimated, and ultrastructural changes in the intestinal mucosa were observed. Malondialdehyde, myeloperoxidase, nitric oxide, and tumor necrosis factor α levels were also measured. RESULTS: Two hours after HS and resuscitation, the increase in arterial blood lactate and intestinal wet weight/dry weight ratio declined significantly in rats from Groups LA and PY compared with groups VR and NS, whereas group PY was more advantageous in the changes of these parameters. The intestinal mucosal damage index and ultrastructural changes were also improved in groups LA and PY when compared with groups VR and NS. Protection was more apparent with Pyr-PDS than Lac-PDS. Hemorrhagic shock resulted in a significant increase in malondialdehyde levels and myeloperoxidase activity and was accompanied by overexpression of tumor necrosis factor α and a reduction in nitric oxide levels. These changes were significantly attenuated by Lac-PDS and Pyr-PDS at 2 h after resuscitation, and Pyr-PDS showed more effective protection for the intestine than Lac-PDS. CONCLUSIONS: Direct peritoneal resuscitation with Lac-PDS and Pyr-PDS after VR alleviated intestinal injury from HS in rats, and Pyr-PDS was superior to Lac-PDS in its protective effect. Mechanisms of action might include the elimination of free oxygen radicals, reduction of neutrophil infiltration, inhibition of the inflammatory response, and regulation of intestinal mucosal blood flow and barrier function.

Transduced PEP-1-heme oxygenase-1 fusion protein protects against intestinal ischemia/reperfusion injury.

BACKGROUND: Heme oxygenase-1 (HO-1) has been shown to have antioxidant and anti-apoptotic properties. The present study transduced HO-1 protein into intestinal tissues using PEP-1, a cell-penetrating peptide, and investigated its potentiality in prevention against intestinal ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: PEP-1-HO-1 fusion protein was administered intravenously to explore the time and dose characteristics through measuring serum HO-1 levels. Twenty-four male Sprague-Dawley rats were randomly divided into three groups: sham, intestinal I/R (II/R), II/R + PEP-1-HO-1 fusion protein (HO). The model was established by occluding the superior mesenteric artery for 45 min followed by 120 min reperfusion. In HO group, PEP-1-HO-1 was administered intravenously 30 min before ischemia, whereas animals in sham and II/R groups received the equal volume of physiological saline. After the experiment, the intestines were harvested for determination of histologic injury, wet/dry ratio, enzyme activity, apoptosis, and His-probe protein (one part of PEP-1-HO-1). RESULTS: Levels of serum HO-1 were dose- and time-dependent manner after intravenous injection of PEP-1-HO-1. I/R caused deterioration of histologic characteristics and increases in histologic injury scoring, wet/dry ratio, myeloperoxidase activity, malondialdehyde, and intestinal apoptosis. These changes were also accompanied by a decrease in superoxide dismutase activity (P < 0.05). PEP-1-HO-1 treatment significantly reversed these changes (P < 0.05). Furthermore, His-probe protein expression was only detected in PEP-1-HO-1-treated animals. CONCLUSION: Treatment of PEP-1-HO-1 attenuates intestinal I/R injury, which might be attributable to its antioxidant and anti-apoptotic roles of HO-1.

Structure-activity relationship of 39 analogs of laetispicine with antidepressant properties.

The natural product Laetispicine ( N -isobutyl-(3,4-methylendioxyphenyl)-2E, 4E, 9E-undecatrienoamide), was isolated from the Piper laetispicum C. DC and screened, for its antidepressant activity and antinociceptive effects. Structure-functional activities of five natural products indicated that biological activity is dependent on double bonds present within the benzene ring and a conjugated double bond located at positions 2-3 and 4-5 in the molecular structure. To further understand the structural-activity relationship of Laetispicine as a new potent and safe antidepressant, the structural-activity relationship of 39 analogs of Laetispicine were synthetized and tested in forced swimming tests in mice whilst also in protective effects against glutamate or H 2 O 2 induced apoptosis in PC12 cells. The results show that the compound 30 - N -isobutyl-11-(4-chlorophenyl) undeca-2E,4E,9E-trienamide exhibited the same activity as the parental compound Laetispicine, and furthermore, the effective dose of this compound is lower than Laetispicine. Therefore, the compound 30 might be a potentially useful therapy in the treatment of depression. For structure, the conjugated double bonds located at 2-3, 4-5 and isolated double bonds from benzene ring are necessary for the antidepressant activities no matter the different length of carbon chain; the isobutyl connected with acylamino also are necessary; and the benzodioxole moiety is replaceable, the halogen atom in phenyl ring at the para-position could enhance this kind of activity.

The effects of stimulation at acupoint ST36 points against hemorrhagic shock in dogs.

The aim of this study is to investigate the effects of electroacupuncturing (EA) zusanli points on levels of basic hemodynamics, lactate, and cytokines in dogs with hemorrhagic shock. Thirty healthy dogs were randomly divided into 5 groups: sham hemorrhagic shocked group, hemorrhagic shocked group, EA group, nonacupuncturing group, and EA after vagotomy group. Zusanli points were electroacupunctured with constant voltage (10-15 V, 30 Hz) for 30 minutes immediately after the shock models were established. Before the stimulation, a blood pressure transducer was implanted into the right femoral artery for continuous recording of mean arterial pressure (MAP), and a 5F Swan-Ganz pediatric catheter was implanted into the pulmonary artery. The levels of serum tumor necrosis factor α (TNF-α) in the femoral artery were detected at 0, 120, and 180 minutes after hemorrhage. The levels of serum lactate in the femoral artery were detected before hemorrhage (-45 minutes), at 0 minute, and at 180 minutes. In the hemorrhagic shocked group, the levels of MAP, cardiac output, cardiac index, central venous pressure, and pulmonary arterial wedge pressure decreased significantly; at the same time, the levels of serum TNF-α and serum lactate increased significantly. There were no differences between these groups and the hemorrhagic group, but they were different from the sham hemorrhagic shocked group. In the EA group, the levels of MAP, cardiac output, cardiac index, central venous pressure, and pulmonary arterial wedge pressure gradually increased, but the content of serum TNF-α and lactate obviously decreased. The results suggested that EA zusanli points produce a protective effect on hemorrhagic shock in dogs.

[Effect of recombinant trichosanthin on proliferation of human cevical cancer Caski cells].

OBJECTIVE: To observe the effects of high expression of recombinant trichosanthin (rTCS) on the cell proliferation and cell cycle of human cervical cancer Caski cells. METHOD: Eukaryotic expression plasmid pcDNA3.1(-)/6His-TCS was constracted and stably transfected into Caski cells. RT-PCR,Western-blot were used to select the clones with rTCS high-expressing. Using pcDNA3.1(-)-transfected cells as the control, MTT assay and flowcytometry were used to elucidate the effects of rTCS high expression on cell growth and cycle regulation in Caski cells. RESULT: The Caski cells with stable high expression of rTCS was successfully established, which could inhibit the cell growth (P<0.01) and arrest Caski cells in G1 and G2 phases (P<0.05) obviously. CONCLUSION: High expression of rTCS can inhibit the growth of Caski cervical cancer cells, which might provide a new pathway for the therapy of cervical cancer.

Shenfu injection suppresses apoptosis by regulation of Bcl-2 and caspase-3 during hypoxia/reoxygenation in neonatal rat cardiomyocytes in vitro.

Shenfu injection (the major components of which are ginsenosides compound, extract of Panax ginseng shown to have antioxidant properties) is a well-known important Chinese traditional medicine used for the treatment of various diseases especial for cardiac diseases. The precise mechanism of the biological actions of this plant is not fully understood, in order to elucidate the protection of cardiomyocytes. The aim of the present study was to investigate the effect of Shenfu injection on hypoxia/reoxygenation (H/R)-induced apoptosis and the expression of bcl-2 and caspase-3 in cultured neonatal rat cardiomyocytes in vitro. Ventricular myocytes were isolated from neonatal rat hearts and were exposed to 4 h of hypoxia followed by 16 h of reoxygenation. The results indicated that treatment with different doses of Shenfu injection protected cardiacmyocyte cultures from hypoxia/reoxygenation-induced apoptosis. Caspase-3 activation was decreased in hypoxic/reoxygenationed cardiomyocytes co-treated with Shenfu injection when compared to hypoxia/reoxygenation alone treated cultures. Expression of the Bcl-2 proteins was increased in Shenfu injection-treated cardiomyocytes subjected to hypoxia/reoxygenation. In conclusion, ginsenosides compound has obviously protective effects on cardiacmyocytes against apoptosis induced by hypoxia/reoxygenation injury, whose mechanisms probably involve the inhibition of down-regulation of Bcl-2 protein levels and sequential activation of caspase-3.

How does the pre-massage and post-massage 2-glass test compare to the Meares-Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome?

PURPOSE: The Meares-Stamey 4-glass test is the standard method of assessing inflammation and the presence of bacteria in the lower urinary tract in men presenting with the chronic prostatitis syndrome. However, most urologists do not use it in daily practice because of the time and difficulty in performing it, as well as the additional expense. We evaluated a simpler test, the 2-glass pre-massage and post-massage test, and compared it with the Meares-Stamey 4-glass test to detect inflammation and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: The study population included 353 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study with baseline leukocyte counts and 2-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, expressed prostatic secretions, VB3). The chi-square test was performed to assess associations of white blood cell counts in expressed prostatic secretions and VB3. A receiver operating characteristic curve was constructed to determine the optimal cut point of white blood cells in VB3 in predicting white blood cells in expressed prostatic secretions. Sensitivity and specificity of VB3 cultures predicting expressed prostatic secretions and positive Meares-Stamey results were calculated from 2 x 2 contingency tables. RESULTS: Analysis of binary leukocyte outcomes (no white blood cells vs any white blood cells) suggests that white blood cells tend to be present in expressed prostatic secretions when there are any white blood cells in VB3, p <0.0001, the optimal cut point being white blood cell counts of 3 in VB3 (best predictive ability with area under ROC 0.771) to predict 5+ in expressed prostatic secretions with a sensitivity of 76% and specificity of 70%. The optimal cut point of white blood cells in VB3 to predict 10 white blood cells in expressed prostatic secretions was 4 (62% sensitivity and 75% specificity). Uropathogens localizing to expressed prostatic secretions or VB3 confirms a positive 4-glass Meares-Stamey localization test. The sensitivity and specificity of a VB3 localizing culture only in predicting a positive Meares-Stamey 4-glass test result for any uropathogen were 44% to 54% (depending on definition) and 100%, respectively. The pre-massage and post-massage test predicted a correct diagnosis in more than 96% of subjects. CONCLUSIONS: The value of localizing leukocytes and uropathogens to prostate specific specimens remains controversial in chronic heavily pretreated patients, but these data may help direct therapy (anti-inflammatory or antimicrobial) when obtained at first presentation. The pre-massage and post-massage test has strong concordance with the 4-glass test and is a reasonable alternative when expressed prostatic secretions are not obtained.

Diterpenoids from the Chinese herb Caryopteris terniflora and their antibacterial and antitumor activity.

Two ent-kaurene type diterpenoids, diterpenoids A (1) and B (2) were isolated from the Chinese herb Caryopteris terniflora and defined as ent-7beta, 11alpha,14-trihydroxy-18-aldehyde-11beta-20-epoxy-kaur-16-en15-one and ent-7beta,14-dihydroxy-11alpha-methoxy-18-aldehyde-11beta-20-epoxy-kaur-16-en-15-one respectively. Compounds 1 and 2 showed significant antibacterial and antitumour activity.

Effect of Shenfu injection on nuclear factor-kappaB during myocardial ischemia/reperfusion injury in rats.

OBJECTIVE: To investigate effects of Shenfu injection on the concentrations of plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), activity of Nuclear Factor kappa B (NF-kappaB) and heart tissue ultrastructure during myocardial ischemia/reperfusion (I/R) injury in rats and its potential mechanism. METHODS: Myocardial ischemia/reperfusion (I/R) was produced by ligation and release of the left anterior descending coronary artery. Ischemia lasted for 30 min and reperfusion for 60 min. Twenty-four healthy male SD rats weighing 230-280 g were randomly divided into three groups (n = 8, each): Group I (Sham-operation group); Group II (I/R group); Group III (Shenfu group), in which Shenfu injection (10 ml/kg) was intraperitoneally injected 30 min before ischemia in animals with I/R. The plasma concentrations of IL-6 and TNF-alpha were measured by ELISA, and the heart was harvested for determination of NF-kappaB levels by Ecl-western blot analysis. Electron microscopy was used to study its ultrastructure. RESULTS: After reperfusion, NF-kappaB binding activity in myocardial nuclei and the plasma concentrations of IL-6 and TNF-alpha were significantly increased in Group II, compared with Group I (P < 0.01), and they were markedly reduced in Group III, compared with Group II (P < 0.01). In addition, electron microscopic examination showed more serious injury of the myocardium ultrastructure in Group II, while in Group III the myocardial ultrastructure was similar to normal state. CONCLUSIONS: Shenfu injection inhibits NF-kappaB activity in I/R myocardium and leads to down-regulation of proinflammatory cytokine expression, which might be one of the molecular mechanisms of Shenfu injection in cardioprotection.